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Efavirenz and Suicidality
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Efavirenz (EFV) commonly causes neuropsychiatric adverse effects in the early days and weeks after initiation, though these generally are mild to moderate in intensity and lessen with time. Many clinicians have been cautious about prescribing EFV for patients with serious psychiatric conditions, though serious adverse effects in these patients have not been well studied. A new analysis of suicidality among patients taking EFV helps characterize the risk of suicidality in persons on EFV-based regimens.

This is a combined analysis of data from 4 ACTG studies of initial treatment that included an EFV-containing arm (A5095, A5142, A5175, and A5202). Patients were randomized to regimens containing EFV (n = 3,241) or regimens without EFV (n = 2,091). The individual studies had somewhat different eligibility criteria (including differences in screening for suicidality) but the two groups were quite well matched at baseline for most factors including depression and use of antidepressant medications. Median follow-up was 96 weeks.

The main findings of the study are:

The incidence of suicidality, defined as suicidal ideation or attempted or completed suicide, was about twice as high in EFV-treated groups, and this held true in a variety of sensitivity analyses (other causes of death were present at essentially the same rate in the EFV and no-EFV groups).
Suicidality incidence (per 1,000 person-years): 8.08 in the EFV group, 3.66 in the no-EFV group (hazard ratio [HR]: 2.28, 95% confidence interval [CI]: 1.27 to 4.10; p = .006).
Attempted or completed suicide: 2.90 vs 1.22 in EFV and no-EFV groups, respectively (HR: 2.58, CI: 0.94 to 7.06; p = .065).
Completed suicides: 8 in the EFV group, 1 in the no-EFV group.
Other factors for increased hazard of suicidality were history of injection drug use (IDU), documented psychiatric history or recent psychoactive medication IDU, young age (on multivariate analysis).

Clinical Bottom Line
Although this study comes with several important limitations, including the facts that there was no standardized screening for suicidality and that some of the constituent studies were open label, its findings offer an important and sobering caution. It is important to screen carefully for risk of suicidality before prescribing EFV and to monitor regularly during treatment with EFV. This is particularly true for patients who have other risk factors for depression or suicidality.

Mollan KR, Smurzynski M, Eron JJ, et al. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data. Ann Intern Med. 2014 Jul 1;161(1):1-10.