User login
Overcoming the challenges of COVID-19 for Alzheimer’s patients in long-term care, research
An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.1
When ADLs become a matter of survival
For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).
Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.
The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
Resource diversion and mitigation strategies
Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.
Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.
Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).2
Resilience and recovery in a retrospective study
A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.
The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.
Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.3 Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, , which underscores the importance of early diagnosis and intervention.
Genetic and environmental susceptibility
One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.4
Transcending research design
The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.
To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).
Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.5
References
1. Ritchie K. KJZZ. 2020 Nov 16.
2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.
3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.
4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.
5. Alzheimers Dement. 2020 Apr;16(4):587-8.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.
An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.1
When ADLs become a matter of survival
For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).
Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.
The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
Resource diversion and mitigation strategies
Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.
Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.
Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).2
Resilience and recovery in a retrospective study
A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.
The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.
Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.3 Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, , which underscores the importance of early diagnosis and intervention.
Genetic and environmental susceptibility
One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.4
Transcending research design
The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.
To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).
Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.5
References
1. Ritchie K. KJZZ. 2020 Nov 16.
2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.
3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.
4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.
5. Alzheimers Dement. 2020 Apr;16(4):587-8.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.
An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.1
When ADLs become a matter of survival
For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).
Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.
The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
Resource diversion and mitigation strategies
Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.
Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.
Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).2
Resilience and recovery in a retrospective study
A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.
The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.
Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.3 Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, , which underscores the importance of early diagnosis and intervention.
Genetic and environmental susceptibility
One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.4
Transcending research design
The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.
To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).
Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.5
References
1. Ritchie K. KJZZ. 2020 Nov 16.
2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.
3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.
4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.
5. Alzheimers Dement. 2020 Apr;16(4):587-8.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.
How to identify, evaluate, and treat patients with ‘Percocet use disorder’
In recent years, Percocet (oxycodone/paracetamol) has experienced a meteoric rise to prominence because of the presence of conspicuous references in pop culture and the ever-evolving hip-hop scene,1 so much so that even propafenone is being mislabeled as the agent.2 It is of utmost importance for clinicians to be made aware of the adverse effects and the treatment protocols associated with Percocet as well as propafenone.
Propafenone is identified as a class 1C antiarrhythmic with adverse effects associated with that particular class of drugs (e.g., generalized tonic-clonic seizures coupled with widened QRS complex), however, Percocet’s toxidrome is the product of the opioid/nonopioid (in the form of oxycodone/acetaminophen) components found within the formulation. Percocet is often recreationally used with MDMA (“molly”) or ecstasy as popularized by the lyrics of “Mask Off” by Future (“Percocets, Molly, Percocets”).3,4
Addressing the challenge of imitation Percocet pills
Differentiating the untoward effects of Percocet and propafenone isn’t too challenging because the agents belong to separate classes – the problem is the use of deceitful labels on propafenone with both medications sporting the “512 imprint” on their respective pills. Initial symptoms of propafenone ingestion may include weakness and dizziness followed by seizures.5As an emergent situation, the patient should be immediately treated with a sodium bicarbonate infusion to effectively reverse the sodium channel blockade associated with the widened QRS.
However, a more likely scenario is that of Percocet counterfeit pills designed to illicitly emulate the properties of officially marketed Percocet. As expected, Percocet overdose management will require that the clinician be familiar with treating general opioid toxicity (in this case, derived from the oxycodone component), in particular respiratory or CNS depression. Symptoms of opioid overdose also include the loss of consciousness with pupillary miosis. Therapy entails the use of naloxone and/or mechanical ventilation for respiratory support. The patient can also exhibit cardiovascular compromise. If further information is elicited during a patient interview, it may reveal a history of drug procurement from the streets.
Epidemiologists from Georgia collaborated with the state’s department of public health’s office of emergency services, forensic experts, and drug enforcement professionals to evaluate almost 40 cases of counterfeit Percocet overdoses during the period spanning the second week of June 2017. Of these cases, a cluster triad was identified consisting of general opioid toxicity symptoms (for example, CNS or respiratory depression with concomitant pupillary constriction, a history of drug procurement, and a history of ingesting only one or two pills with rapid deterioration.6 Unfortunately, the screening process is often hindered by the fact that synthetic opioids such as Percocet are not readily identified on urine drug screens (UDS).
Despite shortcomings in assessment procedures, a UDS will yield positive results for multiple drugs, a feature that is common to seasoned opioid users and serves as an instrumental diagnostic clue in the investigative process. To address the crisis and prevent further spread, numerous Georgia agencies (e.g., drug trafficking and legal authorities) worked with the health care community to expediently identify cases of interest and bring forth public awareness concerning the ongoing perils of counterfeit drug intake. Future investigations might benefit from the implementation of DNA-verified UDS, because those screens are versatile enough to detect the presence of synthetic urine substitutes within the context of opioid use.7,8 Moreover, an expanded panel could be tailored to provide coverage for semisynthetics, including hydrocodone, oxycodone, hydromorphone, and oxymorphone.9
As a well-received painkiller from the opioid family, Percocet derives its analgesic properties from the fast-acting oxycodone; hepatic failure is also possible from Percocet (because of the acetaminophen component) or counterfeit Percocet overdose but is less common unless the Tylenol content approaches 4 grams. By binding to the brain’s opiate receptors, Percocet modulates pain pathways leading to a dulling of pain sensation along with euphoria, which is particularly attractive to drug seekers. Chronic Percocet use corresponds with a myriad of psychological and physical consequences, and the Drug Enforcement Administration recognizes oxycodone as a Schedule II drug.
A chronic Percocet user may try to disrupt the cycle of symptoms by abruptly ceasing use of the offending agent. This can precipitate the development of classical opioid-based withdrawal symptoms, including but not limited to nausea, vomiting, irritability, tachycardia, body aches, and episodes of cold sweats. Physicians have noted that misuse (i.e., deviations from intended prescribed) might include crushing and snorting as well as “doctor-shopping” behaviors for a continuous supply of Percocet.
Treatment recommendations
According to Sarah Wakeman, MD, medical director of the substance use disorders initiative at Massachusetts General Hospital in Boston, there are apparently two clinical manifestations of Percocet use. The primary consequence is derived from the oxycodone component of Percocet; as an opioid, oxycodone toxicity leads to disrupted breathing and oxygenation, negatively impacting vital organs such as the brain or the heart. Patients experiencing a lack of oxygen will often display cyanosis and may not respond appropriately to stimuli. For individuals suspected of succumbing to overdose, Dr. Wakeman reportedly advised that the clinician or trained professional rub his or her knuckles along the breastbone of the potential user – a drug overdose patient will fail to wake up. On the other hand, a Percocet user may exhibit the symptoms of liver failure depending on the overall level of acetaminophen in the formulation. To prevent relapses, Percocet use disorder is best managed in a professional setting under the direction of trained clinicians; users are provided medications to address ongoing cravings and symptoms associated with the withdrawal process. A detoxification center can tailor the treatment with opioid-based medications such as methadone, buprenorphine, and naltrexone to help patients be weaned off Percocet.
Clinicians may further improve the efficacy of a therapeutic regimen by incorporating a personalized plan with a comprehensive substance UDS panel for monitoring and treatment purposes. This may prove to be beneficial in the event of suspected polysubstance use, as is the case with patients who dabble with Percocet and “molly.” Preparations can also be instituted at the outset of therapy with genetic testing implemented in high-risk patients who exhibit an inclination for opioid use disorder.10 Genetic polymorphisms provide robust clinical assets for evaluating patients most at risk for relapse. For individuals with biological susceptibility, arrangements can be made to incorporate nonopioid treatment alternatives.
References
1. Thomas BB. The death of Lil Peep: How the U.S. prescription drug epidemic is changing hip-hop. The Guardian. 2017 Nov 16.
2. D’Orazio JL and Curtis JA. J Emer Med. 2011 Aug 1;41(2):172-5.
3. Levy L. These are the drugs influencing pop culture now. Vulture. 2018 Feb 6.
4. Kounang N and Bender M. “What is Percocet? Drug facts, side effects, abuse and more.” CNN. 2018 Jul 12.
5. The dangers of Percocet use and overdose. American Addiction Centers. Last updated 2020 Feb 3. https://americanaddictioncenters.org/percocet-treatment/dangers-of-use-and-overdose.
6. Edison L et al. MMWR. 2017 Oct 20;66(41):1119-20.
7. Choudhry Z et al. J Psychiatry. 2015. doi: 10.4172/2378-5756.10000319.
8. Islam F and Choudhry Z. Current Psychiatry. 2018 Dec;17(12):43-4.
9. Jupe N. Ask the Experts: DOT 5-panel drug test regimen. Quest Diagnostics. 2018 Mar 21. https://blog.employersolutions.com/ask-experts-dot-5-panel-drug-test-regimen/.
10. Ahmed S et al. Pharmacogenomics. 2019 Jun 28;20(9):685-703.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam reported no relevant disclosures. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He reported no relevant disclosures.
In recent years, Percocet (oxycodone/paracetamol) has experienced a meteoric rise to prominence because of the presence of conspicuous references in pop culture and the ever-evolving hip-hop scene,1 so much so that even propafenone is being mislabeled as the agent.2 It is of utmost importance for clinicians to be made aware of the adverse effects and the treatment protocols associated with Percocet as well as propafenone.
Propafenone is identified as a class 1C antiarrhythmic with adverse effects associated with that particular class of drugs (e.g., generalized tonic-clonic seizures coupled with widened QRS complex), however, Percocet’s toxidrome is the product of the opioid/nonopioid (in the form of oxycodone/acetaminophen) components found within the formulation. Percocet is often recreationally used with MDMA (“molly”) or ecstasy as popularized by the lyrics of “Mask Off” by Future (“Percocets, Molly, Percocets”).3,4
Addressing the challenge of imitation Percocet pills
Differentiating the untoward effects of Percocet and propafenone isn’t too challenging because the agents belong to separate classes – the problem is the use of deceitful labels on propafenone with both medications sporting the “512 imprint” on their respective pills. Initial symptoms of propafenone ingestion may include weakness and dizziness followed by seizures.5As an emergent situation, the patient should be immediately treated with a sodium bicarbonate infusion to effectively reverse the sodium channel blockade associated with the widened QRS.
However, a more likely scenario is that of Percocet counterfeit pills designed to illicitly emulate the properties of officially marketed Percocet. As expected, Percocet overdose management will require that the clinician be familiar with treating general opioid toxicity (in this case, derived from the oxycodone component), in particular respiratory or CNS depression. Symptoms of opioid overdose also include the loss of consciousness with pupillary miosis. Therapy entails the use of naloxone and/or mechanical ventilation for respiratory support. The patient can also exhibit cardiovascular compromise. If further information is elicited during a patient interview, it may reveal a history of drug procurement from the streets.
Epidemiologists from Georgia collaborated with the state’s department of public health’s office of emergency services, forensic experts, and drug enforcement professionals to evaluate almost 40 cases of counterfeit Percocet overdoses during the period spanning the second week of June 2017. Of these cases, a cluster triad was identified consisting of general opioid toxicity symptoms (for example, CNS or respiratory depression with concomitant pupillary constriction, a history of drug procurement, and a history of ingesting only one or two pills with rapid deterioration.6 Unfortunately, the screening process is often hindered by the fact that synthetic opioids such as Percocet are not readily identified on urine drug screens (UDS).
Despite shortcomings in assessment procedures, a UDS will yield positive results for multiple drugs, a feature that is common to seasoned opioid users and serves as an instrumental diagnostic clue in the investigative process. To address the crisis and prevent further spread, numerous Georgia agencies (e.g., drug trafficking and legal authorities) worked with the health care community to expediently identify cases of interest and bring forth public awareness concerning the ongoing perils of counterfeit drug intake. Future investigations might benefit from the implementation of DNA-verified UDS, because those screens are versatile enough to detect the presence of synthetic urine substitutes within the context of opioid use.7,8 Moreover, an expanded panel could be tailored to provide coverage for semisynthetics, including hydrocodone, oxycodone, hydromorphone, and oxymorphone.9
As a well-received painkiller from the opioid family, Percocet derives its analgesic properties from the fast-acting oxycodone; hepatic failure is also possible from Percocet (because of the acetaminophen component) or counterfeit Percocet overdose but is less common unless the Tylenol content approaches 4 grams. By binding to the brain’s opiate receptors, Percocet modulates pain pathways leading to a dulling of pain sensation along with euphoria, which is particularly attractive to drug seekers. Chronic Percocet use corresponds with a myriad of psychological and physical consequences, and the Drug Enforcement Administration recognizes oxycodone as a Schedule II drug.
A chronic Percocet user may try to disrupt the cycle of symptoms by abruptly ceasing use of the offending agent. This can precipitate the development of classical opioid-based withdrawal symptoms, including but not limited to nausea, vomiting, irritability, tachycardia, body aches, and episodes of cold sweats. Physicians have noted that misuse (i.e., deviations from intended prescribed) might include crushing and snorting as well as “doctor-shopping” behaviors for a continuous supply of Percocet.
Treatment recommendations
According to Sarah Wakeman, MD, medical director of the substance use disorders initiative at Massachusetts General Hospital in Boston, there are apparently two clinical manifestations of Percocet use. The primary consequence is derived from the oxycodone component of Percocet; as an opioid, oxycodone toxicity leads to disrupted breathing and oxygenation, negatively impacting vital organs such as the brain or the heart. Patients experiencing a lack of oxygen will often display cyanosis and may not respond appropriately to stimuli. For individuals suspected of succumbing to overdose, Dr. Wakeman reportedly advised that the clinician or trained professional rub his or her knuckles along the breastbone of the potential user – a drug overdose patient will fail to wake up. On the other hand, a Percocet user may exhibit the symptoms of liver failure depending on the overall level of acetaminophen in the formulation. To prevent relapses, Percocet use disorder is best managed in a professional setting under the direction of trained clinicians; users are provided medications to address ongoing cravings and symptoms associated with the withdrawal process. A detoxification center can tailor the treatment with opioid-based medications such as methadone, buprenorphine, and naltrexone to help patients be weaned off Percocet.
Clinicians may further improve the efficacy of a therapeutic regimen by incorporating a personalized plan with a comprehensive substance UDS panel for monitoring and treatment purposes. This may prove to be beneficial in the event of suspected polysubstance use, as is the case with patients who dabble with Percocet and “molly.” Preparations can also be instituted at the outset of therapy with genetic testing implemented in high-risk patients who exhibit an inclination for opioid use disorder.10 Genetic polymorphisms provide robust clinical assets for evaluating patients most at risk for relapse. For individuals with biological susceptibility, arrangements can be made to incorporate nonopioid treatment alternatives.
References
1. Thomas BB. The death of Lil Peep: How the U.S. prescription drug epidemic is changing hip-hop. The Guardian. 2017 Nov 16.
2. D’Orazio JL and Curtis JA. J Emer Med. 2011 Aug 1;41(2):172-5.
3. Levy L. These are the drugs influencing pop culture now. Vulture. 2018 Feb 6.
4. Kounang N and Bender M. “What is Percocet? Drug facts, side effects, abuse and more.” CNN. 2018 Jul 12.
5. The dangers of Percocet use and overdose. American Addiction Centers. Last updated 2020 Feb 3. https://americanaddictioncenters.org/percocet-treatment/dangers-of-use-and-overdose.
6. Edison L et al. MMWR. 2017 Oct 20;66(41):1119-20.
7. Choudhry Z et al. J Psychiatry. 2015. doi: 10.4172/2378-5756.10000319.
8. Islam F and Choudhry Z. Current Psychiatry. 2018 Dec;17(12):43-4.
9. Jupe N. Ask the Experts: DOT 5-panel drug test regimen. Quest Diagnostics. 2018 Mar 21. https://blog.employersolutions.com/ask-experts-dot-5-panel-drug-test-regimen/.
