Current Psychiatry

The incidence of diabetes in people with schizophrenia is 2- to 3-fold that of the general population—which has been attributed to several variables, including adverse effects of antipsychotic drugs, susceptibility related to mental illness, lifestyle, and social health determinants.¹ Controlling diabetes is important because cardiovascular consequences of the disease contribute to the shortened life expectancy seen in patients with schizophrenia.²

The dosing frequency of a newer formulation of exenatide, a glucose-lowering drug that has been available for almost a decade, can help manage type 2 diabetes mellitus in your patient with schizophrenia.

What is the new formulation and why is it appealing?

Exenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2
diabetes mellitus. GLP-1 agonists lower the blood glucose level by enhancing glucose-dependent insulin secretion, suppressing glucagon secretion, slowing gastric emptying, and enhancing satiety. Exenatide was approved by the FDA
in 2005 as a twice-daily subcutaneous injection (brand name, Byetta); the once-weekly formulation, also for subcutaneous injection (brand name, Bydureon), was approved in 2012.

Practical use for psychiatric patients

Because psychiatric patients face medication adherence challenges, the once-
weekly formulation of exenatide is appealing. The patient or a member of his (her) care team can administer the once-weekly injection.

Practitioners might be concerned that patients with comorbid psychiatric illness and diabetes will overreact to an elevated blood glucose reading by overusing medications such as oral hypoglycemics and insulin. The fixed-dosage of weekly exenatide minimizes the risk that a patient will react to a single elevated blood glucose reading.

Exenatide can produce weight loss, which might benefit patients who suffer from the metabolic adverse effects of an atypical antipsychotic, including an elevated blood glucose level and weight gain.

Real-world application

We have used once-weekly exenatide successfully in a female patient with schizophrenia who was taking quetiapine and haloperidol, and had uncontrolled diabetes resulting from medication nonadherence and lack of insight into diabetes.

The patient’s hemoglobin A_1c level remained at 8.8% (target A_1c, <7%, as set by the American Diabetes Association), despite taking 3 oral diabetes medications at maximum dosage.

The care team determined that daily insulin injections were too risky, given the patient’s compulsive behavior; she had a history of medication overuse in response to significantly elevated blood glucose.

Once-weekly exenatide, however, was a feasible alternative. Three months after she was started on once-weekly exenatide, and with additional lifestyle modifications, her hemoglobin A_1c level had fallen to 6.4%, without any hypoglycemic episodes.

Select patients carefully

Exenatide is not a first-line therapy because of its potential side effects (Table), route of administration, and cost. Consider the once-weekly formulation of the drug on a patient-by-patient basis for patients with schizophrenia whose diabetes otherwise cannot be controlled.

Disclosure

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

The incidence of diabetes in people with schizophrenia is 2- to 3-fold that of the general population—which has been attributed to several variables, including adverse effects of antipsychotic drugs, susceptibility related to mental illness, lifestyle, and social health determinants.¹ Controlling diabetes is important because cardiovascular consequences of the disease contribute to the shortened life expectancy seen in patients with schizophrenia.²

The dosing frequency of a newer formulation of exenatide, a glucose-lowering drug that has been available for almost a decade, can help manage type 2 diabetes mellitus in your patient with schizophrenia.

What is the new formulation and why is it appealing?

Exenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2
diabetes mellitus. GLP-1 agonists lower the blood glucose level by enhancing glucose-dependent insulin secretion, suppressing glucagon secretion, slowing gastric emptying, and enhancing satiety. Exenatide was approved by the FDA
in 2005 as a twice-daily subcutaneous injection (brand name, Byetta); the once-weekly formulation, also for subcutaneous injection (brand name, Bydureon), was approved in 2012.

Practical use for psychiatric patients

Because psychiatric patients face medication adherence challenges, the once-
weekly formulation of exenatide is appealing. The patient or a member of his (her) care team can administer the once-weekly injection.

Practitioners might be concerned that patients with comorbid psychiatric illness and diabetes will overreact to an elevated blood glucose reading by overusing medications such as oral hypoglycemics and insulin. The fixed-dosage of weekly exenatide minimizes the risk that a patient will react to a single elevated blood glucose reading.

Exenatide can produce weight loss, which might benefit patients who suffer from the metabolic adverse effects of an atypical antipsychotic, including an elevated blood glucose level and weight gain.

Real-world application

We have used once-weekly exenatide successfully in a female patient with schizophrenia who was taking quetiapine and haloperidol, and had uncontrolled diabetes resulting from medication nonadherence and lack of insight into diabetes.

The patient’s hemoglobin A_1c level remained at 8.8% (target A_1c, <7%, as set by the American Diabetes Association), despite taking 3 oral diabetes medications at maximum dosage.

The care team determined that daily insulin injections were too risky, given the patient’s compulsive behavior; she had a history of medication overuse in response to significantly elevated blood glucose.

Once-weekly exenatide, however, was a feasible alternative. Three months after she was started on once-weekly exenatide, and with additional lifestyle modifications, her hemoglobin A_1c level had fallen to 6.4%, without any hypoglycemic episodes.

Select patients carefully

Exenatide is not a first-line therapy because of its potential side effects (Table), route of administration, and cost. Consider the once-weekly formulation of the drug on a patient-by-patient basis for patients with schizophrenia whose diabetes otherwise cannot be controlled.

Disclosure

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

The incidence of diabetes in people with schizophrenia is 2- to 3-fold that of the general population—which has been attributed to several variables, including adverse effects of antipsychotic drugs, susceptibility related to mental illness, lifestyle, and social health determinants.¹ Controlling diabetes is important because cardiovascular consequences of the disease contribute to the shortened life expectancy seen in patients with schizophrenia.²

The dosing frequency of a newer formulation of exenatide, a glucose-lowering drug that has been available for almost a decade, can help manage type 2 diabetes mellitus in your patient with schizophrenia.

What is the new formulation and why is it appealing?

Exenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2
diabetes mellitus. GLP-1 agonists lower the blood glucose level by enhancing glucose-dependent insulin secretion, suppressing glucagon secretion, slowing gastric emptying, and enhancing satiety. Exenatide was approved by the FDA
in 2005 as a twice-daily subcutaneous injection (brand name, Byetta); the once-weekly formulation, also for subcutaneous injection (brand name, Bydureon), was approved in 2012.

Practical use for psychiatric patients

Because psychiatric patients face medication adherence challenges, the once-
weekly formulation of exenatide is appealing. The patient or a member of his (her) care team can administer the once-weekly injection.

Practitioners might be concerned that patients with comorbid psychiatric illness and diabetes will overreact to an elevated blood glucose reading by overusing medications such as oral hypoglycemics and insulin. The fixed-dosage of weekly exenatide minimizes the risk that a patient will react to a single elevated blood glucose reading.

Exenatide can produce weight loss, which might benefit patients who suffer from the metabolic adverse effects of an atypical antipsychotic, including an elevated blood glucose level and weight gain.

Real-world application

We have used once-weekly exenatide successfully in a female patient with schizophrenia who was taking quetiapine and haloperidol, and had uncontrolled diabetes resulting from medication nonadherence and lack of insight into diabetes.

The patient’s hemoglobin A_1c level remained at 8.8% (target A_1c, <7%, as set by the American Diabetes Association), despite taking 3 oral diabetes medications at maximum dosage.

The care team determined that daily insulin injections were too risky, given the patient’s compulsive behavior; she had a history of medication overuse in response to significantly elevated blood glucose.

Once-weekly exenatide, however, was a feasible alternative. Three months after she was started on once-weekly exenatide, and with additional lifestyle modifications, her hemoglobin A_1c level had fallen to 6.4%, without any hypoglycemic episodes.

Select patients carefully

Exenatide is not a first-line therapy because of its potential side effects (Table), route of administration, and cost. Consider the once-weekly formulation of the drug on a patient-by-patient basis for patients with schizophrenia whose diabetes otherwise cannot be controlled.

Disclosure

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

The suicide of a patient is a relatively frequent occurrence in psychiatry. As many as 68% of consultant psychiatrists acknowledge the loss of a patient to suicide.¹ Conservative estimates are that as many as 54% of psychiatry resident trainees experience patient suicide.²

Up to 57% of psychiatrists who have experienced a patient’s suicide have developed symptoms of posttraumatic stress disorder.³ There are steps you can take personally, with your staff, and with the patient’s family to mitigate social,
ethical, and legal consequences of a patient committing suicide, and to improve risk management.

Steps to take for yourself

1. In an inpatient psychiatric facility, be aware of standard operating procedures after a suicide; inform only an immediate supervisor if you learn of a suicide. In a group practice, inform the owner of the practice and receive advice on how to proceed. Do not contact the coroner’s office, the police, the deceased’s family, or legal counsel until advised to do so by a direct supervisor.

2. Be prepared to work with the coroner’s or medical examiner’s office. Write a detailed note summarizing the patient’s clinical history before the suicide; describe the clinical team’s work with the patient, the treatment plan, and an estimate of suicide risk.

3. Contact a trusted colleague or mentor; seeking formal and informal support from colleagues has shown to be helpful in coping with patient suicide.⁴ Group
support helps diminish feelings of pain and loneliness and helps one regain a sense of empowerment and willingness to treat other suicidal patients.

4. If possible, attend the patient’s funeral. This gesture often is welcomed by the family and facilitates the grieving process. Attending the funeral is not an admission of responsibility for the suicide.

5. Participate in the audit process (ie, what went wrong?, Could something have been done differently?).

Steps to take with the patient’s family

1. Once standard operating procedure allows, and, preferably within 24 hours of the suicide, contact the patient’s family to express your grief; give the family an opportunity to ask questions. Early communication and support reduces anger displaced on the psychiatrist. Initial contact can be used to provide support and as an opportunity to share and communicate.

2. When speaking with the family, discuss treatment efforts and emphasize that all realistic efforts were made to help the patient. Let family members vent their anger and hostility; the grieving process is hard, complex, and painful when a loved one has committed suicide.

3. Support the family’s decisions about mourning rituals specific to their culture and needs; involving the clergy early on can be helpful. Discussing the autopsy report with the family can be another way to show support.

4. Continue to offer support through stressful times, such as anniversaries and birthdays.

Steps to take with staff

1. Make staff aware of the death as a group; encourage them to attend funeral services.

2. Avoid placing blame; encourage group support and venting of emotions.

3. Be available to the staff so that they can share feelings of hurt and disappointment with you.

4. Maintain the schedule on unit, restoring a sense of stability and normalcy.

5. A so-called psychological autopsy exercise is recommended, in which you can emphasize the learning experience and focus on improvements⁴ that can help formulate policy reforms for providing better care.

Steps to improve risk management

1. If you work in a hospital, immediately contact the risk management team.

2. Seek legal counsel as soon as possible and involve counsel at all stages.

3. Notify your malpractice insurance carrier.

4. Complete the patient’s medical record and describe the facts as they occurred. Date the records accurately with clarification on notes entered after the suicide. Avoid drawing conclusions. Do not apologize for, or justify, your treatment decisions.

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

The suicide of a patient is a relatively frequent occurrence in psychiatry. As many as 68% of consultant psychiatrists acknowledge the loss of a patient to suicide.¹ Conservative estimates are that as many as 54% of psychiatry resident trainees experience patient suicide.²

Up to 57% of psychiatrists who have experienced a patient’s suicide have developed symptoms of posttraumatic stress disorder.³ There are steps you can take personally, with your staff, and with the patient’s family to mitigate social,
ethical, and legal consequences of a patient committing suicide, and to improve risk management.

Steps to take for yourself

1. In an inpatient psychiatric facility, be aware of standard operating procedures after a suicide; inform only an immediate supervisor if you learn of a suicide. In a group practice, inform the owner of the practice and receive advice on how to proceed. Do not contact the coroner’s office, the police, the deceased’s family, or legal counsel until advised to do so by a direct supervisor.

2. Be prepared to work with the coroner’s or medical examiner’s office. Write a detailed note summarizing the patient’s clinical history before the suicide; describe the clinical team’s work with the patient, the treatment plan, and an estimate of suicide risk.

3. Contact a trusted colleague or mentor; seeking formal and informal support from colleagues has shown to be helpful in coping with patient suicide.⁴ Group
support helps diminish feelings of pain and loneliness and helps one regain a sense of empowerment and willingness to treat other suicidal patients.

4. If possible, attend the patient’s funeral. This gesture often is welcomed by the family and facilitates the grieving process. Attending the funeral is not an admission of responsibility for the suicide.

5. Participate in the audit process (ie, what went wrong?, Could something have been done differently?).

Steps to take with the patient’s family

1. Once standard operating procedure allows, and, preferably within 24 hours of the suicide, contact the patient’s family to express your grief; give the family an opportunity to ask questions. Early communication and support reduces anger displaced on the psychiatrist. Initial contact can be used to provide support and as an opportunity to share and communicate.

2. When speaking with the family, discuss treatment efforts and emphasize that all realistic efforts were made to help the patient. Let family members vent their anger and hostility; the grieving process is hard, complex, and painful when a loved one has committed suicide.

3. Support the family’s decisions about mourning rituals specific to their culture and needs; involving the clergy early on can be helpful. Discussing the autopsy report with the family can be another way to show support.

4. Continue to offer support through stressful times, such as anniversaries and birthdays.

Steps to take with staff

1. Make staff aware of the death as a group; encourage them to attend funeral services.

2. Avoid placing blame; encourage group support and venting of emotions.

3. Be available to the staff so that they can share feelings of hurt and disappointment with you.

4. Maintain the schedule on unit, restoring a sense of stability and normalcy.

5. A so-called psychological autopsy exercise is recommended, in which you can emphasize the learning experience and focus on improvements⁴ that can help formulate policy reforms for providing better care.

Steps to improve risk management

1. If you work in a hospital, immediately contact the risk management team.

2. Seek legal counsel as soon as possible and involve counsel at all stages.

3. Notify your malpractice insurance carrier.

4. Complete the patient’s medical record and describe the facts as they occurred. Date the records accurately with clarification on notes entered after the suicide. Avoid drawing conclusions. Do not apologize for, or justify, your treatment decisions.

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

The suicide of a patient is a relatively frequent occurrence in psychiatry. As many as 68% of consultant psychiatrists acknowledge the loss of a patient to suicide.¹ Conservative estimates are that as many as 54% of psychiatry resident trainees experience patient suicide.²

Up to 57% of psychiatrists who have experienced a patient’s suicide have developed symptoms of posttraumatic stress disorder.³ There are steps you can take personally, with your staff, and with the patient’s family to mitigate social,
ethical, and legal consequences of a patient committing suicide, and to improve risk management.

Steps to take for yourself

1. In an inpatient psychiatric facility, be aware of standard operating procedures after a suicide; inform only an immediate supervisor if you learn of a suicide. In a group practice, inform the owner of the practice and receive advice on how to proceed. Do not contact the coroner’s office, the police, the deceased’s family, or legal counsel until advised to do so by a direct supervisor.

2. Be prepared to work with the coroner’s or medical examiner’s office. Write a detailed note summarizing the patient’s clinical history before the suicide; describe the clinical team’s work with the patient, the treatment plan, and an estimate of suicide risk.

