The prevalence of HIV in persons with untreated psychiatric illness may be 10 to 20 times that of the general population.¹ The U.S. Preventive Services Task Force has recommended HIV screening of all persons age 15 to 65 because 20% to 25% of individuals with HIV infection are unaware that they are HIV-positive.² Because >20% of new HIV infections in the United States are undiagnosed,³ it is crucial to educate patients with mental illness about HIV prevention, make condoms available, and offer HIV testing.

As psychiatrists, we have a unique role in caring for patients at risk for or infected with HIV because in addition to comprehensive medical and psychiatric histories, we routinely take histories of substance use, sexual activities, relationships, and trauma, including childhood neglect and emotional, physical, and sexual abuse. We develop long-term, trusting relationships and work with individuals to change behaviors and maximize life potential.

Increasing awareness of stigma, discrimination, and psychiatric factors involved with the HIV pandemic can lead to decreased transmission of HIV infection and early diagnosis and treatment. Compassionate medical and psychiatric care can mitigate suffering in persons at risk for, infected with, or affected by HIV.

Preventing HIV transmission

AIDS differs from other complex, severe illnesses in 2 ways that are relevant to psychiatrists:

•  it is almost entirely preventable

•  HIV and AIDS are associated with sex, drugs, and AIDS-associated stigma and discrimination (“AIDSism”).^4-6

Unsafe exposure of mucosal surfaces to the virus—primarily from exchanging body fluids in unprotected sexual encounters—accounts for 80% of new HIV infections.⁷ HIV transmission via sexual encounters is preventable with condoms. Percutaneous or intravenous infection with HIV—primarily from sharing needles in injection drug use—accounts for 20% of new infections.⁷ Use of alcohol or other substances can lead to sexual coercion, unprotected sex, and exchange of sex for drugs or money. Hence, treating substance use disorders can prevent HIV transmission.

Early diagnosis of HIV can lead to appropriate medical care, quicker onset of antiretroviral (ARV) treatment, and better outcomes. Recent research has shown that pre-exposure prophylaxis with ARV treatment can prevent transmission of HIV⁸; therefore, becoming aware of risk behaviors and prevention can be lifesaving for serodiscordant couples.

One of the most important ways to prevent HIV’s impact on the brain and CNS is to diagnose HIV shortly after transmission at onset of acute infection. If HIV is diagnosed very early—preferably as soon as possible after inoculation with HIV or at onset of the first flu-like symptoms—and treated with ARVs, the brain has less of an opportunity to act as an independent reservoir for HIV-infected cells and therefore to develop HIV-associated neurocognitive disorders.^9,10Table 1 outlines steps psychiatrists can take to help prevent HIV transmission.

Psychiatric disorders and HIV

Psychiatric disorders and distress play a significant role in transmission of, exposure to, and infection with HIV (Table 2).^4-6,11 They are relevant for prevention, clinical care, and adherence throughout every aspect of illness.

Comprehensive, compassionate, nonjudgmental care of persons at risk for or infected with HIV begins with a thorough psychiatric evaluation designed to provide an ego-supportive, sensitive, and comprehensive assessment that can guide other clinicians in providing care.¹² Setting the tone and demonstrating compassion and respect includes shaking hands, which takes on special relevance in the context of AIDSism and stigma. Assessing the impact of HIV seropositivity or AIDS is best done by asking about the individual’s understanding of his or her diagnosis or illness and its impact. For some persons with HIV, verbalizing this understanding can be relieving as well as revealing. It is a chance for the patient to reveal painful experiences encountered in the home, school, camp, workplace, or community and the anguish of AIDSism and stigma.

Pay attention to sensitive and sometimes painful issues related to sexual history and sexuality. Questions related to sexual history and sexuality in heterosexual men and women as well as gay, lesbian, bisexual, and transgender individuals—such as “What is your sexual function like since you have been ill?” “Do feelings about your sexual identity play a role in your current level of distress?” and “What kind of barrier contraception are you using?”—are included in the comprehensive assessment described by Cohen et al.¹²

Comprehensive psychiatric evaluations can provide diagnoses, inform treatment, and mitigate anguish, distress, depression, anxiety, and substance use in persons with HIV and AIDS.¹² A thorough and comprehensive assessment is crucial because HIV has an affinity for brain and neural tissue and can cause CNS complications such as HIV-associated neurocognitive disorders (HAND), even in otherwise healthy HIV-seropositive individuals. See this article at CurrentPsychiatry.com for a discussion of HAND and delirium in patients with HIV.

Some persons with HIV and AIDS do not have a psychiatric disorder, while others have multiple complex psychiatric disorders that are responses to illness or treatments or are associated with HIV/AIDS (such as HAND) or other medical illnesses and treatments (such as hepatitis C, cirrhosis, end-stage liver disease, HIV nephropathy, end-stage renal disease, anemia, coronary artery disease, and cancer). See this article at CurrentPsychiatry.com for case studies of HIV patients with delirium, depression, posttraumatic stress disorder (PTSD), and substance dependence.

Mood disorders. Depression is common among persons with HIV. Demoralization and bereavement may masquerade as depression and can complicate diagnosis and treatment. Depression and other mood disorders may be related to stigma and AIDSism as well as to biologic, psychological, social, and genetic factors. Because suicide is prevalent among persons with HIV and AIDS,¹³ every patient with HIV should be evaluated for depression and suicidal ideation.

PTSD is prevalent among persons with HIV. It is a risky diagnosis because it is associated with a sense of a foreshortened future, which leads to a lack of adequate self-care, poor adherence to medical care, risky behaviors, and comorbid substance dependence to help numb the pain of trauma.^14,15 Persons with PTSD may have difficulty trusting clinicians and other authority figures if their trauma was a high-betrayal trauma, such as incest or military trauma.^14,15

In patients with HIV, PTSD often is overlooked because it may be overshadowed by other psychiatric diagnoses. Intimate partner violence, history of childhood trauma, and childhood sexual abuse are risk factors for HIV infection and PTSD. Increased severity of HIV-related PTSD symptoms is associated with having a greater number of HIV-related physical symptoms, history of pre-HIV trauma, decreased social support, increased perception of stigma, and negative life events.

PTSD also is associated with nonadherence to risk reduction strategies and medical care.^14,15 Diagnosis is further complicated by repression or retrograde amnesia of traumatic events and difficulties forming trusting relationships and disclosing HIV status to sexual partners or potential sexual partners because of fear of rejection. 

Substance use disorders. Dependence on alcohol and other drugs complicates and perpetuates the HIV pandemic. Sharing needles and other drug paraphernalia is instrumental in HIV transmission. The indirect effects of alcohol and substance abuse include:

•  the impact of intimate partner violence, child abuse, neglect, and/or abandonment

•  development of PTSD in adults, with early childhood trauma leading to repeating their own history

•  lack of self-care

•  unhealthy partner choices

•  use of drugs and alcohol to numb the pain associated with trauma.

Persons who are using alcohol or other drugs may have difficulty attending to their health, and substance dependence may prevent persons at risk from seeking HIV testing.

Intoxication from alcohol and drug use frequently leads to inappropriate partner choice, violent and coercive sexual behaviors, and lack of condom use. Substance dependence also may lead individuals to exchange sex for drugs and to fail to adhere to safer sexual practices or use sterile drug paraphernalia.

Treating persons with HIV/AIDS

Several organizations publish evidence-based clinical guidelines for treating depression, anxiety, substance abuse, and other psychiatric disorders in patients with HIV/AIDS. One such set of guidelines is available from the New York State Department of Health AIDS Institute at www.hivguidelines.org. As is the case with patients who do not have HIV, psychotherapy and pharmacotherapy are common first-line treatments.

Psychotherapy. Patients with HIV/AIDS with psychiatric comorbidities generally respond well to psychotherapeutic treatments.^16,17 The choice of therapy needs to be tailored to the needs of individuals, couples, and families coping with AIDS. Options include:

•  individual, couple, family, and group psychotherapy

•  crisis intervention

•  12-step programs (Alcohol Anonymous, Narcotics Anonymous, etc.)

•  adult survivors of child abuse programs (www.ascasupport.org), groups, and workbooks

•  palliative psychiatry

•  bereavement therapy

•  spiritual support

•  relaxation response

•  wellness interventions such as exercise, yoga, keeping a journal, writing a life narrative, reading, artwork, movement therapy, listening to music or books on tape, and working on crossword puzzles and jigsaw puzzles.

Psychopharmacotherapy. Accurate diagnosis and awareness of drug-drug and drug-illness interactions are important when treating patients with HIV/AIDS; consult resources in the literature¹⁸ and online resources that are updated regularly (see Related Resources). Because persons with AIDS are particularly vulnerable to extrapyramidal and anticholinergic side effects of psychotropics, the principle start very low and go very slow is critical. For patients who are opioid-dependent, be cautious when prescribing medications that are cytochrome P450 3A4 inducers—such as carbamazepine, efavirenz, nevirapine, and ritonavir—because these medications can lower methadone levels in persons receiving agonist treatment and might lead to opioid withdrawal symptoms, discontinuation of ARVs, or relapse to opioids.¹⁸ When a person with AIDS is experiencing pain and is on a maintenance dose of methadone for heroin withdrawal, pain should be treated as a separate problem with additional opioids. Methadone for relapse prevention will target opioid tolerance needs and prevent withdrawal but will not provide analgesia for pain.

HIV through the life cycle

From prevention of prenatal transmission to the care of children with HIV to reproductive issues in serodiscordant couples, HIV complicates patients’ development. Table 3 outlines concerns regarding HIV transmission and treatment at different stages of a patient’s life.

Bottom Line

HIV transmission and effective treatment are complicated by a high prevalence of psychiatric comorbidities, including depression and other mood disorders, posttraumatic stress disorder, substance use disorders, and cognitive disorders. With an increased understanding of the issues faced by patients at risk for or infected with HIV, psychiatrists can help prevent HIV transmission, improve adherence to medical care, and diminish suffering, morbidity, and mortality.

Related Resources

• Academy of Psychosomatic Medicine HIV/AIDS Psychiatry Special Interest Group. www.apm.org/sigs/oap.
• New York State Department of Health AIDS Institute. HIV Clinical Resource. www.hivguidelines.org.
• University of Liverpool. HIV drug interactions list. www.hiv-druginteractions.org.
• Toronto General Hospital Immunodeficiency Clinic. Drug interactions tables. www.hivclinic.ca/main/drugs_interact.html.

Drug Brand Names

Bupropion • Wellbutrin, Zyban
Nevirapine • Viramune
Carbamazepine • Carbatrol, Tegretol, others
Olanzapine • Zyprexa
Quetiapine • Seroquel
Clonazepam • Klonopin
Ritonavir • Norvir
Efavirenz • Sustiva
Venlafaxine • Effexor
Escitalopram • Lexapro

Disclosure

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

References

1. Blank MB, Mandell DS, Aiken L, et al. Co-occurrence of HIV and serious mental illness among Medicaid recipients. Psychiatr Serv. 2002;53(7):868-873.

2.Moyer VA, on behalf of the U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force recommendation statement [published online April 30, 2013]. Ann Intern Med. doi:10.7326/0003-4819-159-1-201307020-00645.

3. Hall HI, Song R, Rhodes P, et al. Estimation of HIV incidence in the United States. JAMA. 2008;300(5):520-529.

4. Cohen MA. AIDSism, a new form of discrimination. Am Med News. 1989;32:43.

5. Cohen MA, Gorman JM. Comprehensive textbook of AIDS psychiatry. New York, NY: Oxford University Press; 2008.

6. Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010.

7. World Health Organization, United Nations Children’s Fund, Joint United Nations Programme on HIV/AIDS. Global HIV/AIDS response. Epidemic update and health sector progress towards universal access. Progress report 2011. http://www.unaids.org/en/media/unaids/
contentassets/documents/unaidspublication/2011/
20111130_UA_Report_en.pdf. Accessed April 25, 2013.

8. Centers for Disease Control and Prevention (CDC). Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR Morb Mortal Wkly Rep. 2012;61(31):586-589.

9. Cysique LA, Murray JM, Dunbar M, et al. A screening algorithm for HIV-associated neurocognitive disorders. HIV Med. 2010;11(10):642-649.