10. Ahmed S et al. Pharmacogenomics. 2019 Jun 28;20(9):685-703.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam reported no relevant disclosures. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He reported no relevant disclosures.
In recent years, Percocet (oxycodone/paracetamol) has experienced a meteoric rise to prominence because of the presence of conspicuous references in pop culture and the ever-evolving hip-hop scene,1 so much so that even propafenone is being mislabeled as the agent.2 It is of utmost importance for clinicians to be made aware of the adverse effects and the treatment protocols associated with Percocet as well as propafenone.
Propafenone is identified as a class 1C antiarrhythmic with adverse effects associated with that particular class of drugs (e.g., generalized tonic-clonic seizures coupled with widened QRS complex), however, Percocet’s toxidrome is the product of the opioid/nonopioid (in the form of oxycodone/acetaminophen) components found within the formulation. Percocet is often recreationally used with MDMA (“molly”) or ecstasy as popularized by the lyrics of “Mask Off” by Future (“Percocets, Molly, Percocets”).3,4
Addressing the challenge of imitation Percocet pills
Differentiating the untoward effects of Percocet and propafenone isn’t too challenging because the agents belong to separate classes – the problem is the use of deceitful labels on propafenone with both medications sporting the “512 imprint” on their respective pills. Initial symptoms of propafenone ingestion may include weakness and dizziness followed by seizures.5As an emergent situation, the patient should be immediately treated with a sodium bicarbonate infusion to effectively reverse the sodium channel blockade associated with the widened QRS.
However, a more likely scenario is that of Percocet counterfeit pills designed to illicitly emulate the properties of officially marketed Percocet. As expected, Percocet overdose management will require that the clinician be familiar with treating general opioid toxicity (in this case, derived from the oxycodone component), in particular respiratory or CNS depression. Symptoms of opioid overdose also include the loss of consciousness with pupillary miosis. Therapy entails the use of naloxone and/or mechanical ventilation for respiratory support. The patient can also exhibit cardiovascular compromise. If further information is elicited during a patient interview, it may reveal a history of drug procurement from the streets.
Epidemiologists from Georgia collaborated with the state’s department of public health’s office of emergency services, forensic experts, and drug enforcement professionals to evaluate almost 40 cases of counterfeit Percocet overdoses during the period spanning the second week of June 2017. Of these cases, a cluster triad was identified consisting of general opioid toxicity symptoms (for example, CNS or respiratory depression with concomitant pupillary constriction, a history of drug procurement, and a history of ingesting only one or two pills with rapid deterioration.6 Unfortunately, the screening process is often hindered by the fact that synthetic opioids such as Percocet are not readily identified on urine drug screens (UDS).
Despite shortcomings in assessment procedures, a UDS will yield positive results for multiple drugs, a feature that is common to seasoned opioid users and serves as an instrumental diagnostic clue in the investigative process. To address the crisis and prevent further spread, numerous Georgia agencies (e.g., drug trafficking and legal authorities) worked with the health care community to expediently identify cases of interest and bring forth public awareness concerning the ongoing perils of counterfeit drug intake. Future investigations might benefit from the implementation of DNA-verified UDS, because those screens are versatile enough to detect the presence of synthetic urine substitutes within the context of opioid use.7,8 Moreover, an expanded panel could be tailored to provide coverage for semisynthetics, including hydrocodone, oxycodone, hydromorphone, and oxymorphone.9
As a well-received painkiller from the opioid family, Percocet derives its analgesic properties from the fast-acting oxycodone; hepatic failure is also possible from Percocet (because of the acetaminophen component) or counterfeit Percocet overdose but is less common unless the Tylenol content approaches 4 grams. By binding to the brain’s opiate receptors, Percocet modulates pain pathways leading to a dulling of pain sensation along with euphoria, which is particularly attractive to drug seekers. Chronic Percocet use corresponds with a myriad of psychological and physical consequences, and the Drug Enforcement Administration recognizes oxycodone as a Schedule II drug.
A chronic Percocet user may try to disrupt the cycle of symptoms by abruptly ceasing use of the offending agent. This can precipitate the development of classical opioid-based withdrawal symptoms, including but not limited to nausea, vomiting, irritability, tachycardia, body aches, and episodes of cold sweats. Physicians have noted that misuse (i.e., deviations from intended prescribed) might include crushing and snorting as well as “doctor-shopping” behaviors for a continuous supply of Percocet.
Treatment recommendations
According to Sarah Wakeman, MD, medical director of the substance use disorders initiative at Massachusetts General Hospital in Boston, there are apparently two clinical manifestations of Percocet use. The primary consequence is derived from the oxycodone component of Percocet; as an opioid, oxycodone toxicity leads to disrupted breathing and oxygenation, negatively impacting vital organs such as the brain or the heart. Patients experiencing a lack of oxygen will often display cyanosis and may not respond appropriately to stimuli. For individuals suspected of succumbing to overdose, Dr. Wakeman reportedly advised that the clinician or trained professional rub his or her knuckles along the breastbone of the potential user – a drug overdose patient will fail to wake up. On the other hand, a Percocet user may exhibit the symptoms of liver failure depending on the overall level of acetaminophen in the formulation. To prevent relapses, Percocet use disorder is best managed in a professional setting under the direction of trained clinicians; users are provided medications to address ongoing cravings and symptoms associated with the withdrawal process. A detoxification center can tailor the treatment with opioid-based medications such as methadone, buprenorphine, and naltrexone to help patients be weaned off Percocet.
Clinicians may further improve the efficacy of a therapeutic regimen by incorporating a personalized plan with a comprehensive substance UDS panel for monitoring and treatment purposes. This may prove to be beneficial in the event of suspected polysubstance use, as is the case with patients who dabble with Percocet and “molly.” Preparations can also be instituted at the outset of therapy with genetic testing implemented in high-risk patients who exhibit an inclination for opioid use disorder.10 Genetic polymorphisms provide robust clinical assets for evaluating patients most at risk for relapse. For individuals with biological susceptibility, arrangements can be made to incorporate nonopioid treatment alternatives.
References
1. Thomas BB. The death of Lil Peep: How the U.S. prescription drug epidemic is changing hip-hop. The Guardian. 2017 Nov 16.
2. D’Orazio JL and Curtis JA. J Emer Med. 2011 Aug 1;41(2):172-5.
3. Levy L. These are the drugs influencing pop culture now. Vulture. 2018 Feb 6.
4. Kounang N and Bender M. “What is Percocet? Drug facts, side effects, abuse and more.” CNN. 2018 Jul 12.
5. The dangers of Percocet use and overdose. American Addiction Centers. Last updated 2020 Feb 3. https://americanaddictioncenters.org/percocet-treatment/dangers-of-use-and-overdose.
6. Edison L et al. MMWR. 2017 Oct 20;66(41):1119-20.
7. Choudhry Z et al. J Psychiatry. 2015. doi: 10.4172/2378-5756.10000319.
8. Islam F and Choudhry Z. Current Psychiatry. 2018 Dec;17(12):43-4.
9. Jupe N. Ask the Experts: DOT 5-panel drug test regimen. Quest Diagnostics. 2018 Mar 21. https://blog.employersolutions.com/ask-experts-dot-5-panel-drug-test-regimen/.
10. Ahmed S et al. Pharmacogenomics. 2019 Jun 28;20(9):685-703.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam reported no relevant disclosures. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He reported no relevant disclosures.
Separating myth from reality: The role of cannabinoids in COVID-19
An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.
Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.
For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.1
An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.2 A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
Riding the cytokine storm
Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.
Benefits and drawbacks of immunosuppressive agents
To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.
They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.3
SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.
From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.4 CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.
Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.
According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.5 As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.5 Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.
COVID-19 safety protocols for cannabis users
Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.
Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.
A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.6
Conclusion
The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.
COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
References
1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.
2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.
3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.
4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.
5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html
6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.
An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.
Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.
For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.1
An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.2 A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
Riding the cytokine storm
Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.
Benefits and drawbacks of immunosuppressive agents
To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.
They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.3
SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.
From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.4 CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.
Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.
According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.5 As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.5 Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.
COVID-19 safety protocols for cannabis users
Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.
Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.
A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.6
Conclusion
The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.
COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
References
1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.
2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.
3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.
4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.
5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html
6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.
An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.
Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.
For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.1
An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.2 A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
Riding the cytokine storm
Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.
Benefits and drawbacks of immunosuppressive agents
To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.
They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.3
SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.
From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.4 CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.
Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.
According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.5 As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.5 Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.
COVID-19 safety protocols for cannabis users
Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.
Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.
A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.6
Conclusion
The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.
COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
References
1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.
2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.
3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.
4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.
5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html
6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.
Evaluate, manage the stress response in susceptible individuals affected by COVID-19
Steroid therapy should be explored for quarantined mental health patients
Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”1
The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.
We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.2
In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.3 (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)
Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.4
In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
Challenges of neuroendocrine medications for COVID-19
COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.
Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.5 Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.
and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.
In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.
Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.
The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.
Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
Behavioral manifestations and psychosocial health
As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.7 Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.
We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.8
An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”9
The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.
Strategies aimed at supporting mental health
Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.
In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
Employing assessment scales
To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.10
As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.10 As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
Moving forward: The next step in COVID-19 preparedness
As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.
For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.
It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.11 There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.12
References
1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.
2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.
3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.
4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.
5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.
6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.
7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.
8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.
9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.
10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.
11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.
12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.
Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.
Steroid therapy should be explored for quarantined mental health patients
Steroid therapy should be explored for quarantined mental health patients
Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”1
The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.
We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.2
In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.3 (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)
Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.4
In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
Challenges of neuroendocrine medications for COVID-19
COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.
Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.5 Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.
and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.
In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.
Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.
The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.
Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
Behavioral manifestations and psychosocial health
As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.7 Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.
We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.8
An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”9
The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.
Strategies aimed at supporting mental health
Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.
In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
Employing assessment scales
To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.10
As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.10 As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
Moving forward: The next step in COVID-19 preparedness
As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.
For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.
It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.11 There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.12
References
1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.
2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.
3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.
4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.
5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.
6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.
7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.
8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.
9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.
10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.
11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.
12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.
Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.
Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”1
The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.
We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.2
In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.3 (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)
Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.4
In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
Challenges of neuroendocrine medications for COVID-19
COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.
Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.5 Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.
and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.
In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.
Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.
The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.
Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
Behavioral manifestations and psychosocial health
As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.7 Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.
We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.8
An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”9
The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.
Strategies aimed at supporting mental health
Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.
In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
Employing assessment scales
To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.10
As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.10 As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
Moving forward: The next step in COVID-19 preparedness
As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.
For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.
It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.11 There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.12
References
1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.
2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.
3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.
4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.
5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.
6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.
7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.
8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.
9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.
10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.
11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.
12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.
Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.
Revisiting Xanax amid the coronavirus crisis
One of the more alarming trends that has emerged during the coronavirus crisis is the concomitant rise in the use of benzodiazepines, such as Xanax. It has been reported that at-risk individuals began seeking prescription anxiolytics as early as mid-February with a consequent peak of 34% the following month, coinciding with the World Health Organization’s declaration of a global pandemic.1
Consistent with the available literature indicating that women are twice as likely to be affected by anxiety disorders, the prescription spikes were almost double when compared with those of their male counterparts.2 The pandemic has instilled a sense of fear in people, leading to social repercussions, such as estrangement, insomnia, and paranoia for at-risk populations.3,4
“Benzos” are commonly prescribed to help people sleep or to assist them in overcoming a host of anxiety disorders. The rapid onset of effects make Xanax a desirable and efficacious benzodiazepine.5 The use of these medications might not be an immediate cause for concern because patients might be taking it as intended. Nevertheless, clinicians are shying away from medical management in favor of counseling or therapy.
Dangerous trends
Numerous factors might contribute to this grim scenario, including patient dependence on benzodiazepines, paranoia about engaging with health care professionals because of fear tied to potential COVID-19 exposure, and/or increased access to illicit counterfeit pills from drug dealers or the dark web markets.
Lessons can be gleaned from the most extensive dark web drug busts in Britain’s history, in which a deluge of “pharmaceutical grade” Xanax pills made it to the hands of drug dealers and consumers between 2015 and 2017.6 A similar phenomenon emerged stateside.7 Virtually indistinguishable from recognized 2-mg Xanax pills, these fake pills posed a serious challenge to forensic scientists.8 The threat of overdose is very real for users targeted by the counterfeit Xanax trade, especially since those at risk often bypass professional health care guidelines.
In broad daylight, the drug dealers ran their operations revolving around two fake Xanax products: a primary knockoff and a limited edition – and vastly more potent “Red Devil” variant that was intentionally dyed for branding purposes. Because the “Red Devil” formulations contained 2.5 times the dose of the 2-mg pill, it had even more pronounced tolerance, dependence, and withdrawal effects (for example, panic attacks, anxiety, and/or hallucinations) – fatal consequences for users involved in consuming other drugs, such as alcohol or opioids. Preexisting drug users tend to gravitate toward benzodiazepines, such as alprazolam (Xanax), perhaps in part, because of its relatively rapid onset of action. Xanax also is known for inducing proeuphoric states at higher doses, hence the appeal of the “Red Devil” pills.
Benzodiazepines, as a class of drugs, facilitate the neurotransmitter gamma-aminobutryric acid’s (GABA) effect on the brain, producing anxiolytic, hypnotic, and/or anticonvulsant states within the user.9 Unbeknownst to numerous users is the fact that drugs such as alcohol and opioids, like Xanax, also serve as respiratory depressants, overriding the brain’s governance of the breathing mechanism. This, in turn, leads to unintended overdose deaths, even among seasoned drug seekers.
Overdose deaths have been steadily climbing over the years because it is common for some users to consume alcohol while being on Xanax therapy – without realizing that both substances are depressants and that taking them together can lead to side effects such as respiratory depression.
Forensic cases also have revealed that preexisting opioid consumers were drawn to Xanax; the drug’s potent mechanism of action would likely appeal to habituated users. A typical behavioral pattern has emerged among users and must be addressed. According to Australian Professor Shane Darke: “So they take their Xanax, they take their painkiller, then they get drunk, that could be enough to kill them.”
Fatalities are more likely when benzodiazepines are combined with other drug classes or if the existing supply is contaminated or laced (for example, with fentanyl).8
As far as deaths by accidental benzodiazepine overdose are concerned, a similar epidemic has been recorded in the United States. In 2013, almost one-third of all prescription overdose deaths can be attributed to the use of benzodiazepines (for example, Xanax, Valium, and Ativan). However, media attention has been considerably muted, especially when compared with that of narcotic abuse. This is even more puzzling when taking into account that three-quarters of benzodiazepine mortalities co-occur within the context of narcotic consumption. Substance Abuse and Mental Health Services Administration data confirm the ubiquitous nature of benzodiazepine (such as alprazolam) coprescriptions, accounting for roughly half of the 176,000 emergency department cases for 2011. The Centers for Disease Control and Prevention noted that there was a 67% increase in benzodiazepine prescriptions between 1996 and 2013, which warranted more stringent regulations for this particular class of drugs.
