HIV Drug Linked to Suicidality Risk

Initial HIV treatment with a widely used medication was associated with a small increase in the risk of suicidality in patients, researchers reported.

An analysis of four large randomized trials of efavirenz (Sustiva) showed that patients taking the drug had more than double the risk of suicidality than those who did not, according to Camlin Tierney, PhD, of the Harvard School of Public Health, and colleagues.

But the actual numbers remained small - just 62 events among more than 5,300 patients followed for a median of 96 weeks, Tierney and colleagues reported in the July 1 issue of Annals of Internal Medicine.

Suicidality, which was defined as suicidal thoughts or attempted or completed suicide, "occurred uncommonly but with increased frequency in patients treated with efavirenz," the researchers reported.

Given that efavirenz is widely used, "the observed increased risk is clinically relevant," they argued.

The issue has bothered clinicians for years. Efavirenz has known neurological effects early in treatment, often manifested in vivid and disturbing dreams but including depression and anxiety.

Indeed, the package insert for the drug warns of "rare but serious" psychiatric events including suicide, the researchers noted, although the warning cautions that a "causal relationship cannot be determined from postmarketing reports."

On the other hand, they argued, the data in this analysis comes from randomized trials, which "increases the likelihood that these results represent a causal relationship between efavirenz and suicidality."

The finding will not be "a surprise or a shock" to physicians treating people with HIV, commented Carl Fichtenbaum, MD, of the University of Cincinnati.

But the researchers have "put together a large body of data that really documents this very well," he told MedPage Today.

"Oftentimes we don't have the opportunity to look at adverse effects of medications because most of the research is really driven by industry, and it's not in their best interests to look at adverse effects," he added.

The drug is a non-nucleoside reverse transcriptase inhibitor and is one of the preferred agents recommended for initial HIV treatment by the International Antiviral Society-USA (IAS-USA).

The IAS-USA is expected to issue new guidelines next month, at the International AIDS Conference in Melbourne, but the preferred position of efavirenz is not likely to change.

In a retrospective analysis of randomized trials, antiretroviral regimens containing efavirenz were associated with an increased risk for suicidality in patients with HIV, compared with efavirenz-free regimens.

Completed suicides, although small in number, were also increased in the efavirenz group.