Antidepressant may improve cognitive symptoms in people with HIV

In a small, placebo-controlled clinical trial, Johns Hopkins physicians report that the antidepressant paroxetine modestly improves decision-making and reaction time, and suppresses inflammation in people with HIV-associated cognitive impairment. The researchers say they believe this is the first time that a SSRI (selective serotonin reuptake inhibitor) has been shown to improve key measures of cognition in people with HIV in a controlled study.

The researchers note that many patients with HIV-associated neurocognitive disorders may already be benefiting cognitively by taking SSRIs in the dosages used in their study to treat depression, but the new study lends more rigorous scientific support to the drug's value.

The Johns Hopkins researchers are expected to present their findings Feb. 25 at the Conference on Retroviruses and Opportunistic Infections in Boston.

"Over a period of 20 years and after 10 clinical trials, this is the first time we've been able to clearly demonstrate benefit in a summary measure of cognitive performance for patients with HIV-associated neurocognitive disorders," says lead author Ned Sacktor, M.D., professor of neurology at the Johns Hopkins University School of Medicine.

HIV-associated neurocognitive disorders occur when infection with the virus that causes AIDS triggers nerve-damaging inflammation in the brain, leading to problems with learning, memory, decision-making and motor coordination. Up to 50 percent of people with HIV taking a cocktail of antiretroviral drugs are estimated to suffer from cognitive impairment, the researchers say.

In a search for a drug to safely blunt inflammation and reverse impairment, the investigators chose to test two drugs that looked promising based on earlier data published in 2014 by co-author Joseph Steiner, Ph.D., an adjunct associate professor of neurology.

Steiner had tested Food and Drug Administration-approved drugs paroxetine and the antifungal fluconazole, and showed that they protect neurons from death in laboratory cultures of rat nerve cells. Both drugs also cross the blood-brain barrier.

"There is a huge advantage to incorporating FDA-approved drugs into a clinical trial rather than developing whole new ones," says senior author Justin McArthur, M.B.B.S., M.P.H., professor and director of the Department of Neurology. "It's quicker, cheaper and very unlikely that there will be any surprises or any untoward side effects because the drug has been given to tens of thousands of people already."

The physicians enrolled 45 patients with HIV and cognitive impairment in a 24-week trial. Study participants couldn't have taken an SSRI within a month of the study's start. Participants received either 20 milligrams per day of paroxetine, 100 milligrams twice a day of fluconazole, the same doses of both paroxetine and fluconazole, or placebo drugs. In this study, both drugs were shown to be safe in combination with antiretroviral treatment regimens.