Case-Based Review

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Mr. B, age 32, was diagnosed with human immunodeficiency virus (HIV) approximately 10 years ago. His current HIV regimen is highly active antiretroviral therapy, which includes the protease inhibitor (PI) indinavir and the combination product lamivudine and zidovudine, 2 nucleoside reverse transcriptase inhibitors. He shows no symptoms and his viral load has been undetectable for 9 years.

Several months ago, Mr. B reported to his primary care physician feelings of depressed mood, anhedonia, significant weight loss, fatigue, and feelings of worthlessness. He was diagnosed with major depressive disorder and started venlafaxine, 150 mg/d. The depressive episode is now in remission and the only major side effect he experiences is lethargy. His physician decides to check Mr. B’s viral load, which is 1,100 copies/mL. This viral load value indicates a significant elevation from the baseline (<48 copies/mL), which although still low, is considered virologic failure.¹ To rule out a lab error the viral load test is replicated, but the result is the same.

Mr. B’s case may represent an interaction between his antidepressant and one of his antiviral drugs that is a P-glycoprotein substrate. This protein transports a variety of drug substrates across cell membranes and affects the distribution and elimination of many prescription and nonprescription medications. Whether a drug induces or inhibits P-glycoprotein can affect plasma and cellular concentrations of drugs and can lead to unexpected increases or decreases in plasma concentrations of the affected drug. Understanding P-glycoprotein’s role can help you choose effective psychotropics for patients such as Mr. B.

Change in drug effect

Because depression is common among patients with HIV, my colleagues and I evaluated the pharmacokinetic effects of indinavir on venlafaxine and venlafaxine on indinavir to determine if venlafaxine would be safe to use in a patient taking a PI because of potential cytochrome P450 (CYP450) drug interactions in both classes of medications.² Adding venlafaxine resulted in a 36% decrease in maximum concentrations for indinavir and a 28% decrease in area under the curve Figure.² Study participants were healthy individuals; however, we concluded that had we studied patients with HIV, indinavir efficacy could decrease, resulting in an increased viral load. After this study, the manufacturer of venlafaxine included a caution about this combination in the product labeling.³ Because the extended-release formulation includes the same compound, the same effect could be expected and was included in the most recent version of the extended-release venlafaxine prescribing information.⁴

What is interesting about the venlafaxine-indinavir interaction is that there was no change in either agent’s half-life and therefore no reason to assume this effect was a traditional CYP450 drug interaction. The investigators considered other types of drug interactions and focused on mechanisms that could be presystemic, ie, affecting the absorption and bioavailability of indinavir. This led investigators to believe that the mechanism involved a drug transport protein such as P-glycoprotein, which is present in gut lumen. Subsequent studies have shown in a cellular model that venlafaxine—but not desvenlafaxine—is an inducer of P-glycoprotein and breast cancer resistant protein (BCRP).^5,6 Researchers are conducting animal studies to attempt to duplicate the cellular models. However, it could be presumed that the study of venlafaxine and indinavir in healthy individuals already had demonstrated this effect.²

Figure: Indinavir area under the curve before and after steady state venlafaxine
Decrease in area under the curve (AUC) for indinavir when healthy individuals achieved steady state dosing of venlafaxine
Source: Reference 2

Cause and effect

P-glycoprotein transports drugs or other foreign compounds out of the cells (efflux) of the target tissue so they can be further metabolized by metabolic enzymes for elimination. These proteins are called efflux proteins. There are many efflux proteins in addition to P-glycoprotein; a common one is BCRP, which confers resistance to some anticancer drugs. In addition to the gut lumen and breast tissue, efflux proteins are present in most tissues throughout the body, including the blood-brain barrier.

If drug A inhibits an efflux protein, then drug B would be able to enter the target tissue with greater ease and not be “kicked out” because the efflux system would be disabled. This could result in higher-than-expected tissue concentrations of drug B. Pharmaceutical companies often perform P-glycoprotein inhibition studies before a drug is marketed and include this data in the prescribing information.

If, on the other hand, drug A induces an efflux protein, then drug B would be “kicked out” at a greater rate than normal because the efflux system would be working in overdrive. In this case, tissue concentrations of drug B would be lower than expected and could lead to therapeutic failure. Typically, pharmaceutical companies either do not conduct these induction studies, or if they are performed, they often are not described in prescribing information. This lack of efficacy has been well documented with chemotherapeutic failure caused by drug efflux by BCRP.⁷ It is likely that Mr. B’s viral load increased when venlafaxine was added to his regimen—the antidepressant induced P-glycoprotein, which reduced indinavir concentrations and subsequent therapeutic effect.

Clinicians should review specific medications they are considering using if the drugs have a narrow therapeutic index or if therapeutic failure from subtherapeutic or supratherapeutic doses would be considered problematic Table.⁸ Kim⁹ provides a comprehensive list of P-glycoprotein substrates, inhibitors, and inducers. However, keep in mind that the list of substrates, inhibitors, and inducers changes regularly as new research becomes available.

Table

Selected psychotropics that affect P-glycoprotein

Related Resources

• Linnet K, Ejsing TB. A review on the impact of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs. Eur Neuropsychopharmacol. 2008;18(3):157-169.
• Weiss J, Dormann SM, Martin-Facklam M, et al. Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003;305(1):197-204.

Drug Brand Names

• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Chlorpromazine • Thorazine
• Citalopram • Celexa
• Desipramine • Norpramin
• Desvenlafaxine • Pristiq
• Disulfiram • Antabuse
• Doxepin • Adapin, Silenor
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Indinavir • Crixivan
• Lamivudine and zidovudine • Combivir
• Nefazodone • Serzone
• Nortriptyline • Aventyl, Pamelor
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Thioridazine • Melleril
• Topiramate • Topamax
• Trazodone • Desyrel, Oleptro
• Trifluoperazine • Stelazine
• Trimipramine • Surmontil
• Venlafaxine • Effexor

Disclosure

Dr. Levin receives grant/research support from Pfizer.

Discuss this article at www.facebook.com/CurrentPsychiatry

Mr. B, age 32, was diagnosed with human immunodeficiency virus (HIV) approximately 10 years ago. His current HIV regimen is highly active antiretroviral therapy, which includes the protease inhibitor (PI) indinavir and the combination product lamivudine and zidovudine, 2 nucleoside reverse transcriptase inhibitors. He shows no symptoms and his viral load has been undetectable for 9 years.

Several months ago, Mr. B reported to his primary care physician feelings of depressed mood, anhedonia, significant weight loss, fatigue, and feelings of worthlessness. He was diagnosed with major depressive disorder and started venlafaxine, 150 mg/d. The depressive episode is now in remission and the only major side effect he experiences is lethargy. His physician decides to check Mr. B’s viral load, which is 1,100 copies/mL. This viral load value indicates a significant elevation from the baseline (<48 copies/mL), which although still low, is considered virologic failure.¹ To rule out a lab error the viral load test is replicated, but the result is the same.

Mr. B’s case may represent an interaction between his antidepressant and one of his antiviral drugs that is a P-glycoprotein substrate. This protein transports a variety of drug substrates across cell membranes and affects the distribution and elimination of many prescription and nonprescription medications. Whether a drug induces or inhibits P-glycoprotein can affect plasma and cellular concentrations of drugs and can lead to unexpected increases or decreases in plasma concentrations of the affected drug. Understanding P-glycoprotein’s role can help you choose effective psychotropics for patients such as Mr. B.

Change in drug effect

Because depression is common among patients with HIV, my colleagues and I evaluated the pharmacokinetic effects of indinavir on venlafaxine and venlafaxine on indinavir to determine if venlafaxine would be safe to use in a patient taking a PI because of potential cytochrome P450 (CYP450) drug interactions in both classes of medications.² Adding venlafaxine resulted in a 36% decrease in maximum concentrations for indinavir and a 28% decrease in area under the curve Figure.² Study participants were healthy individuals; however, we concluded that had we studied patients with HIV, indinavir efficacy could decrease, resulting in an increased viral load. After this study, the manufacturer of venlafaxine included a caution about this combination in the product labeling.³ Because the extended-release formulation includes the same compound, the same effect could be expected and was included in the most recent version of the extended-release venlafaxine prescribing information.⁴

What is interesting about the venlafaxine-indinavir interaction is that there was no change in either agent’s half-life and therefore no reason to assume this effect was a traditional CYP450 drug interaction. The investigators considered other types of drug interactions and focused on mechanisms that could be presystemic, ie, affecting the absorption and bioavailability of indinavir. This led investigators to believe that the mechanism involved a drug transport protein such as P-glycoprotein, which is present in gut lumen. Subsequent studies have shown in a cellular model that venlafaxine—but not desvenlafaxine—is an inducer of P-glycoprotein and breast cancer resistant protein (BCRP).^5,6 Researchers are conducting animal studies to attempt to duplicate the cellular models. However, it could be presumed that the study of venlafaxine and indinavir in healthy individuals already had demonstrated this effect.²

Figure: Indinavir area under the curve before and after steady state venlafaxine
Decrease in area under the curve (AUC) for indinavir when healthy individuals achieved steady state dosing of venlafaxine
Source: Reference 2

Cause and effect

P-glycoprotein transports drugs or other foreign compounds out of the cells (efflux) of the target tissue so they can be further metabolized by metabolic enzymes for elimination. These proteins are called efflux proteins. There are many efflux proteins in addition to P-glycoprotein; a common one is BCRP, which confers resistance to some anticancer drugs. In addition to the gut lumen and breast tissue, efflux proteins are present in most tissues throughout the body, including the blood-brain barrier.

If drug A inhibits an efflux protein, then drug B would be able to enter the target tissue with greater ease and not be “kicked out” because the efflux system would be disabled. This could result in higher-than-expected tissue concentrations of drug B. Pharmaceutical companies often perform P-glycoprotein inhibition studies before a drug is marketed and include this data in the prescribing information.

If, on the other hand, drug A induces an efflux protein, then drug B would be “kicked out” at a greater rate than normal because the efflux system would be working in overdrive. In this case, tissue concentrations of drug B would be lower than expected and could lead to therapeutic failure. Typically, pharmaceutical companies either do not conduct these induction studies, or if they are performed, they often are not described in prescribing information. This lack of efficacy has been well documented with chemotherapeutic failure caused by drug efflux by BCRP.⁷ It is likely that Mr. B’s viral load increased when venlafaxine was added to his regimen—the antidepressant induced P-glycoprotein, which reduced indinavir concentrations and subsequent therapeutic effect.

Clinicians should review specific medications they are considering using if the drugs have a narrow therapeutic index or if therapeutic failure from subtherapeutic or supratherapeutic doses would be considered problematic Table.⁸ Kim⁹ provides a comprehensive list of P-glycoprotein substrates, inhibitors, and inducers. However, keep in mind that the list of substrates, inhibitors, and inducers changes regularly as new research becomes available.

Table

Selected psychotropics that affect P-glycoprotein

Related Resources

• Linnet K, Ejsing TB. A review on the impact of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs. Eur Neuropsychopharmacol. 2008;18(3):157-169.
• Weiss J, Dormann SM, Martin-Facklam M, et al. Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003;305(1):197-204.

Drug Brand Names

• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Chlorpromazine • Thorazine
• Citalopram • Celexa
• Desipramine • Norpramin
• Desvenlafaxine • Pristiq
• Disulfiram • Antabuse
• Doxepin • Adapin, Silenor
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Indinavir • Crixivan
• Lamivudine and zidovudine • Combivir
• Nefazodone • Serzone
• Nortriptyline • Aventyl, Pamelor
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Thioridazine • Melleril
• Topiramate • Topamax
• Trazodone • Desyrel, Oleptro
• Trifluoperazine • Stelazine
• Trimipramine • Surmontil
• Venlafaxine • Effexor

Disclosure

Dr. Levin receives grant/research support from Pfizer.

Discuss this article at www.facebook.com/CurrentPsychiatry

Mr. B, age 32, was diagnosed with human immunodeficiency virus (HIV) approximately 10 years ago. His current HIV regimen is highly active antiretroviral therapy, which includes the protease inhibitor (PI) indinavir and the combination product lamivudine and zidovudine, 2 nucleoside reverse transcriptase inhibitors. He shows no symptoms and his viral load has been undetectable for 9 years.

