Antidepressant improves cognitive impairment related to HIV

Image © Russell Kightley
Image © Russell Kightley

SSRIs, such as the antidepressant Paxil paroxetine (), have been associated with a modest improvement in cognitive function and reduction of central nervous system inflammation among people with HIV and cognitive deficiency related to the disorder, but the antifungal drug fluconazole showed no apparent benefit despite a reduction in oxidative stress (designative of the imbalance between the level of oxidizing substances (free radicals), which can cause damage at the cellular level, and the body's defenses - source Infopédia ), according to a study presented in the Conference on Retroviruses and Opportunistic Infections (CROI 2016) last month in Boston.

Although advanced HIV-related dementia is not commonly seen among people receiving antiretroviral therapy as effective (ART), more subtle changes in cognitive function, cas cognitive disorder related to HIV, is more prevalent (15% to 50%, depending on how it is evaluated). However, the precise causes of cognitive problems - for example, HIV in the brain, resulting inflammation, anti-retroviral toxicities - and how best to manage all of this has yet to be fully understood.

Ned Sacktor of 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 the 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 for compound 2000 for neuroprotective effects in one model in vitro oxidative stress, nerve cells from rats exposed to neurotoxins including HIV Tat protein, after finding that paroxetine and fluconazole appeared as protective in the laboratory, and they reevaluated this point in this small clinical trial.

Participants in the study 45 seropositive subjects on stable ART for at least 3 months that demonstrated evidence of impairment in at least 2 neuropsychological tests. A subset of 24 patients with better adhesion than 90% were included in the analysis of one treatment.

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

Participants in this double-blind study (a double-blind study is one in which physician and patients do not know who is taking the medication or placebo for the purpose of being compat- ible) were randomly assigned to receive 20 mg once to the oral day of paroxetine, 100 mg twice daily, fluconazole, the same doses of both drugs, or placebo for 24 weeks.

The researchers evaluated the changes in neuropsychological testing and motor system performance using the "NPZ8" 8 summary test summary (including trail, symbol digits, reaction time and timed progress) and the "CalCAP" computerized executive function test. Depression was assessed using the Beck Depression Inventory. Biomarkers of neuronal injury, oxidative stress (including ceramides), macrophages / monocyte activation (CD163), and inflammation in serum and cerebrospinal fluid (CSF) were measured.

Results

  • Participants in the arms of paroxetine - alone or in combination with fluconazole - showed a small but significant improvement in their NPZ8 score, whereas those who fluconazol alone or placebo experienced a decline after adjustment for depression (mean change + 0.16 vs establish one, respectively).
  • Participants to paroxetine also showed a significant improvement in the sequential CalCAP reaction time test (mean change 0,41 vs 0,06, respectively).
  • People who took fluconazole did not show improvement but rather worsened some tests of performance tests on neuropsychological tests.
  • There was no significant difference in symptoms of depression or changes in the arms with or without paroxetine.
  • People taking paroxetine had a decrease in CD163, indicating reduction of inflammation and activation of macrophages.
  • Those who took fluconazole, either alone or with paroxetine, had changes in the CSF lipid markers, indicating reduction of oxidative stress.
  • Paroxetine and fluconazole, either alone or in combination, were generally safe and well tolerated, with similar global frequency of adverse events across the arms.

"Treatment of paroxetine may be associated with cognitive improvement, even after adjusting for the symptomatology of depression," the researchers summed up. "Paroxetine may also be associated with decreased activation of the systemic macrophagia. However, cognitive improvement with paroxetine was not associated with a decrease in the CSF markers of lipid oxidative stress. "

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

"For a period of twenty years and after ten clinical trials, this is the first time we have been able to clearly demonstrate benefit in a summary measure of cognitive performance of HIV patients associated with cognitive disorders," Sacktor said. press release published by 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: Problems Neurocognitives

Posted on Thursday, 24 2016 March 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.

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