3. Contact a trusted colleague or mentor; seeking formal and informal support from colleagues has shown to be helpful in coping with patient suicide.⁴ Group
support helps diminish feelings of pain and loneliness and helps one regain a sense of empowerment and willingness to treat other suicidal patients.

4. If possible, attend the patient’s funeral. This gesture often is welcomed by the family and facilitates the grieving process. Attending the funeral is not an admission of responsibility for the suicide.

5. Participate in the audit process (ie, what went wrong?, Could something have been done differently?).

Steps to take with the patient’s family

1. Once standard operating procedure allows, and, preferably within 24 hours of the suicide, contact the patient’s family to express your grief; give the family an opportunity to ask questions. Early communication and support reduces anger displaced on the psychiatrist. Initial contact can be used to provide support and as an opportunity to share and communicate.

2. When speaking with the family, discuss treatment efforts and emphasize that all realistic efforts were made to help the patient. Let family members vent their anger and hostility; the grieving process is hard, complex, and painful when a loved one has committed suicide.

3. Support the family’s decisions about mourning rituals specific to their culture and needs; involving the clergy early on can be helpful. Discussing the autopsy report with the family can be another way to show support.

4. Continue to offer support through stressful times, such as anniversaries and birthdays.

Steps to take with staff

1. Make staff aware of the death as a group; encourage them to attend funeral services.

2. Avoid placing blame; encourage group support and venting of emotions.

3. Be available to the staff so that they can share feelings of hurt and disappointment with you.

4. Maintain the schedule on unit, restoring a sense of stability and normalcy.

5. A so-called psychological autopsy exercise is recommended, in which you can emphasize the learning experience and focus on improvements⁴ that can help formulate policy reforms for providing better care.

Steps to improve risk management

1. If you work in a hospital, immediately contact the risk management team.

2. Seek legal counsel as soon as possible and involve counsel at all stages.

3. Notify your malpractice insurance carrier.

4. Complete the patient’s medical record and describe the facts as they occurred. Date the records accurately with clarification on notes entered after the suicide. Avoid drawing conclusions. Do not apologize for, or justify, your treatment decisions.

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

Vortioxetine is FDA-approved to treat major depressive disorder (MDD) (Table 1), having shown efficacy in relieving depressive symptoms in clinical trials.¹ Vortioxetine’s mechanism of action enhances CNS serotonergic activity through inhibiting serotonin (5-HT) reuptake, agonizing the 5-HT1A receptor, partially agonizing the 5-HT1B receptor, and antagonizing the 5-HT3, 5-HT1D, and 5-HT7 receptors.

Clinical implications

It is hypothesized that depression is a heterogeneous disease caused by dysregulation of serotonin, norepinephrine, and dopamine, subsequently producing mood and neurovegetative symptoms of depression. Preclinical, in vivo studies indicate that vortioxetine enhances levels of serotonin, norepinephrine, dopamine, acetylcholine, and histamine in specific areas of the brain with the ability to improve depressive symptoms. Vortioxetine’s multimodal activity can be a useful alternative to other serotonergic antidepressants for some patients who are partial responders or non-responders to other treatment options. In addition, vortioxetine appears to have minimal effect on weight² and sexual function—the latter being dose-dependent.³

How does it work?

Vortioxetine differs from other antidepressants in its multimodal activity (ie, affecting G-protein mode receptors, ion channel mode receptors, and neurotransmitter transporters). It inhibits the serotonin transporter (Ki = 1.6 nM), causing subsequent inhibition of serotonin reuptake into presynaptic neurons as well as selectively acting on the other subtypes of serotonergic receptors; however, activity on the norepinephrine transporter (Ki = 113 nM) and dopamine transporter (Ki > 1000 nM) is minimal. It is believed that mood-regulating effects of vortioxetine are caused by inhibition of serotonin reuptake, prolonged availability of serotonin to the postsynaptic neurons, its agonist activity on the 5-HT1A receptor (Ki = 15 nM), and partial agonist activity on the 5-HT1B receptor (Ki = 33 nM). Vortioxetine has strong affinity for the 5-HT3 receptor (Ki = 3.7 nM), which plays a role in modulation of centrally mediated nausea and vomiting. Positron emission tomography studies in humans determined that the occupancy of 5-HT transporter was 50% at 5 mg/d, 65% at 10 mg/d, and 80% at 20 mg/d.^1,4 Human studies did not show that vortioxetine causes QTc prolongation.  

Pharmacokinetics

Therapeutic activity of vortioxetine is thought to be due to the parent drug. It has a half-life of approximately 66 hours, and achieves steady state in 13.5 to 19 days. Bioavailability of vortioxetine is 75%; absorption does not depend on food; and 98% of drug is bound on plasma proteins.

Vortioxetine has linear pharmacokinetics, with maximum plasma concentration 7 to 11 hours after ingestion. The medication is metabolized primarily by oxidation through cytochrome P (CYP) 450: CYP2D6 (primary), CYP 3A4/5, CYP 2C19, CYP 2C9, CYP2A6, CYP2C8, and CYP2B6 with subsequent glucuronidation. This predisposes vortioxetine to potential pharmacokinetic drug-drug interaction warranting dose adjustment consideration when vortioxetine is coadministered with compounds inhibiting CYP2D6 or inducing CYP3A4 for ≥14 days, or for patients identified as poor 2D6 metabolizers.

In addition, coadministration of vortioxetine with serotonergic medications such as triptans, other antidepressants, and tramadol can cause potentially life-threatening serotonin syndrome, characterized by mental status changes, autonomic instability, neuromuscular aberrations, and GI symptoms. Concomitant use of vortioxetine and a nonsteroidal anti-inflammatory drug, aspirin, or warfarin can result in abnormal bleeding. Coadministration of vortioxetine with another highly protein-bound drug may increase or decrease the free concentration of either drug depending on the binding affinity of the drug for the protein.

Efficacy

Vortioxetine reduced depressive symptoms in 6 positive, 6- to 8-week, double-blind, placebo controlled and randomized studies and 1 maintenance study.¹ Subjects were adults (Studies 1 to 5) and geriatric patients from age 64 to 88 who had ≥1 depressive episode before age 60 (Study 6). All met DSM-IV-TR criteria for MDD. Subjects with cognitive impairment scoring <24 on the Mini-Mental Status Examination and children were excluded. Depending on the study, response to the treatment was primarily measured on the Montgomery-Åsberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D).

See Table 2 for a description of the positive studies, including dosages. In all studies, vortioxetine was superior to placebo at least one dosage for treating depression. In the 6- to 8-week placebo-controlled studies, an effect of vortioxetine based on the primary efficacy measure was generally observed starting at Week 2; that effect increased in subsequent weeks with the full antidepressant effect of vortioxetine generally not seen until study Week 4 or later.¹

The maintenance treatment study included 639 patients who met DSM-IV-TR criteria for MDD. This study lasted for as long as 64 weeks. The first 12-week period was open-label, during which patients were treated with vortioxetine, 5 mg/d or 10 mg/d, with a possibility to adjust the dosage in the first 8 weeks. By the end of Week 12, 396 subjects achieved remission (MADRS <10), 75% of whom were taking vortioxetine, 10 mg/d. These patients were then randomly assigned to placebo or the dosage of vortioxetine to which they had responded, and continued the study for as long as 64 weeks. Time to relapse (MADRS total score ≥22) or an insufficient therapeutic response (as judged by the investigator) was the primary efficacy outcome, and demonstrated that vortioxetine was superior to placebo.

Tolerability

The tolerability of vortioxetine is comparable with other serotonergic antidepressants. In pooled analysis of pre-marketing studies, 5% to 8% of patients receiving vortioxetine (5 to 20 mg/d) discontinued treatment because of adverse effects (AEs), compared with 4% in the placebo group. Nausea was the most commonly reported AE leading to discontinuation and appeared to be dose dependent.

AEs, such as nausea, constipation, and vomiting, most commonly occurred in the first week of treatment, with a median duration of 2 weeks.⁵ In the 6- to 8-week trials, the most common AEs were nausea, constipation, and vomiting. In longer trials (24 to 64 weeks), the most common AE was nausea.

In 6- to 8-week placebo-controlled studies, vortioxetine was not associated with any clinically significant effect on vital signs or laboratory values in hematology, urinalysis, or serum chemistry (except sodium). Hyponatremia, the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), has occurred. The risk of developing SIADH and resultant hyponatremia is greater in geriatric patients and patients taking a diuretic.

Abruptly discontinuing vortioxetine can cause transient withdrawal symptoms, including headache and muscle tension, especially at a higher dosage (15 to 20 mg/d). Gradual tapering can reduce withdrawal symptoms. 

Specific clinical issues

All antidepressants have a “black-box” warning about the potential for clinical worsening and increased suicidality early in treatment. Closely monitor patients for suicidal ideation and behaviors during the first months of treatment and with dosage changes.

Vortioxetine is categorized as pregnancy category C. Newborns exposed to a selective serotonin reuptake inhibitor (SSRI) in pregnancy may have an increased risk of persistent pulmonary hypertension during the neonatal period. When taken during the third trimester of pregnancy, SSRIs and serotonin-norepinephrine reuptake inhibitors can cause serious neonatal complications, including respiratory distress, cyanosis, apnea, and seizures, which may require longer hospitalization, respiratory support, or tube feeding for the infant. Consider risks and benefits of third-trimester use of an antidepressant. It is not known if vortioxetine is present in human breast milk.

Clinical studies on vortioxetine in pediatric patients have not been conducted.

No dosage adjustment is recommended on the basis of age for geriatric patients. No dose adjustment of vortioxetine is necessary on the basis of race, sex, ethnicity, renal function, or mild to moderate hepatic impairment. See Table 3 for practice points when prescribing vortioxetine. See Table 4 for contraindications to vortioxetine.

Dosing

The recommended starting dosage is 10 mg, administered orally once daily without regard to meals. Dosage should then be increased to 20 mg/d, as clinically warranted and tolerated. Consider a dosage decrease to 5 mg/d in patients who do not tolerate higher dosages or require drug adjustment because of drug-drug interaction or poor 2D6 metabolizer status.

Bottom Line

FDA-approved for major depressive disorder in adults, vortioxetine reduced depressive symptoms in 6 positive, double-blind, placebo-controlled, and randomized studies. The multimodal activity of vortioxeine can be a useful alternative to serotonergic antidepressants for some patients who are partial responders or nonresponders. Tolerability is comparable with other serotonergic antidepressants.

Related Resources

• Alam MY, Jacobsen PL, Chen Y, et al. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-label, flexible-dose, 52-week extension study. Int Clin Psychopharmacol. 2014; 29(1):36-44.

• Mahableshwarkar AR, Jacobsen PL, Chen Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin. 2013;29(3):217-226.

Drug Brand Names

Linezolid • Zyvox                             Vortioxetine • Brintellix

Methylene blue • Urolene Blue          Warfarin • Coumadin

Tramadol • Ultram

Disclosure

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

Vortioxetine is FDA-approved to treat major depressive disorder (MDD) (Table 1), having shown efficacy in relieving depressive symptoms in clinical trials.¹ Vortioxetine’s mechanism of action enhances CNS serotonergic activity through inhibiting serotonin (5-HT) reuptake, agonizing the 5-HT1A receptor, partially agonizing the 5-HT1B receptor, and antagonizing the 5-HT3, 5-HT1D, and 5-HT7 receptors.

Clinical implications

It is hypothesized that depression is a heterogeneous disease caused by dysregulation of serotonin, norepinephrine, and dopamine, subsequently producing mood and neurovegetative symptoms of depression. Preclinical, in vivo studies indicate that vortioxetine enhances levels of serotonin, norepinephrine, dopamine, acetylcholine, and histamine in specific areas of the brain with the ability to improve depressive symptoms. Vortioxetine’s multimodal activity can be a useful alternative to other serotonergic antidepressants for some patients who are partial responders or non-responders to other treatment options. In addition, vortioxetine appears to have minimal effect on weight² and sexual function—the latter being dose-dependent.³

How does it work?

Vortioxetine differs from other antidepressants in its multimodal activity (ie, affecting G-protein mode receptors, ion channel mode receptors, and neurotransmitter transporters). It inhibits the serotonin transporter (Ki = 1.6 nM), causing subsequent inhibition of serotonin reuptake into presynaptic neurons as well as selectively acting on the other subtypes of serotonergic receptors; however, activity on the norepinephrine transporter (Ki = 113 nM) and dopamine transporter (Ki > 1000 nM) is minimal. It is believed that mood-regulating effects of vortioxetine are caused by inhibition of serotonin reuptake, prolonged availability of serotonin to the postsynaptic neurons, its agonist activity on the 5-HT1A receptor (Ki = 15 nM), and partial agonist activity on the 5-HT1B receptor (Ki = 33 nM). Vortioxetine has strong affinity for the 5-HT3 receptor (Ki = 3.7 nM), which plays a role in modulation of centrally mediated nausea and vomiting. Positron emission tomography studies in humans determined that the occupancy of 5-HT transporter was 50% at 5 mg/d, 65% at 10 mg/d, and 80% at 20 mg/d.^1,4 Human studies did not show that vortioxetine causes QTc prolongation.  

Pharmacokinetics

Therapeutic activity of vortioxetine is thought to be due to the parent drug. It has a half-life of approximately 66 hours, and achieves steady state in 13.5 to 19 days. Bioavailability of vortioxetine is 75%; absorption does not depend on food; and 98% of drug is bound on plasma proteins.

Vortioxetine has linear pharmacokinetics, with maximum plasma concentration 7 to 11 hours after ingestion. The medication is metabolized primarily by oxidation through cytochrome P (CYP) 450: CYP2D6 (primary), CYP 3A4/5, CYP 2C19, CYP 2C9, CYP2A6, CYP2C8, and CYP2B6 with subsequent glucuronidation. This predisposes vortioxetine to potential pharmacokinetic drug-drug interaction warranting dose adjustment consideration when vortioxetine is coadministered with compounds inhibiting CYP2D6 or inducing CYP3A4 for ≥14 days, or for patients identified as poor 2D6 metabolizers.

In addition, coadministration of vortioxetine with serotonergic medications such as triptans, other antidepressants, and tramadol can cause potentially life-threatening serotonin syndrome, characterized by mental status changes, autonomic instability, neuromuscular aberrations, and GI symptoms. Concomitant use of vortioxetine and a nonsteroidal anti-inflammatory drug, aspirin, or warfarin can result in abnormal bleeding. Coadministration of vortioxetine with another highly protein-bound drug may increase or decrease the free concentration of either drug depending on the binding affinity of the drug for the protein.

Efficacy

Vortioxetine reduced depressive symptoms in 6 positive, 6- to 8-week, double-blind, placebo controlled and randomized studies and 1 maintenance study.¹ Subjects were adults (Studies 1 to 5) and geriatric patients from age 64 to 88 who had ≥1 depressive episode before age 60 (Study 6). All met DSM-IV-TR criteria for MDD. Subjects with cognitive impairment scoring <24 on the Mini-Mental Status Examination and children were excluded. Depending on the study, response to the treatment was primarily measured on the Montgomery-Åsberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D).

See Table 2 for a description of the positive studies, including dosages. In all studies, vortioxetine was superior to placebo at least one dosage for treating depression. In the 6- to 8-week placebo-controlled studies, an effect of vortioxetine based on the primary efficacy measure was generally observed starting at Week 2; that effect increased in subsequent weeks with the full antidepressant effect of vortioxetine generally not seen until study Week 4 or later.¹

The maintenance treatment study included 639 patients who met DSM-IV-TR criteria for MDD. This study lasted for as long as 64 weeks. The first 12-week period was open-label, during which patients were treated with vortioxetine, 5 mg/d or 10 mg/d, with a possibility to adjust the dosage in the first 8 weeks. By the end of Week 12, 396 subjects achieved remission (MADRS <10), 75% of whom were taking vortioxetine, 10 mg/d. These patients were then randomly assigned to placebo or the dosage of vortioxetine to which they had responded, and continued the study for as long as 64 weeks. Time to relapse (MADRS total score ≥22) or an insufficient therapeutic response (as judged by the investigator) was the primary efficacy outcome, and demonstrated that vortioxetine was superior to placebo.

Tolerability

The tolerability of vortioxetine is comparable with other serotonergic antidepressants. In pooled analysis of pre-marketing studies, 5% to 8% of patients receiving vortioxetine (5 to 20 mg/d) discontinued treatment because of adverse effects (AEs), compared with 4% in the placebo group. Nausea was the most commonly reported AE leading to discontinuation and appeared to be dose dependent.

AEs, such as nausea, constipation, and vomiting, most commonly occurred in the first week of treatment, with a median duration of 2 weeks.⁵ In the 6- to 8-week trials, the most common AEs were nausea, constipation, and vomiting. In longer trials (24 to 64 weeks), the most common AE was nausea.

In 6- to 8-week placebo-controlled studies, vortioxetine was not associated with any clinically significant effect on vital signs or laboratory values in hematology, urinalysis, or serum chemistry (except sodium). Hyponatremia, the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), has occurred. The risk of developing SIADH and resultant hyponatremia is greater in geriatric patients and patients taking a diuretic.

Abruptly discontinuing vortioxetine can cause transient withdrawal symptoms, including headache and muscle tension, especially at a higher dosage (15 to 20 mg/d). Gradual tapering can reduce withdrawal symptoms. 

Specific clinical issues

All antidepressants have a “black-box” warning about the potential for clinical worsening and increased suicidality early in treatment. Closely monitor patients for suicidal ideation and behaviors during the first months of treatment and with dosage changes.

Vortioxetine is categorized as pregnancy category C. Newborns exposed to a selective serotonin reuptake inhibitor (SSRI) in pregnancy may have an increased risk of persistent pulmonary hypertension during the neonatal period. When taken during the third trimester of pregnancy, SSRIs and serotonin-norepinephrine reuptake inhibitors can cause serious neonatal complications, including respiratory distress, cyanosis, apnea, and seizures, which may require longer hospitalization, respiratory support, or tube feeding for the infant. Consider risks and benefits of third-trimester use of an antidepressant. It is not known if vortioxetine is present in human breast milk.

Clinical studies on vortioxetine in pediatric patients have not been conducted.

No dosage adjustment is recommended on the basis of age for geriatric patients. No dose adjustment of vortioxetine is necessary on the basis of race, sex, ethnicity, renal function, or mild to moderate hepatic impairment. See Table 3 for practice points when prescribing vortioxetine. See Table 4 for contraindications to vortioxetine.

Dosing

The recommended starting dosage is 10 mg, administered orally once daily without regard to meals. Dosage should then be increased to 20 mg/d, as clinically warranted and tolerated. Consider a dosage decrease to 5 mg/d in patients who do not tolerate higher dosages or require drug adjustment because of drug-drug interaction or poor 2D6 metabolizer status.

Bottom Line

FDA-approved for major depressive disorder in adults, vortioxetine reduced depressive symptoms in 6 positive, double-blind, placebo-controlled, and randomized studies. The multimodal activity of vortioxeine can be a useful alternative to serotonergic antidepressants for some patients who are partial responders or nonresponders. Tolerability is comparable with other serotonergic antidepressants.

Related Resources

• Alam MY, Jacobsen PL, Chen Y, et al. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-label, flexible-dose, 52-week extension study. Int Clin Psychopharmacol. 2014; 29(1):36-44.

• Mahableshwarkar AR, Jacobsen PL, Chen Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin. 2013;29(3):217-226.

Drug Brand Names

Linezolid • Zyvox                             Vortioxetine • Brintellix

Methylene blue • Urolene Blue          Warfarin • Coumadin

Tramadol • Ultram

Disclosure

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

Vortioxetine is FDA-approved to treat major depressive disorder (MDD) (Table 1), having shown efficacy in relieving depressive symptoms in clinical trials.¹ Vortioxetine’s mechanism of action enhances CNS serotonergic activity through inhibiting serotonin (5-HT) reuptake, agonizing the 5-HT1A receptor, partially agonizing the 5-HT1B receptor, and antagonizing the 5-HT3, 5-HT1D, and 5-HT7 receptors.

Clinical implications

It is hypothesized that depression is a heterogeneous disease caused by dysregulation of serotonin, norepinephrine, and dopamine, subsequently producing mood and neurovegetative symptoms of depression. Preclinical, in vivo studies indicate that vortioxetine enhances levels of serotonin, norepinephrine, dopamine, acetylcholine, and histamine in specific areas of the brain with the ability to improve depressive symptoms. Vortioxetine’s multimodal activity can be a useful alternative to other serotonergic antidepressants for some patients who are partial responders or non-responders to other treatment options. In addition, vortioxetine appears to have minimal effect on weight² and sexual function—the latter being dose-dependent.³

How does it work?

Vortioxetine differs from other antidepressants in its multimodal activity (ie, affecting G-protein mode receptors, ion channel mode receptors, and neurotransmitter transporters). It inhibits the serotonin transporter (Ki = 1.6 nM), causing subsequent inhibition of serotonin reuptake into presynaptic neurons as well as selectively acting on the other subtypes of serotonergic receptors; however, activity on the norepinephrine transporter (Ki = 113 nM) and dopamine transporter (Ki > 1000 nM) is minimal. It is believed that mood-regulating effects of vortioxetine are caused by inhibition of serotonin reuptake, prolonged availability of serotonin to the postsynaptic neurons, its agonist activity on the 5-HT1A receptor (Ki = 15 nM), and partial agonist activity on the 5-HT1B receptor (Ki = 33 nM). Vortioxetine has strong affinity for the 5-HT3 receptor (Ki = 3.7 nM), which plays a role in modulation of centrally mediated nausea and vomiting. Positron emission tomography studies in humans determined that the occupancy of 5-HT transporter was 50% at 5 mg/d, 65% at 10 mg/d, and 80% at 20 mg/d.^1,4 Human studies did not show that vortioxetine causes QTc prolongation.  

Pharmacokinetics

Therapeutic activity of vortioxetine is thought to be due to the parent drug. It has a half-life of approximately 66 hours, and achieves steady state in 13.5 to 19 days. Bioavailability of vortioxetine is 75%; absorption does not depend on food; and 98% of drug is bound on plasma proteins.

Vortioxetine has linear pharmacokinetics, with maximum plasma concentration 7 to 11 hours after ingestion. The medication is metabolized primarily by oxidation through cytochrome P (CYP) 450: CYP2D6 (primary), CYP 3A4/5, CYP 2C19, CYP 2C9, CYP2A6, CYP2C8, and CYP2B6 with subsequent glucuronidation. This predisposes vortioxetine to potential pharmacokinetic drug-drug interaction warranting dose adjustment consideration when vortioxetine is coadministered with compounds inhibiting CYP2D6 or inducing CYP3A4 for ≥14 days, or for patients identified as poor 2D6 metabolizers.

In addition, coadministration of vortioxetine with serotonergic medications such as triptans, other antidepressants, and tramadol can cause potentially life-threatening serotonin syndrome, characterized by mental status changes, autonomic instability, neuromuscular aberrations, and GI symptoms. Concomitant use of vortioxetine and a nonsteroidal anti-inflammatory drug, aspirin, or warfarin can result in abnormal bleeding. Coadministration of vortioxetine with another highly protein-bound drug may increase or decrease the free concentration of either drug depending on the binding affinity of the drug for the protein.

Efficacy

Vortioxetine reduced depressive symptoms in 6 positive, 6- to 8-week, double-blind, placebo controlled and randomized studies and 1 maintenance study.¹ Subjects were adults (Studies 1 to 5) and geriatric patients from age 64 to 88 who had ≥1 depressive episode before age 60 (Study 6). All met DSM-IV-TR criteria for MDD. Subjects with cognitive impairment scoring <24 on the Mini-Mental Status Examination and children were excluded. Depending on the study, response to the treatment was primarily measured on the Montgomery-Åsberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D).

See Table 2 for a description of the positive studies, including dosages. In all studies, vortioxetine was superior to placebo at least one dosage for treating depression. In the 6- to 8-week placebo-controlled studies, an effect of vortioxetine based on the primary efficacy measure was generally observed starting at Week 2; that effect increased in subsequent weeks with the full antidepressant effect of vortioxetine generally not seen until study Week 4 or later.¹

The maintenance treatment study included 639 patients who met DSM-IV-TR criteria for MDD. This study lasted for as long as 64 weeks. The first 12-week period was open-label, during which patients were treated with vortioxetine, 5 mg/d or 10 mg/d, with a possibility to adjust the dosage in the first 8 weeks. By the end of Week 12, 396 subjects achieved remission (MADRS <10), 75% of whom were taking vortioxetine, 10 mg/d. These patients were then randomly assigned to placebo or the dosage of vortioxetine to which they had responded, and continued the study for as long as 64 weeks. Time to relapse (MADRS total score ≥22) or an insufficient therapeutic response (as judged by the investigator) was the primary efficacy outcome, and demonstrated that vortioxetine was superior to placebo.

Tolerability

The tolerability of vortioxetine is comparable with other serotonergic antidepressants. In pooled analysis of pre-marketing studies, 5% to 8% of patients receiving vortioxetine (5 to 20 mg/d) discontinued treatment because of adverse effects (AEs), compared with 4% in the placebo group. Nausea was the most commonly reported AE leading to discontinuation and appeared to be dose dependent.

AEs, such as nausea, constipation, and vomiting, most commonly occurred in the first week of treatment, with a median duration of 2 weeks.⁵ In the 6- to 8-week trials, the most common AEs were nausea, constipation, and vomiting. In longer trials (24 to 64 weeks), the most common AE was nausea.

In 6- to 8-week placebo-controlled studies, vortioxetine was not associated with any clinically significant effect on vital signs or laboratory values in hematology, urinalysis, or serum chemistry (except sodium). Hyponatremia, the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), has occurred. The risk of developing SIADH and resultant hyponatremia is greater in geriatric patients and patients taking a diuretic.

Abruptly discontinuing vortioxetine can cause transient withdrawal symptoms, including headache and muscle tension, especially at a higher dosage (15 to 20 mg/d). Gradual tapering can reduce withdrawal symptoms. 

Specific clinical issues

All antidepressants have a “black-box” warning about the potential for clinical worsening and increased suicidality early in treatment. Closely monitor patients for suicidal ideation and behaviors during the first months of treatment and with dosage changes.

Vortioxetine is categorized as pregnancy category C. Newborns exposed to a selective serotonin reuptake inhibitor (SSRI) in pregnancy may have an increased risk of persistent pulmonary hypertension during the neonatal period. When taken during the third trimester of pregnancy, SSRIs and serotonin-norepinephrine reuptake inhibitors can cause serious neonatal complications, including respiratory distress, cyanosis, apnea, and seizures, which may require longer hospitalization, respiratory support, or tube feeding for the infant. Consider risks and benefits of third-trimester use of an antidepressant. It is not known if vortioxetine is present in human breast milk.

Clinical studies on vortioxetine in pediatric patients have not been conducted.

No dosage adjustment is recommended on the basis of age for geriatric patients. No dose adjustment of vortioxetine is necessary on the basis of race, sex, ethnicity, renal function, or mild to moderate hepatic impairment. See Table 3 for practice points when prescribing vortioxetine. See Table 4 for contraindications to vortioxetine.

Dosing

The recommended starting dosage is 10 mg, administered orally once daily without regard to meals. Dosage should then be increased to 20 mg/d, as clinically warranted and tolerated. Consider a dosage decrease to 5 mg/d in patients who do not tolerate higher dosages or require drug adjustment because of drug-drug interaction or poor 2D6 metabolizer status.

Bottom Line

FDA-approved for major depressive disorder in adults, vortioxetine reduced depressive symptoms in 6 positive, double-blind, placebo-controlled, and randomized studies. The multimodal activity of vortioxeine can be a useful alternative to serotonergic antidepressants for some patients who are partial responders or nonresponders. Tolerability is comparable with other serotonergic antidepressants.

Related Resources

• Alam MY, Jacobsen PL, Chen Y, et al. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-label, flexible-dose, 52-week extension study. Int Clin Psychopharmacol. 2014; 29(1):36-44.

• Mahableshwarkar AR, Jacobsen PL, Chen Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin. 2013;29(3):217-226.

Drug Brand Names

Linezolid • Zyvox                             Vortioxetine • Brintellix

Methylene blue • Urolene Blue          Warfarin • Coumadin

Tramadol • Ultram

Disclosure

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

Estimates are that 50 to 70 million Americans suffer from a chronic disorder of sleep and wakefulness, hindering daily functioning and affecting health.¹ Psychiatric illness is common among people who have a sleep disorder. The relationship between psychiatric illness and sleep disorders is bidirectional: People with mental illness often have sleep complaints, and a primary sleep disorder often results in neuropsychiatric complications.

What is obstructive sleep apnea?

The most common type of sleep-disordered breathing, obstructive sleep apnea (OSA) is characterized by frequent cessations of breathing during sleep because of an obstruction of the upper airway. The obstruction occurs secondary to inadequate motor tone of the tongue or airway dilator muscles, or both.¹ In addition, many people with OSA have central apneic episodes, in which breathing stops temporarily without airway blockage or respiratory effort.²

The prevalence of OSA is growing as obesity in the United States increases. Risk factors for OSA include obesity, a craniofacial abnormality, an upper-airway abnormality, heredity, smoking, and nasal congestion. OSA plays a role in causing and exacerbating medical illness in people with severe and persistent mental illness, contributing to a significantly shortened life span. Attending to the general health of people who suffer from severe mental illness—including effective treatment of illnesses such as OSA—is crucial.³

Clinical features of OSA

OSA is characterized by hypopnea (a decrease in breathing during sleep) or apnea (an actual pause in breathing). Pauses in breathing during sleep of at least 10 seconds, with obstruction of oronasal airflow despite continuous chest and abdominal movements, are referred to as obstructive apneas. These pauses are associated with a decrease in oxygen saturation or arousal from sleep, or both.¹

Primary features of OSA include sleep fragmentation accompanied by nocturnal hypoxemia and hypercapnia, with resulting excessive daytime sleepiness, mood problems, and poor neurocognitive performance (Table 1). OSA often causes potentially serious organ system dysfunction, including adverse cardiovascular and metabolic effects. Studies have suggested that executive dysfunction can be a feature of OSA, which is thought to be related to prefrontal lobe dysfunction caused by intermittent hypoxia. All of these conditions can contribute significantly to decreased quality of life.¹

The prevalence of OSA in the general population is approximately 20% when the condition is defined as an apnea-hypopnea index >5 events an hour. The index is the number of apnea and hypopnea episodes that occur during 1 hour of sleep.⁴

OSA and psychiatric illness

Psychiatric disorders often are comorbid with OSA. These include depression, anxiety, bipolar disorder, schizophrenia, posttraumatic stress disorder (PTSD), panic disorder, and substance use disorder.

