The largest detailed, prospective clinical study of the mental side effects of a potent anti-AIDS drug, efavirenz, has revealed that the anxiety, dizziness, “funny feelings” and vivid dreams triggered by the drug fade away within a month, possibly clearing the way for more widespread use.
“Efavirenz is the first drug from its class that lasts long enough to be taken once a day, and that makes it a potentially valuable drug for AIDS treatment,” said the study’s lead author, David B. Clifford, M.D., the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology and professor of medicine at the School of Medicine.
Clifford and other scientists at the University’s AIDS Clinical Trials Unit (ACTU) studied 300 patients who were part of a larger multicenter trial. As a part of that study’s protocol, patients were randomly and blindly taking either the anti-AIDS drug efavirenz or a placebo with alternative HIV therapy.
The findings were published in The Annals of Internal Medicine.
To keep the evasive virus that causes AIDS in check, patients take different types of drugs to impair or attack it on different fronts. Efavirenz was the first of a class of drugs known as non-nucleoside reverse transcriptase inhibitors that could be taken only once a day, which boosts the chances that patients will stick to the treatment regimen and keep the virus under control.
However, there have been lingering concerns over the mental side effects of efavirenz, which begin soon after patients start taking it.
“Patients complain of ‘feeling funny’ or not feeling right almost with the first dose,” Clifford said. “Given that a chronic disorder such as AIDS is already likely to be associated with serious neuropsychiatric conditions including depression and anxiety, this was leading some physicians to shy away from prescribing efa-virenz when they would prefer to see the patient taking the drug.”
Physicians and patients also were concerned about the potential for efavirenz’s mental side effects to impair performance when driving a car, operating machinery or doing other complex tasks.
Clifford and his colleagues at the ACTU developed a questionnaire to assess efavirenz’s effects on sleep and levels of depression and anxiety in a group evenly divided between patients taking efavirenz and patients taking a placebo. The patients took the survey one week, one month, three months and six months after they started treatment. They also took standardized tests of mental performance and response times.
“People who have a viral infection do suffer declines in brain function,” Clifford said. “Treatment reverses those declines, improving performance, and we found that both the patients who took efavirenz and those who didn’t had a similar improvement in performance that resulted from better suppression of HIV. Use of efavirenz was not associated with any decline in brain function.”
Results from the questionnaire revealed no difference in depression between the group taking efavirenz and the group taking a placebo. The efavirenz group did have more anxiety, dizziness and vivid dreams after they began therapy, but those effects faded by the end of the first month.
“This drug really does do something in the brain, and we’ve had a very hard time determining how it causes these effects,” Clifford says. “But the important thing is that the effects wash out in the first month of using the drug. People now can be told that the chances are very good that if they just can stick with this drug for a few weeks they shouldn’t have ongoing problems.”
Clifford hopes to collaborate with inner ear researchers to get a better feel for how efavirenz might trigger dizziness in the first month of use. He also is continuing to give his questionnaire to patients in the study group as they continue to take efavirenz.