Several months ago, Mr. B reported to his primary care physician feelings of depressed mood, anhedonia, significant weight loss, fatigue, and feelings of worthlessness. He was diagnosed with major depressive disorder and started venlafaxine, 150 mg/d. The depressive episode is now in remission and the only major side effect he experiences is lethargy. His physician decides to check Mr. B’s viral load, which is 1,100 copies/mL. This viral load value indicates a significant elevation from the baseline (<48 copies/mL), which although still low, is considered virologic failure.¹ To rule out a lab error the viral load test is replicated, but the result is the same.

Mr. B’s case may represent an interaction between his antidepressant and one of his antiviral drugs that is a P-glycoprotein substrate. This protein transports a variety of drug substrates across cell membranes and affects the distribution and elimination of many prescription and nonprescription medications. Whether a drug induces or inhibits P-glycoprotein can affect plasma and cellular concentrations of drugs and can lead to unexpected increases or decreases in plasma concentrations of the affected drug. Understanding P-glycoprotein’s role can help you choose effective psychotropics for patients such as Mr. B.

Change in drug effect

Because depression is common among patients with HIV, my colleagues and I evaluated the pharmacokinetic effects of indinavir on venlafaxine and venlafaxine on indinavir to determine if venlafaxine would be safe to use in a patient taking a PI because of potential cytochrome P450 (CYP450) drug interactions in both classes of medications.² Adding venlafaxine resulted in a 36% decrease in maximum concentrations for indinavir and a 28% decrease in area under the curve Figure.² Study participants were healthy individuals; however, we concluded that had we studied patients with HIV, indinavir efficacy could decrease, resulting in an increased viral load. After this study, the manufacturer of venlafaxine included a caution about this combination in the product labeling.³ Because the extended-release formulation includes the same compound, the same effect could be expected and was included in the most recent version of the extended-release venlafaxine prescribing information.⁴

What is interesting about the venlafaxine-indinavir interaction is that there was no change in either agent’s half-life and therefore no reason to assume this effect was a traditional CYP450 drug interaction. The investigators considered other types of drug interactions and focused on mechanisms that could be presystemic, ie, affecting the absorption and bioavailability of indinavir. This led investigators to believe that the mechanism involved a drug transport protein such as P-glycoprotein, which is present in gut lumen. Subsequent studies have shown in a cellular model that venlafaxine—but not desvenlafaxine—is an inducer of P-glycoprotein and breast cancer resistant protein (BCRP).^5,6 Researchers are conducting animal studies to attempt to duplicate the cellular models. However, it could be presumed that the study of venlafaxine and indinavir in healthy individuals already had demonstrated this effect.²

Figure: Indinavir area under the curve before and after steady state venlafaxine
Decrease in area under the curve (AUC) for indinavir when healthy individuals achieved steady state dosing of venlafaxine
Source: Reference 2

Cause and effect

P-glycoprotein transports drugs or other foreign compounds out of the cells (efflux) of the target tissue so they can be further metabolized by metabolic enzymes for elimination. These proteins are called efflux proteins. There are many efflux proteins in addition to P-glycoprotein; a common one is BCRP, which confers resistance to some anticancer drugs. In addition to the gut lumen and breast tissue, efflux proteins are present in most tissues throughout the body, including the blood-brain barrier.

If drug A inhibits an efflux protein, then drug B would be able to enter the target tissue with greater ease and not be “kicked out” because the efflux system would be disabled. This could result in higher-than-expected tissue concentrations of drug B. Pharmaceutical companies often perform P-glycoprotein inhibition studies before a drug is marketed and include this data in the prescribing information.

If, on the other hand, drug A induces an efflux protein, then drug B would be “kicked out” at a greater rate than normal because the efflux system would be working in overdrive. In this case, tissue concentrations of drug B would be lower than expected and could lead to therapeutic failure. Typically, pharmaceutical companies either do not conduct these induction studies, or if they are performed, they often are not described in prescribing information. This lack of efficacy has been well documented with chemotherapeutic failure caused by drug efflux by BCRP.⁷ It is likely that Mr. B’s viral load increased when venlafaxine was added to his regimen—the antidepressant induced P-glycoprotein, which reduced indinavir concentrations and subsequent therapeutic effect.

Clinicians should review specific medications they are considering using if the drugs have a narrow therapeutic index or if therapeutic failure from subtherapeutic or supratherapeutic doses would be considered problematic Table.⁸ Kim⁹ provides a comprehensive list of P-glycoprotein substrates, inhibitors, and inducers. However, keep in mind that the list of substrates, inhibitors, and inducers changes regularly as new research becomes available.

Table

Selected psychotropics that affect P-glycoprotein

Related Resources

• Linnet K, Ejsing TB. A review on the impact of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs. Eur Neuropsychopharmacol. 2008;18(3):157-169.
• Weiss J, Dormann SM, Martin-Facklam M, et al. Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003;305(1):197-204.

Drug Brand Names

• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Chlorpromazine • Thorazine
• Citalopram • Celexa
• Desipramine • Norpramin
• Desvenlafaxine • Pristiq
• Disulfiram • Antabuse
• Doxepin • Adapin, Silenor
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Indinavir • Crixivan
• Lamivudine and zidovudine • Combivir
• Nefazodone • Serzone
• Nortriptyline • Aventyl, Pamelor
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Thioridazine • Melleril
• Topiramate • Topamax
• Trazodone • Desyrel, Oleptro
• Trifluoperazine • Stelazine
• Trimipramine • Surmontil
• Venlafaxine • Effexor

Disclosure

Dr. Levin receives grant/research support from Pfizer.

CASE: Hurt and confused

Emergency medical services (EMS) are called to Ms. K’s apartment after her roommate found her lying on the floor moaning. The roommate tells EMS that Ms. K, age 29, appeared confused and was slurring her words, and reports that this change in her awareness progressed rapidly over a few hours. EMS personnel find that Ms. K has multiple contusions on her arms and face, which they presume to be self-inflicted. A marijuana pipe is discovered at Ms. K’s apartment.

In the emergency room (ER), Ms. K is inattentive and has difficulty following simple commands. Her speech is mumbled and her thoughts are disorganized. She displays psychomotor restlessness in the form of combativeness. Ms. K cannot provide meaningful historical data and is disoriented to place and time. The ER staff requests a psychiatric consultation.

Family members reveal that Ms. K has no preexisting medical conditions, is not taking prescription medications, but has a history of substance abuse (sporadic cocaine and cannabis use). Her family is unaware of recent substance use.

Physical examination reveals tachycardia (heart rate 110 to 120 beats per minute), hypotension (blood pressure 78/49 mm Hg), hypothermia (temperature 88ºF), and peripheral pulse oximetry of 84%. Her pupils are dilated and reactive to light; no conjunctival injection is noted. Her lung fields are clear on auscultation, but she is noted to have a rapid, irregular heartbeat. The abdomen is positive for bowel sounds, soft on palpation, and without any repositioning or notable overt signs of tenderness. Ms. K’s toes show purple discoloration with poor capillary refill. The dorsalis pedis pulses are reported to be 1+ bilaterally; however, the remainder of the arterial pulse examination is normal.

Her sodium, potassium, and chloride values are normal, but she has an abnormal anion gap (28.1 mEq/L), blood urea nitrogen (53 mg/dL), creatinine (2.9 mg/dL), creatine kinase (10,857 U/L), creatine kinase MB (432.6 ng/mL), and hyperglycemia (glucose 425 mg/dL). Arterial blood gas reveals hypoxia (Po₂ of 55 mm Hg), with metabolic acidosis (sodium bicarbonate 10 with compensatory Pco₂ of 33 mm Hg). Her urine is cloudy, positive for protein, ketones, hemoglobin, and glucose. She is thought to have a high anion gap acidosis related to dehydration, lactic acidosis (lactic acid 20 mEq/L), and hyperglycemia. Urine toxicology is positive for cannabinoids; ethylene glycol and methanol screen negatively, which rules these out as potential contributors to her high anion gap acidosis.

Ms. K is intubated and IV fluids are initiated for rhabdomyolysis and acute renal failure. Dialysis is implemented on a short-term basis. Her mental state improves gradually over 3 days.

The authors’ observations

Based on the abrupt onset of inattention and confusion, disorganized speech, memory impairments, and psychomotor agitation, we made an initial diagnosis of delirium; however, the precise etiology remained unclear. DSM-IV-TR diagnostic criteria for delirium are described in Table 1. Although delirium due to multiple etiologies does not have a DSM-IV-TR coding designation, we speculated that multiple causes contributed to Ms. K’s presentation. Acute renal failure secondary to dehydration as well as rhabdomyolysis, hypoxia, and hyperglycemia were implicated as general medical conditions etiologically linked to delirium. Because Ms. K has no preexisting medical conditions and her roommate and family stated she had a history of substance abuse, we also considered a presumptive diagnosis of substance-induced delirium. The medical team speculated that, based on information provided by her family, Ms. K may have had a seizure or may have fallen, which would account for her multiple contusions, and could have led to muscle injury and breakdown and the resultant rhabdomyolysis.

The possibility of cannabinoid-induced delirium has been reported, albeit rarely.^1-3 However, Ms. K’s presentation—hypothermia, variable heart rate, lack of dry mucous membranes—was not consistent with significant anticholinergic toxicity or cannabinoid intoxication (Table 2).

By contrast, cocaine-induced delirium has been reported and initially appeared to be a plausible cause of Ms. K’s symptoms (Table 2). Delirium related to excess ingestion of cocaine may be related to the drug’s secondary effects resulting in rhabdomyolysis and renal dysfunction.^4-6 Although several mechanisms underlying this relationship have been proposed, no single specific mechanism has been identified. The basis for cocaine ingestion and the resultant metabolic and renal effects, as observed in Ms. K’s case, likely are multifactorial. Mechanisms of the rhabdomyolysis might include:

• blockade of synaptic catecholamine reuptake and induction of adrenergic agonism, resulting in vasoconstriction and ischemia and leading to muscle damage
• cocaine-induced seizures and/or prolonged unconsciousness, leading to muscle compression and breakdown of muscle tissue
• a period of exertion induced by cocaine, precipitating an excited delirium and associated rhabdomyolysis
• a surge in dopamine concentrations, similar to neuroleptic malignant syndrome, precipitates hyperthermia, muscle rigidity, and psychomotor agitation, disrupting neuromuscular homeostasis and leading to rhabdomyolysis.

We were uncertain about the plausibility that acute cocaine intoxication caused Ms. K’s medical sequelae, in light of her toxicology findings. If cocaine use was the inciting event, and because the delirium reportedly had developed over several hours, we would expect cocaine to be detected in the toxicology screen. However, it was not detected. Cocaine can remain detectable in urine for 2 to 4 days,⁷ which raised our speculation that remote cocaine abuse could account for Ms. K’s current presentation and the timeline the roommate initially relayed to EMS personnel was inaccurate. We needed to clarify the timeline and progression of Ms. K’s symptoms with the roommate. In addition, we suggested to the medical team that alternative substances of abuse could be causing Ms. K’s symptoms and the roommate might be the only person who could unveil this possibility.

Table 1

DSM-IV-TR criteria for delirium due to multiple etiologies

Table 2

Diagnostic criteria for cannabis and cocaine intoxication

HISTORY: Unknown substance

Ms. K’s roommate is contacted for supplemental history. The roommate reports that recently he observed Ms. K “snorting” a brown/tan-colored substance. He had not seen her use this substance previously, and when he asked her what it was, she reportedly said that it was “PeeVee” (also called “bath salts”) purchased over the Internet.

The authors’ observations

MDPV is a novel chemical compound that is used as a recreational drug (Table 3).⁸ It commonly is acquired from Internet sources and sold as “bath salts.” Its use first emerged in approximately 2004, and its popularity has been increasing because of its easy availability and relatively low cost.⁹ The American Association of Poison Control Centers received 302 calls related to MDPV toxicity in 2010 and 5,625 calls related to MDPV use between January 1 and October 31, 2011.^10,11

MDPV has psychoactive properties, with stimulant effects acting as a norepinephrine-dopamine reuptake inhibitor.^8,9,12 When snorted, ingested orally, or inserted rectally, the agent produces effects comparable to cocaine or psychostimulants such as methylphenidate or dextroamphetamine.

