Prolonged CNS side-effects of efavirenz can be severe and lead to treatment discontinuation
Paul Blanchard, HIV i-Base
Side effects attributable to the central nervous system (CNS) effects of efavirenz commonly occur within the first days following initiation of this drug and normally resolve within two to four weeks.
These short term side effects have been reported to affect 53 % of patients initiating efavirenz. Some physicians and patients, however, have experienced much longer lasting neuropsychological adverse reactions.
Reynes and colleagues reported the results of their Sensio study which focused on the neuropsychological adverse reactions (NPAR) self-reported by HIV positive patients being treated with an ARV regimen including efavirenz. Data collection was by questionnaire measuring frequency, severity and outcome of efavirenz related NPAR. Thirty three items were included addressing sleep disturbances, behavioural changes, mood disturbances, anxiety, cognitive disorders, hallucinations, dizziness and general impact on quality of life. All patients administered the questionnaire had received efavirenz for a minimum of three months. 
Patients with frequent symptoms before initiation of efavirenz were excluded and only symptoms appearing under treatment with efavirenz focused upon. A total of 199 questionnaires were analysed.
More severe psychiatric disorders were reported in some patients. 10.3% (n=18) reported emergent suicidal ideations after initiation of efavirenz associated with other depressive symptoms. Late onset suicidal ideation occurred in XX% (n=8) and had been long lasting in XX% (n=10). Symptomatic treatment of NPAR was necessary in 10.3% (n=18) usually consisting of benzodiazepines alone or in combination with antidepressants. Overall 6.3% of patients discontinued efavirenz later than three months after initiation due to intolerability of NPAR.
The study investigators concluded that;
- Sleep disturbances and dizziness occurred mostly at the beginning of efavirenz therapy
- NPAR which persisted or worsened over the three month treatment period were anxiety, behavioural troubles, sadness and cognitive disorders
- A high percentage of patients reported suicidal ideations at the time of study whereas none did before efavirenz initiation
- NPAR related to efavirenz seriously affects patients quality of life (23.1%) although most patients are able to maintain efavirenz in their regimen.
It is clear from this study that patients can and will tolerate the adverse effects of efavirenz over many months despite a measurable impact on quality of life. Perhaps both practitioners and patients should be less tolerant, and more ready to switch to acceptable alternatives within a regimen.
Postscript: this study was later published in HIV Medicine. 
- Lochet P, Peyriere H, Mauboussin JM et al. Sensio study: assessment of late neuropsychiatric adverse reactions (NPAR) to efavirenz. XIV International AIDS Conference, Barcelona, July 7-12, 2002. Abstract B3250.
- Lochet P et al. Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz. HIV Med. 2003 Jan;4(1):62-6.