10. Simioni S, Cavassini M, Annoni JM, et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. 2010;24(9):1243-1250.

11. Cohen M, Hoffman RG, Cromwell C, et al. The prevalence of distress in persons with human immunodeficiency virus infection. Psychosomatics. 2002;43(1):10-15.

12. Cohen MA, Batista SM, Lux JZ. A biopsychosocial approach to psychiatric consultation in persons with HIV and AIDS. In: Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010:33-60.

13. Carrico AW. Elevated suicide rate among HIV-positive persons despite benefits of antiretroviral therapy: implications for a stress and coping model of suicide. Am J Psychiatry. 2010;167(2):117-119.

14. Cohen MA, Alfonso CA, Hoffman RG, et al. The impact of PTSD on treatment adherence in persons with HIV infection. Gen Hosp Psychiatry. 2001;23(5):294-296.

15. Boarts JM, Sledjeski EM, Bogart LM, et al. The differential impact of PTSD and depression on HIV disease markers and adherence to HAART in people living with HIV. AIDS Behav. 2006;10(3):253-261.

16. Sikkema KJ, Hansen NB, Ghebremichael M, et al. A randomized controlled trial of a coping group intervention for adults with HIV who are AIDS bereaved: longitudinal effects on grief. Health Psychol. 2006;25(5):563-570.

17. Cohen MA. Psychodynamic psychotherapy in an AIDS nursing home. J Am Acad Psychoanal. 1999;27(1):121-133.

18. Cozza KL, Goforth HW, Batista SM. Psychopharmacologic treatment issues in AIDS psychiatry. In: Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010:147-199.

The prevalence of HIV in persons with untreated psychiatric illness may be 10 to 20 times that of the general population.¹ The U.S. Preventive Services Task Force has recommended HIV screening of all persons age 15 to 65 because 20% to 25% of individuals with HIV infection are unaware that they are HIV-positive.² Because >20% of new HIV infections in the United States are undiagnosed,³ it is crucial to educate patients with mental illness about HIV prevention, make condoms available, and offer HIV testing.

As psychiatrists, we have a unique role in caring for patients at risk for or infected with HIV because in addition to comprehensive medical and psychiatric histories, we routinely take histories of substance use, sexual activities, relationships, and trauma, including childhood neglect and emotional, physical, and sexual abuse. We develop long-term, trusting relationships and work with individuals to change behaviors and maximize life potential.

Increasing awareness of stigma, discrimination, and psychiatric factors involved with the HIV pandemic can lead to decreased transmission of HIV infection and early diagnosis and treatment. Compassionate medical and psychiatric care can mitigate suffering in persons at risk for, infected with, or affected by HIV.

Preventing HIV transmission

AIDS differs from other complex, severe illnesses in 2 ways that are relevant to psychiatrists:

•  it is almost entirely preventable

•  HIV and AIDS are associated with sex, drugs, and AIDS-associated stigma and discrimination (“AIDSism”).^4-6

Unsafe exposure of mucosal surfaces to the virus—primarily from exchanging body fluids in unprotected sexual encounters—accounts for 80% of new HIV infections.⁷ HIV transmission via sexual encounters is preventable with condoms. Percutaneous or intravenous infection with HIV—primarily from sharing needles in injection drug use—accounts for 20% of new infections.⁷ Use of alcohol or other substances can lead to sexual coercion, unprotected sex, and exchange of sex for drugs or money. Hence, treating substance use disorders can prevent HIV transmission.

Early diagnosis of HIV can lead to appropriate medical care, quicker onset of antiretroviral (ARV) treatment, and better outcomes. Recent research has shown that pre-exposure prophylaxis with ARV treatment can prevent transmission of HIV⁸; therefore, becoming aware of risk behaviors and prevention can be lifesaving for serodiscordant couples.

One of the most important ways to prevent HIV’s impact on the brain and CNS is to diagnose HIV shortly after transmission at onset of acute infection. If HIV is diagnosed very early—preferably as soon as possible after inoculation with HIV or at onset of the first flu-like symptoms—and treated with ARVs, the brain has less of an opportunity to act as an independent reservoir for HIV-infected cells and therefore to develop HIV-associated neurocognitive disorders.^9,10Table 1 outlines steps psychiatrists can take to help prevent HIV transmission.

Psychiatric disorders and HIV

Psychiatric disorders and distress play a significant role in transmission of, exposure to, and infection with HIV (Table 2).^4-6,11 They are relevant for prevention, clinical care, and adherence throughout every aspect of illness.

Comprehensive, compassionate, nonjudgmental care of persons at risk for or infected with HIV begins with a thorough psychiatric evaluation designed to provide an ego-supportive, sensitive, and comprehensive assessment that can guide other clinicians in providing care.¹² Setting the tone and demonstrating compassion and respect includes shaking hands, which takes on special relevance in the context of AIDSism and stigma. Assessing the impact of HIV seropositivity or AIDS is best done by asking about the individual’s understanding of his or her diagnosis or illness and its impact. For some persons with HIV, verbalizing this understanding can be relieving as well as revealing. It is a chance for the patient to reveal painful experiences encountered in the home, school, camp, workplace, or community and the anguish of AIDSism and stigma.

Pay attention to sensitive and sometimes painful issues related to sexual history and sexuality. Questions related to sexual history and sexuality in heterosexual men and women as well as gay, lesbian, bisexual, and transgender individuals—such as “What is your sexual function like since you have been ill?” “Do feelings about your sexual identity play a role in your current level of distress?” and “What kind of barrier contraception are you using?”—are included in the comprehensive assessment described by Cohen et al.¹²

Comprehensive psychiatric evaluations can provide diagnoses, inform treatment, and mitigate anguish, distress, depression, anxiety, and substance use in persons with HIV and AIDS.¹² A thorough and comprehensive assessment is crucial because HIV has an affinity for brain and neural tissue and can cause CNS complications such as HIV-associated neurocognitive disorders (HAND), even in otherwise healthy HIV-seropositive individuals. See this article at CurrentPsychiatry.com for a discussion of HAND and delirium in patients with HIV.

Some persons with HIV and AIDS do not have a psychiatric disorder, while others have multiple complex psychiatric disorders that are responses to illness or treatments or are associated with HIV/AIDS (such as HAND) or other medical illnesses and treatments (such as hepatitis C, cirrhosis, end-stage liver disease, HIV nephropathy, end-stage renal disease, anemia, coronary artery disease, and cancer). See this article at CurrentPsychiatry.com for case studies of HIV patients with delirium, depression, posttraumatic stress disorder (PTSD), and substance dependence.

Mood disorders. Depression is common among persons with HIV. Demoralization and bereavement may masquerade as depression and can complicate diagnosis and treatment. Depression and other mood disorders may be related to stigma and AIDSism as well as to biologic, psychological, social, and genetic factors. Because suicide is prevalent among persons with HIV and AIDS,¹³ every patient with HIV should be evaluated for depression and suicidal ideation.

PTSD is prevalent among persons with HIV. It is a risky diagnosis because it is associated with a sense of a foreshortened future, which leads to a lack of adequate self-care, poor adherence to medical care, risky behaviors, and comorbid substance dependence to help numb the pain of trauma.^14,15 Persons with PTSD may have difficulty trusting clinicians and other authority figures if their trauma was a high-betrayal trauma, such as incest or military trauma.^14,15

In patients with HIV, PTSD often is overlooked because it may be overshadowed by other psychiatric diagnoses. Intimate partner violence, history of childhood trauma, and childhood sexual abuse are risk factors for HIV infection and PTSD. Increased severity of HIV-related PTSD symptoms is associated with having a greater number of HIV-related physical symptoms, history of pre-HIV trauma, decreased social support, increased perception of stigma, and negative life events.

PTSD also is associated with nonadherence to risk reduction strategies and medical care.^14,15 Diagnosis is further complicated by repression or retrograde amnesia of traumatic events and difficulties forming trusting relationships and disclosing HIV status to sexual partners or potential sexual partners because of fear of rejection. 

Substance use disorders. Dependence on alcohol and other drugs complicates and perpetuates the HIV pandemic. Sharing needles and other drug paraphernalia is instrumental in HIV transmission. The indirect effects of alcohol and substance abuse include:

•  the impact of intimate partner violence, child abuse, neglect, and/or abandonment

•  development of PTSD in adults, with early childhood trauma leading to repeating their own history

•  lack of self-care

•  unhealthy partner choices

•  use of drugs and alcohol to numb the pain associated with trauma.

Persons who are using alcohol or other drugs may have difficulty attending to their health, and substance dependence may prevent persons at risk from seeking HIV testing.

Intoxication from alcohol and drug use frequently leads to inappropriate partner choice, violent and coercive sexual behaviors, and lack of condom use. Substance dependence also may lead individuals to exchange sex for drugs and to fail to adhere to safer sexual practices or use sterile drug paraphernalia.

Treating persons with HIV/AIDS

Several organizations publish evidence-based clinical guidelines for treating depression, anxiety, substance abuse, and other psychiatric disorders in patients with HIV/AIDS. One such set of guidelines is available from the New York State Department of Health AIDS Institute at www.hivguidelines.org. As is the case with patients who do not have HIV, psychotherapy and pharmacotherapy are common first-line treatments.

Psychotherapy. Patients with HIV/AIDS with psychiatric comorbidities generally respond well to psychotherapeutic treatments.^16,17 The choice of therapy needs to be tailored to the needs of individuals, couples, and families coping with AIDS. Options include:

•  individual, couple, family, and group psychotherapy

•  crisis intervention

•  12-step programs (Alcohol Anonymous, Narcotics Anonymous, etc.)

•  adult survivors of child abuse programs (www.ascasupport.org), groups, and workbooks

•  palliative psychiatry

•  bereavement therapy

•  spiritual support

•  relaxation response

•  wellness interventions such as exercise, yoga, keeping a journal, writing a life narrative, reading, artwork, movement therapy, listening to music or books on tape, and working on crossword puzzles and jigsaw puzzles.

Psychopharmacotherapy. Accurate diagnosis and awareness of drug-drug and drug-illness interactions are important when treating patients with HIV/AIDS; consult resources in the literature¹⁸ and online resources that are updated regularly (see Related Resources). Because persons with AIDS are particularly vulnerable to extrapyramidal and anticholinergic side effects of psychotropics, the principle start very low and go very slow is critical. For patients who are opioid-dependent, be cautious when prescribing medications that are cytochrome P450 3A4 inducers—such as carbamazepine, efavirenz, nevirapine, and ritonavir—because these medications can lower methadone levels in persons receiving agonist treatment and might lead to opioid withdrawal symptoms, discontinuation of ARVs, or relapse to opioids.¹⁸ When a person with AIDS is experiencing pain and is on a maintenance dose of methadone for heroin withdrawal, pain should be treated as a separate problem with additional opioids. Methadone for relapse prevention will target opioid tolerance needs and prevent withdrawal but will not provide analgesia for pain.

HIV through the life cycle

From prevention of prenatal transmission to the care of children with HIV to reproductive issues in serodiscordant couples, HIV complicates patients’ development. Table 3 outlines concerns regarding HIV transmission and treatment at different stages of a patient’s life.

Bottom Line

HIV transmission and effective treatment are complicated by a high prevalence of psychiatric comorbidities, including depression and other mood disorders, posttraumatic stress disorder, substance use disorders, and cognitive disorders. With an increased understanding of the issues faced by patients at risk for or infected with HIV, psychiatrists can help prevent HIV transmission, improve adherence to medical care, and diminish suffering, morbidity, and mortality.

Related Resources

• Academy of Psychosomatic Medicine HIV/AIDS Psychiatry Special Interest Group. www.apm.org/sigs/oap.
• New York State Department of Health AIDS Institute. HIV Clinical Resource. www.hivguidelines.org.
• University of Liverpool. HIV drug interactions list. www.hiv-druginteractions.org.
• Toronto General Hospital Immunodeficiency Clinic. Drug interactions tables. www.hivclinic.ca/main/drugs_interact.html.

Drug Brand Names

Bupropion • Wellbutrin, Zyban
Nevirapine • Viramune
Carbamazepine • Carbatrol, Tegretol, others
Olanzapine • Zyprexa
Quetiapine • Seroquel
Clonazepam • Klonopin
Ritonavir • Norvir
Efavirenz • Sustiva
Venlafaxine • Effexor
Escitalopram • Lexapro

Disclosure

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

References

1. Blank MB, Mandell DS, Aiken L, et al. Co-occurrence of HIV and serious mental illness among Medicaid recipients. Psychiatr Serv. 2002;53(7):868-873.

