Researchers at the Johns Hopkins University School of Medicine have discovered that paroxetine, an antidepressant, is able to improve cognitive function in patients suffering from HIV-associated cognitive impairment.
Currently, many HIV patients on antiretroviral drugs (drugs that prevent the proliferation of these viruses) suffer from cognitive impairment. The reduced cognitive function is derived from an infection that causes inflammation in the brain. This inflammation leads to damaged nerves, which affects cognitive abilities such as learning, decision-making and motor coordination.
However, researchers have discovered that patients who take paroxetine in conjunction with their existing HIV treatments could reduce the level of inflammation in the brain, which could benefit HIV patients’ cognitive functions.
“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,” Ned Sacktor, lead author and professor of neurology at the Johns Hopkins University School of Medicine, said in a press release.
In this clinical trial, the research team chose to experiment with two FDA-approved drugs, paroxetine and fluconazole. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) — a class of antidepressants that prevents serotonin, the “happiness” hormone, from being reabsorbed by the nerve synapse that released it, resulting in an increase in the concentration of serotonin that is available to bind to and stimulate the receptors of the recipient cell. Fluconazole is an antifungal. These drugs were both shown to prevent cell death in cultures of rat neurons and hypothesized to show potential for reducing inflammation. They have also already been proven to be safe when combined with additional antiretroviral treatments. The usage of previously-approved and well-known drugs is a technique that offers several benefits over the trial of newly developed drugs.
“There is a huge advantage to incorporating FDA-approved drugs into a clinical trial rather than developing whole new ones. 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,” Justin McArthur, director of the Department of Neurology at Johns Hopkins University Medicine, said in a press release.
The research team collected quantitative measurements for cognitive ability of a group of 45 patients with HIV through several neuropsychological assessments. These tests evaluated the motor skills and decision-making performances of the study participants. The average of all test results gives a score, called the NPZ8, that relates HIV positive test scores to HIV negative test scores.
From the clinical results of the experiment, the researchers not only discovered that the HIV positive participants who took paroxetine performed better on the cognitive tests than their HIV positive counterparts who did not take the medication, but those with HIV who took paroxetine also had higher cognitive ability scores, on average, than those of the HIV negative population. This suggests that the medication could potentially have impacts on other populations that display low cognitive ability scores.
In addition to the NPZ8 scores, another test quantifying reaction time, called the California Computerized Assessment Package (CalCAP), showed similar results to the other tests. Participants who were given paroxetine had higher reaction times, while those who were not given the drug had similar reaction times to the HIV-negative control group. Once again, this suggests that the drug does not simply reduce inflammation — there could be an additional mechanism of the SSRI that has not yet been discovered.
Furthermore the results of the laboratory data confirmed that the drug treatments reduced inflammation — blood samples from the patients that were taken at the start of the study had greater quantities of inflammatory proteins than the blood samples that were taken 24 weeks after the medication was first prescribed.
The usage of paroxetine did result in several side effects commonly found in SSRIs, including headaches, insomnia and sexual dysfunction. It should be noted that several study participants experienced these adverse side effects and dropped out of the study.
Unfortunately the other drug involved in the study, fluconazole, did not display the same benefits of cognitive function that paroxetine did. The next step for research of SSRIs impact on cognitive function would most likely include further studies that compare paroxetine alone to a placebo.