Acute effects of MDPV include heightened alertness, diminished need for sleep, hyperarousal, and euphoria.^8,9 These symptoms often are accompanied by increases in heart rate and blood pressure, sweating, and peripheral vasoconstriction. Individuals may abuse MDPV to acquire sustained attention, reduce their need for sleep, or for aphrodisiac effects. In many cases, anxiety and irritability can accompany the desired euphoric effects. For some, the euphoric effects can be superseded by anxiety or agitation. Mood and attention effects are estimated to last 3 to 4 hours; however, tachycardia and hypertension can persist for 6 to 8 hours.

MDPV use can trigger cravings and lead to binging. Euphoric stimulation with MDPV can become dysphoric as the dose and duration of use increase. Extended use has been associated with agitation, irritability, aggression, panic and marked anxiety, psychosis, and delirium.^8,9 Anxiety can range from mild dysphoric stimulation to extreme panic-like states. In moderate forms, a state of sympathetic discharge can occur, producing physiologic effects resembling panic attacks, including hypertension, tachycardia, sweating, and peripheral vasoconstriction. In more severe cases, users may experience a feeling of impending doom, marked distress, and frank psychosis. Patients may experience disorientation and unsystematized paranoid delusions. Case reports of intoxication have described self-injurious behaviors, such as cutting, which may account for the contusions observed on Ms. K’s face and arms. Increasingly, MDPV use has resulted in ER presentations with patients manifesting abrupt onset confusion, anxiety, and self-injurious behaviors.

The mechanisms underlying MDPV-induced delirium have not been definitively identified. Given the similarities in mechanism of action between MDPV and cocaine, causes for delirium related to MDPV are similarly presumed to be multifactorial. The course of delirium associated with MDPV intoxication is self-limited and requires supportive measures.^8,9

Suspect MDPV abuse in patients who present with signs or symptoms of stimulant intoxication but have a negative toxicology screen for cocaine and other psychostimulants. MDPV is not detected on routine toxicology assessments; however, it can be identified through laboratories with gas chromatography/mass spectroscopy capabilities. However, the time needed to obtain the results may exceed the clinical course of the patient’s delirium. One of the limitations in Ms. K’s case was the lack of gas chromatography/mass spectroscopy to confirm MDPV ingestion. Ms. K’s roommate could not locate any unused brown powder within their apartment to bring in for laboratory investigations. Recently, screening assessments for MDPV have become commercially available (see Related Resources).

Table 3

Overview of MDPV features

OUTCOME: Referral to treatment

Dialysis is discontinued within 1 day of hospitalization. Ms. K’s peripheral arterial perfusion improves, as does her thermoregulatory status. Her mental status improvements coincide with improvements in her physical and metabolic status.

Ms. K is able to sustain attention when speaking with interviewers. She is aware of her surroundings and is no longer distracted by extraneous stimuli. Her speech is articulate and her thoughts are linear. There is no evidence of any residual thought disorganization, delusions, or hallucinations.

Initially, Ms. K is reluctant to acknowledge her substance use, but eventually, she concedes to acquiring a stimulant from an Internet source and abusing it in undetermined amounts. She had no experience with using MDPV and did not know how to avoid ingesting dangerous amounts. We educate Ms. K about the dangers she faced during this hospitalization and the potential life-threatening outcomes. She is amenable to pursuing outpatient substance abuse treatment. Her roommate is enlisted to facilitate her follow-up with this treatment.

The authors’ observations

Managing MDPV toxicity presents a diagnostic dilemma for medical personnel and psychiatrists when evaluating and managing acute delirium. MDPV ingestion may go unrecognized in clinical settings because toxicology assessments for it are not readily available and patients’ historical information may be unreliable.

Because of the seriousness of sequelae associated with MDPV use, state and federal agencies have intervened. Until recently, bath salts did not have a controlled substance designation. In October 2011, the US Drug Enforcement Administration (DEA) ruled to make MDPV a controlled substance for 1 year, with the possibility of a 6-month extension.¹³ Although this ruling is temporary, it makes possession, sale, or distribution of these chemicals, or the products that contain them, illegal in the United States. In the interim, the DEA and the US Department of Health and Human Services will determine whether MDPV should remain a controlled substance.

Related Resources

• American Screening Corp. (MDPV screening). www.americanscreeningcorp.com.
• U.S. Drug Enforcement Administration. 3, 4-Methylenedioxypyrovalerone (MDPV). www.deadiversion.usdoj.gov/drugs_concern/mdpv.pdf.
• Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones [published online ahead of print November 23, 2011]. J Med Toxicol. doi: 10.1007/s13181-011-0193-z.

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Hurt and confused

Emergency medical services (EMS) are called to Ms. K’s apartment after her roommate found her lying on the floor moaning. The roommate tells EMS that Ms. K, age 29, appeared confused and was slurring her words, and reports that this change in her awareness progressed rapidly over a few hours. EMS personnel find that Ms. K has multiple contusions on her arms and face, which they presume to be self-inflicted. A marijuana pipe is discovered at Ms. K’s apartment.

In the emergency room (ER), Ms. K is inattentive and has difficulty following simple commands. Her speech is mumbled and her thoughts are disorganized. She displays psychomotor restlessness in the form of combativeness. Ms. K cannot provide meaningful historical data and is disoriented to place and time. The ER staff requests a psychiatric consultation.

Family members reveal that Ms. K has no preexisting medical conditions, is not taking prescription medications, but has a history of substance abuse (sporadic cocaine and cannabis use). Her family is unaware of recent substance use.

Physical examination reveals tachycardia (heart rate 110 to 120 beats per minute), hypotension (blood pressure 78/49 mm Hg), hypothermia (temperature 88ºF), and peripheral pulse oximetry of 84%. Her pupils are dilated and reactive to light; no conjunctival injection is noted. Her lung fields are clear on auscultation, but she is noted to have a rapid, irregular heartbeat. The abdomen is positive for bowel sounds, soft on palpation, and without any repositioning or notable overt signs of tenderness. Ms. K’s toes show purple discoloration with poor capillary refill. The dorsalis pedis pulses are reported to be 1+ bilaterally; however, the remainder of the arterial pulse examination is normal.

Her sodium, potassium, and chloride values are normal, but she has an abnormal anion gap (28.1 mEq/L), blood urea nitrogen (53 mg/dL), creatinine (2.9 mg/dL), creatine kinase (10,857 U/L), creatine kinase MB (432.6 ng/mL), and hyperglycemia (glucose 425 mg/dL). Arterial blood gas reveals hypoxia (Po₂ of 55 mm Hg), with metabolic acidosis (sodium bicarbonate 10 with compensatory Pco₂ of 33 mm Hg). Her urine is cloudy, positive for protein, ketones, hemoglobin, and glucose. She is thought to have a high anion gap acidosis related to dehydration, lactic acidosis (lactic acid 20 mEq/L), and hyperglycemia. Urine toxicology is positive for cannabinoids; ethylene glycol and methanol screen negatively, which rules these out as potential contributors to her high anion gap acidosis.

Ms. K is intubated and IV fluids are initiated for rhabdomyolysis and acute renal failure. Dialysis is implemented on a short-term basis. Her mental state improves gradually over 3 days.

The authors’ observations

Based on the abrupt onset of inattention and confusion, disorganized speech, memory impairments, and psychomotor agitation, we made an initial diagnosis of delirium; however, the precise etiology remained unclear. DSM-IV-TR diagnostic criteria for delirium are described in Table 1. Although delirium due to multiple etiologies does not have a DSM-IV-TR coding designation, we speculated that multiple causes contributed to Ms. K’s presentation. Acute renal failure secondary to dehydration as well as rhabdomyolysis, hypoxia, and hyperglycemia were implicated as general medical conditions etiologically linked to delirium. Because Ms. K has no preexisting medical conditions and her roommate and family stated she had a history of substance abuse, we also considered a presumptive diagnosis of substance-induced delirium. The medical team speculated that, based on information provided by her family, Ms. K may have had a seizure or may have fallen, which would account for her multiple contusions, and could have led to muscle injury and breakdown and the resultant rhabdomyolysis.

The possibility of cannabinoid-induced delirium has been reported, albeit rarely.^1-3 However, Ms. K’s presentation—hypothermia, variable heart rate, lack of dry mucous membranes—was not consistent with significant anticholinergic toxicity or cannabinoid intoxication (Table 2).

By contrast, cocaine-induced delirium has been reported and initially appeared to be a plausible cause of Ms. K’s symptoms (Table 2). Delirium related to excess ingestion of cocaine may be related to the drug’s secondary effects resulting in rhabdomyolysis and renal dysfunction.^4-6 Although several mechanisms underlying this relationship have been proposed, no single specific mechanism has been identified. The basis for cocaine ingestion and the resultant metabolic and renal effects, as observed in Ms. K’s case, likely are multifactorial. Mechanisms of the rhabdomyolysis might include:

• blockade of synaptic catecholamine reuptake and induction of adrenergic agonism, resulting in vasoconstriction and ischemia and leading to muscle damage
• cocaine-induced seizures and/or prolonged unconsciousness, leading to muscle compression and breakdown of muscle tissue
• a period of exertion induced by cocaine, precipitating an excited delirium and associated rhabdomyolysis
• a surge in dopamine concentrations, similar to neuroleptic malignant syndrome, precipitates hyperthermia, muscle rigidity, and psychomotor agitation, disrupting neuromuscular homeostasis and leading to rhabdomyolysis.

We were uncertain about the plausibility that acute cocaine intoxication caused Ms. K’s medical sequelae, in light of her toxicology findings. If cocaine use was the inciting event, and because the delirium reportedly had developed over several hours, we would expect cocaine to be detected in the toxicology screen. However, it was not detected. Cocaine can remain detectable in urine for 2 to 4 days,⁷ which raised our speculation that remote cocaine abuse could account for Ms. K’s current presentation and the timeline the roommate initially relayed to EMS personnel was inaccurate. We needed to clarify the timeline and progression of Ms. K’s symptoms with the roommate. In addition, we suggested to the medical team that alternative substances of abuse could be causing Ms. K’s symptoms and the roommate might be the only person who could unveil this possibility.

Table 1

DSM-IV-TR criteria for delirium due to multiple etiologies

Table 2

Diagnostic criteria for cannabis and cocaine intoxication

HISTORY: Unknown substance

Ms. K’s roommate is contacted for supplemental history. The roommate reports that recently he observed Ms. K “snorting” a brown/tan-colored substance. He had not seen her use this substance previously, and when he asked her what it was, she reportedly said that it was “PeeVee” (also called “bath salts”) purchased over the Internet.

The authors’ observations

MDPV is a novel chemical compound that is used as a recreational drug (Table 3).⁸ It commonly is acquired from Internet sources and sold as “bath salts.” Its use first emerged in approximately 2004, and its popularity has been increasing because of its easy availability and relatively low cost.⁹ The American Association of Poison Control Centers received 302 calls related to MDPV toxicity in 2010 and 5,625 calls related to MDPV use between January 1 and October 31, 2011.^10,11

MDPV has psychoactive properties, with stimulant effects acting as a norepinephrine-dopamine reuptake inhibitor.^8,9,12 When snorted, ingested orally, or inserted rectally, the agent produces effects comparable to cocaine or psychostimulants such as methylphenidate or dextroamphetamine.

Acute effects of MDPV include heightened alertness, diminished need for sleep, hyperarousal, and euphoria.^8,9 These symptoms often are accompanied by increases in heart rate and blood pressure, sweating, and peripheral vasoconstriction. Individuals may abuse MDPV to acquire sustained attention, reduce their need for sleep, or for aphrodisiac effects. In many cases, anxiety and irritability can accompany the desired euphoric effects. For some, the euphoric effects can be superseded by anxiety or agitation. Mood and attention effects are estimated to last 3 to 4 hours; however, tachycardia and hypertension can persist for 6 to 8 hours.

MDPV use can trigger cravings and lead to binging. Euphoric stimulation with MDPV can become dysphoric as the dose and duration of use increase. Extended use has been associated with agitation, irritability, aggression, panic and marked anxiety, psychosis, and delirium.^8,9 Anxiety can range from mild dysphoric stimulation to extreme panic-like states. In moderate forms, a state of sympathetic discharge can occur, producing physiologic effects resembling panic attacks, including hypertension, tachycardia, sweating, and peripheral vasoconstriction. In more severe cases, users may experience a feeling of impending doom, marked distress, and frank psychosis. Patients may experience disorientation and unsystematized paranoid delusions. Case reports of intoxication have described self-injurious behaviors, such as cutting, which may account for the contusions observed on Ms. K’s face and arms. Increasingly, MDPV use has resulted in ER presentations with patients manifesting abrupt onset confusion, anxiety, and self-injurious behaviors.