2.Moyer VA, on behalf of the U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force recommendation statement [published online April 30, 2013]. Ann Intern Med. doi:10.7326/0003-4819-159-1-201307020-00645.

3. Hall HI, Song R, Rhodes P, et al. Estimation of HIV incidence in the United States. JAMA. 2008;300(5):520-529.

4. Cohen MA. AIDSism, a new form of discrimination. Am Med News. 1989;32:43.

5. Cohen MA, Gorman JM. Comprehensive textbook of AIDS psychiatry. New York, NY: Oxford University Press; 2008.

6. Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010.

7. World Health Organization, United Nations Children’s Fund, Joint United Nations Programme on HIV/AIDS. Global HIV/AIDS response. Epidemic update and health sector progress towards universal access. Progress report 2011. http://www.unaids.org/en/media/unaids/
contentassets/documents/unaidspublication/2011/
20111130_UA_Report_en.pdf. Accessed April 25, 2013.

8. Centers for Disease Control and Prevention (CDC). Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR Morb Mortal Wkly Rep. 2012;61(31):586-589.

9. Cysique LA, Murray JM, Dunbar M, et al. A screening algorithm for HIV-associated neurocognitive disorders. HIV Med. 2010;11(10):642-649.

10. Simioni S, Cavassini M, Annoni JM, et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. 2010;24(9):1243-1250.

11. Cohen M, Hoffman RG, Cromwell C, et al. The prevalence of distress in persons with human immunodeficiency virus infection. Psychosomatics. 2002;43(1):10-15.

12. Cohen MA, Batista SM, Lux JZ. A biopsychosocial approach to psychiatric consultation in persons with HIV and AIDS. In: Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010:33-60.

13. Carrico AW. Elevated suicide rate among HIV-positive persons despite benefits of antiretroviral therapy: implications for a stress and coping model of suicide. Am J Psychiatry. 2010;167(2):117-119.

14. Cohen MA, Alfonso CA, Hoffman RG, et al. The impact of PTSD on treatment adherence in persons with HIV infection. Gen Hosp Psychiatry. 2001;23(5):294-296.

15. Boarts JM, Sledjeski EM, Bogart LM, et al. The differential impact of PTSD and depression on HIV disease markers and adherence to HAART in people living with HIV. AIDS Behav. 2006;10(3):253-261.

16. Sikkema KJ, Hansen NB, Ghebremichael M, et al. A randomized controlled trial of a coping group intervention for adults with HIV who are AIDS bereaved: longitudinal effects on grief. Health Psychol. 2006;25(5):563-570.

17. Cohen MA. Psychodynamic psychotherapy in an AIDS nursing home. J Am Acad Psychoanal. 1999;27(1):121-133.

18. Cozza KL, Goforth HW, Batista SM. Psychopharmacologic treatment issues in AIDS psychiatry. In: Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010:147-199.

The prevalence of HIV in persons with untreated psychiatric illness may be 10 to 20 times that of the general population.¹ The U.S. Preventive Services Task Force has recommended HIV screening of all persons age 15 to 65 because 20% to 25% of individuals with HIV infection are unaware that they are HIV-positive.² Because >20% of new HIV infections in the United States are undiagnosed,³ it is crucial to educate patients with mental illness about HIV prevention, make condoms available, and offer HIV testing.

As psychiatrists, we have a unique role in caring for patients at risk for or infected with HIV because in addition to comprehensive medical and psychiatric histories, we routinely take histories of substance use, sexual activities, relationships, and trauma, including childhood neglect and emotional, physical, and sexual abuse. We develop long-term, trusting relationships and work with individuals to change behaviors and maximize life potential.

Increasing awareness of stigma, discrimination, and psychiatric factors involved with the HIV pandemic can lead to decreased transmission of HIV infection and early diagnosis and treatment. Compassionate medical and psychiatric care can mitigate suffering in persons at risk for, infected with, or affected by HIV.

Preventing HIV transmission

AIDS differs from other complex, severe illnesses in 2 ways that are relevant to psychiatrists:

•  it is almost entirely preventable

•  HIV and AIDS are associated with sex, drugs, and AIDS-associated stigma and discrimination (“AIDSism”).^4-6

Unsafe exposure of mucosal surfaces to the virus—primarily from exchanging body fluids in unprotected sexual encounters—accounts for 80% of new HIV infections.⁷ HIV transmission via sexual encounters is preventable with condoms. Percutaneous or intravenous infection with HIV—primarily from sharing needles in injection drug use—accounts for 20% of new infections.⁷ Use of alcohol or other substances can lead to sexual coercion, unprotected sex, and exchange of sex for drugs or money. Hence, treating substance use disorders can prevent HIV transmission.

Early diagnosis of HIV can lead to appropriate medical care, quicker onset of antiretroviral (ARV) treatment, and better outcomes. Recent research has shown that pre-exposure prophylaxis with ARV treatment can prevent transmission of HIV⁸; therefore, becoming aware of risk behaviors and prevention can be lifesaving for serodiscordant couples.

One of the most important ways to prevent HIV’s impact on the brain and CNS is to diagnose HIV shortly after transmission at onset of acute infection. If HIV is diagnosed very early—preferably as soon as possible after inoculation with HIV or at onset of the first flu-like symptoms—and treated with ARVs, the brain has less of an opportunity to act as an independent reservoir for HIV-infected cells and therefore to develop HIV-associated neurocognitive disorders.^9,10Table 1 outlines steps psychiatrists can take to help prevent HIV transmission.

Psychiatric disorders and HIV

Psychiatric disorders and distress play a significant role in transmission of, exposure to, and infection with HIV (Table 2).^4-6,11 They are relevant for prevention, clinical care, and adherence throughout every aspect of illness.

Comprehensive, compassionate, nonjudgmental care of persons at risk for or infected with HIV begins with a thorough psychiatric evaluation designed to provide an ego-supportive, sensitive, and comprehensive assessment that can guide other clinicians in providing care.¹² Setting the tone and demonstrating compassion and respect includes shaking hands, which takes on special relevance in the context of AIDSism and stigma. Assessing the impact of HIV seropositivity or AIDS is best done by asking about the individual’s understanding of his or her diagnosis or illness and its impact. For some persons with HIV, verbalizing this understanding can be relieving as well as revealing. It is a chance for the patient to reveal painful experiences encountered in the home, school, camp, workplace, or community and the anguish of AIDSism and stigma.

Pay attention to sensitive and sometimes painful issues related to sexual history and sexuality. Questions related to sexual history and sexuality in heterosexual men and women as well as gay, lesbian, bisexual, and transgender individuals—such as “What is your sexual function like since you have been ill?” “Do feelings about your sexual identity play a role in your current level of distress?” and “What kind of barrier contraception are you using?”—are included in the comprehensive assessment described by Cohen et al.¹²

Comprehensive psychiatric evaluations can provide diagnoses, inform treatment, and mitigate anguish, distress, depression, anxiety, and substance use in persons with HIV and AIDS.¹² A thorough and comprehensive assessment is crucial because HIV has an affinity for brain and neural tissue and can cause CNS complications such as HIV-associated neurocognitive disorders (HAND), even in otherwise healthy HIV-seropositive individuals. See this article at CurrentPsychiatry.com for a discussion of HAND and delirium in patients with HIV.

Some persons with HIV and AIDS do not have a psychiatric disorder, while others have multiple complex psychiatric disorders that are responses to illness or treatments or are associated with HIV/AIDS (such as HAND) or other medical illnesses and treatments (such as hepatitis C, cirrhosis, end-stage liver disease, HIV nephropathy, end-stage renal disease, anemia, coronary artery disease, and cancer). See this article at CurrentPsychiatry.com for case studies of HIV patients with delirium, depression, posttraumatic stress disorder (PTSD), and substance dependence.

Mood disorders. Depression is common among persons with HIV. Demoralization and bereavement may masquerade as depression and can complicate diagnosis and treatment. Depression and other mood disorders may be related to stigma and AIDSism as well as to biologic, psychological, social, and genetic factors. Because suicide is prevalent among persons with HIV and AIDS,¹³ every patient with HIV should be evaluated for depression and suicidal ideation.

PTSD is prevalent among persons with HIV. It is a risky diagnosis because it is associated with a sense of a foreshortened future, which leads to a lack of adequate self-care, poor adherence to medical care, risky behaviors, and comorbid substance dependence to help numb the pain of trauma.^14,15 Persons with PTSD may have difficulty trusting clinicians and other authority figures if their trauma was a high-betrayal trauma, such as incest or military trauma.^14,15

In patients with HIV, PTSD often is overlooked because it may be overshadowed by other psychiatric diagnoses. Intimate partner violence, history of childhood trauma, and childhood sexual abuse are risk factors for HIV infection and PTSD. Increased severity of HIV-related PTSD symptoms is associated with having a greater number of HIV-related physical symptoms, history of pre-HIV trauma, decreased social support, increased perception of stigma, and negative life events.

PTSD also is associated with nonadherence to risk reduction strategies and medical care.^14,15 Diagnosis is further complicated by repression or retrograde amnesia of traumatic events and difficulties forming trusting relationships and disclosing HIV status to sexual partners or potential sexual partners because of fear of rejection. 

Substance use disorders. Dependence on alcohol and other drugs complicates and perpetuates the HIV pandemic. Sharing needles and other drug paraphernalia is instrumental in HIV transmission. The indirect effects of alcohol and substance abuse include:

•  the impact of intimate partner violence, child abuse, neglect, and/or abandonment

•  development of PTSD in adults, with early childhood trauma leading to repeating their own history

•  lack of self-care

•  unhealthy partner choices

•  use of drugs and alcohol to numb the pain associated with trauma.

Persons who are using alcohol or other drugs may have difficulty attending to their health, and substance dependence may prevent persons at risk from seeking HIV testing.

Intoxication from alcohol and drug use frequently leads to inappropriate partner choice, violent and coercive sexual behaviors, and lack of condom use. Substance dependence also may lead individuals to exchange sex for drugs and to fail to adhere to safer sexual practices or use sterile drug paraphernalia.

Treating persons with HIV/AIDS

Several organizations publish evidence-based clinical guidelines for treating depression, anxiety, substance abuse, and other psychiatric disorders in patients with HIV/AIDS. One such set of guidelines is available from the New York State Department of Health AIDS Institute at www.hivguidelines.org. As is the case with patients who do not have HIV, psychotherapy and pharmacotherapy are common first-line treatments.

Psychotherapy. Patients with HIV/AIDS with psychiatric comorbidities generally respond well to psychotherapeutic treatments.^16,17 The choice of therapy needs to be tailored to the needs of individuals, couples, and families coping with AIDS. Options include:

•  individual, couple, family, and group psychotherapy

•  crisis intervention

•  12-step programs (Alcohol Anonymous, Narcotics Anonymous, etc.)

•  adult survivors of child abuse programs (www.ascasupport.org), groups, and workbooks

•  palliative psychiatry

•  bereavement therapy

•  spiritual support

•  relaxation response

•  wellness interventions such as exercise, yoga, keeping a journal, writing a life narrative, reading, artwork, movement therapy, listening to music or books on tape, and working on crossword puzzles and jigsaw puzzles.

Psychopharmacotherapy. Accurate diagnosis and awareness of drug-drug and drug-illness interactions are important when treating patients with HIV/AIDS; consult resources in the literature¹⁸ and online resources that are updated regularly (see Related Resources). Because persons with AIDS are particularly vulnerable to extrapyramidal and anticholinergic side effects of psychotropics, the principle start very low and go very slow is critical. For patients who are opioid-dependent, be cautious when prescribing medications that are cytochrome P450 3A4 inducers—such as carbamazepine, efavirenz, nevirapine, and ritonavir—because these medications can lower methadone levels in persons receiving agonist treatment and might lead to opioid withdrawal symptoms, discontinuation of ARVs, or relapse to opioids.¹⁸ When a person with AIDS is experiencing pain and is on a maintenance dose of methadone for heroin withdrawal, pain should be treated as a separate problem with additional opioids. Methadone for relapse prevention will target opioid tolerance needs and prevent withdrawal but will not provide analgesia for pain.

