Antidepressant May Improve Cognitive Problems Among HIV Patients

Study finds reducing inflammation carries the added benefit of improving cognition among patients with HIV.

Due to cognitive impairment issues HIV-positive patients can suffer, an antidepressant may be able to greatly improve decision making and reaction time, while suppressing inflammation, according to researchers at Johns Hopkins.

It is estimated that 50% of HIV patients on antiretroviral drugs suffer from cognitive impairment. This impairment occurs when the virus triggers nerve damaging inflammation in the brain, which leads to learning and memory problems, as in addition to issues with decision making and motor coordination.

"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," said lead author Ned Sacktor, MD.

Researchers looked at 2 promising drugs that could help stop inflammation and impairment. When the FDA-approved drugs paroxetine and fluconazole were tested on rat nerve cell cultures, it showed that both drugs could cross the blood-brain barrier and protect the neurons from death.

"There is a huge advantage to incorporating FDA approved drugs into a clinical trial rather than developing whole new ones," said senior study author Justin McArthur, MBBS, MPH. "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."

During a clinical trial that lasted 24 weeks, 45 HIV positive patients with cognitive impairment were enrolled. Patients were restricted from taking SSRIs a month prior to the start of the study.

The enrollees were administered 20 milligrams of paroxetine daily, 100 milligrams twice a day of fluconazole, equal doses of paroxetine and fluconazole, or placebo drugs.

In order to evaluate the psychomotor and motor speed performance and decision making skills of patients, researchers used 8 neuropsychological tests (NPZ8).

In order to get an NPZ8 score, an average is taken of the 8 test results. The score is then evaluated using a statistical test that compares HIV positive patient scores against HIV negative scores.

The results of the study showed that those administered paroxetine alone or in combination with fluconazole improved their NPZ8 test scores by an average of 0.15. Patients who did not take paroxetine showed a decline in test scores by -0.33.

Participants were also tested on reaction times with the California Computerized Assessment Package (CalCAP) test at the start and end of the trial.

The results of the study on reaction times showed that patients who took paroxetine had an improvement in test scores by an increase of 0.5 over the baseline measurement. Patients who did not take paroxetine showed no significant improvement with only a 0.06 change.

Lastly, physicians took blood samples from participants at the start and end of the 24 week regimen to measure the levels of reduced inflammation. HIV patients with associated neurocognitive disorders tend to have higher than average levels of CD163.

HIV positive patients had an average of 802 nanograms per milliliter of CD163 protein in the blood prior to treatment. The levels dropped to 738 nanograms per milliliter after treatment with paroxetine. Those who were not given paroxetine had a rise in CD163 levels by an average of nearly 400 nanograms per milliliter.

"By reducing inflammation, we hoped to have the added benefit of improving cognition, and our results show that to be the case," said Sacktor.

Paroxetine typically costs less than $15 a month and participants had typical side effects associated with paroxetine that is commonly found in other SSRIs, such as: sexual dysfunction (3 people), headache (2 patients), insomnia (2 patients) or vivid dreams (2 patients).

Within the study there were no real cognitive improvements when fluconazole was used alone, so researchers might switch focus to a larger scaled study using only paroxetine. The precise of SSRIs improving cognitive impairment is still unknown.