The mechanisms underlying MDPV-induced delirium have not been definitively identified. Given the similarities in mechanism of action between MDPV and cocaine, causes for delirium related to MDPV are similarly presumed to be multifactorial. The course of delirium associated with MDPV intoxication is self-limited and requires supportive measures.^8,9

Suspect MDPV abuse in patients who present with signs or symptoms of stimulant intoxication but have a negative toxicology screen for cocaine and other psychostimulants. MDPV is not detected on routine toxicology assessments; however, it can be identified through laboratories with gas chromatography/mass spectroscopy capabilities. However, the time needed to obtain the results may exceed the clinical course of the patient’s delirium. One of the limitations in Ms. K’s case was the lack of gas chromatography/mass spectroscopy to confirm MDPV ingestion. Ms. K’s roommate could not locate any unused brown powder within their apartment to bring in for laboratory investigations. Recently, screening assessments for MDPV have become commercially available (see Related Resources).

Table 3

Overview of MDPV features

OUTCOME: Referral to treatment

Dialysis is discontinued within 1 day of hospitalization. Ms. K’s peripheral arterial perfusion improves, as does her thermoregulatory status. Her mental status improvements coincide with improvements in her physical and metabolic status.

Ms. K is able to sustain attention when speaking with interviewers. She is aware of her surroundings and is no longer distracted by extraneous stimuli. Her speech is articulate and her thoughts are linear. There is no evidence of any residual thought disorganization, delusions, or hallucinations.

Initially, Ms. K is reluctant to acknowledge her substance use, but eventually, she concedes to acquiring a stimulant from an Internet source and abusing it in undetermined amounts. She had no experience with using MDPV and did not know how to avoid ingesting dangerous amounts. We educate Ms. K about the dangers she faced during this hospitalization and the potential life-threatening outcomes. She is amenable to pursuing outpatient substance abuse treatment. Her roommate is enlisted to facilitate her follow-up with this treatment.

The authors’ observations

Managing MDPV toxicity presents a diagnostic dilemma for medical personnel and psychiatrists when evaluating and managing acute delirium. MDPV ingestion may go unrecognized in clinical settings because toxicology assessments for it are not readily available and patients’ historical information may be unreliable.

Because of the seriousness of sequelae associated with MDPV use, state and federal agencies have intervened. Until recently, bath salts did not have a controlled substance designation. In October 2011, the US Drug Enforcement Administration (DEA) ruled to make MDPV a controlled substance for 1 year, with the possibility of a 6-month extension.¹³ Although this ruling is temporary, it makes possession, sale, or distribution of these chemicals, or the products that contain them, illegal in the United States. In the interim, the DEA and the US Department of Health and Human Services will determine whether MDPV should remain a controlled substance.

Related Resources

• American Screening Corp. (MDPV screening). www.americanscreeningcorp.com.
• U.S. Drug Enforcement Administration. 3, 4-Methylenedioxypyrovalerone (MDPV). www.deadiversion.usdoj.gov/drugs_concern/mdpv.pdf.
• Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones [published online ahead of print November 23, 2011]. J Med Toxicol. doi: 10.1007/s13181-011-0193-z.

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Hurt and confused

Emergency medical services (EMS) are called to Ms. K’s apartment after her roommate found her lying on the floor moaning. The roommate tells EMS that Ms. K, age 29, appeared confused and was slurring her words, and reports that this change in her awareness progressed rapidly over a few hours. EMS personnel find that Ms. K has multiple contusions on her arms and face, which they presume to be self-inflicted. A marijuana pipe is discovered at Ms. K’s apartment.

In the emergency room (ER), Ms. K is inattentive and has difficulty following simple commands. Her speech is mumbled and her thoughts are disorganized. She displays psychomotor restlessness in the form of combativeness. Ms. K cannot provide meaningful historical data and is disoriented to place and time. The ER staff requests a psychiatric consultation.

Family members reveal that Ms. K has no preexisting medical conditions, is not taking prescription medications, but has a history of substance abuse (sporadic cocaine and cannabis use). Her family is unaware of recent substance use.

Physical examination reveals tachycardia (heart rate 110 to 120 beats per minute), hypotension (blood pressure 78/49 mm Hg), hypothermia (temperature 88ºF), and peripheral pulse oximetry of 84%. Her pupils are dilated and reactive to light; no conjunctival injection is noted. Her lung fields are clear on auscultation, but she is noted to have a rapid, irregular heartbeat. The abdomen is positive for bowel sounds, soft on palpation, and without any repositioning or notable overt signs of tenderness. Ms. K’s toes show purple discoloration with poor capillary refill. The dorsalis pedis pulses are reported to be 1+ bilaterally; however, the remainder of the arterial pulse examination is normal.

Her sodium, potassium, and chloride values are normal, but she has an abnormal anion gap (28.1 mEq/L), blood urea nitrogen (53 mg/dL), creatinine (2.9 mg/dL), creatine kinase (10,857 U/L), creatine kinase MB (432.6 ng/mL), and hyperglycemia (glucose 425 mg/dL). Arterial blood gas reveals hypoxia (Po₂ of 55 mm Hg), with metabolic acidosis (sodium bicarbonate 10 with compensatory Pco₂ of 33 mm Hg). Her urine is cloudy, positive for protein, ketones, hemoglobin, and glucose. She is thought to have a high anion gap acidosis related to dehydration, lactic acidosis (lactic acid 20 mEq/L), and hyperglycemia. Urine toxicology is positive for cannabinoids; ethylene glycol and methanol screen negatively, which rules these out as potential contributors to her high anion gap acidosis.

Ms. K is intubated and IV fluids are initiated for rhabdomyolysis and acute renal failure. Dialysis is implemented on a short-term basis. Her mental state improves gradually over 3 days.

The authors’ observations

Based on the abrupt onset of inattention and confusion, disorganized speech, memory impairments, and psychomotor agitation, we made an initial diagnosis of delirium; however, the precise etiology remained unclear. DSM-IV-TR diagnostic criteria for delirium are described in Table 1. Although delirium due to multiple etiologies does not have a DSM-IV-TR coding designation, we speculated that multiple causes contributed to Ms. K’s presentation. Acute renal failure secondary to dehydration as well as rhabdomyolysis, hypoxia, and hyperglycemia were implicated as general medical conditions etiologically linked to delirium. Because Ms. K has no preexisting medical conditions and her roommate and family stated she had a history of substance abuse, we also considered a presumptive diagnosis of substance-induced delirium. The medical team speculated that, based on information provided by her family, Ms. K may have had a seizure or may have fallen, which would account for her multiple contusions, and could have led to muscle injury and breakdown and the resultant rhabdomyolysis.

The possibility of cannabinoid-induced delirium has been reported, albeit rarely.^1-3 However, Ms. K’s presentation—hypothermia, variable heart rate, lack of dry mucous membranes—was not consistent with significant anticholinergic toxicity or cannabinoid intoxication (Table 2).

By contrast, cocaine-induced delirium has been reported and initially appeared to be a plausible cause of Ms. K’s symptoms (Table 2). Delirium related to excess ingestion of cocaine may be related to the drug’s secondary effects resulting in rhabdomyolysis and renal dysfunction.^4-6 Although several mechanisms underlying this relationship have been proposed, no single specific mechanism has been identified. The basis for cocaine ingestion and the resultant metabolic and renal effects, as observed in Ms. K’s case, likely are multifactorial. Mechanisms of the rhabdomyolysis might include:

• blockade of synaptic catecholamine reuptake and induction of adrenergic agonism, resulting in vasoconstriction and ischemia and leading to muscle damage
• cocaine-induced seizures and/or prolonged unconsciousness, leading to muscle compression and breakdown of muscle tissue
• a period of exertion induced by cocaine, precipitating an excited delirium and associated rhabdomyolysis
• a surge in dopamine concentrations, similar to neuroleptic malignant syndrome, precipitates hyperthermia, muscle rigidity, and psychomotor agitation, disrupting neuromuscular homeostasis and leading to rhabdomyolysis.

We were uncertain about the plausibility that acute cocaine intoxication caused Ms. K’s medical sequelae, in light of her toxicology findings. If cocaine use was the inciting event, and because the delirium reportedly had developed over several hours, we would expect cocaine to be detected in the toxicology screen. However, it was not detected. Cocaine can remain detectable in urine for 2 to 4 days,⁷ which raised our speculation that remote cocaine abuse could account for Ms. K’s current presentation and the timeline the roommate initially relayed to EMS personnel was inaccurate. We needed to clarify the timeline and progression of Ms. K’s symptoms with the roommate. In addition, we suggested to the medical team that alternative substances of abuse could be causing Ms. K’s symptoms and the roommate might be the only person who could unveil this possibility.

Table 1

DSM-IV-TR criteria for delirium due to multiple etiologies

Table 2

Diagnostic criteria for cannabis and cocaine intoxication

HISTORY: Unknown substance

Ms. K’s roommate is contacted for supplemental history. The roommate reports that recently he observed Ms. K “snorting” a brown/tan-colored substance. He had not seen her use this substance previously, and when he asked her what it was, she reportedly said that it was “PeeVee” (also called “bath salts”) purchased over the Internet.

The authors’ observations

MDPV is a novel chemical compound that is used as a recreational drug (Table 3).⁸ It commonly is acquired from Internet sources and sold as “bath salts.” Its use first emerged in approximately 2004, and its popularity has been increasing because of its easy availability and relatively low cost.⁹ The American Association of Poison Control Centers received 302 calls related to MDPV toxicity in 2010 and 5,625 calls related to MDPV use between January 1 and October 31, 2011.^10,11

MDPV has psychoactive properties, with stimulant effects acting as a norepinephrine-dopamine reuptake inhibitor.^8,9,12 When snorted, ingested orally, or inserted rectally, the agent produces effects comparable to cocaine or psychostimulants such as methylphenidate or dextroamphetamine.

Acute effects of MDPV include heightened alertness, diminished need for sleep, hyperarousal, and euphoria.^8,9 These symptoms often are accompanied by increases in heart rate and blood pressure, sweating, and peripheral vasoconstriction. Individuals may abuse MDPV to acquire sustained attention, reduce their need for sleep, or for aphrodisiac effects. In many cases, anxiety and irritability can accompany the desired euphoric effects. For some, the euphoric effects can be superseded by anxiety or agitation. Mood and attention effects are estimated to last 3 to 4 hours; however, tachycardia and hypertension can persist for 6 to 8 hours.

MDPV use can trigger cravings and lead to binging. Euphoric stimulation with MDPV can become dysphoric as the dose and duration of use increase. Extended use has been associated with agitation, irritability, aggression, panic and marked anxiety, psychosis, and delirium.^8,9 Anxiety can range from mild dysphoric stimulation to extreme panic-like states. In moderate forms, a state of sympathetic discharge can occur, producing physiologic effects resembling panic attacks, including hypertension, tachycardia, sweating, and peripheral vasoconstriction. In more severe cases, users may experience a feeling of impending doom, marked distress, and frank psychosis. Patients may experience disorientation and unsystematized paranoid delusions. Case reports of intoxication have described self-injurious behaviors, such as cutting, which may account for the contusions observed on Ms. K’s face and arms. Increasingly, MDPV use has resulted in ER presentations with patients manifesting abrupt onset confusion, anxiety, and self-injurious behaviors.

The mechanisms underlying MDPV-induced delirium have not been definitively identified. Given the similarities in mechanism of action between MDPV and cocaine, causes for delirium related to MDPV are similarly presumed to be multifactorial. The course of delirium associated with MDPV intoxication is self-limited and requires supportive measures.^8,9

Suspect MDPV abuse in patients who present with signs or symptoms of stimulant intoxication but have a negative toxicology screen for cocaine and other psychostimulants. MDPV is not detected on routine toxicology assessments; however, it can be identified through laboratories with gas chromatography/mass spectroscopy capabilities. However, the time needed to obtain the results may exceed the clinical course of the patient’s delirium. One of the limitations in Ms. K’s case was the lack of gas chromatography/mass spectroscopy to confirm MDPV ingestion. Ms. K’s roommate could not locate any unused brown powder within their apartment to bring in for laboratory investigations. Recently, screening assessments for MDPV have become commercially available (see Related Resources).