In 2016, the CDC issued new guidelines for opioid use acknowledging the danger of benzodiazepine coprescriptions. Food and Drug Administration “black box” warnings now grace the prescriptions of both of these drug classes.10 This trend remains on an upward trajectory, even more so during the pandemic, as there are 9.7 million prescriptions of anxiolytics/hypnotics such as Xanax, Ativan, and Klonopin in the United States as of March 2020, which represents a 10% increase over the previous year. , as well as the implementation of urine drug screening monitoring for drug adherence/compliance and diversion in those with suspected benzodiazepine addiction or a history of polysubstance abuse.11,12
Clinical correlates
For patients who present acutely with Xanax toxicity in the emergency room setting, we will need to initially stabilize the vital signs and address the ongoing symptoms. It is advisable to arrange health care accommodations for patients with physical dependence to monitor and treat their withdrawal symptoms. The patient should be enrolled in a comprehensive addiction facility after undergoing formal detoxification; a tapered treatment protocol will need to be implemented because quitting “cold turkey” can lead to convulsions and, in some cases, death. Patient education, talk therapy, and alternatives to benzodiazepines should be discussed with the clinician.13,145
However, to truly address the elephant in the room, we will need to consider institutional reforms to prevent a similar situation from arising in the future. Primary care physician shortages are compounded by changes in insurance policies. Nurses and physician assistants will need to be trained to manage benzodiazepine prescriptions. If there are community shortages in physicians, patients might turn to illegal means to secure their benzodiazepine supply, and it is imperative that we have the necessary fellowship and education programs to educate nonphysician health care clinicians with benzodiazepine management. Because physicians were prescribing benzodiazepines liberally, the Prescription Drug Monitoring Programs (PDMP) was enacted to monitor physician practices. Unfortunately, this ultimately intimidated physicians and effectively curbed reasonable physician prescribing patterns. It might be necessary to revisit existing prescription monitoring programs, encourage drug evaluations and guidelines based on evidence-based medicine and embrace telemedicine in order to facilitate patient-physician communication.
As of now, it is too early to prescribe Xanax routinely for ongoing anxiety experienced during the coronavirus crisis, and several physicians are cautious about prescribing antianxiety medications for more than a few months.17 Surprisingly, researchers in Barcelona have even explored the role of Xanax as potentially inhibiting Mpro, the primary protease of coronavirus, thereby forestalling the virus’s ability to replicate.16 However, it is worth noting that, given the preliminary nature of the results, any attempts at conclusively integrating Xanax within the context of coronavirus therapy would be premature.
References
1. Luhby T. Anti-anxiety medication prescriptions up 34% since coronavirus. CNN. 2020 Apr 16.
2. Women and Anxiety. Anxiety and Depression Association of America.
3. Shigemura J et al. Psychiatry Clin Neurosci. 2012 Apr 7;74(4):281-2.
4. Petersen A. More people are taking drugs for anxiety and insomnia, and doctors are worried. The Wall Street Journal. 2020 May 25.
5. Downey M. Xanax overdose and related deaths. National Drug & Alcohol Research Centre. UNSW Sydney.
6. Bryant B. Fake Xanax: The UK’s biggest ever dark net drugs bust. BBC. 2018 Mar 10.
7. Reinberg S. Fatal overdoses rising from sedatives like Valium, Xanax. HealthDay. 2016 Feb.
8. Is counterfeit Xanax dangerous? American Addiction Centers. Updated 2018 Nov 14.
9. McLaren E. Xanax history and statistics. Drugabuse.com.
10. Benzodiazepines and opioids. National Institute on Drug Abuse. 2018 Mar 15.
11. Choudhry Z et al. J Psychiatry. 2015;18(5). doi: 10.4172/2378-5756.1000319.
12. Islam FA et al. Current Psychiatry. 2018 Dec 17(12):43-4.
13. Adams M. Xanax death rate on the rise. White Sands Treatment. 2017 Sept.NEED LINK
14. Storrs C. Benzodiazepine overdose deaths soared in recent years, study finds. CNN. 2016 Feb. 18.
15. Hanscom DA. Plan A – Thrive and survive COVID-19. Back in Control. 2020.
16. Smith C. Xanax, a common anxiety medication, might actually block coronavirus. BGR. 2020 May 29.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Mr. Choudhry is a research assistant at the IMCHF. He has no disclosures.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.
One of the more alarming trends that has emerged during the coronavirus crisis is the concomitant rise in the use of benzodiazepines, such as Xanax. It has been reported that at-risk individuals began seeking prescription anxiolytics as early as mid-February with a consequent peak of 34% the following month, coinciding with the World Health Organization’s declaration of a global pandemic.1
Consistent with the available literature indicating that women are twice as likely to be affected by anxiety disorders, the prescription spikes were almost double when compared with those of their male counterparts.2 The pandemic has instilled a sense of fear in people, leading to social repercussions, such as estrangement, insomnia, and paranoia for at-risk populations.3,4
“Benzos” are commonly prescribed to help people sleep or to assist them in overcoming a host of anxiety disorders. The rapid onset of effects make Xanax a desirable and efficacious benzodiazepine.5 The use of these medications might not be an immediate cause for concern because patients might be taking it as intended. Nevertheless, clinicians are shying away from medical management in favor of counseling or therapy.
Dangerous trends
Numerous factors might contribute to this grim scenario, including patient dependence on benzodiazepines, paranoia about engaging with health care professionals because of fear tied to potential COVID-19 exposure, and/or increased access to illicit counterfeit pills from drug dealers or the dark web markets.
Lessons can be gleaned from the most extensive dark web drug busts in Britain’s history, in which a deluge of “pharmaceutical grade” Xanax pills made it to the hands of drug dealers and consumers between 2015 and 2017.6 A similar phenomenon emerged stateside.7 Virtually indistinguishable from recognized 2-mg Xanax pills, these fake pills posed a serious challenge to forensic scientists.8 The threat of overdose is very real for users targeted by the counterfeit Xanax trade, especially since those at risk often bypass professional health care guidelines.
In broad daylight, the drug dealers ran their operations revolving around two fake Xanax products: a primary knockoff and a limited edition – and vastly more potent “Red Devil” variant that was intentionally dyed for branding purposes. Because the “Red Devil” formulations contained 2.5 times the dose of the 2-mg pill, it had even more pronounced tolerance, dependence, and withdrawal effects (for example, panic attacks, anxiety, and/or hallucinations) – fatal consequences for users involved in consuming other drugs, such as alcohol or opioids. Preexisting drug users tend to gravitate toward benzodiazepines, such as alprazolam (Xanax), perhaps in part, because of its relatively rapid onset of action. Xanax also is known for inducing proeuphoric states at higher doses, hence the appeal of the “Red Devil” pills.
Benzodiazepines, as a class of drugs, facilitate the neurotransmitter gamma-aminobutryric acid’s (GABA) effect on the brain, producing anxiolytic, hypnotic, and/or anticonvulsant states within the user.9 Unbeknownst to numerous users is the fact that drugs such as alcohol and opioids, like Xanax, also serve as respiratory depressants, overriding the brain’s governance of the breathing mechanism. This, in turn, leads to unintended overdose deaths, even among seasoned drug seekers.
Overdose deaths have been steadily climbing over the years because it is common for some users to consume alcohol while being on Xanax therapy – without realizing that both substances are depressants and that taking them together can lead to side effects such as respiratory depression.
Forensic cases also have revealed that preexisting opioid consumers were drawn to Xanax; the drug’s potent mechanism of action would likely appeal to habituated users. A typical behavioral pattern has emerged among users and must be addressed. According to Australian Professor Shane Darke: “So they take their Xanax, they take their painkiller, then they get drunk, that could be enough to kill them.”
Fatalities are more likely when benzodiazepines are combined with other drug classes or if the existing supply is contaminated or laced (for example, with fentanyl).8
As far as deaths by accidental benzodiazepine overdose are concerned, a similar epidemic has been recorded in the United States. In 2013, almost one-third of all prescription overdose deaths can be attributed to the use of benzodiazepines (for example, Xanax, Valium, and Ativan). However, media attention has been considerably muted, especially when compared with that of narcotic abuse. This is even more puzzling when taking into account that three-quarters of benzodiazepine mortalities co-occur within the context of narcotic consumption. Substance Abuse and Mental Health Services Administration data confirm the ubiquitous nature of benzodiazepine (such as alprazolam) coprescriptions, accounting for roughly half of the 176,000 emergency department cases for 2011. The Centers for Disease Control and Prevention noted that there was a 67% increase in benzodiazepine prescriptions between 1996 and 2013, which warranted more stringent regulations for this particular class of drugs.
In 2016, the CDC issued new guidelines for opioid use acknowledging the danger of benzodiazepine coprescriptions. Food and Drug Administration “black box” warnings now grace the prescriptions of both of these drug classes.10 This trend remains on an upward trajectory, even more so during the pandemic, as there are 9.7 million prescriptions of anxiolytics/hypnotics such as Xanax, Ativan, and Klonopin in the United States as of March 2020, which represents a 10% increase over the previous year. , as well as the implementation of urine drug screening monitoring for drug adherence/compliance and diversion in those with suspected benzodiazepine addiction or a history of polysubstance abuse.11,12
Clinical correlates
For patients who present acutely with Xanax toxicity in the emergency room setting, we will need to initially stabilize the vital signs and address the ongoing symptoms. It is advisable to arrange health care accommodations for patients with physical dependence to monitor and treat their withdrawal symptoms. The patient should be enrolled in a comprehensive addiction facility after undergoing formal detoxification; a tapered treatment protocol will need to be implemented because quitting “cold turkey” can lead to convulsions and, in some cases, death. Patient education, talk therapy, and alternatives to benzodiazepines should be discussed with the clinician.13,145
However, to truly address the elephant in the room, we will need to consider institutional reforms to prevent a similar situation from arising in the future. Primary care physician shortages are compounded by changes in insurance policies. Nurses and physician assistants will need to be trained to manage benzodiazepine prescriptions. If there are community shortages in physicians, patients might turn to illegal means to secure their benzodiazepine supply, and it is imperative that we have the necessary fellowship and education programs to educate nonphysician health care clinicians with benzodiazepine management. Because physicians were prescribing benzodiazepines liberally, the Prescription Drug Monitoring Programs (PDMP) was enacted to monitor physician practices. Unfortunately, this ultimately intimidated physicians and effectively curbed reasonable physician prescribing patterns. It might be necessary to revisit existing prescription monitoring programs, encourage drug evaluations and guidelines based on evidence-based medicine and embrace telemedicine in order to facilitate patient-physician communication.
As of now, it is too early to prescribe Xanax routinely for ongoing anxiety experienced during the coronavirus crisis, and several physicians are cautious about prescribing antianxiety medications for more than a few months.17 Surprisingly, researchers in Barcelona have even explored the role of Xanax as potentially inhibiting Mpro, the primary protease of coronavirus, thereby forestalling the virus’s ability to replicate.16 However, it is worth noting that, given the preliminary nature of the results, any attempts at conclusively integrating Xanax within the context of coronavirus therapy would be premature.
References
1. Luhby T. Anti-anxiety medication prescriptions up 34% since coronavirus. CNN. 2020 Apr 16.
2. Women and Anxiety. Anxiety and Depression Association of America.
3. Shigemura J et al. Psychiatry Clin Neurosci. 2012 Apr 7;74(4):281-2.
4. Petersen A. More people are taking drugs for anxiety and insomnia, and doctors are worried. The Wall Street Journal. 2020 May 25.
5. Downey M. Xanax overdose and related deaths. National Drug & Alcohol Research Centre. UNSW Sydney.
6. Bryant B. Fake Xanax: The UK’s biggest ever dark net drugs bust. BBC. 2018 Mar 10.
7. Reinberg S. Fatal overdoses rising from sedatives like Valium, Xanax. HealthDay. 2016 Feb.
8. Is counterfeit Xanax dangerous? American Addiction Centers. Updated 2018 Nov 14.
9. McLaren E. Xanax history and statistics. Drugabuse.com.
10. Benzodiazepines and opioids. National Institute on Drug Abuse. 2018 Mar 15.
11. Choudhry Z et al. J Psychiatry. 2015;18(5). doi: 10.4172/2378-5756.1000319.
12. Islam FA et al. Current Psychiatry. 2018 Dec 17(12):43-4.
13. Adams M. Xanax death rate on the rise. White Sands Treatment. 2017 Sept.NEED LINK
14. Storrs C. Benzodiazepine overdose deaths soared in recent years, study finds. CNN. 2016 Feb. 18.
15. Hanscom DA. Plan A – Thrive and survive COVID-19. Back in Control. 2020.
16. Smith C. Xanax, a common anxiety medication, might actually block coronavirus. BGR. 2020 May 29.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Mr. Choudhry is a research assistant at the IMCHF. He has no disclosures.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.
One of the more alarming trends that has emerged during the coronavirus crisis is the concomitant rise in the use of benzodiazepines, such as Xanax. It has been reported that at-risk individuals began seeking prescription anxiolytics as early as mid-February with a consequent peak of 34% the following month, coinciding with the World Health Organization’s declaration of a global pandemic.1
Consistent with the available literature indicating that women are twice as likely to be affected by anxiety disorders, the prescription spikes were almost double when compared with those of their male counterparts.2 The pandemic has instilled a sense of fear in people, leading to social repercussions, such as estrangement, insomnia, and paranoia for at-risk populations.3,4
“Benzos” are commonly prescribed to help people sleep or to assist them in overcoming a host of anxiety disorders. The rapid onset of effects make Xanax a desirable and efficacious benzodiazepine.5 The use of these medications might not be an immediate cause for concern because patients might be taking it as intended. Nevertheless, clinicians are shying away from medical management in favor of counseling or therapy.
Dangerous trends
Numerous factors might contribute to this grim scenario, including patient dependence on benzodiazepines, paranoia about engaging with health care professionals because of fear tied to potential COVID-19 exposure, and/or increased access to illicit counterfeit pills from drug dealers or the dark web markets.
Lessons can be gleaned from the most extensive dark web drug busts in Britain’s history, in which a deluge of “pharmaceutical grade” Xanax pills made it to the hands of drug dealers and consumers between 2015 and 2017.6 A similar phenomenon emerged stateside.7 Virtually indistinguishable from recognized 2-mg Xanax pills, these fake pills posed a serious challenge to forensic scientists.8 The threat of overdose is very real for users targeted by the counterfeit Xanax trade, especially since those at risk often bypass professional health care guidelines.
In broad daylight, the drug dealers ran their operations revolving around two fake Xanax products: a primary knockoff and a limited edition – and vastly more potent “Red Devil” variant that was intentionally dyed for branding purposes. Because the “Red Devil” formulations contained 2.5 times the dose of the 2-mg pill, it had even more pronounced tolerance, dependence, and withdrawal effects (for example, panic attacks, anxiety, and/or hallucinations) – fatal consequences for users involved in consuming other drugs, such as alcohol or opioids. Preexisting drug users tend to gravitate toward benzodiazepines, such as alprazolam (Xanax), perhaps in part, because of its relatively rapid onset of action. Xanax also is known for inducing proeuphoric states at higher doses, hence the appeal of the “Red Devil” pills.
Benzodiazepines, as a class of drugs, facilitate the neurotransmitter gamma-aminobutryric acid’s (GABA) effect on the brain, producing anxiolytic, hypnotic, and/or anticonvulsant states within the user.9 Unbeknownst to numerous users is the fact that drugs such as alcohol and opioids, like Xanax, also serve as respiratory depressants, overriding the brain’s governance of the breathing mechanism. This, in turn, leads to unintended overdose deaths, even among seasoned drug seekers.
Overdose deaths have been steadily climbing over the years because it is common for some users to consume alcohol while being on Xanax therapy – without realizing that both substances are depressants and that taking them together can lead to side effects such as respiratory depression.
Forensic cases also have revealed that preexisting opioid consumers were drawn to Xanax; the drug’s potent mechanism of action would likely appeal to habituated users. A typical behavioral pattern has emerged among users and must be addressed. According to Australian Professor Shane Darke: “So they take their Xanax, they take their painkiller, then they get drunk, that could be enough to kill them.”
Fatalities are more likely when benzodiazepines are combined with other drug classes or if the existing supply is contaminated or laced (for example, with fentanyl).8
As far as deaths by accidental benzodiazepine overdose are concerned, a similar epidemic has been recorded in the United States. In 2013, almost one-third of all prescription overdose deaths can be attributed to the use of benzodiazepines (for example, Xanax, Valium, and Ativan). However, media attention has been considerably muted, especially when compared with that of narcotic abuse. This is even more puzzling when taking into account that three-quarters of benzodiazepine mortalities co-occur within the context of narcotic consumption. Substance Abuse and Mental Health Services Administration data confirm the ubiquitous nature of benzodiazepine (such as alprazolam) coprescriptions, accounting for roughly half of the 176,000 emergency department cases for 2011. The Centers for Disease Control and Prevention noted that there was a 67% increase in benzodiazepine prescriptions between 1996 and 2013, which warranted more stringent regulations for this particular class of drugs.