HIV through the life cycle

From prevention of prenatal transmission to the care of children with HIV to reproductive issues in serodiscordant couples, HIV complicates patients’ development. Table 3 outlines concerns regarding HIV transmission and treatment at different stages of a patient’s life.

Bottom Line

HIV transmission and effective treatment are complicated by a high prevalence of psychiatric comorbidities, including depression and other mood disorders, posttraumatic stress disorder, substance use disorders, and cognitive disorders. With an increased understanding of the issues faced by patients at risk for or infected with HIV, psychiatrists can help prevent HIV transmission, improve adherence to medical care, and diminish suffering, morbidity, and mortality.

Related Resources

• Academy of Psychosomatic Medicine HIV/AIDS Psychiatry Special Interest Group. www.apm.org/sigs/oap.
• New York State Department of Health AIDS Institute. HIV Clinical Resource. www.hivguidelines.org.
• University of Liverpool. HIV drug interactions list. www.hiv-druginteractions.org.
• Toronto General Hospital Immunodeficiency Clinic. Drug interactions tables. www.hivclinic.ca/main/drugs_interact.html.

Drug Brand Names

Bupropion • Wellbutrin, Zyban
Nevirapine • Viramune
Carbamazepine • Carbatrol, Tegretol, others
Olanzapine • Zyprexa
Quetiapine • Seroquel
Clonazepam • Klonopin
Ritonavir • Norvir
Efavirenz • Sustiva
Venlafaxine • Effexor
Escitalopram • Lexapro

Disclosure

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

References

1. Blank MB, Mandell DS, Aiken L, et al. Co-occurrence of HIV and serious mental illness among Medicaid recipients. Psychiatr Serv. 2002;53(7):868-873.

2.Moyer VA, on behalf of the U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force recommendation statement [published online April 30, 2013]. Ann Intern Med. doi:10.7326/0003-4819-159-1-201307020-00645.

3. Hall HI, Song R, Rhodes P, et al. Estimation of HIV incidence in the United States. JAMA. 2008;300(5):520-529.

4. Cohen MA. AIDSism, a new form of discrimination. Am Med News. 1989;32:43.

5. Cohen MA, Gorman JM. Comprehensive textbook of AIDS psychiatry. New York, NY: Oxford University Press; 2008.

6. Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010.

7. World Health Organization, United Nations Children’s Fund, Joint United Nations Programme on HIV/AIDS. Global HIV/AIDS response. Epidemic update and health sector progress towards universal access. Progress report 2011. http://www.unaids.org/en/media/unaids/
contentassets/documents/unaidspublication/2011/
20111130_UA_Report_en.pdf. Accessed April 25, 2013.

8. Centers for Disease Control and Prevention (CDC). Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR Morb Mortal Wkly Rep. 2012;61(31):586-589.

9. Cysique LA, Murray JM, Dunbar M, et al. A screening algorithm for HIV-associated neurocognitive disorders. HIV Med. 2010;11(10):642-649.

10. Simioni S, Cavassini M, Annoni JM, et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. 2010;24(9):1243-1250.

11. Cohen M, Hoffman RG, Cromwell C, et al. The prevalence of distress in persons with human immunodeficiency virus infection. Psychosomatics. 2002;43(1):10-15.

12. Cohen MA, Batista SM, Lux JZ. A biopsychosocial approach to psychiatric consultation in persons with HIV and AIDS. In: Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010:33-60.

13. Carrico AW. Elevated suicide rate among HIV-positive persons despite benefits of antiretroviral therapy: implications for a stress and coping model of suicide. Am J Psychiatry. 2010;167(2):117-119.

14. Cohen MA, Alfonso CA, Hoffman RG, et al. The impact of PTSD on treatment adherence in persons with HIV infection. Gen Hosp Psychiatry. 2001;23(5):294-296.

15. Boarts JM, Sledjeski EM, Bogart LM, et al. The differential impact of PTSD and depression on HIV disease markers and adherence to HAART in people living with HIV. AIDS Behav. 2006;10(3):253-261.

16. Sikkema KJ, Hansen NB, Ghebremichael M, et al. A randomized controlled trial of a coping group intervention for adults with HIV who are AIDS bereaved: longitudinal effects on grief. Health Psychol. 2006;25(5):563-570.

17. Cohen MA. Psychodynamic psychotherapy in an AIDS nursing home. J Am Acad Psychoanal. 1999;27(1):121-133.

18. Cozza KL, Goforth HW, Batista SM. Psychopharmacologic treatment issues in AIDS psychiatry. In: Cohen MA, Goforth HW, Lux JZ, et al, eds. Handbook of AIDS psychiatry. New York, NY: Oxford University Press; 2010:147-199.

When evaluating a patient’s risk of violence, the presence of psychosis is a crucial concern. Douglas et al¹ found that psychosis was the most important predictor of violent behavior in an analysis of 204 studies examining the relationship between psychopathology and aggression. Clinicians need to be familiar with aspects of persecutory delusions and command auditory hallucinations that are associated with an increased risk of aggression because accurately assessing patients who are experiencing these 2 symptoms is an important part of a comprehensive violence risk assessment.

This article highlights the importance of investigating persecutory delusions and command auditory hallucinations when evaluating a psychotic patient’s risk for violence. We provide specific questions to ask to help gauge risk associated with these 2 symptoms.

Evaluating persecutory delusions

Do persecutory delusions increase the risk that a person will behave violently? Research examining delusions’ contribution to violent behavior does not provide a clear answer. Earlier studies suggested that persecutory delusions were associated with an increased risk of aggression.² Delusions noted to increase the risk of violence were characterized by threat/control-override (TCO) symptoms. TCO symptoms are beliefs that one is being threatened (eg, being followed or poisoned) or is losing control to an external source (eg, one’s mind is dominated by forces beyond his or her control).³ Similarly, using data from the Epidemiologic Catchment Area surveys, Swanson et al⁴ found that patients who reported TCO symptoms were approximately twice as likely to engage in assaultive behavior compared with patients with other psychotic symptoms.

In contrast, the MacArthur Study of Mental Disorder and Violence^5,6 showed that the presence of delusions did not predict higher rates of violence among recently discharged psychiatric patients. In particular, researchers did not find a relationship between the presence of TCO delusions and violent behavior. In a study comparing male criminal offenders with schizophrenia found not guilty by reason of insanity with matched non-offending schizophrenia patients, Stompe et al⁷ found no significant association between TCO symptoms and severity of violent behavior; prevalence of TCO symptoms did not differ between the 2 groups. However, nondelusional suspiciousness—such as misperceiving others’ behavior as indicating hostile intent—was associated with subsequent violence.⁶

Nederlof et al⁸ conducted a cross-sectional multicenter study to further examine whether TCO symptoms are related to aggressive behavior. Their study included 124 patients (88% men) who had paranoid schizophrenia (70%), “other forms” of schizophrenia (16%), schizoaffective disorder (3%), delusional disorder (1%), and psychosis not otherwise specified (10%). To measure TCO symptoms in a more detailed manner than in previous research, these researchers developed the Threat/Control-Override Questionnaire (TCOQ), a 14-item, self-report scale. The 7 threat items specific to the TCOQ are:⁸

• I am under the control of an external force that determines my actions.
• Other people have tried to poison me or to do me harm.
• Someone has deliberately tried to make me ill.
• Other people have been secretly plotting to ruin me.
• Someone has had evil intentions against me.
• I have the thought that I was being followed for a special reason.
• People have tried to drive me insane.

The 7 control-override items on the TCOQ are:⁸

• Other people control my way of movements.
• Other people can insert thoughts into my head.
• My thoughts are dominated by an external force.
• I have the feeling that other people can determine my thoughts.
• Other people can insert thoughts into my mind.
• I have the feeling that other people have control over me.
• My life is being determined by something or someone except for myself.

Nederlof et al⁸ determined that TCO symptoms were a significant correlate of aggression in their study sample. When the 2 domains of TCO symptoms were evaluated separately, only threat symptoms made a significant contribution to aggressive behavior. These researchers suggested that varying methods of measuring TCO symptoms may underlie previous studies’ seemingly contradictory findings.⁸ These recent findings indicate that the debate regarding the contribution of TCO symptoms, particularly threat symptoms, to future violence remains active.

Appelbaum et al⁹ used the MacArthur-Maudsley Delusions Assessment Schedule to examine the contribution of non-content-related delusional material to violence in interviews with 328 delusional hospitalized psychiatric patients. The 7 dimensions of the MacArthur-Maudsley Delusions Assessment Schedule are:

• Conviction—the degree of certainty about the delusional belief
• Negative affect—whether the delusional belief makes the patient unhappy, frightened, anxious, or angry
• Action—the extent to which the patient’s actions are motivated by the delusional belief
• Inaction—whether the patient has refrained from any action as a result of the delusional belief
• Preoccupation—the extent to which the patient indicates his or her thoughts focus exclusively on the delusion
• Pervasiveness—the degree to which the delusional belief penetrates all aspects of the patient’s experiences
• Fluidity—the degree to which the delusional belief changed frequently during the interview.

Patients with persecutory delusions had significantly higher scores on “action” and “negative affect” dimensions, indicating that those with persecutory delusions may be more likely to react in response to the dysphoric aspects of their symptoms.⁹ Subsequent research has demonstrated that patients who suffer from persecutory delusions and negative affect are more likely to act on their delusions^2,10 and to act violently¹¹ than patients without these symptoms.

When evaluating a patient who experiences persecutory delusions, inquire if he or she has employed “safety actions.” These are specific behaviors—such as avoiding a perceived persecutor or escaping a fearful situation—the individual has employed with the intention of minimizing a misperceived threat. In a study of 100 patients with persecutory delusions, 96% reported using safety behaviors in the past month.¹² In this study, individuals with a history of violence reported a greater use of safety behaviors.

Table 1 lists 10 questions to ask patients to explore persecutory delusions and associated risk factors for aggression.

Table 1

Evaluating persecutory delusions: 10 questions

Assessing auditory hallucinations

A careful inquiry about hallucinations can help determine whether their presence increases a patient’s risk of committing a violent act. Command hallucinations provide some type of directive to the patient. Approximately 50% of hallucinating psychiatric patients experience command hallucinations.¹³ Most command hallucinations are nonviolent, and patients are more likely to obey nonviolent instructions than violent commands.¹⁴

Research on factors associated with a patient acting on harmful command hallucinations has been mixed. In a review of 7 controlled studies, no study demonstrated a positive relationship between command hallucinations and violence, and 1 found an inverse relationship.¹⁵ In contrast, in a study of 103 psychiatric inpatients, McNiel et al¹⁶ found 30% reported having command hallucinations to harm others during the past year and 22% reported they complied with such commands. These researchers concluded that compared with those without command hallucinations, patients in their study who experienced command hallucinations to harm others were more than twice as likely to be violent.

Much of the literature examining the relationship between a patient’s actions and command hallucinations has examined the patient’s response to all command hallucinations, without delineating factors specific to violent commands. Seven factors are associated with acting on command hallucinations:¹³

• the presence of coexisting delusions¹⁷
• having delusions that relate to the hallucination¹⁸
• knowing the voice’s identity¹⁸
• believing the voices to be real¹⁹
• believing that the voices are benevolent²⁰
• having few coping strategies to deal with the voices¹⁷
• not feeling in control over the voices.²⁰

These factors also have been found to indicate increased compliance with acting on violent command hallucinations.^18,20 Studies that have examined compliance specific to harmful command hallucinations provide additional guidance when evaluating the patient’s risk of harm. Aspects relevant to increased compliance to violent command hallucinations include a belief that the voice is powerful,^13,21 a patient’s sense of personal superiority,²¹ a belief that command hallucinations benefit the patient,¹³ delusions that were congruent with the action described,¹³ and hallucinations that generate negative emotions such as anger, anxiety, and sadness.¹¹

Table 2 lists 10 questions to ask to further investigate general command auditory hallucinations and violent command auditory hallucinations.

Table 2

Evaluating command auditory hallucinations: 10 questions

Related Resources

• MacArthur Research Network on Mental Health and the Law. The MacArthur Violence Risk Assessment Study.http://macarthur.virginia.edu/risk.html.
• Witt K, van Dorn R, Fazel S. Risk factors for violence in psychosis: systematic review and meta-regression analysis of 110 studies [published online February 13, 2013]. PLoS One. 2013;8(2):e55942. doi: 10.1371/journal.pone.0055942.

