Evidence-Based Reviews

Using psychotropics safely in patients with HIV/AIDS: Watch for drug-drug interactions with antiretrovirals

Author and Disclosure Information



Psychiatric patients—especially those with substance abuse disorders—are at high risk for HIV infection, which puts psychiatrists on the AIDS pandemic’s front lines.

In the wake of last month’s International AIDS Conference in Thailand, this article supplements American Psychiatric Association guidelines for managing patients with HIV/AIDS.1 Here is updated information on:

  • who is at greatest risk for HIV infection today
  • neuropsychiatric side effects of HIV medications
  • in-office assessment of HIV-associated cognitive changes
  • how to avoid psychotropic/antiretroviral interactions.

HIV and psychiatric patients

Psychiatric patients are among those at highest risk for HIV (Box).2-4 Cournos and McKinnon5 found that HIV seroprevalence among persons with severe mental illness was 4% to 23%compared with 0.4% in the general population.6 They defined severe mental illness as schizophrenia, schizoaffective disorder, major depression, or bipolar disorder accompanied by significant functional impairment, disruption of normal life tasks, periods of hospitalization, and need for psychotropics.

Infection rates varied with HIV geographic concentration, presence of comorbid substance use disorders, age, and ethnicity, but not psychiatric diagnosis. Unsafe sex and drug use (including noninjection) were associated with infection, and women were as likely to be infected as men.

Side effects and interactions

‘Triple therapy.’ Combining three antiretroviral agents—highly-active antiretroviral therapy (HAART) or “triple therapy”—is standard treatment for HIV infection in the United States. Initially, HAART was recommended for all patients with early-stage HIV, even if asymptomatic. This changed as antiretrovirals’ side effects—such as peripheral neuropathy with didanosine— and drug resistance from suboptimal adherence became apparent. Viral resistance develops if patients are <95% adherent to antiretroviral regimens.7

Antiretroviral therapy is usually started when:

  • CD4 lymphocyte count is <200 cells/mm3 or abruptly decreasing
  • plasma viral load is >55,000 copies/mL or abruptly increasing
  • symptomatic AIDS emerges.

Psychiatric side effects. Psychiatric symptoms—such as depression, anxiety, confusion, psychosis, hallucinations, insomnia, and mania—are common side effects of antiretrovirals and other drugs used to treat HIV and its opportunistic infections and cancers (Table 1).8 Two antiretrovirals are of particular interest to psychiatrists:

Efavirenz is a non-nucleoside reverse transcriptase inhibitor that causes vivid dreams, especially when initiated.


U.S. high-risk factors for HIV: Age under 25, male-to-male sex, drug use

AIDS death rates have declined in the United States since antiretroviral therapies were introduced in 1996, but the rate of new HIV infection has not changed.2 An estimated 850,000 to 950,000 Americans have HIV, and 25% do not know it.3

Changing demographics. Some 40,000 new HIV infections occur in the United States each year (70% among men), and one-half of the newly-infected are under age 25. African Americans and Hispanics represent 51% of total AIDS cases in men and 77% in women. From 1998 to 2002—the most recent data available from the Centers for Disease Control and Prevention (CDC)—AIDS incidence steadily decreased among whites and Hispanics but increased among blacks, Asian/Pacific Islanders, and American Indian/Alaska Natives.

Transmission routes. Approximately 60% of men with HIV are infected through male-to-male sex, 25% through IV drug use, and 15% through heterosexual sex. Unprotected anal sex appears to be occurring more frequently in some urban centers, particularly among young men who have sex with men.4 Approximately 75% of women with HIV are infected through heterosexual sex and 25% through IV drug use.

Ritonavir is a protease inhibitor that may inhibit psychotropics metabolized by cytochrome P450 3A4 and 2D6 isoenzymes.

Other HIV medications increase or decrease psychotropic blood levels via inhibition or induction of CYP isoenzymes (Table 2).9 When a patient is taking ritonavir or another protease inhibitor, reduced starting dosages of selective serotonin reuptake inhibitors (SSRIs) may be appropriate. Benzodiazepine dosages may need to be increased because of ritonavir induction of the enzyme glucuronosyltransferase.

Table 1

Psychiatric side effects of common HIV medications

DrugSide effects, by frequency
AcyclovirUnknown: hallucination, confusion, thought insertion, insomnia
Amphotericin B>5%: confusion, insomnia, somnolence; 1-5%: agitation, anxiety, depression, hallucination, nervousness, psychosis; Unkown: delirium
β-Lactam antibiotics<1%: insomnia, somnolence, anxiety, nervousness, impaired concentration, confusion, nightmares, hallucination; Unkown: paranoia, mania
Trimethoprim/sulfamethoxazoleUnknown: hallucinations, depression, apathy, nervousness
Cycloserine Unknown:psychosis, somnolence, depression, confusion, irritability, anxiety
DidanosineUnknown: nervousness, anxiety, confusion, seizures, insomnia
Efavirenz13-16%: depression; 8-11%: anxiety; 2-6%: nervousness; >5%: headache, seizures, confusion; <2%: suicidal ideation and behavior, aggression
Unknown:agitation, lability, neurosis, psychosis, insomnia, impaired concentration, somnolence, euphoria, amnesia, hallucination
Foscarnet>5%: depression, confusion, anxiety; 1-5%: insomnia, somnolence, amnesia, nervousness, agitation, aggression, hallucination
Interferon-a6-19%: depression; 12-16%: irritability; 6-12%: insomnia; 3-8%: impaired concentration; >5%: anxiety: <5%: confusion, mania, aggression, delirium, lability, suicidal ideation, psychosis, personality disorder, alcohol intolerance
IsoniazidUnknown: depression, agitation, hallucination, paranoia, anxiety, psychosis
Lamivudine<11%: insomnia; <9%: mania, depressive disorders, dreams
MethotrexateUnknown: cognitive and mood changes
PentamidineUnknown: confusion, lability, hallucination; Rare: anxiety, fatigue
ProcarbazineUnknown: hallucination, depression, nervousness, apprehension, mania, loss of appetite, insomnia, nightmares, confusion, malaise
Quinolones<1%: somnolence, insomnia; Occasional: agitation, anxiety, depression, panic attacks, confusion, hallucination, aggression, psychosis, paranoia;
Rare:suicidal ideation and suicide (no relationship with drug confirmed)
StavudineUnknown: confusion, depression, seizures, anxiety, mania, sleep problems
SulfonamidesUnknown: psychosis, delirium, confusion, depression, hallucinations
ThiabendazoleUnknown: hallucination, fatigue, irritability, confusion, depression
VinblastineUnknown: depression
VincristineUnknown: hallucination
ZalcitabineUnknown: acute psychosis, agitation, amnesia, anxiety, lability, euphoria, hallucination, insomnia, mania, paranoia, suicidal behavior, confusion, impaired concentration, somnolence, depression
ZidovudineUnknown: Insomnia, vivid dreams, agitation, mania, hallucination, confusion


Next Article: