Long‐term assessment of neuropsychiatric adverse reactions associated with efavirenz

Abstract

The Sensio study objectives were to assess the outcome of neuropsychiatric adverse reactions (NPAR) that develop after initiation of efavirenz (EFV) therapy, to ascertain the late NPAR after a 3-month treatment period, to evaluate the impact of NPAR on patients' quality of life (QoL) in a real-life population. MethodsDuring a 6-month period, consecutive HIV-infected adult outpatients receiving an ongoing EFV therapy for at least 3 months were asked to ®ll in a speci®cally designed self-administered questionnaire addressing sleep disturbances, behavioural changes, mood disturbances, anxiety, cognitive disorders, hallucinations, dizziness and the general impact on patients' QoL. ResultsA total of 174 questionnaires were analyzed. The main late emergent NPAR were sleep disorders: abnormal dreams 24.7%, nocturnal waking 19.6%, trouble falling asleep 17.8%; cognitive disorders: memory disorders 23.0%, impaired concentration 18.9%; anxiety 15.5%; mood disorders: sadness 19.3%, suicidal ideations 9.2%. Global neuropsychic discomfort was moderate to severe in 23% of patients after a 3-month treatment period. ConclusionNPAR occur mainly during the ®rst month of EFV therapy but often persist thereafter. A signi®cant percentage of patients reported suicidal ideations at the time of the study. Our results suggest the need for routine screening for NPAR among patients receiving EFV therapy and better management. IntroductionNeuropsychiatric adverse reactions (NPAR) commonly occur within the ®rst days following initiation of treatment with efavirenz (EFV) and resolve in 2±4 weeks of EFV use [1]. NPAR have been reported in about 50% of the patients treated with this drug in clinical trials. Central nervous system disturbances range from dizziness to hallucinations, including frequent nightmares, unusual dreams and insomnia. Symptoms are usually mild to moderate [2]. The Sensio study was focused on the NPAR self-reported by HIV-positive patients with an ongoing antiretroviral regimen including EFV in real-life conditions. The objectives were to assess the outcome of NPAR that develop after initiation of EFV therapy, to ascertain the late adverse reactions of EFV after a 3-month treatment period, and to evaluate the NPAR impact on patients' quality of life (QoL). Patients and methodsDuring a 6-month period, in three HIV outpatient units, all consecutive HIV-infected adults receiving an ongoing EFV therapy for at least 3 months were concerned by the Sensio study. Capacity to understand and answer a questionnaire in the French language was required. Patients meeting these inclusion criteria were asked by investigators to complete [7]. First, patients had to report their current antiretroviral treatment and the date of EFV initiation. Then, patients assessed their own psychological and physical status by completing the following items: sleep disturbances (trouble falling asleep, nocturnal waking, early morning waking, nightmares, perturbed dreams, day-time drowsiness, fatigue) behavioural changes (euphoria, irritability, tobacco ...

Risk of clinically significant depression in HIV‐infected patients: effect of antiretroviral drugs

“…The association of efavirenz use with depression or suicide remains controversial [17][18][19][20]. Unfortunately, investigations attempting to address this issue have been either cross-sectional studies or clinical trials with a relatively short follow-up period.…”

“…Efavirenz induces depressive-like behaviour and increases stress response in rats [13], and treatment with this drug is often associated with acute central nervous system (CNS) adverse reactions, including insomnia, dizziness and vivid dreams [14,15]. Although these symptoms generally resolve after a few weeks of efavirenz use, a minority of patients may show longer term neuropsychiatric problems [14][15][16].The association of efavirenz use with depression or suicide remains controversial [17][18][19][20]. Unfortunately, investigations attempting to address this issue have been either cross-sectional studies or clinical trials with a relatively short follow-up period.…”

Non-Hepatic Adverse Effects of Antiretroviral Therapy for HIV Treatment and Care

“…This happens in about 50% of HIV patients and this prevalence decreases to 23% within 3 months. However, the disorders subside after 6 months of therapy [14,22,23]. Efavirenz is not recommended during pregnancy because it can cause hyperlipidemia and liver toxicity.…”

Incidence of neuropsychiatric side effects of efavirenz in HIV-positive treatment-naïve patients in public-sector clinics in the Eastern Cape

“…3,4,5 Commonly reported side effects include dizziness, insomnia, headache, abnormal dreams and impaired concentration. 4,6,7 These side effects tend to occur within the first few weeks of treatment and spontaneously resolve within that time.…”

“…3 It has also been shown that these side effects may persist longer than a few weeks after the initiation of efavirenz. 5 They may in fact persist for up to 2 years and this may influence the long-term adherence to efavirenz. 8,9 The plasma levels of efavirenz as well as genetic polymorphisms in certain populations are thought to be the cause of these neuropsychiatric side effects.…”