Depression. Several studies have documented that OSA and depressive disorder often are comorbid. Many symptoms are common to both, including fatigue, daytime sleepiness, poor concentration, irritability, and weight gain (Figure), although some core symptoms of depression (eg, sadness, anhedonia, guilt, and agitation) are clearly distinguishable from symptoms of OSA. The current recommendation is that a mood disorder should be considered secondary to OSA, and treated accordingly.⁵

Anxiety. OSA also has been linked to anxiety and nocturnal panic attacks. Frequent awakening due to choking from breathing cessation might play a role in the development of anxiety in patients with OSA, although the association is unproven. Studies have shown a correlation between anxiety disorders and excessive daytime sleepiness, one of the core symptoms of OSA.⁶ OSA is highly prevalent among combat veterans who have PTSD and complain of being overly vigilant at night; experiencing nightmares and frequent awakening; and having non-restorative sleep.⁷ Anecdotal reports suggest an association between OSA and bipolar disorder: namely, that continuous positive airway pressure (CPAP) treatment (see “How is OSA treated?,” below) might switch depressed patients to mania.⁸

Schizophrenia. A strong association exists between OSA and schizophrenia. In a study,⁹ an OSA diagnosis was made 6 times more often in patients with schizophrenia than in patients with other psychiatric illnesses. Obesity, male sex, and chronic antipsychotic administration were risk factors for OSA in patients with
schizophrenia.⁹ OSA might be underdiagnosed in patients with schizophrenia because excessive daytime sleepiness, the most common daytime symptom of OSA, can be misattributed as a negative symptom of the disease or a side effect of pharmacotherapy.

OSA and medical illness

OSA can be comorbid with several medical conditions (Table 2). Sleep research in the past 15 years has demonstrated that chronic sleep deprivation has multiple untoward health consequences apart from excessive daytime sleepiness.¹⁰ Recent research suggests that chronic sleep loss (<7 hours a night), including sleep loss secondary to OSA, has wide-ranging effects on the cardiovascular, endocrine, immune, and nervous systems, including:

• obesity (adults and children)

• diabetes mellitus and impaired glucose tolerance

• cardiovascular disease and hypertension.

Obesity is one of the primary and more modifiable risk factors for OSA (Box). Studies suggest that reducing the severity of obesity would likely benefit people with a sleep disorder, and that treating sleep deprivation and sleep disorders might benefit persons with obesity.¹² Chronic sleep loss can have a deleterious influence on appetite regulation through effects on 2 hormones, leptin and ghrelin, that play a major role in appetite regulation. Chronic sleep loss causes and perpetuates obesity through its interplay with these, and other, hormones.¹²

Diabetes. The link between obesity and diabetes is well-established, as is the long-term morbidity and mortality of these 2 diseases.¹³ Evidence shows that OSA is associated with impaired glucose tolerance and an increased risk of diabetes.¹⁴

Cardiovascular disease. OSA has a strong association with cardiovascular disease, including systemic hypertension, possibly myocardial infarction, congestive heart failure, and stroke.¹⁵ Institution of appropriate treatment for OSA including CPAP can minimize or reverse many of these effects.¹⁶

Making an OSA diagnosis

A diagnostic polysomnogram (PSG), or sleep study, is the standard test when OSA is suspected. It is performed most often at an attended sleep laboratory. Typically, a PSG measures several physiologic measures, including, but not limited to:

•  airflow through mouth and nose

•  stages of sleep (by means of electroencephalography channels)

•  thoracic and abdominal movements (to assess effort of breathing)

•  muscle activity of the chin

•  oxyhemoglobin saturation (to monitor variability in oxygen saturation [SaO₂] during OSA events).

Portable diagnostic instruments can provide reliable information when a patient cannot be studied in a laboratory. Assessments available on portable instruments include cardiopulmonary monitoring of respiration only; PSG; and peripheral arterial tonometry, which measures autonomic manifestations of respiratory obstructive events.^17,18

The severity of OSA is established by the apnea/hypopnea index, which measures the number of apneas and hypopneas per hour of sleep.

How is OSA treated?

CPAP is still the gold standard for treating OSA. CPAP provides a pneumatic splint for the upper airway by administering positive pressure through a nasal or oronasal mask. CPAP distinctly improves daytime sleepiness.^19,20

Pressure is determined initially by titration during PSG, although a number of automated CPAP machines are available in which pressure is adjusted based on the machine’s response to airflow obstruction. Advantages of using PSG to titrate CPAP are direct observation to control mask leak and the ability to observe the effects of body position and sleep stage and clearly distinguish periods of sleep from wakefulness.

Regrettably, adherence to a nightly regimen of CPAP is less than ideal for several reasons, including claustrophobia, interface failure, and other motivational variables. Some patients who experience claustrophobia can use desensitization techniques; others are, ultimately, unable to use the mask.

Oral appliances. A patient who has mild or moderate OSA but who cannot use the CPAP mask might be a good candidate for an oral appliance. These appliances, which hold the mandible in an advanced position during the night, can be effective in such cases.

CPAP autotitration changes the treatment pressure based on feedback from such patient measures as airflow and airway resistance. Autotitrating devices might have a role in beginning treatment in patients with OSA by means of a portable sleep study, in which CPAP titration is not performed. In addition, autotitrating offers the possibility of changing pressure over time—such as with changes in position during the night or over the longer term in response to weight loss or gain.

Surgery. In patients who are unable to use CPAP, surgery might be indicated to relieve an anatomical obstruction, such as adenotonsillar hypertrophy or other type of mass lesion.

Sleep positioning. A patient who demonstrates OSA exclusively while sleeping supine might benefit from being trained to sleep on either side only or arranging pillows so that he can only sleep on his side.

In conclusion

OSA is common and easily treatable. It coexists with, and exacerbates, medical and psychiatric illness. Treating OSA concomitantly with comorbid medical and psychiatric illness is essential to achieve full symptom remission and prevent associated long-term consequences of both medical and psychiatric illness.

BOTTOM LINE

Obstructive sleep apnea (OSA) and psychiatric illness, especially depression, often co-exist. Screen depressed patients—especially those with risk factors for OSA, such as obesity, smoking, and an upper-airway abnormality—for a sleep disorder. This is especially important if a patient complains of daytime somnolence, fatigue, cognitive problems, poor concentration, or weight gain. For optimal results, treat comorbid psychiatric illness and OSA concurrently; the same is true for other sleep disorders.

Related Resources

• Babson KA, Del Re AC, Bonn-Miller MO, et al. The comorbidity of sleep apnea and mood, anxiety, and substance use disorders among obese military veterans within the Veterans Health Administration. J Clin Sleep Med. 2013; 9(12):1253-1258.

• Karkoulias K, Lykouras D, Sampsonas F, et al. The impact of obstructive sleep apnea syndrome severity on physical performance and mental health. The use of SF-36 questionnaire in sleep apnea. Eur Rev Med Pharmacol Sci. 2013;17(4):531-536.

Disclosures

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

Acknowledgment

Dr. Muhammad Awais Aftab, psychiatry resident at Hamad Medical Corporation, Doha, Qatar, and Umair Amin, final year MBBS student at King Edward Medical University, Lahore, Pakistan, assisted with development of the manuscript of this article.

Estimates are that 50 to 70 million Americans suffer from a chronic disorder of sleep and wakefulness, hindering daily functioning and affecting health.¹ Psychiatric illness is common among people who have a sleep disorder. The relationship between psychiatric illness and sleep disorders is bidirectional: People with mental illness often have sleep complaints, and a primary sleep disorder often results in neuropsychiatric complications.

What is obstructive sleep apnea?

The most common type of sleep-disordered breathing, obstructive sleep apnea (OSA) is characterized by frequent cessations of breathing during sleep because of an obstruction of the upper airway. The obstruction occurs secondary to inadequate motor tone of the tongue or airway dilator muscles, or both.¹ In addition, many people with OSA have central apneic episodes, in which breathing stops temporarily without airway blockage or respiratory effort.²

The prevalence of OSA is growing as obesity in the United States increases. Risk factors for OSA include obesity, a craniofacial abnormality, an upper-airway abnormality, heredity, smoking, and nasal congestion. OSA plays a role in causing and exacerbating medical illness in people with severe and persistent mental illness, contributing to a significantly shortened life span. Attending to the general health of people who suffer from severe mental illness—including effective treatment of illnesses such as OSA—is crucial.³

Clinical features of OSA

OSA is characterized by hypopnea (a decrease in breathing during sleep) or apnea (an actual pause in breathing). Pauses in breathing during sleep of at least 10 seconds, with obstruction of oronasal airflow despite continuous chest and abdominal movements, are referred to as obstructive apneas. These pauses are associated with a decrease in oxygen saturation or arousal from sleep, or both.¹

Primary features of OSA include sleep fragmentation accompanied by nocturnal hypoxemia and hypercapnia, with resulting excessive daytime sleepiness, mood problems, and poor neurocognitive performance (Table 1). OSA often causes potentially serious organ system dysfunction, including adverse cardiovascular and metabolic effects. Studies have suggested that executive dysfunction can be a feature of OSA, which is thought to be related to prefrontal lobe dysfunction caused by intermittent hypoxia. All of these conditions can contribute significantly to decreased quality of life.¹

The prevalence of OSA in the general population is approximately 20% when the condition is defined as an apnea-hypopnea index >5 events an hour. The index is the number of apnea and hypopnea episodes that occur during 1 hour of sleep.⁴

OSA and psychiatric illness

Psychiatric disorders often are comorbid with OSA. These include depression, anxiety, bipolar disorder, schizophrenia, posttraumatic stress disorder (PTSD), panic disorder, and substance use disorder.

Depression. Several studies have documented that OSA and depressive disorder often are comorbid. Many symptoms are common to both, including fatigue, daytime sleepiness, poor concentration, irritability, and weight gain (Figure), although some core symptoms of depression (eg, sadness, anhedonia, guilt, and agitation) are clearly distinguishable from symptoms of OSA. The current recommendation is that a mood disorder should be considered secondary to OSA, and treated accordingly.⁵

Anxiety. OSA also has been linked to anxiety and nocturnal panic attacks. Frequent awakening due to choking from breathing cessation might play a role in the development of anxiety in patients with OSA, although the association is unproven. Studies have shown a correlation between anxiety disorders and excessive daytime sleepiness, one of the core symptoms of OSA.⁶ OSA is highly prevalent among combat veterans who have PTSD and complain of being overly vigilant at night; experiencing nightmares and frequent awakening; and having non-restorative sleep.⁷ Anecdotal reports suggest an association between OSA and bipolar disorder: namely, that continuous positive airway pressure (CPAP) treatment (see “How is OSA treated?,” below) might switch depressed patients to mania.⁸

Schizophrenia. A strong association exists between OSA and schizophrenia. In a study,⁹ an OSA diagnosis was made 6 times more often in patients with schizophrenia than in patients with other psychiatric illnesses. Obesity, male sex, and chronic antipsychotic administration were risk factors for OSA in patients with
schizophrenia.⁹ OSA might be underdiagnosed in patients with schizophrenia because excessive daytime sleepiness, the most common daytime symptom of OSA, can be misattributed as a negative symptom of the disease or a side effect of pharmacotherapy.

OSA and medical illness

OSA can be comorbid with several medical conditions (Table 2). Sleep research in the past 15 years has demonstrated that chronic sleep deprivation has multiple untoward health consequences apart from excessive daytime sleepiness.¹⁰ Recent research suggests that chronic sleep loss (<7 hours a night), including sleep loss secondary to OSA, has wide-ranging effects on the cardiovascular, endocrine, immune, and nervous systems, including:

• obesity (adults and children)

• diabetes mellitus and impaired glucose tolerance

• cardiovascular disease and hypertension.

Obesity is one of the primary and more modifiable risk factors for OSA (Box). Studies suggest that reducing the severity of obesity would likely benefit people with a sleep disorder, and that treating sleep deprivation and sleep disorders might benefit persons with obesity.¹² Chronic sleep loss can have a deleterious influence on appetite regulation through effects on 2 hormones, leptin and ghrelin, that play a major role in appetite regulation. Chronic sleep loss causes and perpetuates obesity through its interplay with these, and other, hormones.¹²

Diabetes. The link between obesity and diabetes is well-established, as is the long-term morbidity and mortality of these 2 diseases.¹³ Evidence shows that OSA is associated with impaired glucose tolerance and an increased risk of diabetes.¹⁴

Cardiovascular disease. OSA has a strong association with cardiovascular disease, including systemic hypertension, possibly myocardial infarction, congestive heart failure, and stroke.¹⁵ Institution of appropriate treatment for OSA including CPAP can minimize or reverse many of these effects.¹⁶

Making an OSA diagnosis

A diagnostic polysomnogram (PSG), or sleep study, is the standard test when OSA is suspected. It is performed most often at an attended sleep laboratory. Typically, a PSG measures several physiologic measures, including, but not limited to:

•  airflow through mouth and nose

•  stages of sleep (by means of electroencephalography channels)

•  thoracic and abdominal movements (to assess effort of breathing)

•  muscle activity of the chin

•  oxyhemoglobin saturation (to monitor variability in oxygen saturation [SaO₂] during OSA events).

Portable diagnostic instruments can provide reliable information when a patient cannot be studied in a laboratory. Assessments available on portable instruments include cardiopulmonary monitoring of respiration only; PSG; and peripheral arterial tonometry, which measures autonomic manifestations of respiratory obstructive events.^17,18

The severity of OSA is established by the apnea/hypopnea index, which measures the number of apneas and hypopneas per hour of sleep.

How is OSA treated?

CPAP is still the gold standard for treating OSA. CPAP provides a pneumatic splint for the upper airway by administering positive pressure through a nasal or oronasal mask. CPAP distinctly improves daytime sleepiness.^19,20

Pressure is determined initially by titration during PSG, although a number of automated CPAP machines are available in which pressure is adjusted based on the machine’s response to airflow obstruction. Advantages of using PSG to titrate CPAP are direct observation to control mask leak and the ability to observe the effects of body position and sleep stage and clearly distinguish periods of sleep from wakefulness.

Regrettably, adherence to a nightly regimen of CPAP is less than ideal for several reasons, including claustrophobia, interface failure, and other motivational variables. Some patients who experience claustrophobia can use desensitization techniques; others are, ultimately, unable to use the mask.