Disclosure

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

When evaluating a patient’s risk of violence, the presence of psychosis is a crucial concern. Douglas et al¹ found that psychosis was the most important predictor of violent behavior in an analysis of 204 studies examining the relationship between psychopathology and aggression. Clinicians need to be familiar with aspects of persecutory delusions and command auditory hallucinations that are associated with an increased risk of aggression because accurately assessing patients who are experiencing these 2 symptoms is an important part of a comprehensive violence risk assessment.

This article highlights the importance of investigating persecutory delusions and command auditory hallucinations when evaluating a psychotic patient’s risk for violence. We provide specific questions to ask to help gauge risk associated with these 2 symptoms.

Evaluating persecutory delusions

Do persecutory delusions increase the risk that a person will behave violently? Research examining delusions’ contribution to violent behavior does not provide a clear answer. Earlier studies suggested that persecutory delusions were associated with an increased risk of aggression.² Delusions noted to increase the risk of violence were characterized by threat/control-override (TCO) symptoms. TCO symptoms are beliefs that one is being threatened (eg, being followed or poisoned) or is losing control to an external source (eg, one’s mind is dominated by forces beyond his or her control).³ Similarly, using data from the Epidemiologic Catchment Area surveys, Swanson et al⁴ found that patients who reported TCO symptoms were approximately twice as likely to engage in assaultive behavior compared with patients with other psychotic symptoms.

In contrast, the MacArthur Study of Mental Disorder and Violence^5,6 showed that the presence of delusions did not predict higher rates of violence among recently discharged psychiatric patients. In particular, researchers did not find a relationship between the presence of TCO delusions and violent behavior. In a study comparing male criminal offenders with schizophrenia found not guilty by reason of insanity with matched non-offending schizophrenia patients, Stompe et al⁷ found no significant association between TCO symptoms and severity of violent behavior; prevalence of TCO symptoms did not differ between the 2 groups. However, nondelusional suspiciousness—such as misperceiving others’ behavior as indicating hostile intent—was associated with subsequent violence.⁶

Nederlof et al⁸ conducted a cross-sectional multicenter study to further examine whether TCO symptoms are related to aggressive behavior. Their study included 124 patients (88% men) who had paranoid schizophrenia (70%), “other forms” of schizophrenia (16%), schizoaffective disorder (3%), delusional disorder (1%), and psychosis not otherwise specified (10%). To measure TCO symptoms in a more detailed manner than in previous research, these researchers developed the Threat/Control-Override Questionnaire (TCOQ), a 14-item, self-report scale. The 7 threat items specific to the TCOQ are:⁸

• I am under the control of an external force that determines my actions.
• Other people have tried to poison me or to do me harm.
• Someone has deliberately tried to make me ill.
• Other people have been secretly plotting to ruin me.
• Someone has had evil intentions against me.
• I have the thought that I was being followed for a special reason.
• People have tried to drive me insane.

The 7 control-override items on the TCOQ are:⁸

• Other people control my way of movements.
• Other people can insert thoughts into my head.
• My thoughts are dominated by an external force.
• I have the feeling that other people can determine my thoughts.
• Other people can insert thoughts into my mind.
• I have the feeling that other people have control over me.
• My life is being determined by something or someone except for myself.

Nederlof et al⁸ determined that TCO symptoms were a significant correlate of aggression in their study sample. When the 2 domains of TCO symptoms were evaluated separately, only threat symptoms made a significant contribution to aggressive behavior. These researchers suggested that varying methods of measuring TCO symptoms may underlie previous studies’ seemingly contradictory findings.⁸ These recent findings indicate that the debate regarding the contribution of TCO symptoms, particularly threat symptoms, to future violence remains active.

Appelbaum et al⁹ used the MacArthur-Maudsley Delusions Assessment Schedule to examine the contribution of non-content-related delusional material to violence in interviews with 328 delusional hospitalized psychiatric patients. The 7 dimensions of the MacArthur-Maudsley Delusions Assessment Schedule are:

• Conviction—the degree of certainty about the delusional belief
• Negative affect—whether the delusional belief makes the patient unhappy, frightened, anxious, or angry
• Action—the extent to which the patient’s actions are motivated by the delusional belief
• Inaction—whether the patient has refrained from any action as a result of the delusional belief
• Preoccupation—the extent to which the patient indicates his or her thoughts focus exclusively on the delusion
• Pervasiveness—the degree to which the delusional belief penetrates all aspects of the patient’s experiences
• Fluidity—the degree to which the delusional belief changed frequently during the interview.

Patients with persecutory delusions had significantly higher scores on “action” and “negative affect” dimensions, indicating that those with persecutory delusions may be more likely to react in response to the dysphoric aspects of their symptoms.⁹ Subsequent research has demonstrated that patients who suffer from persecutory delusions and negative affect are more likely to act on their delusions^2,10 and to act violently¹¹ than patients without these symptoms.

When evaluating a patient who experiences persecutory delusions, inquire if he or she has employed “safety actions.” These are specific behaviors—such as avoiding a perceived persecutor or escaping a fearful situation—the individual has employed with the intention of minimizing a misperceived threat. In a study of 100 patients with persecutory delusions, 96% reported using safety behaviors in the past month.¹² In this study, individuals with a history of violence reported a greater use of safety behaviors.

Table 1 lists 10 questions to ask patients to explore persecutory delusions and associated risk factors for aggression.

Table 1

Evaluating persecutory delusions: 10 questions

Assessing auditory hallucinations

A careful inquiry about hallucinations can help determine whether their presence increases a patient’s risk of committing a violent act. Command hallucinations provide some type of directive to the patient. Approximately 50% of hallucinating psychiatric patients experience command hallucinations.¹³ Most command hallucinations are nonviolent, and patients are more likely to obey nonviolent instructions than violent commands.¹⁴

Research on factors associated with a patient acting on harmful command hallucinations has been mixed. In a review of 7 controlled studies, no study demonstrated a positive relationship between command hallucinations and violence, and 1 found an inverse relationship.¹⁵ In contrast, in a study of 103 psychiatric inpatients, McNiel et al¹⁶ found 30% reported having command hallucinations to harm others during the past year and 22% reported they complied with such commands. These researchers concluded that compared with those without command hallucinations, patients in their study who experienced command hallucinations to harm others were more than twice as likely to be violent.

Much of the literature examining the relationship between a patient’s actions and command hallucinations has examined the patient’s response to all command hallucinations, without delineating factors specific to violent commands. Seven factors are associated with acting on command hallucinations:¹³

• the presence of coexisting delusions¹⁷
• having delusions that relate to the hallucination¹⁸
• knowing the voice’s identity¹⁸
• believing the voices to be real¹⁹
• believing that the voices are benevolent²⁰
• having few coping strategies to deal with the voices¹⁷
• not feeling in control over the voices.²⁰

These factors also have been found to indicate increased compliance with acting on violent command hallucinations.^18,20 Studies that have examined compliance specific to harmful command hallucinations provide additional guidance when evaluating the patient’s risk of harm. Aspects relevant to increased compliance to violent command hallucinations include a belief that the voice is powerful,^13,21 a patient’s sense of personal superiority,²¹ a belief that command hallucinations benefit the patient,¹³ delusions that were congruent with the action described,¹³ and hallucinations that generate negative emotions such as anger, anxiety, and sadness.¹¹

Table 2 lists 10 questions to ask to further investigate general command auditory hallucinations and violent command auditory hallucinations.

Table 2

Evaluating command auditory hallucinations: 10 questions

Related Resources

• MacArthur Research Network on Mental Health and the Law. The MacArthur Violence Risk Assessment Study.http://macarthur.virginia.edu/risk.html.
• Witt K, van Dorn R, Fazel S. Risk factors for violence in psychosis: systematic review and meta-regression analysis of 110 studies [published online February 13, 2013]. PLoS One. 2013;8(2):e55942. doi: 10.1371/journal.pone.0055942.

Disclosure

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

When evaluating a patient’s risk of violence, the presence of psychosis is a crucial concern. Douglas et al¹ found that psychosis was the most important predictor of violent behavior in an analysis of 204 studies examining the relationship between psychopathology and aggression. Clinicians need to be familiar with aspects of persecutory delusions and command auditory hallucinations that are associated with an increased risk of aggression because accurately assessing patients who are experiencing these 2 symptoms is an important part of a comprehensive violence risk assessment.

This article highlights the importance of investigating persecutory delusions and command auditory hallucinations when evaluating a psychotic patient’s risk for violence. We provide specific questions to ask to help gauge risk associated with these 2 symptoms.

Evaluating persecutory delusions

Do persecutory delusions increase the risk that a person will behave violently? Research examining delusions’ contribution to violent behavior does not provide a clear answer. Earlier studies suggested that persecutory delusions were associated with an increased risk of aggression.² Delusions noted to increase the risk of violence were characterized by threat/control-override (TCO) symptoms. TCO symptoms are beliefs that one is being threatened (eg, being followed or poisoned) or is losing control to an external source (eg, one’s mind is dominated by forces beyond his or her control).³ Similarly, using data from the Epidemiologic Catchment Area surveys, Swanson et al⁴ found that patients who reported TCO symptoms were approximately twice as likely to engage in assaultive behavior compared with patients with other psychotic symptoms.

In contrast, the MacArthur Study of Mental Disorder and Violence^5,6 showed that the presence of delusions did not predict higher rates of violence among recently discharged psychiatric patients. In particular, researchers did not find a relationship between the presence of TCO delusions and violent behavior. In a study comparing male criminal offenders with schizophrenia found not guilty by reason of insanity with matched non-offending schizophrenia patients, Stompe et al⁷ found no significant association between TCO symptoms and severity of violent behavior; prevalence of TCO symptoms did not differ between the 2 groups. However, nondelusional suspiciousness—such as misperceiving others’ behavior as indicating hostile intent—was associated with subsequent violence.⁶

Nederlof et al⁸ conducted a cross-sectional multicenter study to further examine whether TCO symptoms are related to aggressive behavior. Their study included 124 patients (88% men) who had paranoid schizophrenia (70%), “other forms” of schizophrenia (16%), schizoaffective disorder (3%), delusional disorder (1%), and psychosis not otherwise specified (10%). To measure TCO symptoms in a more detailed manner than in previous research, these researchers developed the Threat/Control-Override Questionnaire (TCOQ), a 14-item, self-report scale. The 7 threat items specific to the TCOQ are:⁸

• I am under the control of an external force that determines my actions.
• Other people have tried to poison me or to do me harm.
• Someone has deliberately tried to make me ill.
• Other people have been secretly plotting to ruin me.
• Someone has had evil intentions against me.
• I have the thought that I was being followed for a special reason.
• People have tried to drive me insane.

The 7 control-override items on the TCOQ are:⁸

• Other people control my way of movements.
• Other people can insert thoughts into my head.
• My thoughts are dominated by an external force.
• I have the feeling that other people can determine my thoughts.
• Other people can insert thoughts into my mind.
• I have the feeling that other people have control over me.
• My life is being determined by something or someone except for myself.

Nederlof et al⁸ determined that TCO symptoms were a significant correlate of aggression in their study sample. When the 2 domains of TCO symptoms were evaluated separately, only threat symptoms made a significant contribution to aggressive behavior. These researchers suggested that varying methods of measuring TCO symptoms may underlie previous studies’ seemingly contradictory findings.⁸ These recent findings indicate that the debate regarding the contribution of TCO symptoms, particularly threat symptoms, to future violence remains active.

Appelbaum et al⁹ used the MacArthur-Maudsley Delusions Assessment Schedule to examine the contribution of non-content-related delusional material to violence in interviews with 328 delusional hospitalized psychiatric patients. The 7 dimensions of the MacArthur-Maudsley Delusions Assessment Schedule are:

• Conviction—the degree of certainty about the delusional belief
• Negative affect—whether the delusional belief makes the patient unhappy, frightened, anxious, or angry
• Action—the extent to which the patient’s actions are motivated by the delusional belief
• Inaction—whether the patient has refrained from any action as a result of the delusional belief
• Preoccupation—the extent to which the patient indicates his or her thoughts focus exclusively on the delusion
• Pervasiveness—the degree to which the delusional belief penetrates all aspects of the patient’s experiences
• Fluidity—the degree to which the delusional belief changed frequently during the interview.

