Mild neuropsychiatric disorders can persist for two years after starting efavirenz

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Mild neuropsychiatric disturbances can persist for up to two years after starting efavirenz (Sustiva), according to a study published in the April 15th edition of the Journal of Acquired Immune Deficiency Syndromes. However, the investigators from Spain and the Netherlands found that these neuropsychological side-effects were generally tolerable, did not affect quality of life, were not related to high levels of efavirenz in the blood, and did not lead to poorer adherence.

Use of the non-nucleoside analogue (NNRTI) efavirenz has been associated with neuropsychiatric side-effects. Generally these side-effects are considered to be mild and are thought to disappear after a few weeks of treatment. There have, however, been case reports of psychosis, major depression and suicidal ideation amongst individuals taking efavirenz.

Most studies investigating neuropsychiatric disorders amongst patients on an efavirenz-based HAART regimen have only focused on the short-term and data on the long term side-effects of efavirenz are limited. Accordingly, investigators in Barcelona and Nijmegen determined to assess the prevalence of neuropsychiatric disorders amongst individuals who had been taking efavirenz for a year or more.



Term used to indicate how well a particular drug is tolerated when taken by people at the usual dosage. Good tolerability means that drug side-effects do not cause people to stop using the drug.


The fluid portion of the blood.

multivariate analysis

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


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


Mental health problems that stop someone from thinking clearly and telling the difference between reality and their imagination.

A cross-sectional study was designed and recruited a total of 120 patients between autumn 2002 and spring 2003. Sixty individuals were taking efavirenz, the other 60 a protease inhibitor. All the patients had been taking their HAART regimen for at least a year, and none had a history of psychiatric illness or were taking medication to treat a mental illness.

Investigators compared the prevalence of neuropsychiatric disorders between the efavirenz and protease inhibitor groups. Blood samples were obtained from patients taking efavirenz to measure plasma levels of the drug, and all patients completed questionnaires to assess their quality of life and psychological status. All patients also provided a report on their level of adherence during the previous 14 days.

Overall, there were no significant social, demographic or clinical differences between patients taking efavirenz and protease inhibitors. However, the investigators found that patients in protease inhibitor arm had been taking the same HAART regimen for longer than the efavirenz patients (mean 120 weeks versus 91 weeks, p = 0.004), and had higher CD4 cell counts (630 cells/mm3 versus 517 cells/mm3, p = 0.02).

Significantly more patients taking efavirenz reported at least one neuropsychiatric disorder in the previous four weeks (54% versus 27%, p = 0.002). These included dizziness, sadness, mood changes, irritability, lightheadedness, nervousness, poor concentration, disturbed dreams and sleepiness.

When the investigators analysed the plasma levels of efavirenz, they found that they were not significantly different for patients reporting neuropsychiatric disorders (2.5mg/l) and those with no such side effects (2.7mg/l).

Quality of life was not significantly different between patients taking efavirenz and those taking a protease inhibitor. Nor did the investigators find any significant difference in psychological status between patients taking efavirenz and a protease inhibitor.

Only 55% of patients taking a protease inhibitor and 60% of patients taking efavirenz reported adherence of 95% of more in the previous two weeks. In multivariate analysis, the only factors significantly associated with adherence were substance abuse (p = 0.005) and effort to follow a treatment schedule (p = 0.002).

“Our results show that neuropsychiatric disorders persist in more than half of HIV-infected patients on long-term efavirenz therapy”, write the investigators. However they add, “it is important to emphasise that these neuropsychiatric disturbances are usually mild and clinically tolerable”. The investigators also note “these disturbances did not impair patients’ quality of life and psychologic status.”

Although this study was partly funded by Bristol Myers Squibb, manufacturer of efavirenz, the disclosure statement notes that the funding sources had no control over the design of the study or the decision to submit the findings for publication.


Fumaz CR et al. Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues and adherence. J Acquir Immune Defic Syndr 38 (5): 560 – 565, 2005.