Paroxetine May Decrease HIV-Associated Cognitive Impairment
Abstract
There are no treatments other than combination antiretroviral therapy for HIV-associated neurocognitive disorders, which are believed to affect approximately 40 percent of patients living with HIV.
People experiencing cognitive impairments associated with HIV may benefit from taking the selective serotonin reuptake inhibitor paroxetine, according to the results of a small, randomized, controlled trial presented in February at the Conference on Retroviruses and Opportunistic Infections in Boston.
Ned Sacktor, M.D., says that researchers have spent decades trying to identify an adjunctive therapy to address HIV-associated neurocognitive disorder in patients taking antiretrovirals.
“We’ve been looking for ways to treat HANDS [HIV-associated neurocognitive disorders] for almost 20 years,” said Ned Sacktor, M.D., a professor of neurology at Johns Hopkins School of Medicine and the lead researcher of the study. “We really haven’t found any agent that has shown potential to effectively address this issue until now.”
Studies suggest that despite taking antiretrovirals, more than 40 percent of individuals infected with HIV experience cognitive impairment. Sacktor told Psychiatric News that problems with learning, memory, decision making, and motor coordination likely arise when the virus triggers nerve-damaging inflammation in the brain.
A 2014 study suggested that a combination of paroxetine and fluconazole—an FDA-approved antifungal medication—decreased neurodegeneration in a macaque model of HIV-associated central nervous system disease.
To test the effectiveness of paroxetine and fluconazole in people with HIV-associated neurocognitive disorders, Sacktor and his colleagues randomly assigned 45 HIV-positive patients with cognitive impairment to one of four conditions: 20 mg of paroxetine per day, 100 mg of fluconazole twice a day, a combination of 20 mg of paroxetine per day and 100 mg of fluconazole every 12 hours, or placebo for 24 weeks.
The participants completed a series of neuropsychological tests to evaluate reaction time, decision making, and psychomotor and motor speed before starting the medication and at the end of the trial. The researchers also took blood samples from the study participants at the start of the trial and after 24 weeks of treatment.
Participants given paroxetine alone or in combination with fluconazole showed improvements on neuropsychological tests (NPZ8 cognitive test scores increased an average of a 0.15 point from baseline) compared with those not taking paroxetine (NPZ8 score of -0.33). Patients taking paroxetine also had significant improvements in reaction times (0.5 increase over baseline scores on the California Computerized Assessment Package [CalCAP test]), whereas those not taking the antidepressant did not. Fluconazole alone was not associated with cognitive benefits.
Changes in CD163 protein levels also revealed differences between the groups that received paroxetine and those that did not. (CD163 is an inflammatory protein known to be higher than average in patients with HIV-associated neurocognitive disorders.) After 24 weeks of paroxetine treatment, CD163 protein in the blood dropped by an average of 79 ng per milliliter; CD163 protein increased 400 ng per millimeter in those who were not exposed to paroxetine.
“By reducing inflammation,” said Sacktor, “we hoped to have the added benefit of improving cognition, and our results [may possibly] show that to be the case.”
Though the mechanism by which paroxetine elicits these effects remains unknown, Sacktor said that previous studies suggest paroxetine interacts with proteins in the mitochondria to decrease oxidative stress, which may lead to cognitive benefits.
“Studies like these recognize that treating HIV involves more than prescribing a cocktail of antiretrovirals,” Lawrence McGlynn, M.D., chair of APA’s HIV Steering Committee, told Psychiatric News. McGlynn, a professor of psychiatry and behavioral sciences at Stanford University School of Medicine, added that patients with HIV often experience major depression, posttraumatic stress disorder, and cognitive impairment.
“Having a treatment available, such as paroxetine, which may treat co-occurring disorders, would be a major benefit for the field of HIV psychiatry, as we attempt to find ways to treat illnesses without significantly increasing the pill burden.”
According to Sacktor, additional studies examining the specific mechanism by which paroxetine offers neuroprotection are under way.
The study was funded by the National Institute on Mental Health. ■