Patients with persecutory delusions had significantly higher scores on “action” and “negative affect” dimensions, indicating that those with persecutory delusions may be more likely to react in response to the dysphoric aspects of their symptoms.⁹ Subsequent research has demonstrated that patients who suffer from persecutory delusions and negative affect are more likely to act on their delusions^2,10 and to act violently¹¹ than patients without these symptoms.

When evaluating a patient who experiences persecutory delusions, inquire if he or she has employed “safety actions.” These are specific behaviors—such as avoiding a perceived persecutor or escaping a fearful situation—the individual has employed with the intention of minimizing a misperceived threat. In a study of 100 patients with persecutory delusions, 96% reported using safety behaviors in the past month.¹² In this study, individuals with a history of violence reported a greater use of safety behaviors.

Table 1 lists 10 questions to ask patients to explore persecutory delusions and associated risk factors for aggression.

Table 1

Evaluating persecutory delusions: 10 questions

Assessing auditory hallucinations

A careful inquiry about hallucinations can help determine whether their presence increases a patient’s risk of committing a violent act. Command hallucinations provide some type of directive to the patient. Approximately 50% of hallucinating psychiatric patients experience command hallucinations.¹³ Most command hallucinations are nonviolent, and patients are more likely to obey nonviolent instructions than violent commands.¹⁴

Research on factors associated with a patient acting on harmful command hallucinations has been mixed. In a review of 7 controlled studies, no study demonstrated a positive relationship between command hallucinations and violence, and 1 found an inverse relationship.¹⁵ In contrast, in a study of 103 psychiatric inpatients, McNiel et al¹⁶ found 30% reported having command hallucinations to harm others during the past year and 22% reported they complied with such commands. These researchers concluded that compared with those without command hallucinations, patients in their study who experienced command hallucinations to harm others were more than twice as likely to be violent.

Much of the literature examining the relationship between a patient’s actions and command hallucinations has examined the patient’s response to all command hallucinations, without delineating factors specific to violent commands. Seven factors are associated with acting on command hallucinations:¹³

• the presence of coexisting delusions¹⁷
• having delusions that relate to the hallucination¹⁸
• knowing the voice’s identity¹⁸
• believing the voices to be real¹⁹
• believing that the voices are benevolent²⁰
• having few coping strategies to deal with the voices¹⁷
• not feeling in control over the voices.²⁰

These factors also have been found to indicate increased compliance with acting on violent command hallucinations.^18,20 Studies that have examined compliance specific to harmful command hallucinations provide additional guidance when evaluating the patient’s risk of harm. Aspects relevant to increased compliance to violent command hallucinations include a belief that the voice is powerful,^13,21 a patient’s sense of personal superiority,²¹ a belief that command hallucinations benefit the patient,¹³ delusions that were congruent with the action described,¹³ and hallucinations that generate negative emotions such as anger, anxiety, and sadness.¹¹

Table 2 lists 10 questions to ask to further investigate general command auditory hallucinations and violent command auditory hallucinations.

Table 2

Evaluating command auditory hallucinations: 10 questions

Related Resources

• MacArthur Research Network on Mental Health and the Law. The MacArthur Violence Risk Assessment Study.http://macarthur.virginia.edu/risk.html.
• Witt K, van Dorn R, Fazel S. Risk factors for violence in psychosis: systematic review and meta-regression analysis of 110 studies [published online February 13, 2013]. PLoS One. 2013;8(2):e55942. doi: 10.1371/journal.pone.0055942.

Disclosure

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

My mother and I were in the hospital lobby waiting for my father. My normally upbeat, sharp, energetic mom looked sick, weak, and confused. She had just been discharged from the hospital after experiencing a seizure caused by brain metastasis from long-standing breast cancer. Although we had discussed hospice care during my mother’s admission, we left the hospital without setting up the service because we wanted more time to see if she could recover. Two days later, we arranged hospice because of my mother’s rapidly deteriorating condition and our inability to manage her illness on our own. Five days later, she passed away at home surrounded by loved ones.

I am bewildered that my family did not transition my mother to end-of-life care earlier. Several family members and I work in the medical field. Being resourceful, we chose treatment at a large medical center that was a 3-hour drive from our home. Also, we were familiar with palliative care because other family members had died with hospice. Yet, in those last precious moments, we did not initiate end-of-life care for my mother until it became an emergency. This experience cultivated my interest in palliative care and hospice, specifically, in barriers to access and better ways to transition from life-saving treatment to end-of-life care. As a psychiatry resident, I feel it is important to expand opportunities for psychiatrists to participate in palliative care teams.

Barriers to end-of-life care

Poor physician-patient communication near the end of life can be a major barrier to care. Studies suggest that patients and physicians are ambivalent about end-of-life discussions and tend to avoid them.¹ Communication is crucial to helping patients prepare to die well. Researchers have found that end-of-life discussions between patients and physicians can result in fewer aggressive interventions and better quality of life near death.² These discussions did not increase emotional distress and were associated with lower rates of ventilation, resuscitation, and intensive care unit admissions.² End-of-life discussions between physicians and patients also lead to earlier hospice enrollment and improve the quality of end-of-life care.²

Approximately one-third of patients spend <1 week in hospice.³ Studies have suggested that patients who receive >1 week of hospice care have improved quality of life compared with patients who do not receive hospice care.¹ Addressing end-of-life issues early in treatment of terminally ill patients allows them to become familiar with their options as their disease progresses.

Lack of integration between hospice and the medical community is another barrier. According to Medicare guidelines,⁴ to be eligible for hospice a patient must have a terminal illness with a prognosis of ≤6 months. The patient must agree to give up curative treatment. If a patient lives >6 months, hospice benefits can be renewed as long as the patient has shown a persistent decline. Patients must desire and accept a palliative approach rather than a curative focus and agree to have all care provided by Medicare-certified hospices.⁵ These eligibility requirements may give patients and their families a sense that they are losing the forms of health care they had been using, physicians they know, and treatments they had become accustomed to, and are transferring their medical care to a unknown entity. This transition occurs when diseases are progressing and patients may feel vulnerable. In this way, end-of-life care is segregated from the rest of the medical system and can feel foreign and frightening to patients.⁶

Lack of palliative care specialists. The U.S. population is aging, and more people are living longer with chronic illness. Although the palliative care field is growing, only 60% of U.S. hospitals have palliative care programs and there is a shortage of palliative care clinicians.⁷

Psychiatry and end-of-life care

Psychiatry and psycho-oncology can help address these barriers by providing resources and expertise to palliative care teams. Psychiatrists can facilitate communication between families and primary clinicians and help patients mentally prepare for end-of-life options.

The dying process may uncover psychological, psychosocial, and existential suffering in patients and their families that often is underdiagnosed and undertreated.⁸ Psychiatrists can:

• diagnose and treat psychiatric disorders that surface under the stress of a new diagnosis
• aid in the psychodynamics of coping with terminal illness
• assess decision-making capacity
• recognize and treat staff stress
• provide bereavement care.

Because many clinicians believe that mood or anxiety symptoms are “normal reactions” in individuals struggling with end-of-life issues, these patients may not receive psychiatric treatment. However, treating mood and anxiety disorders can improve quality of life in palliative care patients.⁹

In terminally ill patients, psychological pain often manifests as symptoms of depression and anxiety. Diagnostic criteria for depression may need to be reconsidered because in patients with terminal illness depressive symptoms commonly are associated with functional decline. For example, restrictions on a patient’s ability to participate in activities and disengagement from some areas of interest are common among individuals facing the end of life, but if a patient is unable to find pleasure in any event or activity, he or she may meet criteria for depression. Endicott¹⁰ proposed a list of substitute symptoms of depression in terminally ill patients:

• weight loss or gain is substituted with depressed appearance
• loss of energy is substituted with brooding and self-pity
• insomnia or hypersomnia is substituted with social withdrawal
• loss of concentration is substituted with lack of reactivity or inability to be cheered up.

These substitutions are not in DSM-IV-TR but should be considered when assessing a terminally ill patient.

Most recommendations for pharmacologic treatment of depression in terminally ill patients are based on depression treatments for the general population. Selective serotonin reuptake inhibitors are commonly prescribed for terminally ill patients. Mirtazapine, a noradrenergic and serotonergic antidepressant, has been shown to effectively treat adjustment, mood, and anxiety disorders in patients with breast or gynecological cancer.¹¹ Its major side effects—sedation and weight gain—might be beneficial in patients with terminal illness. Psychostimulants also have been shown to elevate mood in patients with advanced malignancies.¹²

Potential triggers for anxiety in terminally ill patients include chemotherapy, radiation therapy, or acute pain. Also consider anxiety related to death and dying. Certain drugs commonly used in palliative care—such as corticosteroids and psychostimulants—may contribute to anxiety and restlessness. Cancer patients may develop posttraumatic stress disorder symptoms, including re-experiencing frightening aspects of their diagnosis and treatment, nightmares, hypervigilance, and autonomic hyperactivity.¹³ Pharmacologic treatment of anxiety in dying patients is similar to that in the general population; benzodiazepines and antidepressants are first-line agents.

Several forms of psychotherapy can help terminally ill patients address existential issues (Box).^14-16

Box

A need for training

In a survey of psychiatry residents, 97% of respondents believed psychiatrists should be trained in end-of-life care and 94% felt there should be formal education on palliative care during residency.¹⁷ A study evaluating psychiatry residents’ attitudes, perceived preparedness, experiences, and needs in end-of-life care education found that residents felt least prepared when dealing with cultural and spiritual aspects of dying and helping patients with reconciliation and saying goodbye.¹⁸ These residents also expressed a desire for more longitudinal exposure to palliative care.

A dedicated palliative care rotation during psychiatry residency training would help build a foundation of knowledge in this field. Residency programs should make a greater effort to incorporate end-of-life issues into consultation-liaison and geriatric rotations. Education on psychosocial, existential, and spiritual distress should be highlighted, with an emphasis on integrating specific psychotherapy techniques into training. These opportunities would provide residents with necessary skills to help patients cope with end-of-life issues.

As a psychiatry resident, I believe training in this field is one way to decrease barriers for patients to access end-of-life care. End-of-life psychiatric training could help build a culture where end-of-life care is integrated into the medical care system, with the goal of helping terminally ill patients die well.

Related Resources

• Chochinov H, Breitbart W. Handbook of psychiatry in palliative medicine. New York, NY: Oxford University Press; 2009.
• Harvard Medical School Center for Palliative Care. www.hms.harvard.edu/pallcare.

Drug Brand Name

• Mirtazapine • Remeron

Disclosure

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

My mother and I were in the hospital lobby waiting for my father. My normally upbeat, sharp, energetic mom looked sick, weak, and confused. She had just been discharged from the hospital after experiencing a seizure caused by brain metastasis from long-standing breast cancer. Although we had discussed hospice care during my mother’s admission, we left the hospital without setting up the service because we wanted more time to see if she could recover. Two days later, we arranged hospice because of my mother’s rapidly deteriorating condition and our inability to manage her illness on our own. Five days later, she passed away at home surrounded by loved ones.

I am bewildered that my family did not transition my mother to end-of-life care earlier. Several family members and I work in the medical field. Being resourceful, we chose treatment at a large medical center that was a 3-hour drive from our home. Also, we were familiar with palliative care because other family members had died with hospice. Yet, in those last precious moments, we did not initiate end-of-life care for my mother until it became an emergency. This experience cultivated my interest in palliative care and hospice, specifically, in barriers to access and better ways to transition from life-saving treatment to end-of-life care. As a psychiatry resident, I feel it is important to expand opportunities for psychiatrists to participate in palliative care teams.

Barriers to end-of-life care

Poor physician-patient communication near the end of life can be a major barrier to care. Studies suggest that patients and physicians are ambivalent about end-of-life discussions and tend to avoid them.¹ Communication is crucial to helping patients prepare to die well. Researchers have found that end-of-life discussions between patients and physicians can result in fewer aggressive interventions and better quality of life near death.² These discussions did not increase emotional distress and were associated with lower rates of ventilation, resuscitation, and intensive care unit admissions.² End-of-life discussions between physicians and patients also lead to earlier hospice enrollment and improve the quality of end-of-life care.²

Approximately one-third of patients spend <1 week in hospice.³ Studies have suggested that patients who receive >1 week of hospice care have improved quality of life compared with patients who do not receive hospice care.¹ Addressing end-of-life issues early in treatment of terminally ill patients allows them to become familiar with their options as their disease progresses.