Oral appliances. A patient who has mild or moderate OSA but who cannot use the CPAP mask might be a good candidate for an oral appliance. These appliances, which hold the mandible in an advanced position during the night, can be effective in such cases.

CPAP autotitration changes the treatment pressure based on feedback from such patient measures as airflow and airway resistance. Autotitrating devices might have a role in beginning treatment in patients with OSA by means of a portable sleep study, in which CPAP titration is not performed. In addition, autotitrating offers the possibility of changing pressure over time—such as with changes in position during the night or over the longer term in response to weight loss or gain.

Surgery. In patients who are unable to use CPAP, surgery might be indicated to relieve an anatomical obstruction, such as adenotonsillar hypertrophy or other type of mass lesion.

Sleep positioning. A patient who demonstrates OSA exclusively while sleeping supine might benefit from being trained to sleep on either side only or arranging pillows so that he can only sleep on his side.

In conclusion

OSA is common and easily treatable. It coexists with, and exacerbates, medical and psychiatric illness. Treating OSA concomitantly with comorbid medical and psychiatric illness is essential to achieve full symptom remission and prevent associated long-term consequences of both medical and psychiatric illness.

BOTTOM LINE

Obstructive sleep apnea (OSA) and psychiatric illness, especially depression, often co-exist. Screen depressed patients—especially those with risk factors for OSA, such as obesity, smoking, and an upper-airway abnormality—for a sleep disorder. This is especially important if a patient complains of daytime somnolence, fatigue, cognitive problems, poor concentration, or weight gain. For optimal results, treat comorbid psychiatric illness and OSA concurrently; the same is true for other sleep disorders.

Related Resources

• Babson KA, Del Re AC, Bonn-Miller MO, et al. The comorbidity of sleep apnea and mood, anxiety, and substance use disorders among obese military veterans within the Veterans Health Administration. J Clin Sleep Med. 2013; 9(12):1253-1258.

• Karkoulias K, Lykouras D, Sampsonas F, et al. The impact of obstructive sleep apnea syndrome severity on physical performance and mental health. The use of SF-36 questionnaire in sleep apnea. Eur Rev Med Pharmacol Sci. 2013;17(4):531-536.

Disclosures

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

Acknowledgment

Dr. Muhammad Awais Aftab, psychiatry resident at Hamad Medical Corporation, Doha, Qatar, and Umair Amin, final year MBBS student at King Edward Medical University, Lahore, Pakistan, assisted with development of the manuscript of this article.

Estimates are that 50 to 70 million Americans suffer from a chronic disorder of sleep and wakefulness, hindering daily functioning and affecting health.¹ Psychiatric illness is common among people who have a sleep disorder. The relationship between psychiatric illness and sleep disorders is bidirectional: People with mental illness often have sleep complaints, and a primary sleep disorder often results in neuropsychiatric complications.

What is obstructive sleep apnea?

The most common type of sleep-disordered breathing, obstructive sleep apnea (OSA) is characterized by frequent cessations of breathing during sleep because of an obstruction of the upper airway. The obstruction occurs secondary to inadequate motor tone of the tongue or airway dilator muscles, or both.¹ In addition, many people with OSA have central apneic episodes, in which breathing stops temporarily without airway blockage or respiratory effort.²

The prevalence of OSA is growing as obesity in the United States increases. Risk factors for OSA include obesity, a craniofacial abnormality, an upper-airway abnormality, heredity, smoking, and nasal congestion. OSA plays a role in causing and exacerbating medical illness in people with severe and persistent mental illness, contributing to a significantly shortened life span. Attending to the general health of people who suffer from severe mental illness—including effective treatment of illnesses such as OSA—is crucial.³

Clinical features of OSA

OSA is characterized by hypopnea (a decrease in breathing during sleep) or apnea (an actual pause in breathing). Pauses in breathing during sleep of at least 10 seconds, with obstruction of oronasal airflow despite continuous chest and abdominal movements, are referred to as obstructive apneas. These pauses are associated with a decrease in oxygen saturation or arousal from sleep, or both.¹

Primary features of OSA include sleep fragmentation accompanied by nocturnal hypoxemia and hypercapnia, with resulting excessive daytime sleepiness, mood problems, and poor neurocognitive performance (Table 1). OSA often causes potentially serious organ system dysfunction, including adverse cardiovascular and metabolic effects. Studies have suggested that executive dysfunction can be a feature of OSA, which is thought to be related to prefrontal lobe dysfunction caused by intermittent hypoxia. All of these conditions can contribute significantly to decreased quality of life.¹

The prevalence of OSA in the general population is approximately 20% when the condition is defined as an apnea-hypopnea index >5 events an hour. The index is the number of apnea and hypopnea episodes that occur during 1 hour of sleep.⁴

OSA and psychiatric illness

Psychiatric disorders often are comorbid with OSA. These include depression, anxiety, bipolar disorder, schizophrenia, posttraumatic stress disorder (PTSD), panic disorder, and substance use disorder.

Depression. Several studies have documented that OSA and depressive disorder often are comorbid. Many symptoms are common to both, including fatigue, daytime sleepiness, poor concentration, irritability, and weight gain (Figure), although some core symptoms of depression (eg, sadness, anhedonia, guilt, and agitation) are clearly distinguishable from symptoms of OSA. The current recommendation is that a mood disorder should be considered secondary to OSA, and treated accordingly.⁵

Anxiety. OSA also has been linked to anxiety and nocturnal panic attacks. Frequent awakening due to choking from breathing cessation might play a role in the development of anxiety in patients with OSA, although the association is unproven. Studies have shown a correlation between anxiety disorders and excessive daytime sleepiness, one of the core symptoms of OSA.⁶ OSA is highly prevalent among combat veterans who have PTSD and complain of being overly vigilant at night; experiencing nightmares and frequent awakening; and having non-restorative sleep.⁷ Anecdotal reports suggest an association between OSA and bipolar disorder: namely, that continuous positive airway pressure (CPAP) treatment (see “How is OSA treated?,” below) might switch depressed patients to mania.⁸

Schizophrenia. A strong association exists between OSA and schizophrenia. In a study,⁹ an OSA diagnosis was made 6 times more often in patients with schizophrenia than in patients with other psychiatric illnesses. Obesity, male sex, and chronic antipsychotic administration were risk factors for OSA in patients with
schizophrenia.⁹ OSA might be underdiagnosed in patients with schizophrenia because excessive daytime sleepiness, the most common daytime symptom of OSA, can be misattributed as a negative symptom of the disease or a side effect of pharmacotherapy.

OSA and medical illness

OSA can be comorbid with several medical conditions (Table 2). Sleep research in the past 15 years has demonstrated that chronic sleep deprivation has multiple untoward health consequences apart from excessive daytime sleepiness.¹⁰ Recent research suggests that chronic sleep loss (<7 hours a night), including sleep loss secondary to OSA, has wide-ranging effects on the cardiovascular, endocrine, immune, and nervous systems, including:

• obesity (adults and children)

• diabetes mellitus and impaired glucose tolerance

• cardiovascular disease and hypertension.

Obesity is one of the primary and more modifiable risk factors for OSA (Box). Studies suggest that reducing the severity of obesity would likely benefit people with a sleep disorder, and that treating sleep deprivation and sleep disorders might benefit persons with obesity.¹² Chronic sleep loss can have a deleterious influence on appetite regulation through effects on 2 hormones, leptin and ghrelin, that play a major role in appetite regulation. Chronic sleep loss causes and perpetuates obesity through its interplay with these, and other, hormones.¹²

Diabetes. The link between obesity and diabetes is well-established, as is the long-term morbidity and mortality of these 2 diseases.¹³ Evidence shows that OSA is associated with impaired glucose tolerance and an increased risk of diabetes.¹⁴

Cardiovascular disease. OSA has a strong association with cardiovascular disease, including systemic hypertension, possibly myocardial infarction, congestive heart failure, and stroke.¹⁵ Institution of appropriate treatment for OSA including CPAP can minimize or reverse many of these effects.¹⁶

Making an OSA diagnosis

A diagnostic polysomnogram (PSG), or sleep study, is the standard test when OSA is suspected. It is performed most often at an attended sleep laboratory. Typically, a PSG measures several physiologic measures, including, but not limited to:

•  airflow through mouth and nose

•  stages of sleep (by means of electroencephalography channels)

•  thoracic and abdominal movements (to assess effort of breathing)

•  muscle activity of the chin

•  oxyhemoglobin saturation (to monitor variability in oxygen saturation [SaO₂] during OSA events).

Portable diagnostic instruments can provide reliable information when a patient cannot be studied in a laboratory. Assessments available on portable instruments include cardiopulmonary monitoring of respiration only; PSG; and peripheral arterial tonometry, which measures autonomic manifestations of respiratory obstructive events.^17,18

The severity of OSA is established by the apnea/hypopnea index, which measures the number of apneas and hypopneas per hour of sleep.

How is OSA treated?

CPAP is still the gold standard for treating OSA. CPAP provides a pneumatic splint for the upper airway by administering positive pressure through a nasal or oronasal mask. CPAP distinctly improves daytime sleepiness.^19,20

Pressure is determined initially by titration during PSG, although a number of automated CPAP machines are available in which pressure is adjusted based on the machine’s response to airflow obstruction. Advantages of using PSG to titrate CPAP are direct observation to control mask leak and the ability to observe the effects of body position and sleep stage and clearly distinguish periods of sleep from wakefulness.

Regrettably, adherence to a nightly regimen of CPAP is less than ideal for several reasons, including claustrophobia, interface failure, and other motivational variables. Some patients who experience claustrophobia can use desensitization techniques; others are, ultimately, unable to use the mask.

Oral appliances. A patient who has mild or moderate OSA but who cannot use the CPAP mask might be a good candidate for an oral appliance. These appliances, which hold the mandible in an advanced position during the night, can be effective in such cases.

CPAP autotitration changes the treatment pressure based on feedback from such patient measures as airflow and airway resistance. Autotitrating devices might have a role in beginning treatment in patients with OSA by means of a portable sleep study, in which CPAP titration is not performed. In addition, autotitrating offers the possibility of changing pressure over time—such as with changes in position during the night or over the longer term in response to weight loss or gain.

Surgery. In patients who are unable to use CPAP, surgery might be indicated to relieve an anatomical obstruction, such as adenotonsillar hypertrophy or other type of mass lesion.

Sleep positioning. A patient who demonstrates OSA exclusively while sleeping supine might benefit from being trained to sleep on either side only or arranging pillows so that he can only sleep on his side.

In conclusion

OSA is common and easily treatable. It coexists with, and exacerbates, medical and psychiatric illness. Treating OSA concomitantly with comorbid medical and psychiatric illness is essential to achieve full symptom remission and prevent associated long-term consequences of both medical and psychiatric illness.

BOTTOM LINE

Obstructive sleep apnea (OSA) and psychiatric illness, especially depression, often co-exist. Screen depressed patients—especially those with risk factors for OSA, such as obesity, smoking, and an upper-airway abnormality—for a sleep disorder. This is especially important if a patient complains of daytime somnolence, fatigue, cognitive problems, poor concentration, or weight gain. For optimal results, treat comorbid psychiatric illness and OSA concurrently; the same is true for other sleep disorders.

Related Resources

• Babson KA, Del Re AC, Bonn-Miller MO, et al. The comorbidity of sleep apnea and mood, anxiety, and substance use disorders among obese military veterans within the Veterans Health Administration. J Clin Sleep Med. 2013; 9(12):1253-1258.

• Karkoulias K, Lykouras D, Sampsonas F, et al. The impact of obstructive sleep apnea syndrome severity on physical performance and mental health. The use of SF-36 questionnaire in sleep apnea. Eur Rev Med Pharmacol Sci. 2013;17(4):531-536.

Disclosures

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

Acknowledgment

Dr. Muhammad Awais Aftab, psychiatry resident at Hamad Medical Corporation, Doha, Qatar, and Umair Amin, final year MBBS student at King Edward Medical University, Lahore, Pakistan, assisted with development of the manuscript of this article.

Mr. W, age 45, is a divorced Army veteran living on the street who has entered alcohol treatment for the sixth time. He has never stayed sober for longer than 1 month after each of his previous treatment episodes.

On a typical day, Mr. W drinks 40 oz of beer, a pint of vodka, and other alcoholic beverages when available. Although he has used drugs, he reports that he did so only to augment the effects of alcohol. Before entering rehab, Mr. W worked for a television network for 16 years and was promoted to associate vice president. He lost that job as a result of drinking.

Mr. W comes from a large Irish Catholic family and has sustained an active religious faith, going to Mass 2 or 3 times a month. Throughout the interview, he appears introspective and describes frequent periods of “going inside” of himself to “rehash” things. He states that he has never been satisfied with his spiritual life and has been unable to “quiet the hunger inside.”

He describes his benders as “mini-retreats” and comments that focusing on the condensation droplets on a glass of beer is nearly a “sacramental experience” for him. He states: “My drinking is a spiritual thing for me. I believe that every time I drink I am on a spiritual search. I believe this with all my heart. I have this emptiness inside of me and alcohol would temporarily fill the enormous hole in my insides. Just for a short period of time, I would feel at peace and connected to others, and maybe even to God.”

Mr. W observes that “Every time I relapse it’s because I’m going through a spiritual withdrawal. Booze filled the void inside of me and now the void is back again. Physically and psychologically I’m fine. I’m just empty inside and when I can’t stand it any longer, I drink again.”

Few patients can so directly articulate the role they feel that spirituality plays in their substance use disorder. It is important for clinicians to be aware of the dynamics of spirituality and religion in the cause, maintenance, and treatment of substance misuse problems.

In this article, we discuss how spirituality can be assessed and suggest ethical and clinical practice concerns that we believe may support treatment of substance use disorder. We do not advocate incorporating spiritual interventions into clinical practice for patients who are uncomfortable with doing so, nor do we feel that consideration of and respect for patients’ spirituality precludes evidence-based pharmaceutical and behavioral treatment strategies. We believe, however, that addressing these issues can enhance treatment adherence in select patients.

Defining spirituality

Although religion and spirituality are related concepts, they differ.

• Religion has been defined as “an organized system of beliefs, practices, rituals, and symbols through which ones’ relationship to God or others is nurtured and exercised.”¹

• Spirituality is more complex and multifaceted. Reflecting his extensive review of articles on spirituality and addiction, Cook² proposed the following definition:

Spirituality is a distinctive, potentially creative, and universal dimension of
human experience arising within inner subjective awareness of individuals and within communities, social groups, and traditions. It may be experienced as relationship with that which is intimately “inner,” immanent, and personal, within the self and others, and/or as relationship with that which is wholly “other,” transcendent and beyond the self. It is experienced as being of fundamental or ultimate importance and is therefore concerned with matters of meaning and purpose in life, truth, and values.

In some religions, any use of alcohol or drugs is forbidden; in most religions, abuse of these substances violates norms. Those who misuse a substance also might be alienated from their religious and social support community. People struggling with addiction might feel they are compromising their spiritual values directly through the action itself and indirectly because of the harm their substance misuse causes to close friends and family. Misuse of substances also might be an attempt to “fill the void,” as Mr. W described it, of a spiritual longing or a consequence of doubts about meaning, purpose in life, and God.