In 2016, the CDC issued new guidelines for opioid use acknowledging the danger of benzodiazepine coprescriptions. Food and Drug Administration “black box” warnings now grace the prescriptions of both of these drug classes.10 This trend remains on an upward trajectory, even more so during the pandemic, as there are 9.7 million prescriptions of anxiolytics/hypnotics such as Xanax, Ativan, and Klonopin in the United States as of March 2020, which represents a 10% increase over the previous year. , as well as the implementation of urine drug screening monitoring for drug adherence/compliance and diversion in those with suspected benzodiazepine addiction or a history of polysubstance abuse.11,12
Clinical correlates
For patients who present acutely with Xanax toxicity in the emergency room setting, we will need to initially stabilize the vital signs and address the ongoing symptoms. It is advisable to arrange health care accommodations for patients with physical dependence to monitor and treat their withdrawal symptoms. The patient should be enrolled in a comprehensive addiction facility after undergoing formal detoxification; a tapered treatment protocol will need to be implemented because quitting “cold turkey” can lead to convulsions and, in some cases, death. Patient education, talk therapy, and alternatives to benzodiazepines should be discussed with the clinician.13,145
However, to truly address the elephant in the room, we will need to consider institutional reforms to prevent a similar situation from arising in the future. Primary care physician shortages are compounded by changes in insurance policies. Nurses and physician assistants will need to be trained to manage benzodiazepine prescriptions. If there are community shortages in physicians, patients might turn to illegal means to secure their benzodiazepine supply, and it is imperative that we have the necessary fellowship and education programs to educate nonphysician health care clinicians with benzodiazepine management. Because physicians were prescribing benzodiazepines liberally, the Prescription Drug Monitoring Programs (PDMP) was enacted to monitor physician practices. Unfortunately, this ultimately intimidated physicians and effectively curbed reasonable physician prescribing patterns. It might be necessary to revisit existing prescription monitoring programs, encourage drug evaluations and guidelines based on evidence-based medicine and embrace telemedicine in order to facilitate patient-physician communication.
As of now, it is too early to prescribe Xanax routinely for ongoing anxiety experienced during the coronavirus crisis, and several physicians are cautious about prescribing antianxiety medications for more than a few months.17 Surprisingly, researchers in Barcelona have even explored the role of Xanax as potentially inhibiting Mpro, the primary protease of coronavirus, thereby forestalling the virus’s ability to replicate.16 However, it is worth noting that, given the preliminary nature of the results, any attempts at conclusively integrating Xanax within the context of coronavirus therapy would be premature.
References
1. Luhby T. Anti-anxiety medication prescriptions up 34% since coronavirus. CNN. 2020 Apr 16.
2. Women and Anxiety. Anxiety and Depression Association of America.
3. Shigemura J et al. Psychiatry Clin Neurosci. 2012 Apr 7;74(4):281-2.
4. Petersen A. More people are taking drugs for anxiety and insomnia, and doctors are worried. The Wall Street Journal. 2020 May 25.
5. Downey M. Xanax overdose and related deaths. National Drug & Alcohol Research Centre. UNSW Sydney.
6. Bryant B. Fake Xanax: The UK’s biggest ever dark net drugs bust. BBC. 2018 Mar 10.
7. Reinberg S. Fatal overdoses rising from sedatives like Valium, Xanax. HealthDay. 2016 Feb.
8. Is counterfeit Xanax dangerous? American Addiction Centers. Updated 2018 Nov 14.
9. McLaren E. Xanax history and statistics. Drugabuse.com.
10. Benzodiazepines and opioids. National Institute on Drug Abuse. 2018 Mar 15.
11. Choudhry Z et al. J Psychiatry. 2015;18(5). doi: 10.4172/2378-5756.1000319.
12. Islam FA et al. Current Psychiatry. 2018 Dec 17(12):43-4.
13. Adams M. Xanax death rate on the rise. White Sands Treatment. 2017 Sept.NEED LINK
14. Storrs C. Benzodiazepine overdose deaths soared in recent years, study finds. CNN. 2016 Feb. 18.
15. Hanscom DA. Plan A – Thrive and survive COVID-19. Back in Control. 2020.
16. Smith C. Xanax, a common anxiety medication, might actually block coronavirus. BGR. 2020 May 29.
Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.
Mr. Choudhry is a research assistant at the IMCHF. He has no disclosures.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.
Preventing arrhythmias and QTc prolongation in COVID-19 patients on psychotropics
Over the last few weeks, several conflicting reports about the efficacy of SARS-CoV-2 treatments have emerged, including high-profile papers that were placed in the limelight and groundbreaking retractions that were issued by the Lancet and New England Journal of Medicine, involving the potential dangers of COVID therapy with findings derived from the Surgisphere database. Hydroxychloroquine has garnered considerable media attention and was touted earlier by President Trump for its therapeutic effects.1 Naturally, there are political connotations associated with the agent, and it is unlikely that hydroxychloroquine will be supplanted in the near future as ongoing clinical trials have demonstrated mixed results amid the controversy.
As clinicians navigating unchartered territory within the hospital setting, we have to come to terms with these new challenges, tailoring treatment protocols accordingly with the best clinical practices in mind. Patients with preexisting mental health conditions and who are being treated for COVID-19 are particularly susceptible to clinical deterioration. Recent studies have indicated that psychiatric patients are more prone to feelings of isolation and/or estrangement as well as exacerbation of symptoms such as paranoia.2 Even more concerning is the medication regimen, namely, the novel combination therapies that arise when agents such as hydroxychloroquine are used in tandem with certain antipsychotics or antidepressants.
What’s at stake for COVID-19–positive mental health care patients?
Although the efficacy of hydroxychloroquine is currently being investigated,3 the antimalarial is usually prescribed in tandem with azithromycin for people with COVID-19. The National Institute of Allergy and Infectious Diseases has advised against that particular combination therapy because of ongoing concerns about toxicities.3,4
In another study, azithromycin was effectively substituted with doxycycline to help minimize systemic effects for patients with cardiac and/or pulmonary issues.5 Azithromycin is notorious in the literature for influencing the electrical activity of the heart with the potential for fatal arrhythmia and sudden cardiac death in individuals at risk for cardiovascular disease.5,6,7 It should be noted that both of these commonly prescribed COVID-19 medications (for example, hydroxychloroquine and azithromycin) could lead to QT interval prolongation especially within the context of combination therapy. This is largely concerning for psychiatrists and various other mental health practitioners for the following reasons: (1) higher rates of metabolic syndrome and cardiovascular diseases among psychiatric patients8 and/or (2) effects of certain antipsychotics (for example, IV haloperidol, thioridazine, and ziprasidone) and antidepressants (for example, citalopram and escitalopram) on the QT interval.9
SARS-CoV-2 and clinical judgment: Evaluating patients at higher risk
Although COVID-19 medication guidelines are still being actively developed, hydroxychloroquine appears to be commonly prescribed by physicians. The medication is known myriad untoward effects, including potential behavioral dysfunction (for example, irritability, agitation, suicidal ideation)10 as well as the aforementioned issues concerning arrhythmia (for example, torsades de pointes). Health care professionals might not have much control over the choice of COVID-19 agents because of a lack of available resources or limited options, but they can exercise clinical judgment with respect to selecting the appropriate psychotropic medications.
Treatment recommendations
1. Establish a baseline EKG
A baseline 12-lead EKG is the standard of care for patients currently being screened for COVID-19. It is necessary to rule out the presence of an underlying cardiovascular disease or a rhythm irregularity. A prolonged QTc interval is generally regarded as being around greater than 450-470 msecs with variations attributable to gender;11 numerous studies have affirmed that the risk of acquiring torsades de pointes is substantial when the QTc interval exceeds 500 msecs.12
2. Medical management and risk assessment
Commonly prescribed antipsychotics such as IV haloperidol and ziprasidone are known for exerting a negative effect on the interval and should readily be substituted with other agents in patients who are being treated for COVID-19; the combination of these antipsychotics alongside some COVID-19 medication regimens (for example, hydroxychloroquine/azithromycin) might prove to be fatal. The same logic applies to COVID-19 patients previously on antidepressant therapeutics such as citalopram and escitalopram.
3. Embrace an individually tailored approach to therapeutics
While American Psychiatric Association guidelines historically supported a cessation or reduction in the offending agent under normal circumstances,12 our team is recommending that the psychotropics associated with QTc interval prolongation are discontinued altogether (or substituted with a low-risk agent) in the event that a patient presents with suspected COVID-19. However, after the patients tests negative with COVID-19, they may resume therapy as indicated under the discretion of the mental health practitioner.
References
1. Offard C. “Lancet, NEJM Retract Surgisphere Studies on COVID-19 Patients.” The Scientist Magazine. 2020 Jun 4.
2. Shigemura J et al. Psychiatry Clin Neurosci. 2020 Apr;74(4):281-2.
3. Keshtkar-Jahromi M and Bavari S. Am J Trop Med Hyg. 2020 May;102(5):932-3.
4. Palca J. “NIH panel recommends against drug combination promoted by Trump for COVID-19.” NPR. 2020 Apr 21.
5. Mongelli L. “Long Island doctor tries new twist on hydroxychloroquine for elderly COVID-19 patients.” New York Post. 2020 Apr 4.
6. Hancox JC et al. Ther Adv Infect Dis. 2013 Oct;(5):155-65.
7. Giudicessi JR and Ackerman MJ. Cleve Clin J Med. 2013 Sep;80(9):539-44.
8. Casey DE. Am J Med. 2005 Apr 1;118(Suppl 2):15S-22S.
9. Beach SR et al. Psychosomatics. 2013 Jan 1;54(1):1-3.
10. Bogaczewicz A and Sobów T. Psychiatria i Psychologia Kliniczna. 2017;17(2):111-4.
11. Chohan PS et al. Pak J Med Sci. 2015 Sep-Oct;31(5):1269-71.
12. Lieberman JA et al. APA guidance on the use of antipsychotic drugs and cardiac sudden death. NYS Office of Mental Health. 2012.
Dr. Faisal A. Islam is medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Faisal Islam disclosed no relevant financial relationships.
Dr. Mohammed Islam is affiliated with the department of psychiatry at the Interfaith Medical Center, New York. He disclosed no relevant financial relationships.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He disclosed no relevant financial relationships.
Over the last few weeks, several conflicting reports about the efficacy of SARS-CoV-2 treatments have emerged, including high-profile papers that were placed in the limelight and groundbreaking retractions that were issued by the Lancet and New England Journal of Medicine, involving the potential dangers of COVID therapy with findings derived from the Surgisphere database. Hydroxychloroquine has garnered considerable media attention and was touted earlier by President Trump for its therapeutic effects.1 Naturally, there are political connotations associated with the agent, and it is unlikely that hydroxychloroquine will be supplanted in the near future as ongoing clinical trials have demonstrated mixed results amid the controversy.
As clinicians navigating unchartered territory within the hospital setting, we have to come to terms with these new challenges, tailoring treatment protocols accordingly with the best clinical practices in mind. Patients with preexisting mental health conditions and who are being treated for COVID-19 are particularly susceptible to clinical deterioration. Recent studies have indicated that psychiatric patients are more prone to feelings of isolation and/or estrangement as well as exacerbation of symptoms such as paranoia.2 Even more concerning is the medication regimen, namely, the novel combination therapies that arise when agents such as hydroxychloroquine are used in tandem with certain antipsychotics or antidepressants.
What’s at stake for COVID-19–positive mental health care patients?
Although the efficacy of hydroxychloroquine is currently being investigated,3 the antimalarial is usually prescribed in tandem with azithromycin for people with COVID-19. The National Institute of Allergy and Infectious Diseases has advised against that particular combination therapy because of ongoing concerns about toxicities.3,4
In another study, azithromycin was effectively substituted with doxycycline to help minimize systemic effects for patients with cardiac and/or pulmonary issues.5 Azithromycin is notorious in the literature for influencing the electrical activity of the heart with the potential for fatal arrhythmia and sudden cardiac death in individuals at risk for cardiovascular disease.5,6,7 It should be noted that both of these commonly prescribed COVID-19 medications (for example, hydroxychloroquine and azithromycin) could lead to QT interval prolongation especially within the context of combination therapy. This is largely concerning for psychiatrists and various other mental health practitioners for the following reasons: (1) higher rates of metabolic syndrome and cardiovascular diseases among psychiatric patients8 and/or (2) effects of certain antipsychotics (for example, IV haloperidol, thioridazine, and ziprasidone) and antidepressants (for example, citalopram and escitalopram) on the QT interval.9
SARS-CoV-2 and clinical judgment: Evaluating patients at higher risk
Although COVID-19 medication guidelines are still being actively developed, hydroxychloroquine appears to be commonly prescribed by physicians. The medication is known myriad untoward effects, including potential behavioral dysfunction (for example, irritability, agitation, suicidal ideation)10 as well as the aforementioned issues concerning arrhythmia (for example, torsades de pointes). Health care professionals might not have much control over the choice of COVID-19 agents because of a lack of available resources or limited options, but they can exercise clinical judgment with respect to selecting the appropriate psychotropic medications.
Treatment recommendations
1. Establish a baseline EKG
A baseline 12-lead EKG is the standard of care for patients currently being screened for COVID-19. It is necessary to rule out the presence of an underlying cardiovascular disease or a rhythm irregularity. A prolonged QTc interval is generally regarded as being around greater than 450-470 msecs with variations attributable to gender;11 numerous studies have affirmed that the risk of acquiring torsades de pointes is substantial when the QTc interval exceeds 500 msecs.12
2. Medical management and risk assessment
Commonly prescribed antipsychotics such as IV haloperidol and ziprasidone are known for exerting a negative effect on the interval and should readily be substituted with other agents in patients who are being treated for COVID-19; the combination of these antipsychotics alongside some COVID-19 medication regimens (for example, hydroxychloroquine/azithromycin) might prove to be fatal. The same logic applies to COVID-19 patients previously on antidepressant therapeutics such as citalopram and escitalopram.
3. Embrace an individually tailored approach to therapeutics
While American Psychiatric Association guidelines historically supported a cessation or reduction in the offending agent under normal circumstances,12 our team is recommending that the psychotropics associated with QTc interval prolongation are discontinued altogether (or substituted with a low-risk agent) in the event that a patient presents with suspected COVID-19. However, after the patients tests negative with COVID-19, they may resume therapy as indicated under the discretion of the mental health practitioner.
References
1. Offard C. “Lancet, NEJM Retract Surgisphere Studies on COVID-19 Patients.” The Scientist Magazine. 2020 Jun 4.
2. Shigemura J et al. Psychiatry Clin Neurosci. 2020 Apr;74(4):281-2.
3. Keshtkar-Jahromi M and Bavari S. Am J Trop Med Hyg. 2020 May;102(5):932-3.
4. Palca J. “NIH panel recommends against drug combination promoted by Trump for COVID-19.” NPR. 2020 Apr 21.
5. Mongelli L. “Long Island doctor tries new twist on hydroxychloroquine for elderly COVID-19 patients.” New York Post. 2020 Apr 4.
6. Hancox JC et al. Ther Adv Infect Dis. 2013 Oct;(5):155-65.
7. Giudicessi JR and Ackerman MJ. Cleve Clin J Med. 2013 Sep;80(9):539-44.
8. Casey DE. Am J Med. 2005 Apr 1;118(Suppl 2):15S-22S.
9. Beach SR et al. Psychosomatics. 2013 Jan 1;54(1):1-3.
10. Bogaczewicz A and Sobów T. Psychiatria i Psychologia Kliniczna. 2017;17(2):111-4.
11. Chohan PS et al. Pak J Med Sci. 2015 Sep-Oct;31(5):1269-71.
12. Lieberman JA et al. APA guidance on the use of antipsychotic drugs and cardiac sudden death. NYS Office of Mental Health. 2012.