Lack of integration between hospice and the medical community is another barrier. According to Medicare guidelines,⁴ to be eligible for hospice a patient must have a terminal illness with a prognosis of ≤6 months. The patient must agree to give up curative treatment. If a patient lives >6 months, hospice benefits can be renewed as long as the patient has shown a persistent decline. Patients must desire and accept a palliative approach rather than a curative focus and agree to have all care provided by Medicare-certified hospices.⁵ These eligibility requirements may give patients and their families a sense that they are losing the forms of health care they had been using, physicians they know, and treatments they had become accustomed to, and are transferring their medical care to a unknown entity. This transition occurs when diseases are progressing and patients may feel vulnerable. In this way, end-of-life care is segregated from the rest of the medical system and can feel foreign and frightening to patients.⁶

Lack of palliative care specialists. The U.S. population is aging, and more people are living longer with chronic illness. Although the palliative care field is growing, only 60% of U.S. hospitals have palliative care programs and there is a shortage of palliative care clinicians.⁷

Psychiatry and end-of-life care

Psychiatry and psycho-oncology can help address these barriers by providing resources and expertise to palliative care teams. Psychiatrists can facilitate communication between families and primary clinicians and help patients mentally prepare for end-of-life options.

The dying process may uncover psychological, psychosocial, and existential suffering in patients and their families that often is underdiagnosed and undertreated.⁸ Psychiatrists can:

• diagnose and treat psychiatric disorders that surface under the stress of a new diagnosis
• aid in the psychodynamics of coping with terminal illness
• assess decision-making capacity
• recognize and treat staff stress
• provide bereavement care.

Because many clinicians believe that mood or anxiety symptoms are “normal reactions” in individuals struggling with end-of-life issues, these patients may not receive psychiatric treatment. However, treating mood and anxiety disorders can improve quality of life in palliative care patients.⁹

In terminally ill patients, psychological pain often manifests as symptoms of depression and anxiety. Diagnostic criteria for depression may need to be reconsidered because in patients with terminal illness depressive symptoms commonly are associated with functional decline. For example, restrictions on a patient’s ability to participate in activities and disengagement from some areas of interest are common among individuals facing the end of life, but if a patient is unable to find pleasure in any event or activity, he or she may meet criteria for depression. Endicott¹⁰ proposed a list of substitute symptoms of depression in terminally ill patients:

• weight loss or gain is substituted with depressed appearance
• loss of energy is substituted with brooding and self-pity
• insomnia or hypersomnia is substituted with social withdrawal
• loss of concentration is substituted with lack of reactivity or inability to be cheered up.

These substitutions are not in DSM-IV-TR but should be considered when assessing a terminally ill patient.

Most recommendations for pharmacologic treatment of depression in terminally ill patients are based on depression treatments for the general population. Selective serotonin reuptake inhibitors are commonly prescribed for terminally ill patients. Mirtazapine, a noradrenergic and serotonergic antidepressant, has been shown to effectively treat adjustment, mood, and anxiety disorders in patients with breast or gynecological cancer.¹¹ Its major side effects—sedation and weight gain—might be beneficial in patients with terminal illness. Psychostimulants also have been shown to elevate mood in patients with advanced malignancies.¹²

Potential triggers for anxiety in terminally ill patients include chemotherapy, radiation therapy, or acute pain. Also consider anxiety related to death and dying. Certain drugs commonly used in palliative care—such as corticosteroids and psychostimulants—may contribute to anxiety and restlessness. Cancer patients may develop posttraumatic stress disorder symptoms, including re-experiencing frightening aspects of their diagnosis and treatment, nightmares, hypervigilance, and autonomic hyperactivity.¹³ Pharmacologic treatment of anxiety in dying patients is similar to that in the general population; benzodiazepines and antidepressants are first-line agents.

Several forms of psychotherapy can help terminally ill patients address existential issues (Box).^14-16

Box

A need for training

In a survey of psychiatry residents, 97% of respondents believed psychiatrists should be trained in end-of-life care and 94% felt there should be formal education on palliative care during residency.¹⁷ A study evaluating psychiatry residents’ attitudes, perceived preparedness, experiences, and needs in end-of-life care education found that residents felt least prepared when dealing with cultural and spiritual aspects of dying and helping patients with reconciliation and saying goodbye.¹⁸ These residents also expressed a desire for more longitudinal exposure to palliative care.

A dedicated palliative care rotation during psychiatry residency training would help build a foundation of knowledge in this field. Residency programs should make a greater effort to incorporate end-of-life issues into consultation-liaison and geriatric rotations. Education on psychosocial, existential, and spiritual distress should be highlighted, with an emphasis on integrating specific psychotherapy techniques into training. These opportunities would provide residents with necessary skills to help patients cope with end-of-life issues.

As a psychiatry resident, I believe training in this field is one way to decrease barriers for patients to access end-of-life care. End-of-life psychiatric training could help build a culture where end-of-life care is integrated into the medical care system, with the goal of helping terminally ill patients die well.

Related Resources

• Chochinov H, Breitbart W. Handbook of psychiatry in palliative medicine. New York, NY: Oxford University Press; 2009.
• Harvard Medical School Center for Palliative Care. www.hms.harvard.edu/pallcare.

Drug Brand Name

• Mirtazapine • Remeron

Disclosure

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

My mother and I were in the hospital lobby waiting for my father. My normally upbeat, sharp, energetic mom looked sick, weak, and confused. She had just been discharged from the hospital after experiencing a seizure caused by brain metastasis from long-standing breast cancer. Although we had discussed hospice care during my mother’s admission, we left the hospital without setting up the service because we wanted more time to see if she could recover. Two days later, we arranged hospice because of my mother’s rapidly deteriorating condition and our inability to manage her illness on our own. Five days later, she passed away at home surrounded by loved ones.

I am bewildered that my family did not transition my mother to end-of-life care earlier. Several family members and I work in the medical field. Being resourceful, we chose treatment at a large medical center that was a 3-hour drive from our home. Also, we were familiar with palliative care because other family members had died with hospice. Yet, in those last precious moments, we did not initiate end-of-life care for my mother until it became an emergency. This experience cultivated my interest in palliative care and hospice, specifically, in barriers to access and better ways to transition from life-saving treatment to end-of-life care. As a psychiatry resident, I feel it is important to expand opportunities for psychiatrists to participate in palliative care teams.

Barriers to end-of-life care

Poor physician-patient communication near the end of life can be a major barrier to care. Studies suggest that patients and physicians are ambivalent about end-of-life discussions and tend to avoid them.¹ Communication is crucial to helping patients prepare to die well. Researchers have found that end-of-life discussions between patients and physicians can result in fewer aggressive interventions and better quality of life near death.² These discussions did not increase emotional distress and were associated with lower rates of ventilation, resuscitation, and intensive care unit admissions.² End-of-life discussions between physicians and patients also lead to earlier hospice enrollment and improve the quality of end-of-life care.²

Approximately one-third of patients spend <1 week in hospice.³ Studies have suggested that patients who receive >1 week of hospice care have improved quality of life compared with patients who do not receive hospice care.¹ Addressing end-of-life issues early in treatment of terminally ill patients allows them to become familiar with their options as their disease progresses.

Lack of integration between hospice and the medical community is another barrier. According to Medicare guidelines,⁴ to be eligible for hospice a patient must have a terminal illness with a prognosis of ≤6 months. The patient must agree to give up curative treatment. If a patient lives >6 months, hospice benefits can be renewed as long as the patient has shown a persistent decline. Patients must desire and accept a palliative approach rather than a curative focus and agree to have all care provided by Medicare-certified hospices.⁵ These eligibility requirements may give patients and their families a sense that they are losing the forms of health care they had been using, physicians they know, and treatments they had become accustomed to, and are transferring their medical care to a unknown entity. This transition occurs when diseases are progressing and patients may feel vulnerable. In this way, end-of-life care is segregated from the rest of the medical system and can feel foreign and frightening to patients.⁶

Lack of palliative care specialists. The U.S. population is aging, and more people are living longer with chronic illness. Although the palliative care field is growing, only 60% of U.S. hospitals have palliative care programs and there is a shortage of palliative care clinicians.⁷

Psychiatry and end-of-life care

Psychiatry and psycho-oncology can help address these barriers by providing resources and expertise to palliative care teams. Psychiatrists can facilitate communication between families and primary clinicians and help patients mentally prepare for end-of-life options.

The dying process may uncover psychological, psychosocial, and existential suffering in patients and their families that often is underdiagnosed and undertreated.⁸ Psychiatrists can:

• diagnose and treat psychiatric disorders that surface under the stress of a new diagnosis
• aid in the psychodynamics of coping with terminal illness
• assess decision-making capacity
• recognize and treat staff stress
• provide bereavement care.

Because many clinicians believe that mood or anxiety symptoms are “normal reactions” in individuals struggling with end-of-life issues, these patients may not receive psychiatric treatment. However, treating mood and anxiety disorders can improve quality of life in palliative care patients.⁹

In terminally ill patients, psychological pain often manifests as symptoms of depression and anxiety. Diagnostic criteria for depression may need to be reconsidered because in patients with terminal illness depressive symptoms commonly are associated with functional decline. For example, restrictions on a patient’s ability to participate in activities and disengagement from some areas of interest are common among individuals facing the end of life, but if a patient is unable to find pleasure in any event or activity, he or she may meet criteria for depression. Endicott¹⁰ proposed a list of substitute symptoms of depression in terminally ill patients:

• weight loss or gain is substituted with depressed appearance
• loss of energy is substituted with brooding and self-pity
• insomnia or hypersomnia is substituted with social withdrawal
• loss of concentration is substituted with lack of reactivity or inability to be cheered up.

These substitutions are not in DSM-IV-TR but should be considered when assessing a terminally ill patient.

Most recommendations for pharmacologic treatment of depression in terminally ill patients are based on depression treatments for the general population. Selective serotonin reuptake inhibitors are commonly prescribed for terminally ill patients. Mirtazapine, a noradrenergic and serotonergic antidepressant, has been shown to effectively treat adjustment, mood, and anxiety disorders in patients with breast or gynecological cancer.¹¹ Its major side effects—sedation and weight gain—might be beneficial in patients with terminal illness. Psychostimulants also have been shown to elevate mood in patients with advanced malignancies.¹²

Potential triggers for anxiety in terminally ill patients include chemotherapy, radiation therapy, or acute pain. Also consider anxiety related to death and dying. Certain drugs commonly used in palliative care—such as corticosteroids and psychostimulants—may contribute to anxiety and restlessness. Cancer patients may develop posttraumatic stress disorder symptoms, including re-experiencing frightening aspects of their diagnosis and treatment, nightmares, hypervigilance, and autonomic hyperactivity.¹³ Pharmacologic treatment of anxiety in dying patients is similar to that in the general population; benzodiazepines and antidepressants are first-line agents.

Several forms of psychotherapy can help terminally ill patients address existential issues (Box).^14-16

Box

A need for training

In a survey of psychiatry residents, 97% of respondents believed psychiatrists should be trained in end-of-life care and 94% felt there should be formal education on palliative care during residency.¹⁷ A study evaluating psychiatry residents’ attitudes, perceived preparedness, experiences, and needs in end-of-life care education found that residents felt least prepared when dealing with cultural and spiritual aspects of dying and helping patients with reconciliation and saying goodbye.¹⁸ These residents also expressed a desire for more longitudinal exposure to palliative care.

A dedicated palliative care rotation during psychiatry residency training would help build a foundation of knowledge in this field. Residency programs should make a greater effort to incorporate end-of-life issues into consultation-liaison and geriatric rotations. Education on psychosocial, existential, and spiritual distress should be highlighted, with an emphasis on integrating specific psychotherapy techniques into training. These opportunities would provide residents with necessary skills to help patients cope with end-of-life issues.