Table 3

Overview of MDPV features

OUTCOME: Referral to treatment

Dialysis is discontinued within 1 day of hospitalization. Ms. K’s peripheral arterial perfusion improves, as does her thermoregulatory status. Her mental status improvements coincide with improvements in her physical and metabolic status.

Ms. K is able to sustain attention when speaking with interviewers. She is aware of her surroundings and is no longer distracted by extraneous stimuli. Her speech is articulate and her thoughts are linear. There is no evidence of any residual thought disorganization, delusions, or hallucinations.

Initially, Ms. K is reluctant to acknowledge her substance use, but eventually, she concedes to acquiring a stimulant from an Internet source and abusing it in undetermined amounts. She had no experience with using MDPV and did not know how to avoid ingesting dangerous amounts. We educate Ms. K about the dangers she faced during this hospitalization and the potential life-threatening outcomes. She is amenable to pursuing outpatient substance abuse treatment. Her roommate is enlisted to facilitate her follow-up with this treatment.

The authors’ observations

Managing MDPV toxicity presents a diagnostic dilemma for medical personnel and psychiatrists when evaluating and managing acute delirium. MDPV ingestion may go unrecognized in clinical settings because toxicology assessments for it are not readily available and patients’ historical information may be unreliable.

Because of the seriousness of sequelae associated with MDPV use, state and federal agencies have intervened. Until recently, bath salts did not have a controlled substance designation. In October 2011, the US Drug Enforcement Administration (DEA) ruled to make MDPV a controlled substance for 1 year, with the possibility of a 6-month extension.¹³ Although this ruling is temporary, it makes possession, sale, or distribution of these chemicals, or the products that contain them, illegal in the United States. In the interim, the DEA and the US Department of Health and Human Services will determine whether MDPV should remain a controlled substance.

Related Resources

• American Screening Corp. (MDPV screening). www.americanscreeningcorp.com.
• U.S. Drug Enforcement Administration. 3, 4-Methylenedioxypyrovalerone (MDPV). www.deadiversion.usdoj.gov/drugs_concern/mdpv.pdf.
• Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones [published online ahead of print November 23, 2011]. J Med Toxicol. doi: 10.1007/s13181-011-0193-z.

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

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Mr. T, age 56, has major depressive disorder that is well controlled with fluoxetine, 40 mg/d. He has smoked ≥1 packs of cigarettes per day for the last 25 years. On a recent visit, he indicates that he has begun using a 21-mg nicotine patch as advised by his pharmacist and that things are going OK, although he has had some “slip ups.” He is on week 7 of his quitting regimen and now is stepping down the patch dosage.

Upon further questioning he says that he has been cutting the 21-mg patches in half to save money. Mr. T also explains that occasionally he has given in to a strong urge to smoke because it was “too much to handle.” He states that he does not think this is a big deal because he uses electronic cigarettes and has heard that these products don’t contain “the bad cancer stuff.” At the end of Mr. T’s visit, he asks for something to help him sleep because has been unable to sleep consistently and has been having vivid dreams since starting the patch. He also wants to know how to reduce itching from the patch.

Approximately 46 million Americans smoke and cigarette smoking accounts for 1 of every 5 deaths in the United States each year.¹ Since the advent of “Stop Smoking” campaigns, bans on smoking in public buildings, over-the-counter (OTC) nicotine replacement products, and Surgeon General recommendations, discussing smoking cessation with patients has become standard practice.

Research suggests that treatment to quit smoking should include a combination of pharmacotherapy and counseling, such as cognitive-behavioral strategies, support groups, and quitting hotlines.² Pharmacotherapy consists of OTC nicotine replacement therapy (NRT) products and prescription medications. This article briefly highlights how to counsel patients about using OTC NRT products (Table 1).^2-5 See Table 2 for a summary of prescription smoking cessation agents

Table 1

Over-the-counter nicotine replacement therapy products

Patches

Nicotine replacement patches are best used for maintenance treatment of nicotine cravings. They deliver a fixed amount of nicotine over 24 hours.³ Patches have a specially formulated transdermal matrix system and should not be cut. Doing so damages the drug delivery system and could lead to drug evaporation from the cut edges.⁴ Mr. T’s psychiatrist advises him not to cut patches but instead purchase the 14-mg patch because he is at this step of the smoking cessation regimen.

Skin irritation caused by adhesive is a common adverse event from nicotine patches. Rotating the location of each patch to a different hairless body area is the best way to prevent or combat skin irritation. If rotating the location of the patch does not relieve irritation, patients can apply a thin layer of an OTC hydrocortisone 1% cream to the affected site 2 to 4 times a day after gently washing the area.⁵ Instruct patients to avoid using occlusive dressings over the topical application.

Nicotine replacement patches also have been reported to cause vivid dreams and insomnia.³ These side effects may be caused by nighttime nicotine absorption, which might be avoided by switching to a different NRT product or removing the 24-hour patch when going to bed.⁴

Combining treatments

Many patients experience nicotine cravings while using the nicotine replacement patch. Stressful situations and events can trigger a patient’s desire for nicotine and withdrawal symptoms that a patch that delivers a continuous amount of nicotine over 24 hours cannot alleviate. Combining different forms of treatment could combat these symptoms.^2,3,5

Combination therapy might consist of using sustained-release bupropion or a nicotine patch with rapid-acting NRT products such as a lozenge, gum, nasal spray, or inhaler. In Mr. T’s case, clinicians recommend that he use nicotine polacrilex gum in addition to the patch to quell his cravings. Also, he is instructed to stop using electronic cigarettes because they are considered tobacco products, are not regulated by the FDA, and may contain toxic substances.⁶

Instruct patients who use nicotine gum to employ the “chew and park” method.⁴ First, they should chew the gum very slowly until they notice a minty taste or tingling feeling, then “park” the gum between the cheek and gums for 1 to 2 minutes to allow nicotine to be absorbed across the gum lining. After 2 minutes or when tingling ceases, patients should slowly resume chewing until a tingling or minty taste returns and then “park” the gum again in a different area of the gums. Tell patients to repeat the “chew and park” method until there is no more taste or tingling (approximately 30 minutes). Explain that chewing the gum too fast may result in nausea or lightheadedness and patients should refrain from eating or drinking 15 minutes before or while using the gum. Mr. T is instructed to use the gum only when the urge to smoke is overbearing, and not regularly.

The nicotine polacrilex gum is more viscous than ordinary chewing gum and may stick to or possibly damage dental work such as fillings, dentures, crowns, and braces. An acceptable alternative is the nicotine polacrilex lozenge. Advise patients who want to try lozenges to:

• place the lozenge in the mouth and allow it to dissolve slowly over 20 to 30 minutes (during this time patients may experience a tingling sensation as nicotine is released)
• rotate the lozenge to different areas of the mouth every few minutes to lessen irritation
• avoid chewing or swallowing the lozenge because doing so will lead to improper release of nicotine and side effects, including nausea, hiccups, and heartburn
• refrain from eating or drinking 15 minutes before or while using the lozenge.

For many patients, the breadth of pharmacologic agents available for smoking cessation has made quitting a more attainable goal. OTC smoking cessation products are available in most drug stores, which gives smokers easy access to taking this important step. Counseling patients on the proper use of OTC products may help them successfully stop smoking.⁷

Although a patient’s medical history, including cardiac status, must be considered before starting specific agents, in many instances patient preference is the prevailing factor when choosing therapy. Often, the risks of continued smoking outweigh the risks of using smoking cessation products. OTC smoking cessation products may be an appropriate first-line treatment for many individuals before trying prescription medications, such as bupropion or varenicline.

Related Resources

For patients

• Treat Tobacco. www.treatobacco.net.
• Smokefree.gov mobile application. http://smokefree.gov/apps.
• Medline Plus. Quitting smoking. www.nlm.nih.gov/medlineplus/quittingsmoking.html.
• Quit for Life Program. www.quitnow.net.
• American Lung Association. Stop Smoking. www.lungusa.org/stop-smoking.

For clinicians

• Agency for Health Research and Quality. Treating tobacco use and dependence: 2008 update. www.ahrq.gov/path/tobacco.htm#clinicians.

Drug Brand Names

• Bupropion SR • Zyban, Wellbutrin SR
• Fluoxetine • Prozac
• Varenicline • Chantix

Disclosure

Dr. Ellingrod receives grant/research support from the National Institute of Mental Health.

Dr. Burghardt reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Table 2

Prescription smoking cessation products^a

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Mr. T, age 56, has major depressive disorder that is well controlled with fluoxetine, 40 mg/d. He has smoked ≥1 packs of cigarettes per day for the last 25 years. On a recent visit, he indicates that he has begun using a 21-mg nicotine patch as advised by his pharmacist and that things are going OK, although he has had some “slip ups.” He is on week 7 of his quitting regimen and now is stepping down the patch dosage.

Upon further questioning he says that he has been cutting the 21-mg patches in half to save money. Mr. T also explains that occasionally he has given in to a strong urge to smoke because it was “too much to handle.” He states that he does not think this is a big deal because he uses electronic cigarettes and has heard that these products don’t contain “the bad cancer stuff.” At the end of Mr. T’s visit, he asks for something to help him sleep because has been unable to sleep consistently and has been having vivid dreams since starting the patch. He also wants to know how to reduce itching from the patch.

Approximately 46 million Americans smoke and cigarette smoking accounts for 1 of every 5 deaths in the United States each year.¹ Since the advent of “Stop Smoking” campaigns, bans on smoking in public buildings, over-the-counter (OTC) nicotine replacement products, and Surgeon General recommendations, discussing smoking cessation with patients has become standard practice.

Research suggests that treatment to quit smoking should include a combination of pharmacotherapy and counseling, such as cognitive-behavioral strategies, support groups, and quitting hotlines.² Pharmacotherapy consists of OTC nicotine replacement therapy (NRT) products and prescription medications. This article briefly highlights how to counsel patients about using OTC NRT products (Table 1).^2-5 See Table 2 for a summary of prescription smoking cessation agents

Table 1

Over-the-counter nicotine replacement therapy products

Patches

Nicotine replacement patches are best used for maintenance treatment of nicotine cravings. They deliver a fixed amount of nicotine over 24 hours.³ Patches have a specially formulated transdermal matrix system and should not be cut. Doing so damages the drug delivery system and could lead to drug evaporation from the cut edges.⁴ Mr. T’s psychiatrist advises him not to cut patches but instead purchase the 14-mg patch because he is at this step of the smoking cessation regimen.

Skin irritation caused by adhesive is a common adverse event from nicotine patches. Rotating the location of each patch to a different hairless body area is the best way to prevent or combat skin irritation. If rotating the location of the patch does not relieve irritation, patients can apply a thin layer of an OTC hydrocortisone 1% cream to the affected site 2 to 4 times a day after gently washing the area.⁵ Instruct patients to avoid using occlusive dressings over the topical application.

Nicotine replacement patches also have been reported to cause vivid dreams and insomnia.³ These side effects may be caused by nighttime nicotine absorption, which might be avoided by switching to a different NRT product or removing the 24-hour patch when going to bed.⁴

Combining treatments

Many patients experience nicotine cravings while using the nicotine replacement patch. Stressful situations and events can trigger a patient’s desire for nicotine and withdrawal symptoms that a patch that delivers a continuous amount of nicotine over 24 hours cannot alleviate. Combining different forms of treatment could combat these symptoms.^2,3,5

Combination therapy might consist of using sustained-release bupropion or a nicotine patch with rapid-acting NRT products such as a lozenge, gum, nasal spray, or inhaler. In Mr. T’s case, clinicians recommend that he use nicotine polacrilex gum in addition to the patch to quell his cravings. Also, he is instructed to stop using electronic cigarettes because they are considered tobacco products, are not regulated by the FDA, and may contain toxic substances.⁶

Instruct patients who use nicotine gum to employ the “chew and park” method.⁴ First, they should chew the gum very slowly until they notice a minty taste or tingling feeling, then “park” the gum between the cheek and gums for 1 to 2 minutes to allow nicotine to be absorbed across the gum lining. After 2 minutes or when tingling ceases, patients should slowly resume chewing until a tingling or minty taste returns and then “park” the gum again in a different area of the gums. Tell patients to repeat the “chew and park” method until there is no more taste or tingling (approximately 30 minutes). Explain that chewing the gum too fast may result in nausea or lightheadedness and patients should refrain from eating or drinking 15 minutes before or while using the gum. Mr. T is instructed to use the gum only when the urge to smoke is overbearing, and not regularly.

