Study finds no link between efavirenz use and depression

This article is more than 18 years old. Click here for more recent articles on this topic

French researchers have found that patients taking efavirenz (Sustiva) do not have a greater risk of depression than those taking a protease inhibitor-based regimen over three years. However, younger patients and those with a history of depression were more likely to develop depression during the study. The study’s results were published in the 15th June edition of Clinical Infectious Diseases.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is widely used for the treatment of HIV infection. It is well established that the drug has side-effects of dizziness, impaired concentration and sleep disturbances in some patients, which are generally short-lived and transient.

However, studies have produced conflicting findings on a link between efavirenz and the development of clinical depression. Some studies have found high rates of depression in patients taking efavirenz, but studies comparing efavirenz to other anti-HIV drugs have found few differences in depression rates.



A mental health problem causing long-lasting low mood that interferes with everyday life.

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

concentration (of a drug)

The level of a drug in the blood or other body fluid or tissue.

To gain more information on the effects of efavirenz, researchers from the French National Agency of AIDS and Viral Hepatitis Research (Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, ANRS) conducted an analysis of data from a large randomised controlled study called ALIZE-ANRS 099.

This study examined the effects of switching 178 patients from an anti-HIV treatment combination of a protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTIs) to a combination of efavirenz, ddI (didanosine, VidexEC) and FTC (emtricitabine, Emtriva). The investigators compared the outcomes of these patients to 177 similar patients, who continued to take their protease inhibitor-based treatment combination.

In the first 48 weeks of the study, there were 30 cases of depressive disorder, including 26 cases of depression and four suicide attempts. Although these rates were high, depressive disorder was seen in similar numbers of patients in the efavirenz and protease inhibitor groups (8 vs. 7%; p = 0.56). Depression was detected through the trial’s system for reporting side-effects and diagnosed using a validated questionnaire that the patients completed themselves.

More patients stopped treatment in the efavirenz arm (13 vs. 3%), but this difference was due to more patients suffering from bad dreams, dizziness and headaches. No patients stopped treatment because of depression.

In a multivariate analysis, the investigators found that younger age and a history of depression were linked to a greater risk of developing depression during the study, but this was unaffected by the patient’s treatment. These trends have been seen in previous studies.

The investigators’ findings were not affected by extending the follow-up period from one to three years. In addition, similar numbers of patients in the two groups were prescribed antidepressants during the entire three-year study (7 vs. 4%, p = 0.27).

“Contrary to the idea widely held among HIV-infected patients, physicians, and researchers, our data showed no evidence of efavirenz having an effect on the risk of depression or suicide in the first 48 weeks of use – or even up to 36 months of use,” the researchers conclude. “However, a higher risk of these conditions occurred among younger patients and among those with a history of depressive disorder.

“A history of depressive disorder should not be a contraindication for prescribing efavirenz treatment,” they add.

The ALIZE-ANRS 099 study was designed to assess the effects of a treatment switch on virological suppression, rather than the psychiatric effects of efavirenz. However, the investigators calculated that the study was large enough to detect a significant difference in depression rates, if it had existed.

A possible limitation of the study is that the patients and doctors knew which drugs they were taking. Although this may have led to increased levels of depression being reported in the efavirenz arm, the investigators' discovery of similar rates in the two groups strengthens their conclusion that depression rates are not elevated by efavirenz treatment.


Journot V et al. Use of efavirenz is not associated with a higher risk of depressive disorders: a substudy of the randomized clinical trial ALIZE-ANRS 099. Clin Infect Dis 42: 1790-1799, 2006.