As a psychiatry resident, I believe training in this field is one way to decrease barriers for patients to access end-of-life care. End-of-life psychiatric training could help build a culture where end-of-life care is integrated into the medical care system, with the goal of helping terminally ill patients die well.

Related Resources

• Chochinov H, Breitbart W. Handbook of psychiatry in palliative medicine. New York, NY: Oxford University Press; 2009.
• Harvard Medical School Center for Palliative Care. www.hms.harvard.edu/pallcare.

Drug Brand Name

• Mirtazapine • Remeron

Disclosure

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

Patients who endorse multiple psychiatric symptoms and meet criteria for several DSM diagnoses pose diagnostic and therapeutic challenges. In community samples, approximately 40% of patients with a DSM diagnosis have >1 illness, and comorbidity is more frequent in clinical trials.¹ We highlight things to consider when managing a patient who has “everything.”

Endorsing ‘everything’ means something in itself. Patients with borderline personality disorder often present with myriad, disparate diagnoses and urgent requests for care.² Also consider primary or secondary gain, particularly if the patient’s descriptions of symptoms are unusual. Saying “yes” to every question or endorsing highly unusual symptoms described by the interviewer may represent suggestibility related to catatonia or confabulation.

Focus on the most impairing symptom. This may help put other symptoms in context and focus treatment.

Find a common goal. If you can’t pick a simple symptom, move on to helping the patient identify his or her goals by asking questions such as, “Four weeks from now, what would you like to be doing?” Picking an achievable, measurable goal may be therapeutic.

Are the symptoms valid? Examine individual symptoms for validity using the SAFER criteria (Table).³

Table

SAFER criteria for symptom validity

Multiple diagnoses may be in play, but start by treating one. Many patients meet criteria for multiple diagnoses. There is little evidence about which diagnosis should be treated first. Use your judgment in picking “the best first step” and treat accordingly.

Resist polypharmacy. Target specific symptoms or goals until a clear diagnostic picture emerges.

Disclosure

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

Patients who endorse multiple psychiatric symptoms and meet criteria for several DSM diagnoses pose diagnostic and therapeutic challenges. In community samples, approximately 40% of patients with a DSM diagnosis have >1 illness, and comorbidity is more frequent in clinical trials.¹ We highlight things to consider when managing a patient who has “everything.”

Endorsing ‘everything’ means something in itself. Patients with borderline personality disorder often present with myriad, disparate diagnoses and urgent requests for care.² Also consider primary or secondary gain, particularly if the patient’s descriptions of symptoms are unusual. Saying “yes” to every question or endorsing highly unusual symptoms described by the interviewer may represent suggestibility related to catatonia or confabulation.

Focus on the most impairing symptom. This may help put other symptoms in context and focus treatment.

Find a common goal. If you can’t pick a simple symptom, move on to helping the patient identify his or her goals by asking questions such as, “Four weeks from now, what would you like to be doing?” Picking an achievable, measurable goal may be therapeutic.

Are the symptoms valid? Examine individual symptoms for validity using the SAFER criteria (Table).³

Table

SAFER criteria for symptom validity

Multiple diagnoses may be in play, but start by treating one. Many patients meet criteria for multiple diagnoses. There is little evidence about which diagnosis should be treated first. Use your judgment in picking “the best first step” and treat accordingly.

Resist polypharmacy. Target specific symptoms or goals until a clear diagnostic picture emerges.

Disclosure

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

Patients who endorse multiple psychiatric symptoms and meet criteria for several DSM diagnoses pose diagnostic and therapeutic challenges. In community samples, approximately 40% of patients with a DSM diagnosis have >1 illness, and comorbidity is more frequent in clinical trials.¹ We highlight things to consider when managing a patient who has “everything.”

Endorsing ‘everything’ means something in itself. Patients with borderline personality disorder often present with myriad, disparate diagnoses and urgent requests for care.² Also consider primary or secondary gain, particularly if the patient’s descriptions of symptoms are unusual. Saying “yes” to every question or endorsing highly unusual symptoms described by the interviewer may represent suggestibility related to catatonia or confabulation.

Focus on the most impairing symptom. This may help put other symptoms in context and focus treatment.

Find a common goal. If you can’t pick a simple symptom, move on to helping the patient identify his or her goals by asking questions such as, “Four weeks from now, what would you like to be doing?” Picking an achievable, measurable goal may be therapeutic.

Are the symptoms valid? Examine individual symptoms for validity using the SAFER criteria (Table).³

Table

SAFER criteria for symptom validity

Multiple diagnoses may be in play, but start by treating one. Many patients meet criteria for multiple diagnoses. There is little evidence about which diagnosis should be treated first. Use your judgment in picking “the best first step” and treat accordingly.

Resist polypharmacy. Target specific symptoms or goals until a clear diagnostic picture emerges.

Disclosure

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

“Poop-out” and “tachyphylaxis” are terms used to describe loss of antidepressant response after initial benefit, but both descriptors are problematic. Poop-out carries a mildly offensive aura that conveys a lack of seriousness about the patient’s suffering. Tachyphylaxis is a pharmacologic term describing rapid or acute reduction in response to a drug after administration; it is not appropriate for antidepressant loss of response, which typically occurs months to years after treatment initiation.¹

Depressive recurrence on antidepressant treatment (DRAT) is a better term to describe recurrence of a major depressive episode despite sustained treatment with an antidepressant that had induced remission. Maintenance studies of antidepressant treatment indicate DRAT occurs in approximately 10% of patients at 6 months and 20% at 2 years.²

Despite this high prevalence, there is little clinical trial data on which to base treatment decisions for patients who experience DRAT. There are 4 options:

1. Raise the dose. In small studies, doubling the dose of fluoxetine or duloxetine led to regaining response in approximately 60% of patients.³ However, these studies lacked a placebo comparison arm, so the specific benefit derived from the dose increase is unknown. Improvement with a dose increase is somewhat at odds with the known mechanism of action of selective serotonin reuptake inhibitors (SSRIs), which are thought to have a flat dose-response curve. That is, once an SSRI blocks approximately 80% of the serotonin transporters, further dose increases produce minimal further blockade and, presumably, little clinical benefit via this mechanism.⁴

2. Switch medication. No studies have examined switching antidepressants after DRAT. Switching to a medication with a different mechanism may be justified based on the results of treatment-resistant depression (TRD) trials, in which patients who failed to respond to an initial medication—typically an SSRI—improved after switching to an antidepressant from a different class. However, the biology of DRAT may differ from that of SSRI nonresponse. Unlike many patients with TRD, patients who experience DRAT while taking an SSRI have demonstrated previous response to serotonergic modulation.

3. Augmentation. Similar to switching, this approach has not been studied specifically for DRAT. This approach is derived from trials in which patients who did not attain response after treatment with a single antidepressant had a second medication added. Again, the biology of these patients may differ from those with DRAT, who at one point did remit with antidepressant treatment.

4. Psychotherapy. This addition is a low-risk option for patients who previously have not received evidence-based psychotherapy for depression.

Clinicians have scant evidence on which to base their decisions for this common and important problem. Dose increase after DRAT represents the best supported, simplest, and perhaps least costly next step in treatment.

Disclosure

Dr. Dunlop receives grant or research support from Bristol-Myers Squibb, Forest Pharmaceuticals, and GlaxoSmithKline, and is a consultant to MedAvante and Roche.

“Poop-out” and “tachyphylaxis” are terms used to describe loss of antidepressant response after initial benefit, but both descriptors are problematic. Poop-out carries a mildly offensive aura that conveys a lack of seriousness about the patient’s suffering. Tachyphylaxis is a pharmacologic term describing rapid or acute reduction in response to a drug after administration; it is not appropriate for antidepressant loss of response, which typically occurs months to years after treatment initiation.¹

Depressive recurrence on antidepressant treatment (DRAT) is a better term to describe recurrence of a major depressive episode despite sustained treatment with an antidepressant that had induced remission. Maintenance studies of antidepressant treatment indicate DRAT occurs in approximately 10% of patients at 6 months and 20% at 2 years.²

Despite this high prevalence, there is little clinical trial data on which to base treatment decisions for patients who experience DRAT. There are 4 options:

1. Raise the dose. In small studies, doubling the dose of fluoxetine or duloxetine led to regaining response in approximately 60% of patients.³ However, these studies lacked a placebo comparison arm, so the specific benefit derived from the dose increase is unknown. Improvement with a dose increase is somewhat at odds with the known mechanism of action of selective serotonin reuptake inhibitors (SSRIs), which are thought to have a flat dose-response curve. That is, once an SSRI blocks approximately 80% of the serotonin transporters, further dose increases produce minimal further blockade and, presumably, little clinical benefit via this mechanism.⁴

2. Switch medication. No studies have examined switching antidepressants after DRAT. Switching to a medication with a different mechanism may be justified based on the results of treatment-resistant depression (TRD) trials, in which patients who failed to respond to an initial medication—typically an SSRI—improved after switching to an antidepressant from a different class. However, the biology of DRAT may differ from that of SSRI nonresponse. Unlike many patients with TRD, patients who experience DRAT while taking an SSRI have demonstrated previous response to serotonergic modulation.

3. Augmentation. Similar to switching, this approach has not been studied specifically for DRAT. This approach is derived from trials in which patients who did not attain response after treatment with a single antidepressant had a second medication added. Again, the biology of these patients may differ from those with DRAT, who at one point did remit with antidepressant treatment.

4. Psychotherapy. This addition is a low-risk option for patients who previously have not received evidence-based psychotherapy for depression.

Clinicians have scant evidence on which to base their decisions for this common and important problem. Dose increase after DRAT represents the best supported, simplest, and perhaps least costly next step in treatment.

Disclosure

Dr. Dunlop receives grant or research support from Bristol-Myers Squibb, Forest Pharmaceuticals, and GlaxoSmithKline, and is a consultant to MedAvante and Roche.

“Poop-out” and “tachyphylaxis” are terms used to describe loss of antidepressant response after initial benefit, but both descriptors are problematic. Poop-out carries a mildly offensive aura that conveys a lack of seriousness about the patient’s suffering. Tachyphylaxis is a pharmacologic term describing rapid or acute reduction in response to a drug after administration; it is not appropriate for antidepressant loss of response, which typically occurs months to years after treatment initiation.¹

Depressive recurrence on antidepressant treatment (DRAT) is a better term to describe recurrence of a major depressive episode despite sustained treatment with an antidepressant that had induced remission. Maintenance studies of antidepressant treatment indicate DRAT occurs in approximately 10% of patients at 6 months and 20% at 2 years.²

Despite this high prevalence, there is little clinical trial data on which to base treatment decisions for patients who experience DRAT. There are 4 options:

1. Raise the dose. In small studies, doubling the dose of fluoxetine or duloxetine led to regaining response in approximately 60% of patients.³ However, these studies lacked a placebo comparison arm, so the specific benefit derived from the dose increase is unknown. Improvement with a dose increase is somewhat at odds with the known mechanism of action of selective serotonin reuptake inhibitors (SSRIs), which are thought to have a flat dose-response curve. That is, once an SSRI blocks approximately 80% of the serotonin transporters, further dose increases produce minimal further blockade and, presumably, little clinical benefit via this mechanism.⁴

2. Switch medication. No studies have examined switching antidepressants after DRAT. Switching to a medication with a different mechanism may be justified based on the results of treatment-resistant depression (TRD) trials, in which patients who failed to respond to an initial medication—typically an SSRI—improved after switching to an antidepressant from a different class. However, the biology of DRAT may differ from that of SSRI nonresponse. Unlike many patients with TRD, patients who experience DRAT while taking an SSRI have demonstrated previous response to serotonergic modulation.

3. Augmentation. Similar to switching, this approach has not been studied specifically for DRAT. This approach is derived from trials in which patients who did not attain response after treatment with a single antidepressant had a second medication added. Again, the biology of these patients may differ from those with DRAT, who at one point did remit with antidepressant treatment.

4. Psychotherapy. This addition is a low-risk option for patients who previously have not received evidence-based psychotherapy for depression.

Clinicians have scant evidence on which to base their decisions for this common and important problem. Dose increase after DRAT represents the best supported, simplest, and perhaps least costly next step in treatment.

Disclosure

Dr. Dunlop receives grant or research support from Bristol-Myers Squibb, Forest Pharmaceuticals, and GlaxoSmithKline, and is a consultant to MedAvante and Roche.