The nicotine polacrilex gum is more viscous than ordinary chewing gum and may stick to or possibly damage dental work such as fillings, dentures, crowns, and braces. An acceptable alternative is the nicotine polacrilex lozenge. Advise patients who want to try lozenges to:

• place the lozenge in the mouth and allow it to dissolve slowly over 20 to 30 minutes (during this time patients may experience a tingling sensation as nicotine is released)
• rotate the lozenge to different areas of the mouth every few minutes to lessen irritation
• avoid chewing or swallowing the lozenge because doing so will lead to improper release of nicotine and side effects, including nausea, hiccups, and heartburn
• refrain from eating or drinking 15 minutes before or while using the lozenge.

For many patients, the breadth of pharmacologic agents available for smoking cessation has made quitting a more attainable goal. OTC smoking cessation products are available in most drug stores, which gives smokers easy access to taking this important step. Counseling patients on the proper use of OTC products may help them successfully stop smoking.⁷

Although a patient’s medical history, including cardiac status, must be considered before starting specific agents, in many instances patient preference is the prevailing factor when choosing therapy. Often, the risks of continued smoking outweigh the risks of using smoking cessation products. OTC smoking cessation products may be an appropriate first-line treatment for many individuals before trying prescription medications, such as bupropion or varenicline.

Related Resources

For patients

• Treat Tobacco. www.treatobacco.net.
• Smokefree.gov mobile application. http://smokefree.gov/apps.
• Medline Plus. Quitting smoking. www.nlm.nih.gov/medlineplus/quittingsmoking.html.
• Quit for Life Program. www.quitnow.net.
• American Lung Association. Stop Smoking. www.lungusa.org/stop-smoking.

For clinicians

• Agency for Health Research and Quality. Treating tobacco use and dependence: 2008 update. www.ahrq.gov/path/tobacco.htm#clinicians.

Drug Brand Names

• Bupropion SR • Zyban, Wellbutrin SR
• Fluoxetine • Prozac
• Varenicline • Chantix

Disclosure

Dr. Ellingrod receives grant/research support from the National Institute of Mental Health.

Dr. Burghardt reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Table 2

Prescription smoking cessation products^a

Discuss this article at www.facebook.com/CurrentPsychiatry

Mr. T, age 56, has major depressive disorder that is well controlled with fluoxetine, 40 mg/d. He has smoked ≥1 packs of cigarettes per day for the last 25 years. On a recent visit, he indicates that he has begun using a 21-mg nicotine patch as advised by his pharmacist and that things are going OK, although he has had some “slip ups.” He is on week 7 of his quitting regimen and now is stepping down the patch dosage.

Upon further questioning he says that he has been cutting the 21-mg patches in half to save money. Mr. T also explains that occasionally he has given in to a strong urge to smoke because it was “too much to handle.” He states that he does not think this is a big deal because he uses electronic cigarettes and has heard that these products don’t contain “the bad cancer stuff.” At the end of Mr. T’s visit, he asks for something to help him sleep because has been unable to sleep consistently and has been having vivid dreams since starting the patch. He also wants to know how to reduce itching from the patch.

Approximately 46 million Americans smoke and cigarette smoking accounts for 1 of every 5 deaths in the United States each year.¹ Since the advent of “Stop Smoking” campaigns, bans on smoking in public buildings, over-the-counter (OTC) nicotine replacement products, and Surgeon General recommendations, discussing smoking cessation with patients has become standard practice.

Research suggests that treatment to quit smoking should include a combination of pharmacotherapy and counseling, such as cognitive-behavioral strategies, support groups, and quitting hotlines.² Pharmacotherapy consists of OTC nicotine replacement therapy (NRT) products and prescription medications. This article briefly highlights how to counsel patients about using OTC NRT products (Table 1).^2-5 See Table 2 for a summary of prescription smoking cessation agents

Table 1

Over-the-counter nicotine replacement therapy products

Patches

Nicotine replacement patches are best used for maintenance treatment of nicotine cravings. They deliver a fixed amount of nicotine over 24 hours.³ Patches have a specially formulated transdermal matrix system and should not be cut. Doing so damages the drug delivery system and could lead to drug evaporation from the cut edges.⁴ Mr. T’s psychiatrist advises him not to cut patches but instead purchase the 14-mg patch because he is at this step of the smoking cessation regimen.

Skin irritation caused by adhesive is a common adverse event from nicotine patches. Rotating the location of each patch to a different hairless body area is the best way to prevent or combat skin irritation. If rotating the location of the patch does not relieve irritation, patients can apply a thin layer of an OTC hydrocortisone 1% cream to the affected site 2 to 4 times a day after gently washing the area.⁵ Instruct patients to avoid using occlusive dressings over the topical application.

Nicotine replacement patches also have been reported to cause vivid dreams and insomnia.³ These side effects may be caused by nighttime nicotine absorption, which might be avoided by switching to a different NRT product or removing the 24-hour patch when going to bed.⁴

Combining treatments

Many patients experience nicotine cravings while using the nicotine replacement patch. Stressful situations and events can trigger a patient’s desire for nicotine and withdrawal symptoms that a patch that delivers a continuous amount of nicotine over 24 hours cannot alleviate. Combining different forms of treatment could combat these symptoms.^2,3,5

Combination therapy might consist of using sustained-release bupropion or a nicotine patch with rapid-acting NRT products such as a lozenge, gum, nasal spray, or inhaler. In Mr. T’s case, clinicians recommend that he use nicotine polacrilex gum in addition to the patch to quell his cravings. Also, he is instructed to stop using electronic cigarettes because they are considered tobacco products, are not regulated by the FDA, and may contain toxic substances.⁶

Instruct patients who use nicotine gum to employ the “chew and park” method.⁴ First, they should chew the gum very slowly until they notice a minty taste or tingling feeling, then “park” the gum between the cheek and gums for 1 to 2 minutes to allow nicotine to be absorbed across the gum lining. After 2 minutes or when tingling ceases, patients should slowly resume chewing until a tingling or minty taste returns and then “park” the gum again in a different area of the gums. Tell patients to repeat the “chew and park” method until there is no more taste or tingling (approximately 30 minutes). Explain that chewing the gum too fast may result in nausea or lightheadedness and patients should refrain from eating or drinking 15 minutes before or while using the gum. Mr. T is instructed to use the gum only when the urge to smoke is overbearing, and not regularly.

The nicotine polacrilex gum is more viscous than ordinary chewing gum and may stick to or possibly damage dental work such as fillings, dentures, crowns, and braces. An acceptable alternative is the nicotine polacrilex lozenge. Advise patients who want to try lozenges to:

• place the lozenge in the mouth and allow it to dissolve slowly over 20 to 30 minutes (during this time patients may experience a tingling sensation as nicotine is released)
• rotate the lozenge to different areas of the mouth every few minutes to lessen irritation
• avoid chewing or swallowing the lozenge because doing so will lead to improper release of nicotine and side effects, including nausea, hiccups, and heartburn
• refrain from eating or drinking 15 minutes before or while using the lozenge.

For many patients, the breadth of pharmacologic agents available for smoking cessation has made quitting a more attainable goal. OTC smoking cessation products are available in most drug stores, which gives smokers easy access to taking this important step. Counseling patients on the proper use of OTC products may help them successfully stop smoking.⁷

Although a patient’s medical history, including cardiac status, must be considered before starting specific agents, in many instances patient preference is the prevailing factor when choosing therapy. Often, the risks of continued smoking outweigh the risks of using smoking cessation products. OTC smoking cessation products may be an appropriate first-line treatment for many individuals before trying prescription medications, such as bupropion or varenicline.

Related Resources

For patients

• Treat Tobacco. www.treatobacco.net.
• Smokefree.gov mobile application. http://smokefree.gov/apps.
• Medline Plus. Quitting smoking. www.nlm.nih.gov/medlineplus/quittingsmoking.html.
• Quit for Life Program. www.quitnow.net.
• American Lung Association. Stop Smoking. www.lungusa.org/stop-smoking.

For clinicians

• Agency for Health Research and Quality. Treating tobacco use and dependence: 2008 update. www.ahrq.gov/path/tobacco.htm#clinicians.

Drug Brand Names

• Bupropion SR • Zyban, Wellbutrin SR
• Fluoxetine • Prozac
• Varenicline • Chantix

Disclosure

Dr. Ellingrod receives grant/research support from the National Institute of Mental Health.

Dr. Burghardt reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Table 2

Prescription smoking cessation products^a

CASE: Space traveler

Mr. O, age 69, is a patient at a long-term psychiatric hospital. He has a 56-year psychiatric history, a current diagnosis of schizoaffective disorder, and suffered a torn rotator cuff approximately 5 years ago. His medication regimen is haloperidol decanoate, 100 mg IM every month, duloxetine, 60 mg/d, and naproxen, as needed for chronic pain.

He frequently lies on the floor. Attendants urge him to get up and join groups or sit with other patients but he complains of pain and soon finds another spot on the floor to use as a bed.

Eight months earlier, a homeless shelter sent Mr. O to the emergency room (ER) because he tried to eat a dollar bill and a sock. In the ER he was inattentive, with loose associations and bizarre delusions; he believed he was on a spaceship. Mr. O was admitted to the hospital, where clinicians noted that his behavior remained bizarre and he complained of insomnia. They also noted a history of setting fires, which complicated discharge planning and contributed to their decision to transfer him to our psychiatric facility for longer-term care.

During our initial interview, Mr. O readily picks himself off the floor. His responses are logical and direct but abrupt and unelaborated. His first and most vehement complaint is pain. Zolpidem, he says, is the only treatment that helps.

He says he began using zolpidem approximately 5 years ago because pain from a shoulder injury kept him awake at night. When he could not obtain the drug by prescription, he bought it on the street. One day when living in the homeless shelter, he took 30 or 40 mg of zolpidem, then “blacked out” and awoke in the ER.

His first experience with psychiatric treatment was the result of problems getting along with his single mother because of “petty things” such as shooting off a BB gun in their apartment, he says. As a teenager he was sent to a boarding school; as a young adult, to a psychiatric hospital. After his release he returned to his mother’s apartment. He worked steadily for 20 years before he obtained Social Security benefits, and then worked intermittently “off the books” until approximately 15 years ago. Mr. O lived with his mother until her death 17 years earlier, and then in her apartment alone until a fire, which he set accidentally by smoking in bed after taking zolpidem, forced him to leave 3 years ago. He says, “My whole life was in that place.” He was admitted to a psychiatric hospital for an unknown reason, which was his first psychiatric admission in 40 years. After he was released from the hospital, Mr. O lived in various homeless shelters and adult homes until his current hospitalization.

The author’s observations

An effective and well-tolerated drug with a reputation for rarely being abused, zolpidem is widely prescribed as a hypnotic. Zolpidem and benzodiazepines have different chemical structures but both act at the GABA_A receptor and have comparable behavioral effects.¹ The reported incidence of zolpidem abuse is much lower than the reported rate of benzodiazepine abuse when used for sleep²; however, abuse, dependence, and withdrawal have been reported.^2-4 Zolpidem abuse seems to be more common among patients with a history of abusing other substances or a history of psychiatric illness.² A French study⁴ found that abusers fell into 2 groups. The younger group (median age 35) used higher doses—a median of 300 mg/d—and took zolpidem in the daytime to achieve euphoria. A second, older group (median age 42) used lower doses—a median of 200 mg/d—at nighttime to sleep.

There are few reports of delirium and symptoms such as visual hallucinations and distortions associated with zolpidem use.^5,6 These reactions have occurred in persons without a history of psychosis. They usually are associated with doses ≥10 mg.

In the ER Mr. O showed a disturbance in consciousness with inability to focus attention and a perceptual disturbance (he believed he was in a spaceship) that developed over hours to days. He met criteria for delirium, possibly caused by zolpidem, but his presentation also could have been attributable to an underlying psychiatric disorder.

ER and inpatient psychiatrists noted Mr. O was intoxicated with zolpidem when the shelter brought him to the ER, but both groups diagnosed schizoaffective disorder and treated him with antipsychotics. They saw his >50-year psychiatric history as evidence of an underlying, long-standing condition such as schizoaffective illness.