Perhaps it isn’t surprising that, among psychiatric disorders, substance abuse problems seem to be most associated with spiritual intervention—especially Alcoholics Anonymous (AA), Narcotics Anonymous (NA), and Cocaine Anonymous (CA). Many of the 12 steps contain references to God and spirituality. Although much of the evidence supporting the effectiveness of the spiritual components of AA/NA/CA is correlational,^3,4 the resonance that many persons who are recovering from substance abuse find in the 12-step model suggests that spiritual issues are relevant to understanding patients’ viewpoints and for planning treatment.

Religion and spirituality in risk and recovery

Although alcohol and drugs can have positive religious significance (eg, wine in the Christian Eucharist or in the Hindu practice of Ayurvedic medicine; peyote in some indigenous American religious rituals), substance use and abuse are less prevalent among persons who identify themselves as highly religious or spiritual.⁵ Studies indicate that alcohol use and abuse are less prevalent among persons who identify as Jewish, Muslim, or conservative Protestant, compared with those who are Catholic or liberal Protestant.⁶

Research suggests that consideration and accommodation of religious and spiritual practices in the recovery process is effective^7-9—and preferred—by many patients.¹⁰ Psychiatrists do not need to and, in many cases, should not deliver overtly spiritual treatments to patients recovering from substance abuse. Spirituality and religion are complex issues largely outside the expertise of psychiatry; it would be naïve to consider spirituality and religion as universally beneficial elements for all patients recovering from substance abuse. Instead, psychiatrists should be equipped to:

• assess for religion and spirituality in patients
• be aware of, and supportive of, resources for integrating spirituality into treatment (eg, clergy and hospital chaplains, local AA/NA/CA groups, community religious organizations, spirituality groups).

Assessment

Post and colleagues¹¹ note: “When patients feel that their spiritual needs are neglected in standard clinical environments, many of them may be driven away from effective medical treatment.” This is of particular concern when working with persons who have a substance use disorder—among whom, regrettably, only a minority avail themselves of professional care. You should carefully gauge the importance of these dimensions in how patients understand their disorder and the components of treatment they think their recovery process should involve.

Asking about the religious and spiritual aspects of patients’ lives shows respect for their views and facilitates a therapeutic alliance by recognizing their autonomy in treatment. Pargament and Lomax¹² state: “Religion speaks to highly sensitive issues that lie at the core of the individual’s identity, commitments, values and world view. Patients are unlikely to engage in a conversation about the deepest side of themselves unless their psychiatrist demonstrates an openness to, interest in, and appreciation of the patient’s religiousness.” This exploration process can suggest natural environmental support systems available to complement recovery efforts and can indicate whether consultation with a clergy­person knowledgeable about and sensitive to their particular religious tradition is appropriate.

Assessment of spirituality and religious practice usually should occur during the initial clinical interview. Examples of revealing interview questions are listed in Box 1.

The Table^13-20 lists well-researched psychometric measures that can provide clues to aspects of your patient’s spirituality. These scales yield quantitative results, yet it may be more useful to review with the patient his (her) responses to the items and to pursue issues further based on the responses.

In discussing responses to questions about their spirituality and religious practices, some patients might ask about your views and whether you agree with their views. You could respond with a direct, concise answer, but refocusing the discussion on why the topic of spirituality is important to understanding one’s life and choices might be more therapeutic. This also might be a good time to remind patients that the treatment plan should reflect their view of the role of religion and spirituality in their life.

Of course, some patients are disinclined to discuss spirituality or religion, or prefer that it not be considered in treatment. This is clearly a matter of patient choice, but be aware that the patient may change his (her) mind as the recovery process continues and that the topic can be revisited if desired.

Recommendations for practice

Give careful consideration to ethical and clinical practice issues related to spiritual components in the recovery process. Plante²¹ and Meador and Koenig¹ addressed several relevant ethical principles in considering spirituality in, respectively, psychological and psychiatric practice. Delaney and co-workers²² also presented similar principles, specifically within the context of substance use treatment. These can be summarized as a series of recommendations:

• Although psychiatrists as a group typically have a lower rate of conventional spirituality and religious practice than many of their patients,^23-25 it is important not to ignore the patient’s perspective and show respect for the patient’s spiritual needs. However, if the psychiatrist has strong personal religious beliefs, he (she) must carefully guard against proselytizing or exerting undue, unintentional influence.

• Given the variety of religious traditions in the United States, understanding their particular features, as with other issues of cultural diversity, requires competence and sensitivity. Your work requires study and consultation with knowledgeable peers and experts in various faith traditions. Clergy and clinically trained chaplains, in particular, can conduct more comprehensive spiritual assessments that can yield additional treatment-relevant information.

• Maintaining professional boundaries is critical when dealing with religious and spiritual aspects of the patient’s life and thinking. Keep in mind issues of transference and the authoritative influence of the psychiatrist. The patient should understand the difference between services offered by a mental health professional and those given by a spiritual counselor or member of the clergy. Spiritual and religious issues, such as addressing concerns over guilt and sin and a relationship with God, should be referred to an appropriate clergyperson.

• Spiritual interventions introduced into the therapeutic process always should derive from the patient’s perspective and value system; they should not be imposed from an external source.

• Referral to AA often will help alcohol-dependent patients. The heart of AA’s philosophy is that addiction should be seen as a spiritual problem and that genuine recovery requires a profound spiritual awakening (Box 2). AA, as well as interventions inspired by it (eg, NA), are based on peer support, are readily available, and free. Although there is a dearth of controlled research demonstrating the efficacy of AA compared with other interventions, many recovering alcoholics credit these 12-step programs with their having maintained sobriety and adopting a positive lifestyle.

Recent research has identified specific components of AA participation that seem to be helpful.²⁶ These include activities that are spiritual in nature and other generally active components of substance abuse care. Patient preference should be respected when encouraging AA involvement. For patients who are uncomfortable with AA—especially with its emphasis on spirituality—alternative peer support groups are available, such as SMART Recovery.^27,28 If the patient adopts AA’s philosophy, it might be helpful for you to employ the language of AA and its constructs when talking with him (her).

Useful strategies on how therapists can encourage AA participation and integrate mutual help groups into treatment planning are described by Nowinski.²⁵ Some AA members believe that use of medication is antithetical to the recovery process, but this is not the position of AA²⁹; using FDA-approved medications, such as naltrexone and acamprosate, is evidence-based and often should be a part of the treatment regimen for alcohol dependence.

Bottom Line

Awareness of, and sensitivity to, the religious and spiritual characteristics of patients with substance use disorder can enhance clinical rapport, inform development of individualized treatment plans, and suggest strategies, such as professional consultation, that might increase the prospects for successful treatment.

Related Resources

• Galanter M. The concept of spirituality in relation to addiction recovery and general psychiatry. Recent Dev Alcohol. 2008;18:125-140.
• Monod S, Brennan M, Rochat E, et al. Instruments measuring spirituality in clinical research: a systematic review. J Gen Intern Med. 2011;26(11):1345-1357.

Drug Brand Names

Acamprosate • Campral

Naltrexone • ReVia, Vivitrol

Disclosure

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

Featured Audio
John P. Allen, PhD, MPA, discusses whether spirituality plays a different role in treating substance use disorder than it might in treating other psychiatric illnesses. Dr. Allen works at the Department of Veterans Affairs, Mid-Atlantic Mental Illness Research, Education and Clinical Center, Division of Addictions Research and Treatment, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina.

Mr. W, age 45, is a divorced Army veteran living on the street who has entered alcohol treatment for the sixth time. He has never stayed sober for longer than 1 month after each of his previous treatment episodes.

On a typical day, Mr. W drinks 40 oz of beer, a pint of vodka, and other alcoholic beverages when available. Although he has used drugs, he reports that he did so only to augment the effects of alcohol. Before entering rehab, Mr. W worked for a television network for 16 years and was promoted to associate vice president. He lost that job as a result of drinking.

Mr. W comes from a large Irish Catholic family and has sustained an active religious faith, going to Mass 2 or 3 times a month. Throughout the interview, he appears introspective and describes frequent periods of “going inside” of himself to “rehash” things. He states that he has never been satisfied with his spiritual life and has been unable to “quiet the hunger inside.”

He describes his benders as “mini-retreats” and comments that focusing on the condensation droplets on a glass of beer is nearly a “sacramental experience” for him. He states: “My drinking is a spiritual thing for me. I believe that every time I drink I am on a spiritual search. I believe this with all my heart. I have this emptiness inside of me and alcohol would temporarily fill the enormous hole in my insides. Just for a short period of time, I would feel at peace and connected to others, and maybe even to God.”

Mr. W observes that “Every time I relapse it’s because I’m going through a spiritual withdrawal. Booze filled the void inside of me and now the void is back again. Physically and psychologically I’m fine. I’m just empty inside and when I can’t stand it any longer, I drink again.”

Few patients can so directly articulate the role they feel that spirituality plays in their substance use disorder. It is important for clinicians to be aware of the dynamics of spirituality and religion in the cause, maintenance, and treatment of substance misuse problems.

In this article, we discuss how spirituality can be assessed and suggest ethical and clinical practice concerns that we believe may support treatment of substance use disorder. We do not advocate incorporating spiritual interventions into clinical practice for patients who are uncomfortable with doing so, nor do we feel that consideration of and respect for patients’ spirituality precludes evidence-based pharmaceutical and behavioral treatment strategies. We believe, however, that addressing these issues can enhance treatment adherence in select patients.

Defining spirituality

Although religion and spirituality are related concepts, they differ.

• Religion has been defined as “an organized system of beliefs, practices, rituals, and symbols through which ones’ relationship to God or others is nurtured and exercised.”¹

• Spirituality is more complex and multifaceted. Reflecting his extensive review of articles on spirituality and addiction, Cook² proposed the following definition:

Spirituality is a distinctive, potentially creative, and universal dimension of
human experience arising within inner subjective awareness of individuals and within communities, social groups, and traditions. It may be experienced as relationship with that which is intimately “inner,” immanent, and personal, within the self and others, and/or as relationship with that which is wholly “other,” transcendent and beyond the self. It is experienced as being of fundamental or ultimate importance and is therefore concerned with matters of meaning and purpose in life, truth, and values.

In some religions, any use of alcohol or drugs is forbidden; in most religions, abuse of these substances violates norms. Those who misuse a substance also might be alienated from their religious and social support community. People struggling with addiction might feel they are compromising their spiritual values directly through the action itself and indirectly because of the harm their substance misuse causes to close friends and family. Misuse of substances also might be an attempt to “fill the void,” as Mr. W described it, of a spiritual longing or a consequence of doubts about meaning, purpose in life, and God.

Perhaps it isn’t surprising that, among psychiatric disorders, substance abuse problems seem to be most associated with spiritual intervention—especially Alcoholics Anonymous (AA), Narcotics Anonymous (NA), and Cocaine Anonymous (CA). Many of the 12 steps contain references to God and spirituality. Although much of the evidence supporting the effectiveness of the spiritual components of AA/NA/CA is correlational,^3,4 the resonance that many persons who are recovering from substance abuse find in the 12-step model suggests that spiritual issues are relevant to understanding patients’ viewpoints and for planning treatment.

Religion and spirituality in risk and recovery

Although alcohol and drugs can have positive religious significance (eg, wine in the Christian Eucharist or in the Hindu practice of Ayurvedic medicine; peyote in some indigenous American religious rituals), substance use and abuse are less prevalent among persons who identify themselves as highly religious or spiritual.⁵ Studies indicate that alcohol use and abuse are less prevalent among persons who identify as Jewish, Muslim, or conservative Protestant, compared with those who are Catholic or liberal Protestant.⁶

Research suggests that consideration and accommodation of religious and spiritual practices in the recovery process is effective^7-9—and preferred—by many patients.¹⁰ Psychiatrists do not need to and, in many cases, should not deliver overtly spiritual treatments to patients recovering from substance abuse. Spirituality and religion are complex issues largely outside the expertise of psychiatry; it would be naïve to consider spirituality and religion as universally beneficial elements for all patients recovering from substance abuse. Instead, psychiatrists should be equipped to:

• assess for religion and spirituality in patients
• be aware of, and supportive of, resources for integrating spirituality into treatment (eg, clergy and hospital chaplains, local AA/NA/CA groups, community religious organizations, spirituality groups).

Assessment

Post and colleagues¹¹ note: “When patients feel that their spiritual needs are neglected in standard clinical environments, many of them may be driven away from effective medical treatment.” This is of particular concern when working with persons who have a substance use disorder—among whom, regrettably, only a minority avail themselves of professional care. You should carefully gauge the importance of these dimensions in how patients understand their disorder and the components of treatment they think their recovery process should involve.

Asking about the religious and spiritual aspects of patients’ lives shows respect for their views and facilitates a therapeutic alliance by recognizing their autonomy in treatment. Pargament and Lomax¹² state: “Religion speaks to highly sensitive issues that lie at the core of the individual’s identity, commitments, values and world view. Patients are unlikely to engage in a conversation about the deepest side of themselves unless their psychiatrist demonstrates an openness to, interest in, and appreciation of the patient’s religiousness.” This exploration process can suggest natural environmental support systems available to complement recovery efforts and can indicate whether consultation with a clergy­person knowledgeable about and sensitive to their particular religious tradition is appropriate.

Assessment of spirituality and religious practice usually should occur during the initial clinical interview. Examples of revealing interview questions are listed in Box 1.

The Table^13-20 lists well-researched psychometric measures that can provide clues to aspects of your patient’s spirituality. These scales yield quantitative results, yet it may be more useful to review with the patient his (her) responses to the items and to pursue issues further based on the responses.

In discussing responses to questions about their spirituality and religious practices, some patients might ask about your views and whether you agree with their views. You could respond with a direct, concise answer, but refocusing the discussion on why the topic of spirituality is important to understanding one’s life and choices might be more therapeutic. This also might be a good time to remind patients that the treatment plan should reflect their view of the role of religion and spirituality in their life.

Of course, some patients are disinclined to discuss spirituality or religion, or prefer that it not be considered in treatment. This is clearly a matter of patient choice, but be aware that the patient may change his (her) mind as the recovery process continues and that the topic can be revisited if desired.

Recommendations for practice

Give careful consideration to ethical and clinical practice issues related to spiritual components in the recovery process. Plante²¹ and Meador and Koenig¹ addressed several relevant ethical principles in considering spirituality in, respectively, psychological and psychiatric practice. Delaney and co-workers²² also presented similar principles, specifically within the context of substance use treatment. These can be summarized as a series of recommendations:

• Although psychiatrists as a group typically have a lower rate of conventional spirituality and religious practice than many of their patients,^23-25 it is important not to ignore the patient’s perspective and show respect for the patient’s spiritual needs. However, if the psychiatrist has strong personal religious beliefs, he (she) must carefully guard against proselytizing or exerting undue, unintentional influence.

