Antidepressant improves cognitive impairment related to HIV

Image © Russell Kightley

Image © Russell Kightley

SSRIs (selective inhibitors receiving serotonin) such as the antidepressant Paxil Paroxetine () was associated with a modest improvement in the cognitive function and reduced inflammation of the central nervous system among people with HIV and cognitive deficiency related disorder, but the antifungal fluconazole drug showed no apparent benefit while reducing oxidative stress (designation of the imbalance between the level of oxidants (free radicals), which can cause damage at the cellular level, and the body's defenses - source Infopédia ), According to a study presented inConference on Retroviruses and Opportunistic Infections (CROI 2016)last month in Boston.

Although advanced dementia related to HIV is not commonly seen among people receiving antiretroviral therapy seen as effective (ART), more subtle changes in cognitive function, conhecidas as cognitive disorder related to HIVIs most prevalent (15% to 50%, depending on how it is measured). However, the precise causes of cognitive disorders - e.g., HIV in the brain, resulting in inflammation, toxicity antiretroviral - and how best to manage all this has not been fully understood.

Ned Sacktor Johns Hopkins University School of Medicine and colleagues studied the safety and efficacy of paroxetine and fluconazole, taken alone or in combination for the treatment of MAO.

Side is associated with persistent inflammation of the central nervous system (CNS), and activation of macrophages and oxidative stress and adjuvants that affect these processes may play a role in its management, the researchers noted as background.

Sacktor team members previously screened 2000 compounds for neuroprotective effects in amodel in vitro oxidative stress, nerve cells of rats exposed to neurotoxins including the Tat protein of HIV, after finding that paroxetine and fluconazole appeared as protective laboratory, and they reevaluated this point in this small clinical trial.

Participated in the study 45 people living with HIV on stable antiretroviral therapy for at least 3 months have shown evidence of impairment in at least 2 neuropsychological tests. A subset of patients with 24 better adhesion than 90% were included in the analysis of a treatment.

Three-quarters of the participants were women, most were black, the average age was about fifty years, and they had a median education level 12 years. Most had undetectable viral load of HIV, the average count was CD4 approximately 500 cells / mm3, And about half had the virus of hepatitis C. They had not taken selective inhibitors of serotonin reuptake inhibitors (SSRIs) in the previous month.

Participants in this double-blind study (Translator's note: A Study "double-blind is one in which doctor and patient do not know who is taking medication or placebo, for the purpose of compatarativo) were randomly assigned to receive 20 mg once per day of paroxetine orally, 100 mg twice a day, fluconazole, the same doses of both drugs, or placebo 24 weeks.

The researchers evaluated changes in neuropsychological tests and engine system performance by using the "NPZ8" summary measure of 8 tests (including trail, digit symbol, reaction time and progress timed) and "CalCAP" computerized test of executive function. Depression was assessed using the Beck Depression Inventory. The measured biomarkers neuronal damage, oxidative stress (including ceramides), macrophage / monocyte activation (CD163), and inflammation in the blood serum and cerebrospinal fluid (CSF).

Results

  • Participants in paroxetine arms - alone or in combination with fluconazole - showed a small but significant improvement in their NPZ8 score, while those who fluconazole alone or placebo showed a decline after adjusting for depression (adjusted mean + 0.16 vs establish one, respectively).
  • Participants paroxetine also showed a significant improvement in sequential reaction time test CalCAP (mean change vs 0,41 0,06, respectively).
  • People who took fluconazole showed no improvement and, yes, worsening of some performance tests of evidence in neuropsychological tests.
  • There was no significant difference in the symptoms of depression or changes in the arms having or not having paroxetine.
  • People taking paroxetine showed a decrease in CD163, indicating a reduction in inflammation and macrophage activation.
  • Those who took fluconazole, either alone or with paroxetine, had changes in lipid markers CSF, indicating reduced oxidative stress.
  • Paroxetine and fluconazole, alone or together, were generally safe and well tolerated, with similar overall frequency of adverse events across the arms.

"Treatment of paroxetine may be associated with cognitive improvement, even after adjustment for symptoms of depression," the researchers summarized. "Paroxetine may also be associated with a lower activation of systemic macrophage. However, cognitive improvement with paroxetine was not associated with a decrease in the CSF markers of lipid oxidative stress ".

"Paroxetine is the first adjunctive agent to demonstrate neurocognitive improvement for a summary measure of cognitive performance in a study double-blind placebo-controlled trial for treatment of MAO and suggests further study, "he said. "Fluconazole was not associated with any cognitive improvement."

"During a period of twenty years and after ten clinical trials, this is the first time we can clearly demonstrate the benefit of a measure of the summary of the cognitive performance of patients with HIV associated cognitive disorders, said Sacktor" inpress release published by the Johns Hopkins Hospital in 24 / 3 / 2016

Translated by Claudio Souza in 25 March 2016 in the original CROI 2016: Antidepressant Improves HIV-Related Cognitive Impairment. Reviewed by Mara Macedo

Category:Problemsneurocognitives

Published on Thursday, 24 March 2016 00: 00

Written by Liz Highleyman

Reference

NSacktor, RL Skolasky, N Haughey, et al. Paroxetine and Fluconazole Therapy for HAND: A Double-Blind, Placebo-Controlled Trial. Conference on Retroviruses and Opportunistic Infections. Boston, February 22-25, 2016.abstract 146.

Other Source

Johns Hopkins. Antidepressant May Improve Cognitive Symptoms in People with HIV.Press release.