Efavirenz, a non-nucleoside analogue inhibitor of the reverse transcriptase, has become commonly used in the treatment of HIV infection. Although highly effective, efavirenz is associated with causing neuropsychiatric side effects in approximately 50% of patients.

To provide an overview of efavirenz-induced neuropsychiatric effects.

Literature review based on PubMed/Medline.

The neuropsychiatric side effects of efavirenz usually begin quickly, commonly peak in the first two weeks after the start of therapy, and can include depression, anxiety, sleep disturbances, impaired concentration, aggressive behavior, paranoia, psychosis. Generally, these events are mild to moderate in severity and time limited, however, in a small number of cases, are late, persistent or intolerable. They are often associated with a negative impact on treatment adhesion. Some factors are known to increase the risk of neuropsychiatric effects in HIV-positive patients. The behavioral effects of efavirenz appear to be dose-dependent and mediated predominately by the 5-HT2A receptor, a primary site of action of lysergic acid diethylamine (LSD). Importantly, the efavirenz-induced neuropsychiatric effects may be difficult to distinguish from HIV-related neuropsychiatric symptoms, preexisting mental disorder or substance use. The neuropsychiatric effects should be treated with non-pharmacologic or pharmacologic interventions, according to severity. The psychiatric status of patients should be closely monitored for at least the first 6 to 12 months of treatment.

Taking into account the high rates of neuropsychiatric side effects, it is crucial that the physicians are familiar with this important subject, and the decision to initiate efavirenz in psychiatric patients is individualized.

The authors have not supplied their declaration of competing interest.