• Given the variety of religious traditions in the United States, understanding their particular features, as with other issues of cultural diversity, requires competence and sensitivity. Your work requires study and consultation with knowledgeable peers and experts in various faith traditions. Clergy and clinically trained chaplains, in particular, can conduct more comprehensive spiritual assessments that can yield additional treatment-relevant information.

• Maintaining professional boundaries is critical when dealing with religious and spiritual aspects of the patient’s life and thinking. Keep in mind issues of transference and the authoritative influence of the psychiatrist. The patient should understand the difference between services offered by a mental health professional and those given by a spiritual counselor or member of the clergy. Spiritual and religious issues, such as addressing concerns over guilt and sin and a relationship with God, should be referred to an appropriate clergyperson.

• Spiritual interventions introduced into the therapeutic process always should derive from the patient’s perspective and value system; they should not be imposed from an external source.

• Referral to AA often will help alcohol-dependent patients. The heart of AA’s philosophy is that addiction should be seen as a spiritual problem and that genuine recovery requires a profound spiritual awakening (Box 2). AA, as well as interventions inspired by it (eg, NA), are based on peer support, are readily available, and free. Although there is a dearth of controlled research demonstrating the efficacy of AA compared with other interventions, many recovering alcoholics credit these 12-step programs with their having maintained sobriety and adopting a positive lifestyle.

Recent research has identified specific components of AA participation that seem to be helpful.²⁶ These include activities that are spiritual in nature and other generally active components of substance abuse care. Patient preference should be respected when encouraging AA involvement. For patients who are uncomfortable with AA—especially with its emphasis on spirituality—alternative peer support groups are available, such as SMART Recovery.^27,28 If the patient adopts AA’s philosophy, it might be helpful for you to employ the language of AA and its constructs when talking with him (her).

Useful strategies on how therapists can encourage AA participation and integrate mutual help groups into treatment planning are described by Nowinski.²⁵ Some AA members believe that use of medication is antithetical to the recovery process, but this is not the position of AA²⁹; using FDA-approved medications, such as naltrexone and acamprosate, is evidence-based and often should be a part of the treatment regimen for alcohol dependence.

Bottom Line

Awareness of, and sensitivity to, the religious and spiritual characteristics of patients with substance use disorder can enhance clinical rapport, inform development of individualized treatment plans, and suggest strategies, such as professional consultation, that might increase the prospects for successful treatment.

Related Resources

• Galanter M. The concept of spirituality in relation to addiction recovery and general psychiatry. Recent Dev Alcohol. 2008;18:125-140.
• Monod S, Brennan M, Rochat E, et al. Instruments measuring spirituality in clinical research: a systematic review. J Gen Intern Med. 2011;26(11):1345-1357.

Drug Brand Names

Acamprosate • Campral

Naltrexone • ReVia, Vivitrol

Disclosure

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

Featured Audio
John P. Allen, PhD, MPA, discusses whether spirituality plays a different role in treating substance use disorder than it might in treating other psychiatric illnesses. Dr. Allen works at the Department of Veterans Affairs, Mid-Atlantic Mental Illness Research, Education and Clinical Center, Division of Addictions Research and Treatment, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina.

Mr. W, age 45, is a divorced Army veteran living on the street who has entered alcohol treatment for the sixth time. He has never stayed sober for longer than 1 month after each of his previous treatment episodes.

On a typical day, Mr. W drinks 40 oz of beer, a pint of vodka, and other alcoholic beverages when available. Although he has used drugs, he reports that he did so only to augment the effects of alcohol. Before entering rehab, Mr. W worked for a television network for 16 years and was promoted to associate vice president. He lost that job as a result of drinking.

Mr. W comes from a large Irish Catholic family and has sustained an active religious faith, going to Mass 2 or 3 times a month. Throughout the interview, he appears introspective and describes frequent periods of “going inside” of himself to “rehash” things. He states that he has never been satisfied with his spiritual life and has been unable to “quiet the hunger inside.”

He describes his benders as “mini-retreats” and comments that focusing on the condensation droplets on a glass of beer is nearly a “sacramental experience” for him. He states: “My drinking is a spiritual thing for me. I believe that every time I drink I am on a spiritual search. I believe this with all my heart. I have this emptiness inside of me and alcohol would temporarily fill the enormous hole in my insides. Just for a short period of time, I would feel at peace and connected to others, and maybe even to God.”

Mr. W observes that “Every time I relapse it’s because I’m going through a spiritual withdrawal. Booze filled the void inside of me and now the void is back again. Physically and psychologically I’m fine. I’m just empty inside and when I can’t stand it any longer, I drink again.”

Few patients can so directly articulate the role they feel that spirituality plays in their substance use disorder. It is important for clinicians to be aware of the dynamics of spirituality and religion in the cause, maintenance, and treatment of substance misuse problems.

In this article, we discuss how spirituality can be assessed and suggest ethical and clinical practice concerns that we believe may support treatment of substance use disorder. We do not advocate incorporating spiritual interventions into clinical practice for patients who are uncomfortable with doing so, nor do we feel that consideration of and respect for patients’ spirituality precludes evidence-based pharmaceutical and behavioral treatment strategies. We believe, however, that addressing these issues can enhance treatment adherence in select patients.

Defining spirituality

Although religion and spirituality are related concepts, they differ.

• Religion has been defined as “an organized system of beliefs, practices, rituals, and symbols through which ones’ relationship to God or others is nurtured and exercised.”¹

• Spirituality is more complex and multifaceted. Reflecting his extensive review of articles on spirituality and addiction, Cook² proposed the following definition:

Spirituality is a distinctive, potentially creative, and universal dimension of
human experience arising within inner subjective awareness of individuals and within communities, social groups, and traditions. It may be experienced as relationship with that which is intimately “inner,” immanent, and personal, within the self and others, and/or as relationship with that which is wholly “other,” transcendent and beyond the self. It is experienced as being of fundamental or ultimate importance and is therefore concerned with matters of meaning and purpose in life, truth, and values.

In some religions, any use of alcohol or drugs is forbidden; in most religions, abuse of these substances violates norms. Those who misuse a substance also might be alienated from their religious and social support community. People struggling with addiction might feel they are compromising their spiritual values directly through the action itself and indirectly because of the harm their substance misuse causes to close friends and family. Misuse of substances also might be an attempt to “fill the void,” as Mr. W described it, of a spiritual longing or a consequence of doubts about meaning, purpose in life, and God.

Perhaps it isn’t surprising that, among psychiatric disorders, substance abuse problems seem to be most associated with spiritual intervention—especially Alcoholics Anonymous (AA), Narcotics Anonymous (NA), and Cocaine Anonymous (CA). Many of the 12 steps contain references to God and spirituality. Although much of the evidence supporting the effectiveness of the spiritual components of AA/NA/CA is correlational,^3,4 the resonance that many persons who are recovering from substance abuse find in the 12-step model suggests that spiritual issues are relevant to understanding patients’ viewpoints and for planning treatment.

Religion and spirituality in risk and recovery

Although alcohol and drugs can have positive religious significance (eg, wine in the Christian Eucharist or in the Hindu practice of Ayurvedic medicine; peyote in some indigenous American religious rituals), substance use and abuse are less prevalent among persons who identify themselves as highly religious or spiritual.⁵ Studies indicate that alcohol use and abuse are less prevalent among persons who identify as Jewish, Muslim, or conservative Protestant, compared with those who are Catholic or liberal Protestant.⁶

Research suggests that consideration and accommodation of religious and spiritual practices in the recovery process is effective^7-9—and preferred—by many patients.¹⁰ Psychiatrists do not need to and, in many cases, should not deliver overtly spiritual treatments to patients recovering from substance abuse. Spirituality and religion are complex issues largely outside the expertise of psychiatry; it would be naïve to consider spirituality and religion as universally beneficial elements for all patients recovering from substance abuse. Instead, psychiatrists should be equipped to:

• assess for religion and spirituality in patients
• be aware of, and supportive of, resources for integrating spirituality into treatment (eg, clergy and hospital chaplains, local AA/NA/CA groups, community religious organizations, spirituality groups).

Assessment

Post and colleagues¹¹ note: “When patients feel that their spiritual needs are neglected in standard clinical environments, many of them may be driven away from effective medical treatment.” This is of particular concern when working with persons who have a substance use disorder—among whom, regrettably, only a minority avail themselves of professional care. You should carefully gauge the importance of these dimensions in how patients understand their disorder and the components of treatment they think their recovery process should involve.

Asking about the religious and spiritual aspects of patients’ lives shows respect for their views and facilitates a therapeutic alliance by recognizing their autonomy in treatment. Pargament and Lomax¹² state: “Religion speaks to highly sensitive issues that lie at the core of the individual’s identity, commitments, values and world view. Patients are unlikely to engage in a conversation about the deepest side of themselves unless their psychiatrist demonstrates an openness to, interest in, and appreciation of the patient’s religiousness.” This exploration process can suggest natural environmental support systems available to complement recovery efforts and can indicate whether consultation with a clergy­person knowledgeable about and sensitive to their particular religious tradition is appropriate.

Assessment of spirituality and religious practice usually should occur during the initial clinical interview. Examples of revealing interview questions are listed in Box 1.

The Table^13-20 lists well-researched psychometric measures that can provide clues to aspects of your patient’s spirituality. These scales yield quantitative results, yet it may be more useful to review with the patient his (her) responses to the items and to pursue issues further based on the responses.

In discussing responses to questions about their spirituality and religious practices, some patients might ask about your views and whether you agree with their views. You could respond with a direct, concise answer, but refocusing the discussion on why the topic of spirituality is important to understanding one’s life and choices might be more therapeutic. This also might be a good time to remind patients that the treatment plan should reflect their view of the role of religion and spirituality in their life.

Of course, some patients are disinclined to discuss spirituality or religion, or prefer that it not be considered in treatment. This is clearly a matter of patient choice, but be aware that the patient may change his (her) mind as the recovery process continues and that the topic can be revisited if desired.

Recommendations for practice

Give careful consideration to ethical and clinical practice issues related to spiritual components in the recovery process. Plante²¹ and Meador and Koenig¹ addressed several relevant ethical principles in considering spirituality in, respectively, psychological and psychiatric practice. Delaney and co-workers²² also presented similar principles, specifically within the context of substance use treatment. These can be summarized as a series of recommendations:

• Although psychiatrists as a group typically have a lower rate of conventional spirituality and religious practice than many of their patients,^23-25 it is important not to ignore the patient’s perspective and show respect for the patient’s spiritual needs. However, if the psychiatrist has strong personal religious beliefs, he (she) must carefully guard against proselytizing or exerting undue, unintentional influence.

• Given the variety of religious traditions in the United States, understanding their particular features, as with other issues of cultural diversity, requires competence and sensitivity. Your work requires study and consultation with knowledgeable peers and experts in various faith traditions. Clergy and clinically trained chaplains, in particular, can conduct more comprehensive spiritual assessments that can yield additional treatment-relevant information.

• Maintaining professional boundaries is critical when dealing with religious and spiritual aspects of the patient’s life and thinking. Keep in mind issues of transference and the authoritative influence of the psychiatrist. The patient should understand the difference between services offered by a mental health professional and those given by a spiritual counselor or member of the clergy. Spiritual and religious issues, such as addressing concerns over guilt and sin and a relationship with God, should be referred to an appropriate clergyperson.

• Spiritual interventions introduced into the therapeutic process always should derive from the patient’s perspective and value system; they should not be imposed from an external source.

• Referral to AA often will help alcohol-dependent patients. The heart of AA’s philosophy is that addiction should be seen as a spiritual problem and that genuine recovery requires a profound spiritual awakening (Box 2). AA, as well as interventions inspired by it (eg, NA), are based on peer support, are readily available, and free. Although there is a dearth of controlled research demonstrating the efficacy of AA compared with other interventions, many recovering alcoholics credit these 12-step programs with their having maintained sobriety and adopting a positive lifestyle.

Recent research has identified specific components of AA participation that seem to be helpful.²⁶ These include activities that are spiritual in nature and other generally active components of substance abuse care. Patient preference should be respected when encouraging AA involvement. For patients who are uncomfortable with AA—especially with its emphasis on spirituality—alternative peer support groups are available, such as SMART Recovery.^27,28 If the patient adopts AA’s philosophy, it might be helpful for you to employ the language of AA and its constructs when talking with him (her).

Useful strategies on how therapists can encourage AA participation and integrate mutual help groups into treatment planning are described by Nowinski.²⁵ Some AA members believe that use of medication is antithetical to the recovery process, but this is not the position of AA²⁹; using FDA-approved medications, such as naltrexone and acamprosate, is evidence-based and often should be a part of the treatment regimen for alcohol dependence.

Bottom Line

Awareness of, and sensitivity to, the religious and spiritual characteristics of patients with substance use disorder can enhance clinical rapport, inform development of individualized treatment plans, and suggest strategies, such as professional consultation, that might increase the prospects for successful treatment.

Related Resources

• Galanter M. The concept of spirituality in relation to addiction recovery and general psychiatry. Recent Dev Alcohol. 2008;18:125-140.
• Monod S, Brennan M, Rochat E, et al. Instruments measuring spirituality in clinical research: a systematic review. J Gen Intern Med. 2011;26(11):1345-1357.

Drug Brand Names

Acamprosate • Campral

Naltrexone • ReVia, Vivitrol

Disclosure

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

Featured Audio
John P. Allen, PhD, MPA, discusses whether spirituality plays a different role in treating substance use disorder than it might in treating other psychiatric illnesses. Dr. Allen works at the Department of Veterans Affairs, Mid-Atlantic Mental Illness Research, Education and Clinical Center, Division of Addictions Research and Treatment, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina.

It might seem business as usual in clinical psychiatry, but major transformative changes in the scientific foundation of the specialty are taking place. The “neuroscientification” of psychiatry, ongoing for more than 3 decades, is now approaching a tipping point: The specialty is on the verge of an unprecedented denouement of the old tenets and assumptions. Just as smartphones have made a 25-volume encyclopedia set obsolete, coming changes in scientific psychiatry will be fully disruptive to your father’s practice of psychiatry.

Many psychiatrists still practice like it’s 1999

That situation will change, soon—as surely as medieval times gave way to the Renaissance. Psychiatry of the future will be drastically different once new models of objective diagnostic tests and physiologically specific interventions emerge from fast-moving discoveries of the molecular biology of the mind and its pathologies.

Most psychiatric practitioners do not regularly read neuroscience journals that describe the accelerating progress in molecular psychiatry, where the text is replete with an alphabet soup of terminology that one day will permeate the medical practice of the new psychiatry.

Fuzzy ambiguities will be cleared away

There are many reasons to be optimistic that transcendent scientific transformations will sweep away the fuzzy biologic, diagnostic, and therapeutic ambiguities that have plagued psychiatry for so long—plagued us because of the herculean challenges of investigating the divinely complex brain and its gloriously enigmatic mind. New methods and tools for exploration and paradigmatic shifts in  conceptualizing the etiopathogenesis of psychiatric brain disorders are rapidly leading to a discarding of many simplistic, even primitive, notions that have guided psychiatry over the past century. Psychopharmacological breakthroughs of the past 50 years, which, admittedly, have yet to cure or eliminate disabilities associated with major psychiatric disorders, are only a prologue to the coming revolution in neuropsychiatry, in which prevention, not just intervention, will change everything. Curing deteriorative brain disorders will be a reality once that revolution in neuroscience enters its propitious translational phase.