Dr. Faisal A. Islam is medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Faisal Islam disclosed no relevant financial relationships.
Dr. Mohammed Islam is affiliated with the department of psychiatry at the Interfaith Medical Center, New York. He disclosed no relevant financial relationships.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He disclosed no relevant financial relationships.
Over the last few weeks, several conflicting reports about the efficacy of SARS-CoV-2 treatments have emerged, including high-profile papers that were placed in the limelight and groundbreaking retractions that were issued by the Lancet and New England Journal of Medicine, involving the potential dangers of COVID therapy with findings derived from the Surgisphere database. Hydroxychloroquine has garnered considerable media attention and was touted earlier by President Trump for its therapeutic effects.1 Naturally, there are political connotations associated with the agent, and it is unlikely that hydroxychloroquine will be supplanted in the near future as ongoing clinical trials have demonstrated mixed results amid the controversy.
As clinicians navigating unchartered territory within the hospital setting, we have to come to terms with these new challenges, tailoring treatment protocols accordingly with the best clinical practices in mind. Patients with preexisting mental health conditions and who are being treated for COVID-19 are particularly susceptible to clinical deterioration. Recent studies have indicated that psychiatric patients are more prone to feelings of isolation and/or estrangement as well as exacerbation of symptoms such as paranoia.2 Even more concerning is the medication regimen, namely, the novel combination therapies that arise when agents such as hydroxychloroquine are used in tandem with certain antipsychotics or antidepressants.
What’s at stake for COVID-19–positive mental health care patients?
Although the efficacy of hydroxychloroquine is currently being investigated,3 the antimalarial is usually prescribed in tandem with azithromycin for people with COVID-19. The National Institute of Allergy and Infectious Diseases has advised against that particular combination therapy because of ongoing concerns about toxicities.3,4
In another study, azithromycin was effectively substituted with doxycycline to help minimize systemic effects for patients with cardiac and/or pulmonary issues.5 Azithromycin is notorious in the literature for influencing the electrical activity of the heart with the potential for fatal arrhythmia and sudden cardiac death in individuals at risk for cardiovascular disease.5,6,7 It should be noted that both of these commonly prescribed COVID-19 medications (for example, hydroxychloroquine and azithromycin) could lead to QT interval prolongation especially within the context of combination therapy. This is largely concerning for psychiatrists and various other mental health practitioners for the following reasons: (1) higher rates of metabolic syndrome and cardiovascular diseases among psychiatric patients8 and/or (2) effects of certain antipsychotics (for example, IV haloperidol, thioridazine, and ziprasidone) and antidepressants (for example, citalopram and escitalopram) on the QT interval.9
SARS-CoV-2 and clinical judgment: Evaluating patients at higher risk
Although COVID-19 medication guidelines are still being actively developed, hydroxychloroquine appears to be commonly prescribed by physicians. The medication is known myriad untoward effects, including potential behavioral dysfunction (for example, irritability, agitation, suicidal ideation)10 as well as the aforementioned issues concerning arrhythmia (for example, torsades de pointes). Health care professionals might not have much control over the choice of COVID-19 agents because of a lack of available resources or limited options, but they can exercise clinical judgment with respect to selecting the appropriate psychotropic medications.
Treatment recommendations
1. Establish a baseline EKG
A baseline 12-lead EKG is the standard of care for patients currently being screened for COVID-19. It is necessary to rule out the presence of an underlying cardiovascular disease or a rhythm irregularity. A prolonged QTc interval is generally regarded as being around greater than 450-470 msecs with variations attributable to gender;11 numerous studies have affirmed that the risk of acquiring torsades de pointes is substantial when the QTc interval exceeds 500 msecs.12
2. Medical management and risk assessment
Commonly prescribed antipsychotics such as IV haloperidol and ziprasidone are known for exerting a negative effect on the interval and should readily be substituted with other agents in patients who are being treated for COVID-19; the combination of these antipsychotics alongside some COVID-19 medication regimens (for example, hydroxychloroquine/azithromycin) might prove to be fatal. The same logic applies to COVID-19 patients previously on antidepressant therapeutics such as citalopram and escitalopram.
3. Embrace an individually tailored approach to therapeutics
While American Psychiatric Association guidelines historically supported a cessation or reduction in the offending agent under normal circumstances,12 our team is recommending that the psychotropics associated with QTc interval prolongation are discontinued altogether (or substituted with a low-risk agent) in the event that a patient presents with suspected COVID-19. However, after the patients tests negative with COVID-19, they may resume therapy as indicated under the discretion of the mental health practitioner.
References
1. Offard C. “Lancet, NEJM Retract Surgisphere Studies on COVID-19 Patients.” The Scientist Magazine. 2020 Jun 4.
2. Shigemura J et al. Psychiatry Clin Neurosci. 2020 Apr;74(4):281-2.
3. Keshtkar-Jahromi M and Bavari S. Am J Trop Med Hyg. 2020 May;102(5):932-3.
4. Palca J. “NIH panel recommends against drug combination promoted by Trump for COVID-19.” NPR. 2020 Apr 21.
5. Mongelli L. “Long Island doctor tries new twist on hydroxychloroquine for elderly COVID-19 patients.” New York Post. 2020 Apr 4.
6. Hancox JC et al. Ther Adv Infect Dis. 2013 Oct;(5):155-65.
7. Giudicessi JR and Ackerman MJ. Cleve Clin J Med. 2013 Sep;80(9):539-44.
8. Casey DE. Am J Med. 2005 Apr 1;118(Suppl 2):15S-22S.
9. Beach SR et al. Psychosomatics. 2013 Jan 1;54(1):1-3.
10. Bogaczewicz A and Sobów T. Psychiatria i Psychologia Kliniczna. 2017;17(2):111-4.
11. Chohan PS et al. Pak J Med Sci. 2015 Sep-Oct;31(5):1269-71.
12. Lieberman JA et al. APA guidance on the use of antipsychotic drugs and cardiac sudden death. NYS Office of Mental Health. 2012.
Dr. Faisal A. Islam is medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Faisal Islam disclosed no relevant financial relationships.
Dr. Mohammed Islam is affiliated with the department of psychiatry at the Interfaith Medical Center, New York. He disclosed no relevant financial relationships.
Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He disclosed no relevant financial relationships.
Recognizing and treating ketamine abuse
The N-methyl-
Physicians need to be aware, however, that many patients use illicit ketamine, either for recreational purposes or as self-treatment to control depressive symptoms. To help clinicians identify the signs of ketamine abuse, we discuss the adverse effects of illicit use, and suggest treatment approaches.
Ad
Ketamine can be consumed in various ways; snorting it in a powder form is a preferred route for recreational use.2 The primary disadvantage of oral use is that it increases the likelihood of nausea and vomiting.2
While ketamine is generally safe in a supervised clinical setting, approximately 2.5 million individuals use various illicit forms of ketamine—which is known as Special K and by other names—in recreational settings (eg, dance clubs) where it might be used with other substances.3 Alcohol, in particular, compounds the sedative effects of ketamine and can lead to death by overdose.
At a subanesthetic dose, ketamine can induce dissociative and/or transcendental states that are particularly attractive to those intrigued by mystical experiences, pronounced changes in perception, or euphoria.4 High doses of ketamine—relative to a commonly used recreational dose—can produce a unique “K-hole” state in which a user is unable to control his/her body and could lose consciousness.5 A K-hole state may trigger a cycle of delirium that warrants immediate clinical attention.3
Researchers have postulated that NMDA antagonism may negatively impact memory consolidation.3,6 Even more troubling is the potential for systemic injuries because illicit ketamine use may contribute to ulcerative cystitis, severely disturbed kidney function (eg, hydronephrosis), or epigastric pain.3 Chronic abuse tends to result in more systemic sequelae, affecting the bladder, kidneys, and heart. Adverse effects that require emergent care include blood in urine, changes in vision (eg, nystagmus), chest discomfort, labored breathing, agitation, seizures, and/or altered consciousness.6
Treating ketamine abuse
Treatment should be tailored to the patient’s symptoms. If the patient presents with “K-bladder” (ie, ketamine bladder syndrome), he/she may need surgical intervention or a cystectomy.4,7 Therapeutic management of K-bladder entails recognizing bladder symptoms that are specific to ketamine use, such as interstitial or ulcerative cystitis and lower urinary tract symptoms.7 Clinicians should monitor patients for increased voiding episodes during the day, voiding urgency, or a general sense of bladder fullness. Patients with K-bladder also may complain of suprapubic pain or blood in the urine.7
Continue to: Consider referring patients to...
Consider referring patients to an individualized, ketamine-specific rehabilitation program that is modeled after other substance-specific rehabilitation programs. It is critical to address withdrawal symptoms (eg, anorexia, fatigue, tremors, chills, tachycardia, nightmares, etc.). Patients undergoing ketamine withdrawal may develop anxiety and depression, with or without suicidal ideation, that might persist during a 4- to 5-day withdrawal period.8
‘Self-medicating’ ketamine users
Clinicians need to be particularly vigilant for situations in which a patient has used ketamine in an attempt to control his/her depressive symptoms. Some researchers have described ketamine as a revolutionary drug for TRD, and it is reasonable to suspect that some patients with depressive symptoms may have consulted Internet sources to learn how to self-medicate using ketamine. Patients who have consumed smaller doses of ketamine recreationally may have developed a tolerance in which the receptors are no longer responsive to the effects at that dose, and therefore might not respond when given ketamine in a clinical setting. Proper history taking and patient education are essential for these users, and clinicians may need to develop a personalized therapeutic plan for ketamine administration. If, on the other hand, a patient has a history of chronic ketamine use (perhaps at high doses), depression may occur secondary to this type of ketamine abuse. For such patients, clinicians should explore alternative treatment modalities, such as transcranial magnetic stimulation.
1. Kurdi MS, Theerth KA, Deva RS. Ketamine: current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283-290.
2. Davis K. What are the uses of ketamine? Medical News Today. https://www.medicalnewstoday.com/articles/302663.php. Updated October 12, 2017. Published October 11, 2019.
3. Chaverneff F. Ketamine: mechanisms of action, uses in pain medicine, and side effects. Clinical Pain Advisor. https://www.clinicalpainadvisor.com/home/conference-highlights/painweek-2018/ketamine-mechanisms-of-action-uses-in-pain-medicine-and-side-effects/. Published 2018. Accessed October 11, 2019.
4. Gao M, Rejaei D, Liu H. Ketamine use in current clinical practice. Acta Pharmacol Sin. 2016;37(7):865-872.
5. Orhurhu VJ, Claus LE, Cohen SP. Ketamine toxicity. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK541087. Updated April 11, 2019. Accessed October 18, 2019.
6. Pai A, Heining M. Ketamine. Continuing Education in Anaesthesia Critical Care & Pain. 20071;7(2):59-63.
7. Logan K. Addressing ketamine bladder syndrome. Nursing Times. https://www.nursingtimes.net/clinical-archive/medicine-management/addressing-ketamine-bladder-syndrome-19-06-2011/. Published June 19, 2011. Accessed October 11, 2019.
8. Lin PC, Lane HY, Lin CH. Spontaneous remission of ketamine withdrawal-related depression. Clin Neuropharmacol. 2016;39(1):51-52.
The N-methyl-
Physicians need to be aware, however, that many patients use illicit ketamine, either for recreational purposes or as self-treatment to control depressive symptoms. To help clinicians identify the signs of ketamine abuse, we discuss the adverse effects of illicit use, and suggest treatment approaches.
Ad
Ketamine can be consumed in various ways; snorting it in a powder form is a preferred route for recreational use.2 The primary disadvantage of oral use is that it increases the likelihood of nausea and vomiting.2
While ketamine is generally safe in a supervised clinical setting, approximately 2.5 million individuals use various illicit forms of ketamine—which is known as Special K and by other names—in recreational settings (eg, dance clubs) where it might be used with other substances.3 Alcohol, in particular, compounds the sedative effects of ketamine and can lead to death by overdose.
At a subanesthetic dose, ketamine can induce dissociative and/or transcendental states that are particularly attractive to those intrigued by mystical experiences, pronounced changes in perception, or euphoria.4 High doses of ketamine—relative to a commonly used recreational dose—can produce a unique “K-hole” state in which a user is unable to control his/her body and could lose consciousness.5 A K-hole state may trigger a cycle of delirium that warrants immediate clinical attention.3
Researchers have postulated that NMDA antagonism may negatively impact memory consolidation.3,6 Even more troubling is the potential for systemic injuries because illicit ketamine use may contribute to ulcerative cystitis, severely disturbed kidney function (eg, hydronephrosis), or epigastric pain.3 Chronic abuse tends to result in more systemic sequelae, affecting the bladder, kidneys, and heart. Adverse effects that require emergent care include blood in urine, changes in vision (eg, nystagmus), chest discomfort, labored breathing, agitation, seizures, and/or altered consciousness.6
Treating ketamine abuse
Treatment should be tailored to the patient’s symptoms. If the patient presents with “K-bladder” (ie, ketamine bladder syndrome), he/she may need surgical intervention or a cystectomy.4,7 Therapeutic management of K-bladder entails recognizing bladder symptoms that are specific to ketamine use, such as interstitial or ulcerative cystitis and lower urinary tract symptoms.7 Clinicians should monitor patients for increased voiding episodes during the day, voiding urgency, or a general sense of bladder fullness. Patients with K-bladder also may complain of suprapubic pain or blood in the urine.7
Continue to: Consider referring patients to...
Consider referring patients to an individualized, ketamine-specific rehabilitation program that is modeled after other substance-specific rehabilitation programs. It is critical to address withdrawal symptoms (eg, anorexia, fatigue, tremors, chills, tachycardia, nightmares, etc.). Patients undergoing ketamine withdrawal may develop anxiety and depression, with or without suicidal ideation, that might persist during a 4- to 5-day withdrawal period.8
‘Self-medicating’ ketamine users
Clinicians need to be particularly vigilant for situations in which a patient has used ketamine in an attempt to control his/her depressive symptoms. Some researchers have described ketamine as a revolutionary drug for TRD, and it is reasonable to suspect that some patients with depressive symptoms may have consulted Internet sources to learn how to self-medicate using ketamine. Patients who have consumed smaller doses of ketamine recreationally may have developed a tolerance in which the receptors are no longer responsive to the effects at that dose, and therefore might not respond when given ketamine in a clinical setting. Proper history taking and patient education are essential for these users, and clinicians may need to develop a personalized therapeutic plan for ketamine administration. If, on the other hand, a patient has a history of chronic ketamine use (perhaps at high doses), depression may occur secondary to this type of ketamine abuse. For such patients, clinicians should explore alternative treatment modalities, such as transcranial magnetic stimulation.
The N-methyl-
Physicians need to be aware, however, that many patients use illicit ketamine, either for recreational purposes or as self-treatment to control depressive symptoms. To help clinicians identify the signs of ketamine abuse, we discuss the adverse effects of illicit use, and suggest treatment approaches.
Ad
Ketamine can be consumed in various ways; snorting it in a powder form is a preferred route for recreational use.2 The primary disadvantage of oral use is that it increases the likelihood of nausea and vomiting.2
While ketamine is generally safe in a supervised clinical setting, approximately 2.5 million individuals use various illicit forms of ketamine—which is known as Special K and by other names—in recreational settings (eg, dance clubs) where it might be used with other substances.3 Alcohol, in particular, compounds the sedative effects of ketamine and can lead to death by overdose.