However, features of Mr. O’s illness are not typical of a chronic psychotic illness. He recalls psychiatric hospitalizations in his youth and recently, but not for the 40 years in between. Mr. O says he has never experienced auditory hallucinations. For these reasons, our treatment team obtains old medical records to investigate his early history (Table).

Table

Mr. O’s clinical course

HISTORY: Destructive and defiant

Mr. O’s mother reported that he had been a nervous, restless child who would scream and yell at the slightest provocation. At age 10 he became wantonly destructive. His mother bought him an expensive toy that he destroyed after a short time; he asked for another toy, which he also destroyed. When such behavior became more frequent, she took him to a city hospital, where he was treated for 6 weeks and released at age 13. He was sent to a boarding school but soon was expelled for drinking and selling beer.

Mr. O was admitted to long-term psychiatric facilities 6 times in the next 10 years, from the late 1950s to the late 1960s. He was first admitted at age 17 for temper tantrums during which he fired an air rifle and smashed windows in the home he shared with his mother. During examination he had no delusions or hallucinations but did have flat affect and a hostile attitude. Doctors documented that almost all his tantrums were as a result of interactions with his mother.

Records from this psychiatric admission state that Mr. O showed no unusual distractibility, “psychotic trends,” or paranoid thinking. After approximately 6 months in the hospital he was discharged home with the diagnosis of primary behavior disorder, simple adult maladjustment. Mr. O, who was age 18 at the time, and his mother were eager for him to complete high school and learn auto mechanics.

Nine months later, he returned to the psychiatric facility because of excessive drinking and inability to secure employment, according to his records. In the hospital, he was productive and reliable. When he was discharged home 3 months later, doctors wrote that his determination to stop drinking was firmly fixed. They encouraged Mr. O to complete high school as a night student and find employment during the day. His mother was delighted with his improvement.

A third admission, less than 2 months later, occurred after he broke a window during an argument with his mother. He had a job but quit. After 5 months he was discharged with the same diagnosis of primary behavior disorder, but his mother would not let him back in her home. He was referred to the social service department to be placed on welfare.

A year later, Mr. O had trouble managing his welfare allotment and moved repeatedly. He said he returned to the psychiatric hospital because his welfare payments had been discontinued. During this admission, doctors noted “psychopathic” symptoms; Mr. O was defiant and resented authority and regular work. Mr. O eloped from the hospital several times and brought beer into the building. After 18 months he was discharged with the same diagnosis, with plans to apply for welfare. He was not prescribed medication.

Mr. O’s fifth admission came nearly 2 years later after his mother complained that he stole from her home and carried a weapon. In the hospital he was described as manageable and without overt psychotic symptoms. When he was discharged a little more than a year after being admitted, doctors wrote that he was a psychopath who had a history of drinking, stealing, and delinquent tendencies as a teenager. His diagnosis remained primary behavior disorder.

A year after this discharge, Mr. O was arrested for causing serious property damage when he was intoxicated on alcohol. Subsequently he was readmitted.

After a few months in the hospital, Mr. O changed. He developed a silly laugh, loose associations, irrelevant and incoherent speech, and a belief that hospital staff were against him. Although Mr. O denied auditory hallucinations, a psychiatrist wrote that he seemed to be experiencing hallucinations and prescribed chlorpromazine. The next day Mr. O slashed his arms and legs in several places, requiring many sutures. His diagnosis was changed to psychosis with psychopathic personality. However, within a few months, psychiatrists determined that Mr. O had recovered, so they stopped chlorpromazine. Months later, clinicians wrote that Mr. O was idle most of the time, neat, clean, and not involved in arguments with other patients. He was discharged after 1 month in the hospital.

Over the years, psychiatrists had differing opinions about Mr. O’s diagnosis. One noted that his mental illness was characterized by emotional instability and poor judgment. He had impulsive reactions without regard for others, rapid mood swings, irritability, and depression with transient paranoia. Another clinician detected evidence of schizoid personality disorder because Mr. O did not experience hallucinations or a gross thought disorder, but did have rambling, circumstantial, autistic (unrealistic), and ambivalent thought content. Another psychiatrist wrote Mr. O best fit in the category of psychosis with psychopathic personality, which was his diagnosis at discharge from his sixth hospitalization.

The author’s observations

Mr. O’s old medical records revealed the diagnostic thinking and treatment practices of a past era. They did not demonstrate that Mr. O met current criteria for schizophrenia or schizoaffective disorder, although he may have had a brief psychotic episode. Because there was little support for a diagnosis of schizoaffective illness and haloperidol use, we stopped the drug but continued duloxetine for chronic pain. It was clear that he has a substance use disorder and perhaps met criteria for antisocial personality disorder.

OUTCOME: Further explanations

Approximately 2 months after stopping haloperidol, Mr. O is more spontaneous, logical, and relevant. He does not have delusions or hallucinations. Despite further attempts at pain management with physical therapy and increased doses of duloxetine, he still complains of pain. We do not prescribe zolpidem.

Mr. O is unwilling to discuss the incident more than 40 years ago when he cut his arms and legs except to say, “That’s the past. My life wasn’t so good at that time.” When we ask why he had been a client of Adult Protective Services 5 years before he was burned out of his apartment, he admitted that he was 21 months in arrears in his rent. “I used to do this thing called crack,” he explains. He was discharged to an adult home with a prescription for duloxetine after he promised to never smoke in his room again.

Related Resource

• Aggarwal A, Sharma DD. Zolpidem withdrawal delirium: a case report. J Neuropsychiatry Clin Neurosci. 2010;22(4):451.

Drug Brand Names

• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Duloxetine • Cymbalta
• Haloperidol decanoate • Haloperidol decanoate
• Haloperidol • Haldol
• Naproxen • Naproxyn, Aleve, others
• Zolpidem • Ambien

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Space traveler

Mr. O, age 69, is a patient at a long-term psychiatric hospital. He has a 56-year psychiatric history, a current diagnosis of schizoaffective disorder, and suffered a torn rotator cuff approximately 5 years ago. His medication regimen is haloperidol decanoate, 100 mg IM every month, duloxetine, 60 mg/d, and naproxen, as needed for chronic pain.

He frequently lies on the floor. Attendants urge him to get up and join groups or sit with other patients but he complains of pain and soon finds another spot on the floor to use as a bed.

Eight months earlier, a homeless shelter sent Mr. O to the emergency room (ER) because he tried to eat a dollar bill and a sock. In the ER he was inattentive, with loose associations and bizarre delusions; he believed he was on a spaceship. Mr. O was admitted to the hospital, where clinicians noted that his behavior remained bizarre and he complained of insomnia. They also noted a history of setting fires, which complicated discharge planning and contributed to their decision to transfer him to our psychiatric facility for longer-term care.

During our initial interview, Mr. O readily picks himself off the floor. His responses are logical and direct but abrupt and unelaborated. His first and most vehement complaint is pain. Zolpidem, he says, is the only treatment that helps.

He says he began using zolpidem approximately 5 years ago because pain from a shoulder injury kept him awake at night. When he could not obtain the drug by prescription, he bought it on the street. One day when living in the homeless shelter, he took 30 or 40 mg of zolpidem, then “blacked out” and awoke in the ER.

His first experience with psychiatric treatment was the result of problems getting along with his single mother because of “petty things” such as shooting off a BB gun in their apartment, he says. As a teenager he was sent to a boarding school; as a young adult, to a psychiatric hospital. After his release he returned to his mother’s apartment. He worked steadily for 20 years before he obtained Social Security benefits, and then worked intermittently “off the books” until approximately 15 years ago. Mr. O lived with his mother until her death 17 years earlier, and then in her apartment alone until a fire, which he set accidentally by smoking in bed after taking zolpidem, forced him to leave 3 years ago. He says, “My whole life was in that place.” He was admitted to a psychiatric hospital for an unknown reason, which was his first psychiatric admission in 40 years. After he was released from the hospital, Mr. O lived in various homeless shelters and adult homes until his current hospitalization.

The author’s observations

An effective and well-tolerated drug with a reputation for rarely being abused, zolpidem is widely prescribed as a hypnotic. Zolpidem and benzodiazepines have different chemical structures but both act at the GABA_A receptor and have comparable behavioral effects.¹ The reported incidence of zolpidem abuse is much lower than the reported rate of benzodiazepine abuse when used for sleep²; however, abuse, dependence, and withdrawal have been reported.^2-4 Zolpidem abuse seems to be more common among patients with a history of abusing other substances or a history of psychiatric illness.² A French study⁴ found that abusers fell into 2 groups. The younger group (median age 35) used higher doses—a median of 300 mg/d—and took zolpidem in the daytime to achieve euphoria. A second, older group (median age 42) used lower doses—a median of 200 mg/d—at nighttime to sleep.

There are few reports of delirium and symptoms such as visual hallucinations and distortions associated with zolpidem use.^5,6 These reactions have occurred in persons without a history of psychosis. They usually are associated with doses ≥10 mg.

In the ER Mr. O showed a disturbance in consciousness with inability to focus attention and a perceptual disturbance (he believed he was in a spaceship) that developed over hours to days. He met criteria for delirium, possibly caused by zolpidem, but his presentation also could have been attributable to an underlying psychiatric disorder.

ER and inpatient psychiatrists noted Mr. O was intoxicated with zolpidem when the shelter brought him to the ER, but both groups diagnosed schizoaffective disorder and treated him with antipsychotics. They saw his >50-year psychiatric history as evidence of an underlying, long-standing condition such as schizoaffective illness.

However, features of Mr. O’s illness are not typical of a chronic psychotic illness. He recalls psychiatric hospitalizations in his youth and recently, but not for the 40 years in between. Mr. O says he has never experienced auditory hallucinations. For these reasons, our treatment team obtains old medical records to investigate his early history (Table).

Table

Mr. O’s clinical course

HISTORY: Destructive and defiant

Mr. O’s mother reported that he had been a nervous, restless child who would scream and yell at the slightest provocation. At age 10 he became wantonly destructive. His mother bought him an expensive toy that he destroyed after a short time; he asked for another toy, which he also destroyed. When such behavior became more frequent, she took him to a city hospital, where he was treated for 6 weeks and released at age 13. He was sent to a boarding school but soon was expelled for drinking and selling beer.

Mr. O was admitted to long-term psychiatric facilities 6 times in the next 10 years, from the late 1950s to the late 1960s. He was first admitted at age 17 for temper tantrums during which he fired an air rifle and smashed windows in the home he shared with his mother. During examination he had no delusions or hallucinations but did have flat affect and a hostile attitude. Doctors documented that almost all his tantrums were as a result of interactions with his mother.

Records from this psychiatric admission state that Mr. O showed no unusual distractibility, “psychotic trends,” or paranoid thinking. After approximately 6 months in the hospital he was discharged home with the diagnosis of primary behavior disorder, simple adult maladjustment. Mr. O, who was age 18 at the time, and his mother were eager for him to complete high school and learn auto mechanics.

Nine months later, he returned to the psychiatric facility because of excessive drinking and inability to secure employment, according to his records. In the hospital, he was productive and reliable. When he was discharged home 3 months later, doctors wrote that his determination to stop drinking was firmly fixed. They encouraged Mr. O to complete high school as a night student and find employment during the day. His mother was delighted with his improvement.

A third admission, less than 2 months later, occurred after he broke a window during an argument with his mother. He had a job but quit. After 5 months he was discharged with the same diagnosis of primary behavior disorder, but his mother would not let him back in her home. He was referred to the social service department to be placed on welfare.

A year later, Mr. O had trouble managing his welfare allotment and moved repeatedly. He said he returned to the psychiatric hospital because his welfare payments had been discontinued. During this admission, doctors noted “psychopathic” symptoms; Mr. O was defiant and resented authority and regular work. Mr. O eloped from the hospital several times and brought beer into the building. After 18 months he was discharged with the same diagnosis, with plans to apply for welfare. He was not prescribed medication.

Mr. O’s fifth admission came nearly 2 years later after his mother complained that he stole from her home and carried a weapon. In the hospital he was described as manageable and without overt psychotic symptoms. When he was discharged a little more than a year after being admitted, doctors wrote that he was a psychopath who had a history of drinking, stealing, and delinquent tendencies as a teenager. His diagnosis remained primary behavior disorder.

