Madison Clinic
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Efavirenz Use in Patients with Psychiatric History

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Efavirenz (EFV) is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 that is generally well-tolerated. The most commonly reported adverse effect is neurologic toxicity, with more than 50% patients in open-label studies reporting dizziness, headache, mild cognitive difficulty, fatigue or sleep disturbance characterized by intense and sometimes disturbing dreams.

The question of whether EFV is associated with depression or suicide or whether it exacerbates psychiatric conditions remains more controversial. Few high-quality peer-reviewed data exist that adequately address this issue – studies vary widely on definitions of depression and methods used to detect depression, as well as population, duration of follow-up and primary study endpoints. Moreover detecting differences in frequency of psychiatric conditions in a high-risk population with high background rates of complex life stressors, substance use and depression is particularly difficult. There have been, however, a few case reports describing exacerbation or even new onset of psychosis or mania attributed to EFV, with resolution of symptoms after discontinuation of therapy.

Given these limitations and the fact that our clinic population is one with a high prevalence of psychiatric comorbidities, we offer following guidelines on initiation of EFV at Madison Clinic:

• Try to avoid in patients with a history of psychosis or mania (either due to organic or functional causes) – esp. untreated schizophrenia, bipolar disorder.

• Cautious use in patients with a history of:

o Depression

• In patients on whom there are any mental health concerns, collaborate closely with mental health team with frequent follow-up early in EFV initiation.


Blanch J, Corbella B, Garcia F, et. al. Manic syndrome associated with efavirenz overdose. Clin Infect Dis. 2001 Jul 15;33(2):270-1.

Boly L, Cafaro V, Dyner T. Depressive symptoms predict increased incidence of neuropsychiatric side effects in patients treated with efavirenz. J Acquir Immune Defic Syndr. 2006 Aug 1;42(4):514-5.

Clifford DB, Evans S, Yang Y, et. al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med. 2005 Nov 15;143(10):714-21.

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