At a subanesthetic dose, ketamine can induce dissociative and/or transcendental states that are particularly attractive to those intrigued by mystical experiences, pronounced changes in perception, or euphoria.4 High doses of ketamine—relative to a commonly used recreational dose—can produce a unique “K-hole” state in which a user is unable to control his/her body and could lose consciousness.5 A K-hole state may trigger a cycle of delirium that warrants immediate clinical attention.3
Researchers have postulated that NMDA antagonism may negatively impact memory consolidation.3,6 Even more troubling is the potential for systemic injuries because illicit ketamine use may contribute to ulcerative cystitis, severely disturbed kidney function (eg, hydronephrosis), or epigastric pain.3 Chronic abuse tends to result in more systemic sequelae, affecting the bladder, kidneys, and heart. Adverse effects that require emergent care include blood in urine, changes in vision (eg, nystagmus), chest discomfort, labored breathing, agitation, seizures, and/or altered consciousness.6
Treating ketamine abuse
Treatment should be tailored to the patient’s symptoms. If the patient presents with “K-bladder” (ie, ketamine bladder syndrome), he/she may need surgical intervention or a cystectomy.4,7 Therapeutic management of K-bladder entails recognizing bladder symptoms that are specific to ketamine use, such as interstitial or ulcerative cystitis and lower urinary tract symptoms.7 Clinicians should monitor patients for increased voiding episodes during the day, voiding urgency, or a general sense of bladder fullness. Patients with K-bladder also may complain of suprapubic pain or blood in the urine.7
Continue to: Consider referring patients to...
Consider referring patients to an individualized, ketamine-specific rehabilitation program that is modeled after other substance-specific rehabilitation programs. It is critical to address withdrawal symptoms (eg, anorexia, fatigue, tremors, chills, tachycardia, nightmares, etc.). Patients undergoing ketamine withdrawal may develop anxiety and depression, with or without suicidal ideation, that might persist during a 4- to 5-day withdrawal period.8
‘Self-medicating’ ketamine users
Clinicians need to be particularly vigilant for situations in which a patient has used ketamine in an attempt to control his/her depressive symptoms. Some researchers have described ketamine as a revolutionary drug for TRD, and it is reasonable to suspect that some patients with depressive symptoms may have consulted Internet sources to learn how to self-medicate using ketamine. Patients who have consumed smaller doses of ketamine recreationally may have developed a tolerance in which the receptors are no longer responsive to the effects at that dose, and therefore might not respond when given ketamine in a clinical setting. Proper history taking and patient education are essential for these users, and clinicians may need to develop a personalized therapeutic plan for ketamine administration. If, on the other hand, a patient has a history of chronic ketamine use (perhaps at high doses), depression may occur secondary to this type of ketamine abuse. For such patients, clinicians should explore alternative treatment modalities, such as transcranial magnetic stimulation.
1. Kurdi MS, Theerth KA, Deva RS. Ketamine: current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283-290.
2. Davis K. What are the uses of ketamine? Medical News Today. https://www.medicalnewstoday.com/articles/302663.php. Updated October 12, 2017. Published October 11, 2019.
3. Chaverneff F. Ketamine: mechanisms of action, uses in pain medicine, and side effects. Clinical Pain Advisor. https://www.clinicalpainadvisor.com/home/conference-highlights/painweek-2018/ketamine-mechanisms-of-action-uses-in-pain-medicine-and-side-effects/. Published 2018. Accessed October 11, 2019.
4. Gao M, Rejaei D, Liu H. Ketamine use in current clinical practice. Acta Pharmacol Sin. 2016;37(7):865-872.
5. Orhurhu VJ, Claus LE, Cohen SP. Ketamine toxicity. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK541087. Updated April 11, 2019. Accessed October 18, 2019.
6. Pai A, Heining M. Ketamine. Continuing Education in Anaesthesia Critical Care & Pain. 20071;7(2):59-63.
7. Logan K. Addressing ketamine bladder syndrome. Nursing Times. https://www.nursingtimes.net/clinical-archive/medicine-management/addressing-ketamine-bladder-syndrome-19-06-2011/. Published June 19, 2011. Accessed October 11, 2019.
8. Lin PC, Lane HY, Lin CH. Spontaneous remission of ketamine withdrawal-related depression. Clin Neuropharmacol. 2016;39(1):51-52.
1. Kurdi MS, Theerth KA, Deva RS. Ketamine: current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283-290.
2. Davis K. What are the uses of ketamine? Medical News Today. https://www.medicalnewstoday.com/articles/302663.php. Updated October 12, 2017. Published October 11, 2019.
3. Chaverneff F. Ketamine: mechanisms of action, uses in pain medicine, and side effects. Clinical Pain Advisor. https://www.clinicalpainadvisor.com/home/conference-highlights/painweek-2018/ketamine-mechanisms-of-action-uses-in-pain-medicine-and-side-effects/. Published 2018. Accessed October 11, 2019.
4. Gao M, Rejaei D, Liu H. Ketamine use in current clinical practice. Acta Pharmacol Sin. 2016;37(7):865-872.
5. Orhurhu VJ, Claus LE, Cohen SP. Ketamine toxicity. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK541087. Updated April 11, 2019. Accessed October 18, 2019.
6. Pai A, Heining M. Ketamine. Continuing Education in Anaesthesia Critical Care & Pain. 20071;7(2):59-63.
7. Logan K. Addressing ketamine bladder syndrome. Nursing Times. https://www.nursingtimes.net/clinical-archive/medicine-management/addressing-ketamine-bladder-syndrome-19-06-2011/. Published June 19, 2011. Accessed October 11, 2019.
8. Lin PC, Lane HY, Lin CH. Spontaneous remission of ketamine withdrawal-related depression. Clin Neuropharmacol. 2016;39(1):51-52.
Urine drug screens: Not just for job applicants
Although urine drug screens (UDS) are most commonly used to screen job applicants, some clinicians have started to use them as a tool for improving their patients’ clinical outcomes.1 Recently, some clinicians have begun using UDS to help patients who experience chronic pain and dependency (mainly on opioids) and for those who use diverted drugs to relieve these conditions. Many psychiatrists are concerned about the high cost of drug diversion, as well as the possibility of diversion-related patient mortality. Clinicians should therefore consider using UDS as a tool to help address these challenges.
Consider individualized UDS monitoring
The standard 5-substance UDS test panel consists of tetrahydrocannabinol, opiates, amphetamines, cocaine, and phencyclidine. Although this panel was sufficient for an employment screening-related UDS, the American Society of Addiction Medicine (ASAM) has rejected its use for patients with substance abuse. As part of its emphasis on the importance of incorporating preventative procedures, diagnostics, and surveillance protocols, the ASAM advocates using a rotating test panel in conjunction with a patient-specific UDS.2 This type of patient-specific regimen would take into account the dynamic nature of a patient’s health profile factors, including comorbid and psychosocial status, subjective pain features, and diverted drug use. Furthermore, the ASAM recommends evaluating patients for the concurrent use of other substances and agents, such as benzodiazepines, sleep-inducing medications, stimulants, and alcohol, because these can interact with opioids.
Consider extending individualized monitoring by implementing standard “cutoff” values for each drug; patients whose levels of a specific substance are above the established cutoff value are categorized as testing positive for the use of that substance. The Substance Abuse Mental Health Services Administration favors adjusting UDS cutoffs, specifically the use of decreased cutoffs, to improve patient compliance.3 However, standardized drug concentration cutoff values may not be applicable for each patient; therefore, such values may need to be carefully tailored to each patient.
Additional drug monitoring techniques
Existing UDS practices, such as medication adherence and compliance, can be supplemented or alternately used with UDS panels that are modified to account for a patient’s fluctuating clinical conditions and concurrent medications. Point-of-care immunoassays, which provide accurate screening for medication compliance and adherence and possible drug diversion, should be used for routine monitoring. Using DNA-authenticated UDS also adds further control in monitoring a patient’s use of different drugs.4,5
In addition to being helpful for monitoring opioid use, a DNA-verified UDS can be used to evaluate for the presence of synthetic urine substitutes.6-8 Diversion remains a growing epidemiologic concern, and the number of cases is vastly underreported in the literature. The DNA-authenticated UDS can give clinicians greater precision in identifying synthetic and substituted urine among patient-provided samples.4
Using a combination of the methods described here can help expand a clinician’s ability to perform individualized drug monitoring, and verify whether a patient is adhering to his or her treatment regimen.
1. Choudhry Z, Islam F, Siddiqui W, et al. UDS in mental health: is it time to move forward? J Psychiatry. 2015;18(5): doi: 10.4172/2378-5756.1000319.
2. Drug testing: a white paper of the American Society of Addiction Medicine. Chevy Chase, MD: American Society of Addiction Medicine; https://www.asam.org/docs/default-source/public-policy-statements/drug-testing-a-white-paper-by-asam.pdf. Published October 26, 2013. Accessed November 13, 2018.
3. Substance Abuse Mental Health Services Administration (SAMHSA). Technical Assistance Publication Series, TAP 32. Clinical drug testing in primary care. Rockville, MD: U.S. Department of Health and Human Services; 2012.
4. Genotox Laboratories. DNA Authenticated Drug Screen (ToxProtect). https://genotoxlabs.com/. Accessed October 11, 2018
5. 3RX Holdings Inc. 3RX Toxicology Urinary Drug Testing. http://3rxholdings.com/. Accessed October 11, 2018.
6. Genetic testing to confirm the identity of laboratory specimens. Document No GENE.00041. Medical Policy. Virginia Beach, VA: Amerigroup; 2018.
7. UnitedHealthcare Services. Drug Testing Policy. Reimbursement policy No 2018R6005A. https://www.uhcprovider.com/content/dam/provider/docs/public/policies/comm-reimbursement/COMM-Drug-Testing-Policy.pdf. Accessed October 12, 2018.
8. OzMed Laboratory Services. DNA-Verified Urine Drug Testing. http://www.ozmed.org/. Accessed October 11, 2018.
Although urine drug screens (UDS) are most commonly used to screen job applicants, some clinicians have started to use them as a tool for improving their patients’ clinical outcomes.1 Recently, some clinicians have begun using UDS to help patients who experience chronic pain and dependency (mainly on opioids) and for those who use diverted drugs to relieve these conditions. Many psychiatrists are concerned about the high cost of drug diversion, as well as the possibility of diversion-related patient mortality. Clinicians should therefore consider using UDS as a tool to help address these challenges.
Consider individualized UDS monitoring
The standard 5-substance UDS test panel consists of tetrahydrocannabinol, opiates, amphetamines, cocaine, and phencyclidine. Although this panel was sufficient for an employment screening-related UDS, the American Society of Addiction Medicine (ASAM) has rejected its use for patients with substance abuse. As part of its emphasis on the importance of incorporating preventative procedures, diagnostics, and surveillance protocols, the ASAM advocates using a rotating test panel in conjunction with a patient-specific UDS.2 This type of patient-specific regimen would take into account the dynamic nature of a patient’s health profile factors, including comorbid and psychosocial status, subjective pain features, and diverted drug use. Furthermore, the ASAM recommends evaluating patients for the concurrent use of other substances and agents, such as benzodiazepines, sleep-inducing medications, stimulants, and alcohol, because these can interact with opioids.
Consider extending individualized monitoring by implementing standard “cutoff” values for each drug; patients whose levels of a specific substance are above the established cutoff value are categorized as testing positive for the use of that substance. The Substance Abuse Mental Health Services Administration favors adjusting UDS cutoffs, specifically the use of decreased cutoffs, to improve patient compliance.3 However, standardized drug concentration cutoff values may not be applicable for each patient; therefore, such values may need to be carefully tailored to each patient.
Additional drug monitoring techniques
Existing UDS practices, such as medication adherence and compliance, can be supplemented or alternately used with UDS panels that are modified to account for a patient’s fluctuating clinical conditions and concurrent medications. Point-of-care immunoassays, which provide accurate screening for medication compliance and adherence and possible drug diversion, should be used for routine monitoring. Using DNA-authenticated UDS also adds further control in monitoring a patient’s use of different drugs.4,5
In addition to being helpful for monitoring opioid use, a DNA-verified UDS can be used to evaluate for the presence of synthetic urine substitutes.6-8 Diversion remains a growing epidemiologic concern, and the number of cases is vastly underreported in the literature. The DNA-authenticated UDS can give clinicians greater precision in identifying synthetic and substituted urine among patient-provided samples.4
Using a combination of the methods described here can help expand a clinician’s ability to perform individualized drug monitoring, and verify whether a patient is adhering to his or her treatment regimen.
Although urine drug screens (UDS) are most commonly used to screen job applicants, some clinicians have started to use them as a tool for improving their patients’ clinical outcomes.1 Recently, some clinicians have begun using UDS to help patients who experience chronic pain and dependency (mainly on opioids) and for those who use diverted drugs to relieve these conditions. Many psychiatrists are concerned about the high cost of drug diversion, as well as the possibility of diversion-related patient mortality. Clinicians should therefore consider using UDS as a tool to help address these challenges.
Consider individualized UDS monitoring
The standard 5-substance UDS test panel consists of tetrahydrocannabinol, opiates, amphetamines, cocaine, and phencyclidine. Although this panel was sufficient for an employment screening-related UDS, the American Society of Addiction Medicine (ASAM) has rejected its use for patients with substance abuse. As part of its emphasis on the importance of incorporating preventative procedures, diagnostics, and surveillance protocols, the ASAM advocates using a rotating test panel in conjunction with a patient-specific UDS.2 This type of patient-specific regimen would take into account the dynamic nature of a patient’s health profile factors, including comorbid and psychosocial status, subjective pain features, and diverted drug use. Furthermore, the ASAM recommends evaluating patients for the concurrent use of other substances and agents, such as benzodiazepines, sleep-inducing medications, stimulants, and alcohol, because these can interact with opioids.
Consider extending individualized monitoring by implementing standard “cutoff” values for each drug; patients whose levels of a specific substance are above the established cutoff value are categorized as testing positive for the use of that substance. The Substance Abuse Mental Health Services Administration favors adjusting UDS cutoffs, specifically the use of decreased cutoffs, to improve patient compliance.3 However, standardized drug concentration cutoff values may not be applicable for each patient; therefore, such values may need to be carefully tailored to each patient.
Additional drug monitoring techniques
Existing UDS practices, such as medication adherence and compliance, can be supplemented or alternately used with UDS panels that are modified to account for a patient’s fluctuating clinical conditions and concurrent medications. Point-of-care immunoassays, which provide accurate screening for medication compliance and adherence and possible drug diversion, should be used for routine monitoring. Using DNA-authenticated UDS also adds further control in monitoring a patient’s use of different drugs.4,5
In addition to being helpful for monitoring opioid use, a DNA-verified UDS can be used to evaluate for the presence of synthetic urine substitutes.6-8 Diversion remains a growing epidemiologic concern, and the number of cases is vastly underreported in the literature. The DNA-authenticated UDS can give clinicians greater precision in identifying synthetic and substituted urine among patient-provided samples.4
Using a combination of the methods described here can help expand a clinician’s ability to perform individualized drug monitoring, and verify whether a patient is adhering to his or her treatment regimen.
1. Choudhry Z, Islam F, Siddiqui W, et al. UDS in mental health: is it time to move forward? J Psychiatry. 2015;18(5): doi: 10.4172/2378-5756.1000319.
2. Drug testing: a white paper of the American Society of Addiction Medicine. Chevy Chase, MD: American Society of Addiction Medicine; https://www.asam.org/docs/default-source/public-policy-statements/drug-testing-a-white-paper-by-asam.pdf. Published October 26, 2013. Accessed November 13, 2018.
3. Substance Abuse Mental Health Services Administration (SAMHSA). Technical Assistance Publication Series, TAP 32. Clinical drug testing in primary care. Rockville, MD: U.S. Department of Health and Human Services; 2012.
4. Genotox Laboratories. DNA Authenticated Drug Screen (ToxProtect). https://genotoxlabs.com/. Accessed October 11, 2018
5. 3RX Holdings Inc. 3RX Toxicology Urinary Drug Testing. http://3rxholdings.com/. Accessed October 11, 2018.
6. Genetic testing to confirm the identity of laboratory specimens. Document No GENE.00041. Medical Policy. Virginia Beach, VA: Amerigroup; 2018.
7. UnitedHealthcare Services. Drug Testing Policy. Reimbursement policy No 2018R6005A. https://www.uhcprovider.com/content/dam/provider/docs/public/policies/comm-reimbursement/COMM-Drug-Testing-Policy.pdf. Accessed October 12, 2018.
8. OzMed Laboratory Services. DNA-Verified Urine Drug Testing. http://www.ozmed.org/. Accessed October 11, 2018.
1. Choudhry Z, Islam F, Siddiqui W, et al. UDS in mental health: is it time to move forward? J Psychiatry. 2015;18(5): doi: 10.4172/2378-5756.1000319.
2. Drug testing: a white paper of the American Society of Addiction Medicine. Chevy Chase, MD: American Society of Addiction Medicine; https://www.asam.org/docs/default-source/public-policy-statements/drug-testing-a-white-paper-by-asam.pdf. Published October 26, 2013. Accessed November 13, 2018.
3. Substance Abuse Mental Health Services Administration (SAMHSA). Technical Assistance Publication Series, TAP 32. Clinical drug testing in primary care. Rockville, MD: U.S. Department of Health and Human Services; 2012.
4. Genotox Laboratories. DNA Authenticated Drug Screen (ToxProtect). https://genotoxlabs.com/. Accessed October 11, 2018
5. 3RX Holdings Inc. 3RX Toxicology Urinary Drug Testing. http://3rxholdings.com/. Accessed October 11, 2018.
6. Genetic testing to confirm the identity of laboratory specimens. Document No GENE.00041. Medical Policy. Virginia Beach, VA: Amerigroup; 2018.
7. UnitedHealthcare Services. Drug Testing Policy. Reimbursement policy No 2018R6005A. https://www.uhcprovider.com/content/dam/provider/docs/public/policies/comm-reimbursement/COMM-Drug-Testing-Policy.pdf. Accessed October 12, 2018.
8. OzMed Laboratory Services. DNA-Verified Urine Drug Testing. http://www.ozmed.org/. Accessed October 11, 2018.
What role does asthma medication have in ADHD or depression?
Asthma medications comprise several drug classes, including leukotriene antagonists and steroid-based inhalers. These drugs have been implicated in behavioral changes, such as increased hyperactivity, similar to symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD)1; this scenario is more of a concern in children than adults. This raises the question of whether these medications are physiologically linked to behavioral symptoms because of a suggested association with serotonin.2,3 If this is the case, it is necessary to identify and evaluate possible psychiatric effects of these asthma agents.
How asthma medications work
Some asthma agents, such as montelukast, act as either leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists. These drugs block production of inflammatory leukotrienes, which cause bronchoconstriction. Leukotrienes also can trigger cytokine synthesis, which can modulate leukotriene receptor function. Therefore, leukotriene antagonists could interfere with cytokine function.3,4
Corticosteroid inhalers suppress inflammatory genes by reversing histone acetylation of inflammatory genes involved in asthma. These inhalers have been shown to reduce cytokine levels in patients with chronic lung disease and those with moderate to
Possible link between asthma and serotonin
Serotonin plays an integral role in observable, dysfunctional behaviors seen in disorders such as ADHD and ODD. In previous studies, serotonin modulated the cytokine network, and patients with asthma had elevated levels of plasma serotonin.2,3 These findings imply that asthma medications could be involved in altering levels of both cytokines and serotonin. Pretorius2 emphasized the importance of monitoring serotonin levels in children who exhibit behavioral dysfunction based on these observations:
- Persons with asthma presenting with medical symptoms have elevated serotonin levels.
- Decreased serotonin levels have been associated with ADHD and ODD; medications for ADHD have been shown to increase serotonin levels.
- Asthma medications have been shown to decrease serotonin levels.2,3
Asthma medications might be partially responsible for behavioral disturbances, and therapeutic management should integrate the role of serotonin with asthma therapy.2,3
Clinical considerations
Therapeutic management of asthma should consider psychiatric conditions and treatments. Future research should investigate the overall predisposition for behavioral dysfunction in persons with respiratory syncytial virus, a precursor for asthma. Once an asthma patient’s risk of a psychiatric disorder has been identified, the clinician can determine the most effective medications for treating the condition. If potential medications or genetic or environmental factors are identified, we might expect a move toward personalized care in the not too distant future.
1. Saricoban HE, Ozen A, Harmanci K, et al. Common behavioral problems among children with asthma: is there a role of asthma treatment? Ann Allergy Asthma Immunol. 2011;106(3):200-204.
2. Pretorius E. Asthma medication may influence the psychological functioning of children. Med Hypotheses. 2004;63(3):409-413.
3. Ménard G, Turmei V, Bissonnette EY. Serotonin modulates the cytokine network in the lung: involvement of prostaglandin E2. Clin Exp Immunol. 2007;150(2):340-348.
4. Rola-Pleszczynski M, Stankova J. Cytokine-leukotriene receptor interactions. Scientific World Journal. 2007;7:1348-1358.
5. Kaur M, Reynolds S, Smyth LJ, et al. The effects of corticosteroids on cytokine production from asthma lung lymphocytes. Int Immunopharmacol. 2014;23(2):581-584.
6. Honda R, Ichiyama T, Sunagawa S, et al. Inhaled corticosteroid therapy reduces cytokine levels in sputum from very preterm infants with chronic lung disease. Acta Paediatr. 2009;98(1):118-122.
7. Pretorius E. Corticosteroids, depression and the role of serotonin. Rev Neurosci. 2004;15(2):109-116.
Asthma medications comprise several drug classes, including leukotriene antagonists and steroid-based inhalers. These drugs have been implicated in behavioral changes, such as increased hyperactivity, similar to symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD)1; this scenario is more of a concern in children than adults. This raises the question of whether these medications are physiologically linked to behavioral symptoms because of a suggested association with serotonin.2,3 If this is the case, it is necessary to identify and evaluate possible psychiatric effects of these asthma agents.
How asthma medications work
Some asthma agents, such as montelukast, act as either leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists. These drugs block production of inflammatory leukotrienes, which cause bronchoconstriction. Leukotrienes also can trigger cytokine synthesis, which can modulate leukotriene receptor function. Therefore, leukotriene antagonists could interfere with cytokine function.3,4
Corticosteroid inhalers suppress inflammatory genes by reversing histone acetylation of inflammatory genes involved in asthma. These inhalers have been shown to reduce cytokine levels in patients with chronic lung disease and those with moderate to
Possible link between asthma and serotonin
Serotonin plays an integral role in observable, dysfunctional behaviors seen in disorders such as ADHD and ODD. In previous studies, serotonin modulated the cytokine network, and patients with asthma had elevated levels of plasma serotonin.2,3 These findings imply that asthma medications could be involved in altering levels of both cytokines and serotonin. Pretorius2 emphasized the importance of monitoring serotonin levels in children who exhibit behavioral dysfunction based on these observations:
- Persons with asthma presenting with medical symptoms have elevated serotonin levels.
- Decreased serotonin levels have been associated with ADHD and ODD; medications for ADHD have been shown to increase serotonin levels.
- Asthma medications have been shown to decrease serotonin levels.2,3
Asthma medications might be partially responsible for behavioral disturbances, and therapeutic management should integrate the role of serotonin with asthma therapy.2,3
Clinical considerations
Therapeutic management of asthma should consider psychiatric conditions and treatments. Future research should investigate the overall predisposition for behavioral dysfunction in persons with respiratory syncytial virus, a precursor for asthma. Once an asthma patient’s risk of a psychiatric disorder has been identified, the clinician can determine the most effective medications for treating the condition. If potential medications or genetic or environmental factors are identified, we might expect a move toward personalized care in the not too distant future.
Asthma medications comprise several drug classes, including leukotriene antagonists and steroid-based inhalers. These drugs have been implicated in behavioral changes, such as increased hyperactivity, similar to symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD)1; this scenario is more of a concern in children than adults. This raises the question of whether these medications are physiologically linked to behavioral symptoms because of a suggested association with serotonin.2,3 If this is the case, it is necessary to identify and evaluate possible psychiatric effects of these asthma agents.
How asthma medications work
Some asthma agents, such as montelukast, act as either leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists. These drugs block production of inflammatory leukotrienes, which cause bronchoconstriction. Leukotrienes also can trigger cytokine synthesis, which can modulate leukotriene receptor function. Therefore, leukotriene antagonists could interfere with cytokine function.3,4
Corticosteroid inhalers suppress inflammatory genes by reversing histone acetylation of inflammatory genes involved in asthma. These inhalers have been shown to reduce cytokine levels in patients with chronic lung disease and those with moderate to
Possible link between asthma and serotonin
Serotonin plays an integral role in observable, dysfunctional behaviors seen in disorders such as ADHD and ODD. In previous studies, serotonin modulated the cytokine network, and patients with asthma had elevated levels of plasma serotonin.2,3 These findings imply that asthma medications could be involved in altering levels of both cytokines and serotonin. Pretorius2 emphasized the importance of monitoring serotonin levels in children who exhibit behavioral dysfunction based on these observations:
- Persons with asthma presenting with medical symptoms have elevated serotonin levels.
- Decreased serotonin levels have been associated with ADHD and ODD; medications for ADHD have been shown to increase serotonin levels.
- Asthma medications have been shown to decrease serotonin levels.2,3
Asthma medications might be partially responsible for behavioral disturbances, and therapeutic management should integrate the role of serotonin with asthma therapy.2,3
Clinical considerations
Therapeutic management of asthma should consider psychiatric conditions and treatments. Future research should investigate the overall predisposition for behavioral dysfunction in persons with respiratory syncytial virus, a precursor for asthma. Once an asthma patient’s risk of a psychiatric disorder has been identified, the clinician can determine the most effective medications for treating the condition. If potential medications or genetic or environmental factors are identified, we might expect a move toward personalized care in the not too distant future.
1. Saricoban HE, Ozen A, Harmanci K, et al. Common behavioral problems among children with asthma: is there a role of asthma treatment? Ann Allergy Asthma Immunol. 2011;106(3):200-204.
2. Pretorius E. Asthma medication may influence the psychological functioning of children. Med Hypotheses. 2004;63(3):409-413.
3. Ménard G, Turmei V, Bissonnette EY. Serotonin modulates the cytokine network in the lung: involvement of prostaglandin E2. Clin Exp Immunol. 2007;150(2):340-348.
4. Rola-Pleszczynski M, Stankova J. Cytokine-leukotriene receptor interactions. Scientific World Journal. 2007;7:1348-1358.
5. Kaur M, Reynolds S, Smyth LJ, et al. The effects of corticosteroids on cytokine production from asthma lung lymphocytes. Int Immunopharmacol. 2014;23(2):581-584.
6. Honda R, Ichiyama T, Sunagawa S, et al. Inhaled corticosteroid therapy reduces cytokine levels in sputum from very preterm infants with chronic lung disease. Acta Paediatr. 2009;98(1):118-122.
7. Pretorius E. Corticosteroids, depression and the role of serotonin. Rev Neurosci. 2004;15(2):109-116.
1. Saricoban HE, Ozen A, Harmanci K, et al. Common behavioral problems among children with asthma: is there a role of asthma treatment? Ann Allergy Asthma Immunol. 2011;106(3):200-204.
2. Pretorius E. Asthma medication may influence the psychological functioning of children. Med Hypotheses. 2004;63(3):409-413.
3. Ménard G, Turmei V, Bissonnette EY. Serotonin modulates the cytokine network in the lung: involvement of prostaglandin E2. Clin Exp Immunol. 2007;150(2):340-348.
4. Rola-Pleszczynski M, Stankova J. Cytokine-leukotriene receptor interactions. Scientific World Journal. 2007;7:1348-1358.
5. Kaur M, Reynolds S, Smyth LJ, et al. The effects of corticosteroids on cytokine production from asthma lung lymphocytes. Int Immunopharmacol. 2014;23(2):581-584.
6. Honda R, Ichiyama T, Sunagawa S, et al. Inhaled corticosteroid therapy reduces cytokine levels in sputum from very preterm infants with chronic lung disease. Acta Paediatr. 2009;98(1):118-122.
7. Pretorius E. Corticosteroids, depression and the role of serotonin. Rev Neurosci. 2004;15(2):109-116.
What to do when adolescents with ADHD self-medicate with bath salts
Designer drugs are rapidly making inroads with young people, primarily because of easier access, lower overall cost, and nebulous legality. These drugs are made as variants of illicit drugs or new formulations and sold as “research chemicals” and labeled as “not for human consumption,” which allows them to fall outside existing laws. The ingredients typically are not detected in a urine drug screen.
Notoriously addictive, these designer drugs, such as bath salts, are known to incorporate synthetic cathinones—namely, methylone, mephedrone or methylenedioxypyrovalerone (MDPV). The stimulant, amphetamine-like effects of bath salts make the drug attractive to adolescents with attention-deficit/hyperactivity disorder (ADHD).
Why do teens gravitate toward bath salts?
Adolescents with undiagnosed ADHD might self-medicate with drugs that are suited for addressing restlessness, intrapsychic turmoil, and other symptoms of ADHD. In 2 case studies, using the self-medication hypothesis, people with ADHD were more likely to seek cocaine by means of “self-selection.”1 These drug-seeking behaviors often led to cocaine dependence, even when other substances, such as alcohol or Cannabis, were available.
Methylphenidate and other ADHD pharmacotherapies influence the nucleus accumbens in a manner similar to that of cocaine. These findings suggest that adolescents with ADHD and cocaine dependence might respond to therapeutic interventions that substitute cocaine with psychostimulants.1
Bath salts fall within the same spectrum of psychostimulant agents as methylphenidate and cocaine. MDPV approximates the effect of methylphenidate at low doses, and cocaine at higher doses. It often is marketed under the name “Ivory Wave” and could be confused with cocaine. Self-administration of MDPV can induce psychoactive effects that help alleviate ADHD symptoms; adolescents might continue to experience enhanced concentration and overall performance.2 Also, because of the low cost of “legal” bath salts, they are an appealing alternative to cocaine for self-medication.
Managing the sequelae of bath salt intoxication
Bath salts may produce sympathomimetic effects greater than cocaine, which require a proactive approach to symptom management. A medley of unknown ingredients in bath salt preparations makes it difficult for clinicians to gauge the pharmacological impact on individual patients; therefore, therapeutic interventions are on a case-by-case basis. However, emergencies concerning amphetamines and amphetamine analogues and derivatives often have similar presentations.
Cardiovascular effects. MDPV-specific urine and blood tests conducted on patients admitted to the emergency room showed a 10-fold increase in overall dopamine levels compared with those who took cocaine. As a sympathomimetic, high doses of dopamine are responsible for raising blood pressure and could lead to the development of pronounced cardiovascular effects.3,4
Agitation. Clinicians generally are advised to treat agitation before providing a more comprehensive assessment of symptoms. Endotracheal intubation often is a required for adequate control of agitation. Bath salt-induced agitation often is treated with IV benzodiazepines.4,5 Monitor patients for excessive sedation or new-onset “paradoxical agitation” as a function of ongoing benzo-diazepine therapy. Clinicians also may choose to co-administer an antipsychotic with benzodiazepines, although the practice is not universally encouraged for agitation control.
Mephedrone produces a delirious state in conjunction with psychotic symptoms. Antipsychotic therapy has been suggested for addressing ongoing agitation.6
Tachycardia. Symptomatic treatment of tachycardia involves beta blockers, such as labetalol. Nitroglycerine has evidence of efficacy for chest pain associated with cocaine intoxication; however, it is unclear whether it is effective for similar drugs of abuse.4
Multi-organ collapse caused by MDPV necessitates aggressive intervention, including prompt dialysis. Carefully evaluate the patient for the presence of organ-specific insults and initiate supportive measures accordingly. Pronounced agitation with hyperthermia might portend severely compromised renal, hepatic, and/or cardiac function in MDPV users.7 Those who present with MDPV intoxication and concomitant renal injury seem to benefit from hemodialysis.8 Repeat intoxication events may yield a presentation of acute renal injury replete with metabolic derangements, including metabolic acidosis, hyperuricemia, and rhabdomyolysis.9 Thorough patient assessments and interventions are useful in determining long-term outcomes, including issues pertaining to mortality.