A year after this discharge, Mr. O was arrested for causing serious property damage when he was intoxicated on alcohol. Subsequently he was readmitted.

After a few months in the hospital, Mr. O changed. He developed a silly laugh, loose associations, irrelevant and incoherent speech, and a belief that hospital staff were against him. Although Mr. O denied auditory hallucinations, a psychiatrist wrote that he seemed to be experiencing hallucinations and prescribed chlorpromazine. The next day Mr. O slashed his arms and legs in several places, requiring many sutures. His diagnosis was changed to psychosis with psychopathic personality. However, within a few months, psychiatrists determined that Mr. O had recovered, so they stopped chlorpromazine. Months later, clinicians wrote that Mr. O was idle most of the time, neat, clean, and not involved in arguments with other patients. He was discharged after 1 month in the hospital.

Over the years, psychiatrists had differing opinions about Mr. O’s diagnosis. One noted that his mental illness was characterized by emotional instability and poor judgment. He had impulsive reactions without regard for others, rapid mood swings, irritability, and depression with transient paranoia. Another clinician detected evidence of schizoid personality disorder because Mr. O did not experience hallucinations or a gross thought disorder, but did have rambling, circumstantial, autistic (unrealistic), and ambivalent thought content. Another psychiatrist wrote Mr. O best fit in the category of psychosis with psychopathic personality, which was his diagnosis at discharge from his sixth hospitalization.

The author’s observations

Mr. O’s old medical records revealed the diagnostic thinking and treatment practices of a past era. They did not demonstrate that Mr. O met current criteria for schizophrenia or schizoaffective disorder, although he may have had a brief psychotic episode. Because there was little support for a diagnosis of schizoaffective illness and haloperidol use, we stopped the drug but continued duloxetine for chronic pain. It was clear that he has a substance use disorder and perhaps met criteria for antisocial personality disorder.

OUTCOME: Further explanations

Approximately 2 months after stopping haloperidol, Mr. O is more spontaneous, logical, and relevant. He does not have delusions or hallucinations. Despite further attempts at pain management with physical therapy and increased doses of duloxetine, he still complains of pain. We do not prescribe zolpidem.

Mr. O is unwilling to discuss the incident more than 40 years ago when he cut his arms and legs except to say, “That’s the past. My life wasn’t so good at that time.” When we ask why he had been a client of Adult Protective Services 5 years before he was burned out of his apartment, he admitted that he was 21 months in arrears in his rent. “I used to do this thing called crack,” he explains. He was discharged to an adult home with a prescription for duloxetine after he promised to never smoke in his room again.

Related Resource

• Aggarwal A, Sharma DD. Zolpidem withdrawal delirium: a case report. J Neuropsychiatry Clin Neurosci. 2010;22(4):451.

Drug Brand Names

• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Duloxetine • Cymbalta
• Haloperidol decanoate • Haloperidol decanoate
• Haloperidol • Haldol
• Naproxen • Naproxyn, Aleve, others
• Zolpidem • Ambien

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Space traveler

Mr. O, age 69, is a patient at a long-term psychiatric hospital. He has a 56-year psychiatric history, a current diagnosis of schizoaffective disorder, and suffered a torn rotator cuff approximately 5 years ago. His medication regimen is haloperidol decanoate, 100 mg IM every month, duloxetine, 60 mg/d, and naproxen, as needed for chronic pain.

He frequently lies on the floor. Attendants urge him to get up and join groups or sit with other patients but he complains of pain and soon finds another spot on the floor to use as a bed.

Eight months earlier, a homeless shelter sent Mr. O to the emergency room (ER) because he tried to eat a dollar bill and a sock. In the ER he was inattentive, with loose associations and bizarre delusions; he believed he was on a spaceship. Mr. O was admitted to the hospital, where clinicians noted that his behavior remained bizarre and he complained of insomnia. They also noted a history of setting fires, which complicated discharge planning and contributed to their decision to transfer him to our psychiatric facility for longer-term care.

During our initial interview, Mr. O readily picks himself off the floor. His responses are logical and direct but abrupt and unelaborated. His first and most vehement complaint is pain. Zolpidem, he says, is the only treatment that helps.

He says he began using zolpidem approximately 5 years ago because pain from a shoulder injury kept him awake at night. When he could not obtain the drug by prescription, he bought it on the street. One day when living in the homeless shelter, he took 30 or 40 mg of zolpidem, then “blacked out” and awoke in the ER.

His first experience with psychiatric treatment was the result of problems getting along with his single mother because of “petty things” such as shooting off a BB gun in their apartment, he says. As a teenager he was sent to a boarding school; as a young adult, to a psychiatric hospital. After his release he returned to his mother’s apartment. He worked steadily for 20 years before he obtained Social Security benefits, and then worked intermittently “off the books” until approximately 15 years ago. Mr. O lived with his mother until her death 17 years earlier, and then in her apartment alone until a fire, which he set accidentally by smoking in bed after taking zolpidem, forced him to leave 3 years ago. He says, “My whole life was in that place.” He was admitted to a psychiatric hospital for an unknown reason, which was his first psychiatric admission in 40 years. After he was released from the hospital, Mr. O lived in various homeless shelters and adult homes until his current hospitalization.

The author’s observations

An effective and well-tolerated drug with a reputation for rarely being abused, zolpidem is widely prescribed as a hypnotic. Zolpidem and benzodiazepines have different chemical structures but both act at the GABA_A receptor and have comparable behavioral effects.¹ The reported incidence of zolpidem abuse is much lower than the reported rate of benzodiazepine abuse when used for sleep²; however, abuse, dependence, and withdrawal have been reported.^2-4 Zolpidem abuse seems to be more common among patients with a history of abusing other substances or a history of psychiatric illness.² A French study⁴ found that abusers fell into 2 groups. The younger group (median age 35) used higher doses—a median of 300 mg/d—and took zolpidem in the daytime to achieve euphoria. A second, older group (median age 42) used lower doses—a median of 200 mg/d—at nighttime to sleep.

There are few reports of delirium and symptoms such as visual hallucinations and distortions associated with zolpidem use.^5,6 These reactions have occurred in persons without a history of psychosis. They usually are associated with doses ≥10 mg.

In the ER Mr. O showed a disturbance in consciousness with inability to focus attention and a perceptual disturbance (he believed he was in a spaceship) that developed over hours to days. He met criteria for delirium, possibly caused by zolpidem, but his presentation also could have been attributable to an underlying psychiatric disorder.

ER and inpatient psychiatrists noted Mr. O was intoxicated with zolpidem when the shelter brought him to the ER, but both groups diagnosed schizoaffective disorder and treated him with antipsychotics. They saw his >50-year psychiatric history as evidence of an underlying, long-standing condition such as schizoaffective illness.

However, features of Mr. O’s illness are not typical of a chronic psychotic illness. He recalls psychiatric hospitalizations in his youth and recently, but not for the 40 years in between. Mr. O says he has never experienced auditory hallucinations. For these reasons, our treatment team obtains old medical records to investigate his early history (Table).

Table

Mr. O’s clinical course

HISTORY: Destructive and defiant

Mr. O’s mother reported that he had been a nervous, restless child who would scream and yell at the slightest provocation. At age 10 he became wantonly destructive. His mother bought him an expensive toy that he destroyed after a short time; he asked for another toy, which he also destroyed. When such behavior became more frequent, she took him to a city hospital, where he was treated for 6 weeks and released at age 13. He was sent to a boarding school but soon was expelled for drinking and selling beer.

Mr. O was admitted to long-term psychiatric facilities 6 times in the next 10 years, from the late 1950s to the late 1960s. He was first admitted at age 17 for temper tantrums during which he fired an air rifle and smashed windows in the home he shared with his mother. During examination he had no delusions or hallucinations but did have flat affect and a hostile attitude. Doctors documented that almost all his tantrums were as a result of interactions with his mother.

Records from this psychiatric admission state that Mr. O showed no unusual distractibility, “psychotic trends,” or paranoid thinking. After approximately 6 months in the hospital he was discharged home with the diagnosis of primary behavior disorder, simple adult maladjustment. Mr. O, who was age 18 at the time, and his mother were eager for him to complete high school and learn auto mechanics.

Nine months later, he returned to the psychiatric facility because of excessive drinking and inability to secure employment, according to his records. In the hospital, he was productive and reliable. When he was discharged home 3 months later, doctors wrote that his determination to stop drinking was firmly fixed. They encouraged Mr. O to complete high school as a night student and find employment during the day. His mother was delighted with his improvement.

A third admission, less than 2 months later, occurred after he broke a window during an argument with his mother. He had a job but quit. After 5 months he was discharged with the same diagnosis of primary behavior disorder, but his mother would not let him back in her home. He was referred to the social service department to be placed on welfare.

A year later, Mr. O had trouble managing his welfare allotment and moved repeatedly. He said he returned to the psychiatric hospital because his welfare payments had been discontinued. During this admission, doctors noted “psychopathic” symptoms; Mr. O was defiant and resented authority and regular work. Mr. O eloped from the hospital several times and brought beer into the building. After 18 months he was discharged with the same diagnosis, with plans to apply for welfare. He was not prescribed medication.

Mr. O’s fifth admission came nearly 2 years later after his mother complained that he stole from her home and carried a weapon. In the hospital he was described as manageable and without overt psychotic symptoms. When he was discharged a little more than a year after being admitted, doctors wrote that he was a psychopath who had a history of drinking, stealing, and delinquent tendencies as a teenager. His diagnosis remained primary behavior disorder.

A year after this discharge, Mr. O was arrested for causing serious property damage when he was intoxicated on alcohol. Subsequently he was readmitted.

After a few months in the hospital, Mr. O changed. He developed a silly laugh, loose associations, irrelevant and incoherent speech, and a belief that hospital staff were against him. Although Mr. O denied auditory hallucinations, a psychiatrist wrote that he seemed to be experiencing hallucinations and prescribed chlorpromazine. The next day Mr. O slashed his arms and legs in several places, requiring many sutures. His diagnosis was changed to psychosis with psychopathic personality. However, within a few months, psychiatrists determined that Mr. O had recovered, so they stopped chlorpromazine. Months later, clinicians wrote that Mr. O was idle most of the time, neat, clean, and not involved in arguments with other patients. He was discharged after 1 month in the hospital.

Over the years, psychiatrists had differing opinions about Mr. O’s diagnosis. One noted that his mental illness was characterized by emotional instability and poor judgment. He had impulsive reactions without regard for others, rapid mood swings, irritability, and depression with transient paranoia. Another clinician detected evidence of schizoid personality disorder because Mr. O did not experience hallucinations or a gross thought disorder, but did have rambling, circumstantial, autistic (unrealistic), and ambivalent thought content. Another psychiatrist wrote Mr. O best fit in the category of psychosis with psychopathic personality, which was his diagnosis at discharge from his sixth hospitalization.

The author’s observations

Mr. O’s old medical records revealed the diagnostic thinking and treatment practices of a past era. They did not demonstrate that Mr. O met current criteria for schizophrenia or schizoaffective disorder, although he may have had a brief psychotic episode. Because there was little support for a diagnosis of schizoaffective illness and haloperidol use, we stopped the drug but continued duloxetine for chronic pain. It was clear that he has a substance use disorder and perhaps met criteria for antisocial personality disorder.

OUTCOME: Further explanations

Approximately 2 months after stopping haloperidol, Mr. O is more spontaneous, logical, and relevant. He does not have delusions or hallucinations. Despite further attempts at pain management with physical therapy and increased doses of duloxetine, he still complains of pain. We do not prescribe zolpidem.

Mr. O is unwilling to discuss the incident more than 40 years ago when he cut his arms and legs except to say, “That’s the past. My life wasn’t so good at that time.” When we ask why he had been a client of Adult Protective Services 5 years before he was burned out of his apartment, he admitted that he was 21 months in arrears in his rent. “I used to do this thing called crack,” he explains. He was discharged to an adult home with a prescription for duloxetine after he promised to never smoke in his room again.

Related Resource

• Aggarwal A, Sharma DD. Zolpidem withdrawal delirium: a case report. J Neuropsychiatry Clin Neurosci. 2010;22(4):451.

Drug Brand Names

• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Duloxetine • Cymbalta
• Haloperidol decanoate • Haloperidol decanoate
• Haloperidol • Haldol
• Naproxen • Naproxyn, Aleve, others
• Zolpidem • Ambien

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.