The Table presents a sampling of scientific progress that is setting the stage for disruptive technologies and probes that will lead to far more advanced diagnosis, prevention, and treatment of neuropsychiatric diseases.

Prepare for psychiatry’s future shock!

We psychiatrists must keep up, regularly reading the latest literature to learn about the latest advances and to make sure we are familiar with the emerging language of psychiatric neuroscience. Instead of remaining fondly attached to ancient constructs such as id, ego, superego, and defense mechanisms, we should be thinking about the default mode network, seeking to understand the connectome, the envirome, the metabolome, and the proteome; microglial activation, inflammatory markers, IL-6, TNF alpha, oxidative and nitrosative stress, and physiologic vs pathologic apoptosis; BDNF, FGF, VEGF, MIF, GFAP, and S100B; neuroplasticity and dendritic spines; and genes such as CLOCK, NOTCH3, and Met-to-Val mutations—and so on.

Those of us who do not adapt to swift transition of knowledge might suffer the fate of clinical dinosaurs, as the massive asteroid of neuroscientific advances smashes into the placid landscape of psychiatry. As Alvin Toffler, author of Future Shock, proposed, the illiterates of the future will not be the people who cannot read or write. They will be the ones who fail to learn.

It might seem business as usual in clinical psychiatry, but major transformative changes in the scientific foundation of the specialty are taking place. The “neuroscientification” of psychiatry, ongoing for more than 3 decades, is now approaching a tipping point: The specialty is on the verge of an unprecedented denouement of the old tenets and assumptions. Just as smartphones have made a 25-volume encyclopedia set obsolete, coming changes in scientific psychiatry will be fully disruptive to your father’s practice of psychiatry.

Many psychiatrists still practice like it’s 1999

That situation will change, soon—as surely as medieval times gave way to the Renaissance. Psychiatry of the future will be drastically different once new models of objective diagnostic tests and physiologically specific interventions emerge from fast-moving discoveries of the molecular biology of the mind and its pathologies.

Most psychiatric practitioners do not regularly read neuroscience journals that describe the accelerating progress in molecular psychiatry, where the text is replete with an alphabet soup of terminology that one day will permeate the medical practice of the new psychiatry.

Fuzzy ambiguities will be cleared away

There are many reasons to be optimistic that transcendent scientific transformations will sweep away the fuzzy biologic, diagnostic, and therapeutic ambiguities that have plagued psychiatry for so long—plagued us because of the herculean challenges of investigating the divinely complex brain and its gloriously enigmatic mind. New methods and tools for exploration and paradigmatic shifts in  conceptualizing the etiopathogenesis of psychiatric brain disorders are rapidly leading to a discarding of many simplistic, even primitive, notions that have guided psychiatry over the past century. Psychopharmacological breakthroughs of the past 50 years, which, admittedly, have yet to cure or eliminate disabilities associated with major psychiatric disorders, are only a prologue to the coming revolution in neuropsychiatry, in which prevention, not just intervention, will change everything. Curing deteriorative brain disorders will be a reality once that revolution in neuroscience enters its propitious translational phase.

The Table presents a sampling of scientific progress that is setting the stage for disruptive technologies and probes that will lead to far more advanced diagnosis, prevention, and treatment of neuropsychiatric diseases.

Prepare for psychiatry’s future shock!

We psychiatrists must keep up, regularly reading the latest literature to learn about the latest advances and to make sure we are familiar with the emerging language of psychiatric neuroscience. Instead of remaining fondly attached to ancient constructs such as id, ego, superego, and defense mechanisms, we should be thinking about the default mode network, seeking to understand the connectome, the envirome, the metabolome, and the proteome; microglial activation, inflammatory markers, IL-6, TNF alpha, oxidative and nitrosative stress, and physiologic vs pathologic apoptosis; BDNF, FGF, VEGF, MIF, GFAP, and S100B; neuroplasticity and dendritic spines; and genes such as CLOCK, NOTCH3, and Met-to-Val mutations—and so on.

Those of us who do not adapt to swift transition of knowledge might suffer the fate of clinical dinosaurs, as the massive asteroid of neuroscientific advances smashes into the placid landscape of psychiatry. As Alvin Toffler, author of Future Shock, proposed, the illiterates of the future will not be the people who cannot read or write. They will be the ones who fail to learn.

It might seem business as usual in clinical psychiatry, but major transformative changes in the scientific foundation of the specialty are taking place. The “neuroscientification” of psychiatry, ongoing for more than 3 decades, is now approaching a tipping point: The specialty is on the verge of an unprecedented denouement of the old tenets and assumptions. Just as smartphones have made a 25-volume encyclopedia set obsolete, coming changes in scientific psychiatry will be fully disruptive to your father’s practice of psychiatry.

Many psychiatrists still practice like it’s 1999

That situation will change, soon—as surely as medieval times gave way to the Renaissance. Psychiatry of the future will be drastically different once new models of objective diagnostic tests and physiologically specific interventions emerge from fast-moving discoveries of the molecular biology of the mind and its pathologies.

Most psychiatric practitioners do not regularly read neuroscience journals that describe the accelerating progress in molecular psychiatry, where the text is replete with an alphabet soup of terminology that one day will permeate the medical practice of the new psychiatry.

Fuzzy ambiguities will be cleared away

There are many reasons to be optimistic that transcendent scientific transformations will sweep away the fuzzy biologic, diagnostic, and therapeutic ambiguities that have plagued psychiatry for so long—plagued us because of the herculean challenges of investigating the divinely complex brain and its gloriously enigmatic mind. New methods and tools for exploration and paradigmatic shifts in  conceptualizing the etiopathogenesis of psychiatric brain disorders are rapidly leading to a discarding of many simplistic, even primitive, notions that have guided psychiatry over the past century. Psychopharmacological breakthroughs of the past 50 years, which, admittedly, have yet to cure or eliminate disabilities associated with major psychiatric disorders, are only a prologue to the coming revolution in neuropsychiatry, in which prevention, not just intervention, will change everything. Curing deteriorative brain disorders will be a reality once that revolution in neuroscience enters its propitious translational phase.

The Table presents a sampling of scientific progress that is setting the stage for disruptive technologies and probes that will lead to far more advanced diagnosis, prevention, and treatment of neuropsychiatric diseases.

Prepare for psychiatry’s future shock!

We psychiatrists must keep up, regularly reading the latest literature to learn about the latest advances and to make sure we are familiar with the emerging language of psychiatric neuroscience. Instead of remaining fondly attached to ancient constructs such as id, ego, superego, and defense mechanisms, we should be thinking about the default mode network, seeking to understand the connectome, the envirome, the metabolome, and the proteome; microglial activation, inflammatory markers, IL-6, TNF alpha, oxidative and nitrosative stress, and physiologic vs pathologic apoptosis; BDNF, FGF, VEGF, MIF, GFAP, and S100B; neuroplasticity and dendritic spines; and genes such as CLOCK, NOTCH3, and Met-to-Val mutations—and so on.

Those of us who do not adapt to swift transition of knowledge might suffer the fate of clinical dinosaurs, as the massive asteroid of neuroscientific advances smashes into the placid landscape of psychiatry. As Alvin Toffler, author of Future Shock, proposed, the illiterates of the future will not be the people who cannot read or write. They will be the ones who fail to learn.

Joint disease is the most common cause of disability and the source of considerable psychological distress. In the United States, 50 million adults complain of joint pain; in 2007, 1.5 million people suffered from rheumatoid arthritis (RA). A chronic inflammatory autoimmune disease of joints, RA can involve almost all organs.¹

The link to mental illness

Mental illness in RA patients often is underdiagnosed and undertreated. These missed opportunities contribute to poor compliance with medical therapy, suboptimal therapeutic response, greater disability, and diminished quality of life.²

Limited mobility, chronic pain, sleep disturbance, fatigue, and immunological factors predispose RA patients to depression and anxiety.³ The proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), IL-6, and interferon-g have a role in inducing affective symptoms. There also is a relationship between an elevated IL-17 level and anxiety.

Research substantiates a relationship between RA and depression.³ The prevalence of affective illness is approximately 6% among the general population, and 13% to 30% among RA patients.⁴ In arthritic populations, 52% exhibit depression and anxiety; joint discomfort contributes to insomnia in 25% to 42% of cases.⁴

Arthritic pain persists despite suppressed inflammation, which suggests involvement of the CNS.⁵ Increased levels of IL-6 and TNF-α can cause insomnia and affect pain perception.⁶ Decreased conditioned pain modulation, a lower pain threshold, and pressure pain intolerance lead to increased pain awareness and heightened discomfort.

How can you help your patient who has RA?

Because the focus of care in RA is on the disease’s physical attributes, psychiatric symptoms sometimes receive less attention.⁷ And because arthritic symptoms overlap with anorexia, weight loss, fatigue, pain, and insomnia, affective illness can go unrecognized.

Depression rating scales can overestimate affective illness, but a history and follow-up questionnaire can facilitate an accurate diagnosis of depression and help determine the need for, and type of, intervention.

Selective serotonin reuptake inhibitors (SSRIs) are considered first‐line treatment of depression associated with RA.⁷ Although SSRIs for RA can be administered to the maximum recommended dosage, titration is advised in accordance with patient response and tolerance.

Tricyclic antidepressants are not as well tolerated in RA, especially in older patients; however, they have more of an analgesic effect, even at lower dosages.

Joint disease activity and mood are associated with sleep disturbance, and vice versa.⁵ Insomnia calls for patient education about sleep hygiene, avoiding caffeine and other stimulants, and an individualized appraisal of options for pharmacotherapy.

Alleviating RA pain is important for psychosocial health.⁸ Although the medical team’s emphasis should be on controlling inflammation to minimize joint damage and pain, be sure to address your RA patients’ mood symptoms to improve the quality of their life.

Disclosure

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

Joint disease is the most common cause of disability and the source of considerable psychological distress. In the United States, 50 million adults complain of joint pain; in 2007, 1.5 million people suffered from rheumatoid arthritis (RA). A chronic inflammatory autoimmune disease of joints, RA can involve almost all organs.¹

The link to mental illness

Mental illness in RA patients often is underdiagnosed and undertreated. These missed opportunities contribute to poor compliance with medical therapy, suboptimal therapeutic response, greater disability, and diminished quality of life.²

Limited mobility, chronic pain, sleep disturbance, fatigue, and immunological factors predispose RA patients to depression and anxiety.³ The proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), IL-6, and interferon-g have a role in inducing affective symptoms. There also is a relationship between an elevated IL-17 level and anxiety.

Research substantiates a relationship between RA and depression.³ The prevalence of affective illness is approximately 6% among the general population, and 13% to 30% among RA patients.⁴ In arthritic populations, 52% exhibit depression and anxiety; joint discomfort contributes to insomnia in 25% to 42% of cases.⁴

Arthritic pain persists despite suppressed inflammation, which suggests involvement of the CNS.⁵ Increased levels of IL-6 and TNF-α can cause insomnia and affect pain perception.⁶ Decreased conditioned pain modulation, a lower pain threshold, and pressure pain intolerance lead to increased pain awareness and heightened discomfort.

How can you help your patient who has RA?

Because the focus of care in RA is on the disease’s physical attributes, psychiatric symptoms sometimes receive less attention.⁷ And because arthritic symptoms overlap with anorexia, weight loss, fatigue, pain, and insomnia, affective illness can go unrecognized.

Depression rating scales can overestimate affective illness, but a history and follow-up questionnaire can facilitate an accurate diagnosis of depression and help determine the need for, and type of, intervention.

Selective serotonin reuptake inhibitors (SSRIs) are considered first‐line treatment of depression associated with RA.⁷ Although SSRIs for RA can be administered to the maximum recommended dosage, titration is advised in accordance with patient response and tolerance.

Tricyclic antidepressants are not as well tolerated in RA, especially in older patients; however, they have more of an analgesic effect, even at lower dosages.

Joint disease activity and mood are associated with sleep disturbance, and vice versa.⁵ Insomnia calls for patient education about sleep hygiene, avoiding caffeine and other stimulants, and an individualized appraisal of options for pharmacotherapy.

Alleviating RA pain is important for psychosocial health.⁸ Although the medical team’s emphasis should be on controlling inflammation to minimize joint damage and pain, be sure to address your RA patients’ mood symptoms to improve the quality of their life.

Disclosure

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

Joint disease is the most common cause of disability and the source of considerable psychological distress. In the United States, 50 million adults complain of joint pain; in 2007, 1.5 million people suffered from rheumatoid arthritis (RA). A chronic inflammatory autoimmune disease of joints, RA can involve almost all organs.¹

The link to mental illness

Mental illness in RA patients often is underdiagnosed and undertreated. These missed opportunities contribute to poor compliance with medical therapy, suboptimal therapeutic response, greater disability, and diminished quality of life.²

Limited mobility, chronic pain, sleep disturbance, fatigue, and immunological factors predispose RA patients to depression and anxiety.³ The proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), IL-6, and interferon-g have a role in inducing affective symptoms. There also is a relationship between an elevated IL-17 level and anxiety.

Research substantiates a relationship between RA and depression.³ The prevalence of affective illness is approximately 6% among the general population, and 13% to 30% among RA patients.⁴ In arthritic populations, 52% exhibit depression and anxiety; joint discomfort contributes to insomnia in 25% to 42% of cases.⁴

Arthritic pain persists despite suppressed inflammation, which suggests involvement of the CNS.⁵ Increased levels of IL-6 and TNF-α can cause insomnia and affect pain perception.⁶ Decreased conditioned pain modulation, a lower pain threshold, and pressure pain intolerance lead to increased pain awareness and heightened discomfort.

How can you help your patient who has RA?

Because the focus of care in RA is on the disease’s physical attributes, psychiatric symptoms sometimes receive less attention.⁷ And because arthritic symptoms overlap with anorexia, weight loss, fatigue, pain, and insomnia, affective illness can go unrecognized.

Depression rating scales can overestimate affective illness, but a history and follow-up questionnaire can facilitate an accurate diagnosis of depression and help determine the need for, and type of, intervention.

Selective serotonin reuptake inhibitors (SSRIs) are considered first‐line treatment of depression associated with RA.⁷ Although SSRIs for RA can be administered to the maximum recommended dosage, titration is advised in accordance with patient response and tolerance.

Tricyclic antidepressants are not as well tolerated in RA, especially in older patients; however, they have more of an analgesic effect, even at lower dosages.

Joint disease activity and mood are associated with sleep disturbance, and vice versa.⁵ Insomnia calls for patient education about sleep hygiene, avoiding caffeine and other stimulants, and an individualized appraisal of options for pharmacotherapy.

Alleviating RA pain is important for psychosocial health.⁸ Although the medical team’s emphasis should be on controlling inflammation to minimize joint damage and pain, be sure to address your RA patients’ mood symptoms to improve the quality of their life.

Disclosure

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