Confronting an epidemic
Adolescents are quickly adopting designer drugs as a readily accessible form of recreational “legal highs.”10 Public awareness and educational initiatives can bring to light the dangers of these substances that exert powerful and, sometimes, unpredictable psychoactive effects on the user.
Self-mutilation and suicidal ideation also have been documented among those who ingested bath salts. These reports appear to be escalating across Europe and the United States. On a national level, U.S. poison centers have reported an almost 20-fold increase in calls regarding bath salts between 2010 and 2011.5 It is of utmost importance for clinicians and emergency personnel to familiarize themselves with the sympathomimetic toxidrome and management for bath salt consumption.
1. Mariani JJ, Khantzian EJ, Levin FR. The self-medication hypothesis and psychostimulant treatment of cocaine dependence: an update. Am J Addict. 2014;23(2):189-193.
2. Deluca P, Schifano F, Davey Z, et al. MDPV Report: Psychonaut Web Mapping Research Project. https://catbull.com/alamut/Bibliothek/PsychonautMDPVreport. pdf. Updated June 8, 2010. Accessed October 27, 2015.
3. National Institute on Drug Abuse. What are bath salts? http://teens.drugabuse.gov/drug-facts/bath-salts. Updated October 23, 2015. Accessed October 27, 2015.
4. Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, “bath salts,” and other amphetamine-related derivatives. Enliven: Toxicology and Allied Clinical Pharmacology. 2014;1(1):1-15.
5. Olives TD, Orozco BS, Stellpflug SJ. Bath salts: the ivory wave of trouble. West J Emerg Med. 2012;13(1):58-62.
6. Kasick DP, McKnight CA, Klisovic E. “Bath salt” ingestion leading to severe intoxication delirium: two cases and a brief review of the emergence of mephedrone use. Am J Drug Alcohol Abuse. 2012;38(2):176-180.
7. Borek HA, Holstege CP. Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med. 2012;60(1):103-105.
8. Regunath H, Ariyamuthu VK, Dalal P, et al. Bath salt intoxication causing acute kidney injury requiring hemodialysis. Hemodial Int. 2012;16(suppl 1):S47-S49.
9. Adebamiro A, Perazella MA. Recurrent acute kidney injury following bath salts intoxication. Am J Kidney Dis. 2012;59(2):273-275.
10. Federation of American Societies for Experimental Biology. New designer drug, ‘bath salts,’ may confer additional risk for adolescents. EurekAlert. http://www.eurekalert.org/ pub_releases/2013-04/foas-ndd041813.php. Published April 23, 2013. Accessed November 10, 2015.
Designer drugs are rapidly making inroads with young people, primarily because of easier access, lower overall cost, and nebulous legality. These drugs are made as variants of illicit drugs or new formulations and sold as “research chemicals” and labeled as “not for human consumption,” which allows them to fall outside existing laws. The ingredients typically are not detected in a urine drug screen.
Notoriously addictive, these designer drugs, such as bath salts, are known to incorporate synthetic cathinones—namely, methylone, mephedrone or methylenedioxypyrovalerone (MDPV). The stimulant, amphetamine-like effects of bath salts make the drug attractive to adolescents with attention-deficit/hyperactivity disorder (ADHD).
Why do teens gravitate toward bath salts?
Adolescents with undiagnosed ADHD might self-medicate with drugs that are suited for addressing restlessness, intrapsychic turmoil, and other symptoms of ADHD. In 2 case studies, using the self-medication hypothesis, people with ADHD were more likely to seek cocaine by means of “self-selection.”1 These drug-seeking behaviors often led to cocaine dependence, even when other substances, such as alcohol or Cannabis, were available.
Methylphenidate and other ADHD pharmacotherapies influence the nucleus accumbens in a manner similar to that of cocaine. These findings suggest that adolescents with ADHD and cocaine dependence might respond to therapeutic interventions that substitute cocaine with psychostimulants.1
Bath salts fall within the same spectrum of psychostimulant agents as methylphenidate and cocaine. MDPV approximates the effect of methylphenidate at low doses, and cocaine at higher doses. It often is marketed under the name “Ivory Wave” and could be confused with cocaine. Self-administration of MDPV can induce psychoactive effects that help alleviate ADHD symptoms; adolescents might continue to experience enhanced concentration and overall performance.2 Also, because of the low cost of “legal” bath salts, they are an appealing alternative to cocaine for self-medication.
Managing the sequelae of bath salt intoxication
Bath salts may produce sympathomimetic effects greater than cocaine, which require a proactive approach to symptom management. A medley of unknown ingredients in bath salt preparations makes it difficult for clinicians to gauge the pharmacological impact on individual patients; therefore, therapeutic interventions are on a case-by-case basis. However, emergencies concerning amphetamines and amphetamine analogues and derivatives often have similar presentations.
Cardiovascular effects. MDPV-specific urine and blood tests conducted on patients admitted to the emergency room showed a 10-fold increase in overall dopamine levels compared with those who took cocaine. As a sympathomimetic, high doses of dopamine are responsible for raising blood pressure and could lead to the development of pronounced cardiovascular effects.3,4
Agitation. Clinicians generally are advised to treat agitation before providing a more comprehensive assessment of symptoms. Endotracheal intubation often is a required for adequate control of agitation. Bath salt-induced agitation often is treated with IV benzodiazepines.4,5 Monitor patients for excessive sedation or new-onset “paradoxical agitation” as a function of ongoing benzo-diazepine therapy. Clinicians also may choose to co-administer an antipsychotic with benzodiazepines, although the practice is not universally encouraged for agitation control.
Mephedrone produces a delirious state in conjunction with psychotic symptoms. Antipsychotic therapy has been suggested for addressing ongoing agitation.6
Tachycardia. Symptomatic treatment of tachycardia involves beta blockers, such as labetalol. Nitroglycerine has evidence of efficacy for chest pain associated with cocaine intoxication; however, it is unclear whether it is effective for similar drugs of abuse.4
Multi-organ collapse caused by MDPV necessitates aggressive intervention, including prompt dialysis. Carefully evaluate the patient for the presence of organ-specific insults and initiate supportive measures accordingly. Pronounced agitation with hyperthermia might portend severely compromised renal, hepatic, and/or cardiac function in MDPV users.7 Those who present with MDPV intoxication and concomitant renal injury seem to benefit from hemodialysis.8 Repeat intoxication events may yield a presentation of acute renal injury replete with metabolic derangements, including metabolic acidosis, hyperuricemia, and rhabdomyolysis.9 Thorough patient assessments and interventions are useful in determining long-term outcomes, including issues pertaining to mortality.
Confronting an epidemic
Adolescents are quickly adopting designer drugs as a readily accessible form of recreational “legal highs.”10 Public awareness and educational initiatives can bring to light the dangers of these substances that exert powerful and, sometimes, unpredictable psychoactive effects on the user.
Self-mutilation and suicidal ideation also have been documented among those who ingested bath salts. These reports appear to be escalating across Europe and the United States. On a national level, U.S. poison centers have reported an almost 20-fold increase in calls regarding bath salts between 2010 and 2011.5 It is of utmost importance for clinicians and emergency personnel to familiarize themselves with the sympathomimetic toxidrome and management for bath salt consumption.
Designer drugs are rapidly making inroads with young people, primarily because of easier access, lower overall cost, and nebulous legality. These drugs are made as variants of illicit drugs or new formulations and sold as “research chemicals” and labeled as “not for human consumption,” which allows them to fall outside existing laws. The ingredients typically are not detected in a urine drug screen.
Notoriously addictive, these designer drugs, such as bath salts, are known to incorporate synthetic cathinones—namely, methylone, mephedrone or methylenedioxypyrovalerone (MDPV). The stimulant, amphetamine-like effects of bath salts make the drug attractive to adolescents with attention-deficit/hyperactivity disorder (ADHD).
Why do teens gravitate toward bath salts?
Adolescents with undiagnosed ADHD might self-medicate with drugs that are suited for addressing restlessness, intrapsychic turmoil, and other symptoms of ADHD. In 2 case studies, using the self-medication hypothesis, people with ADHD were more likely to seek cocaine by means of “self-selection.”1 These drug-seeking behaviors often led to cocaine dependence, even when other substances, such as alcohol or Cannabis, were available.
Methylphenidate and other ADHD pharmacotherapies influence the nucleus accumbens in a manner similar to that of cocaine. These findings suggest that adolescents with ADHD and cocaine dependence might respond to therapeutic interventions that substitute cocaine with psychostimulants.1
Bath salts fall within the same spectrum of psychostimulant agents as methylphenidate and cocaine. MDPV approximates the effect of methylphenidate at low doses, and cocaine at higher doses. It often is marketed under the name “Ivory Wave” and could be confused with cocaine. Self-administration of MDPV can induce psychoactive effects that help alleviate ADHD symptoms; adolescents might continue to experience enhanced concentration and overall performance.2 Also, because of the low cost of “legal” bath salts, they are an appealing alternative to cocaine for self-medication.
Managing the sequelae of bath salt intoxication
Bath salts may produce sympathomimetic effects greater than cocaine, which require a proactive approach to symptom management. A medley of unknown ingredients in bath salt preparations makes it difficult for clinicians to gauge the pharmacological impact on individual patients; therefore, therapeutic interventions are on a case-by-case basis. However, emergencies concerning amphetamines and amphetamine analogues and derivatives often have similar presentations.
Cardiovascular effects. MDPV-specific urine and blood tests conducted on patients admitted to the emergency room showed a 10-fold increase in overall dopamine levels compared with those who took cocaine. As a sympathomimetic, high doses of dopamine are responsible for raising blood pressure and could lead to the development of pronounced cardiovascular effects.3,4
Agitation. Clinicians generally are advised to treat agitation before providing a more comprehensive assessment of symptoms. Endotracheal intubation often is a required for adequate control of agitation. Bath salt-induced agitation often is treated with IV benzodiazepines.4,5 Monitor patients for excessive sedation or new-onset “paradoxical agitation” as a function of ongoing benzo-diazepine therapy. Clinicians also may choose to co-administer an antipsychotic with benzodiazepines, although the practice is not universally encouraged for agitation control.
Mephedrone produces a delirious state in conjunction with psychotic symptoms. Antipsychotic therapy has been suggested for addressing ongoing agitation.6
Tachycardia. Symptomatic treatment of tachycardia involves beta blockers, such as labetalol. Nitroglycerine has evidence of efficacy for chest pain associated with cocaine intoxication; however, it is unclear whether it is effective for similar drugs of abuse.4
Multi-organ collapse caused by MDPV necessitates aggressive intervention, including prompt dialysis. Carefully evaluate the patient for the presence of organ-specific insults and initiate supportive measures accordingly. Pronounced agitation with hyperthermia might portend severely compromised renal, hepatic, and/or cardiac function in MDPV users.7 Those who present with MDPV intoxication and concomitant renal injury seem to benefit from hemodialysis.8 Repeat intoxication events may yield a presentation of acute renal injury replete with metabolic derangements, including metabolic acidosis, hyperuricemia, and rhabdomyolysis.9 Thorough patient assessments and interventions are useful in determining long-term outcomes, including issues pertaining to mortality.
Confronting an epidemic
Adolescents are quickly adopting designer drugs as a readily accessible form of recreational “legal highs.”10 Public awareness and educational initiatives can bring to light the dangers of these substances that exert powerful and, sometimes, unpredictable psychoactive effects on the user.
Self-mutilation and suicidal ideation also have been documented among those who ingested bath salts. These reports appear to be escalating across Europe and the United States. On a national level, U.S. poison centers have reported an almost 20-fold increase in calls regarding bath salts between 2010 and 2011.5 It is of utmost importance for clinicians and emergency personnel to familiarize themselves with the sympathomimetic toxidrome and management for bath salt consumption.
1. Mariani JJ, Khantzian EJ, Levin FR. The self-medication hypothesis and psychostimulant treatment of cocaine dependence: an update. Am J Addict. 2014;23(2):189-193.
2. Deluca P, Schifano F, Davey Z, et al. MDPV Report: Psychonaut Web Mapping Research Project. https://catbull.com/alamut/Bibliothek/PsychonautMDPVreport. pdf. Updated June 8, 2010. Accessed October 27, 2015.
3. National Institute on Drug Abuse. What are bath salts? http://teens.drugabuse.gov/drug-facts/bath-salts. Updated October 23, 2015. Accessed October 27, 2015.
4. Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, “bath salts,” and other amphetamine-related derivatives. Enliven: Toxicology and Allied Clinical Pharmacology. 2014;1(1):1-15.
5. Olives TD, Orozco BS, Stellpflug SJ. Bath salts: the ivory wave of trouble. West J Emerg Med. 2012;13(1):58-62.
6. Kasick DP, McKnight CA, Klisovic E. “Bath salt” ingestion leading to severe intoxication delirium: two cases and a brief review of the emergence of mephedrone use. Am J Drug Alcohol Abuse. 2012;38(2):176-180.
7. Borek HA, Holstege CP. Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med. 2012;60(1):103-105.
8. Regunath H, Ariyamuthu VK, Dalal P, et al. Bath salt intoxication causing acute kidney injury requiring hemodialysis. Hemodial Int. 2012;16(suppl 1):S47-S49.
9. Adebamiro A, Perazella MA. Recurrent acute kidney injury following bath salts intoxication. Am J Kidney Dis. 2012;59(2):273-275.
10. Federation of American Societies for Experimental Biology. New designer drug, ‘bath salts,’ may confer additional risk for adolescents. EurekAlert. http://www.eurekalert.org/ pub_releases/2013-04/foas-ndd041813.php. Published April 23, 2013. Accessed November 10, 2015.
1. Mariani JJ, Khantzian EJ, Levin FR. The self-medication hypothesis and psychostimulant treatment of cocaine dependence: an update. Am J Addict. 2014;23(2):189-193.
2. Deluca P, Schifano F, Davey Z, et al. MDPV Report: Psychonaut Web Mapping Research Project. https://catbull.com/alamut/Bibliothek/PsychonautMDPVreport. pdf. Updated June 8, 2010. Accessed October 27, 2015.
3. National Institute on Drug Abuse. What are bath salts? http://teens.drugabuse.gov/drug-facts/bath-salts. Updated October 23, 2015. Accessed October 27, 2015.
4. Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, “bath salts,” and other amphetamine-related derivatives. Enliven: Toxicology and Allied Clinical Pharmacology. 2014;1(1):1-15.
5. Olives TD, Orozco BS, Stellpflug SJ. Bath salts: the ivory wave of trouble. West J Emerg Med. 2012;13(1):58-62.
6. Kasick DP, McKnight CA, Klisovic E. “Bath salt” ingestion leading to severe intoxication delirium: two cases and a brief review of the emergence of mephedrone use. Am J Drug Alcohol Abuse. 2012;38(2):176-180.
7. Borek HA, Holstege CP. Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med. 2012;60(1):103-105.
8. Regunath H, Ariyamuthu VK, Dalal P, et al. Bath salt intoxication causing acute kidney injury requiring hemodialysis. Hemodial Int. 2012;16(suppl 1):S47-S49.
9. Adebamiro A, Perazella MA. Recurrent acute kidney injury following bath salts intoxication. Am J Kidney Dis. 2012;59(2):273-275.
10. Federation of American Societies for Experimental Biology. New designer drug, ‘bath salts,’ may confer additional risk for adolescents. EurekAlert. http://www.eurekalert.org/ pub_releases/2013-04/foas-ndd041813.php. Published April 23, 2013. Accessed November 10, 2015.