Efavirenz effects worse than reported, study says

Researchers conducted a study at San Francisco General Hospital that suggests a greater incidence rate of severe psychiatric illness resulting from HIV treatment with efavirenz (EFV, Sustiva) than had previously been reported.

“The serious side effects are suicidal depression including agitation, aggression and hallucinations,” said Talia Puzantian, an associate clinical professor at the University of California-San Francisco, and a clinical pharmacist in psychiatry at San Francisco General.

Puzantian and colleagues authored a study about efavirenz that was presented at the 40th annual meeting of the Infectious Diseases Society of America (ISDA) in October 2002 in Chicago. Previous reports had stated that serious efavirenz side effects had less than a 2% incidence rate. Puzantian and co-authors questioned the rate after seeing a number of HIV patients on the drug admitted to the psychiatry unit, she said. The investigators undertook a retrospective study of severe psychiatric side effects and central nervous system side effects, comparing a database of HIV patients – from March 2000 to February 2002 – who had discontinued efavirenz with a group of patients who had discontinued nelfinavir (NFV, Viracept). “We wanted to see the numbers in a real-world setting,” Puzantian said. “We looked at substance use and psychiatric illness, and the efavirenz and nelfinavir groups were similar, so we controlled for that.”

The study found that for HIV patients who had discontinued efavirenz because of side effects, the main problems were psychiatric and CNS side effects, she said. Data showed that 18.3% of subjects on efavirenz reported vivid dreams; 14.7% complained of insomnia; 10% were lethargic or fatigued; 8.3% had headaches, and 7.3% had dizziness. Of those symptoms among the nelfinavir cohort, the only side effect that was greater than 1.1% was fatigue, reported by 7.8%. Other CNS effects included nightmares, subjects feeling like they were stoned or had a hangover, and feelings of euphoria, dysphoria, confusion and trouble concentrating. The most common neuropsychiatric effect was depression, reported by 12% of efavirenz subjects and 1.1% of nelfinavir subjects.

Nelfinavir patients reported no other neuropsychiatric effects, while the efavirenz group reported others including anxiety (9.2%), suicidal depression (2.8%), hallucinations (1.8%) and agitation (1.8%). “Be aware that these psychiatric side effects can occur and probably occur more than we think,” Puzantian said. “We can’t really guess who it’s going to happen to, so we shouldn’t assume that if someone doesn’t have a substance use or psychiatric illness that it won’t occur.”

Copyright © 2003 – Information, Inc., Bethesda, MD. This information is provided by the Centers for Disease Control & Prevention (CDC), HIV/STD/TB Prevention News Update as a public service. Noncommercial reproduction encouraged

Ref: Puzantian T, Lee J, Karasic D et al. Psychiatric Effects Associated with Efavirenz: A Retrospective Study. Annual Meeting of the Infectious Diseases Society of America October 24-27, 2002, Chicago. Abstract 481.

Comment

The range of side effects associated with efavirenz has been well reported in clinical trials and it is noted that this was a retrospective analysis from case notes. Efavirenz also remains one of the most potent antiretroviral agents available, and data from the ACTG 384 study is likely to continue its high prominence in recommendations for treatment in national treatment guidelines.

However, the higher discontinuation rate and greater severity in a real life setting is often reported in smaller studies but has received less attention. These results highlight the importance of close attention for symptoms of depression, anxiety, mood alteration or persistent sleep disturbance in individual patients using this drug.