Neuropsychiatric side effects of efavirenz therapy

Abstract

The non-nucleoside analogue inhibitor of the reverse transcriptase, efavirenz (EFV), has become commonly used in highly active antiretroviral combination therapy in the treatment of HIV infection. Although being effective in suppressing plasma viral load, neuropsychiatric side effects have been reported in individuals treated with EFV. There are early complications, such as acute psychosis resembling reactions to LSD intake, as well as nightmares occurring for several days up to 4 weeks after the start of therapy. Although LSD-like psychosis provokes the necessity of therapy discontinuation, the nightmares, as well as irritability and concentration problems in daily life, disappear after several weeks of treatment. Late complications are depressive episodes that must be carefully differentiated from pre-existing psychiatric disease and virus-induced brain damage. This review describes neuropsychiatric symptoms provoked by EFV, differential-diagnostic procedures and treatment options, and provides pro's and con's for EFV use in clinical practice with respect to drug safety.

Incidence and predictors of adverse drug events in an African cohort of HIV-infected adults treated with efavirenz

“…This finding is consistent with other studies where the most severe toxicity effects of EFV treatment have been consistently reported within the first 2-4 weeks after treatment initiation and symptoms generally cease after 6-8 weeks. 17,18 There are also reports suggesting that as many as half of patients may develop delayed neuropsychiatric disorders with EFV. 19,20 Although the incidence of EFV-associated ADRs was low in this study, they were severe enough to result in the substitution of EFV in almost half of the patients with reported ADR.…”

Future Perspectives in NNRTI-Based Therapy: Bases for Understanding Their Toxicity

“…More severe cases, consisting of depression, delusions, suicidal ideation and paranoid reactions, have been reported in 0.4 -1.6% of EFV-treated patients (Staszewski, 1999;Hawkins, 2005;. These side effects usually appear within the first few days of treatment and are resolved after 2-4 weeks, although there are cases in which they continue to manifest themselves for several months or even longer periods (Muñoz-Moreno, 2009;Arendt, 2007). The clinical evidence available, though extensive, is insufficient to clarify the mechanisms underlying EFV-induced CNS alterations, but recent data implicate neurotoxic events induced by HIV itself and cytokine production by EFV.…”

Antiretroviral Therapy and HIV-Associated Neurocognitive Disorders

“…One major presentation of nNRTI related toxicity is neuropsychiatric disturbances. While NVP-induced CNS side effects, including impaired consciousness and psychotic episodes, have been rare, 40-70% patients on an EFV-containing cART regimen present with a range of CNS-related symptoms, such as insomnia, mood changes, and impaired attention span and concentration (Arendt, de Nocker et al 2007). …”