Benzodiazepine Use Is Associated With an Increased Risk of Neurocognitive Impairment in People Living With HIV

Abstract

Objective: Despite potential for dependence and adverse neurological effects, long-term benzodiazepine (BZD) use is common among people living with HIV (PLWH). As PLWH are at risk for central nervous system dysfunction, we retrospectively examined the association between BZD use and HIV-associated neurocognitive impairment (NCI). Methods: Three hundred six PLWH underwent comprehensive neurobehavioral evaluations. Current BZD use (BZD+) was determined through self-report. Using propensity scores, 153 BZD− individuals were matched to 153 BZD+ participants on demographics and medical comorbidities. Multiple regression models examined NCI and demographically adjusted neurocognitive T-scores as a function of BZD status, adjusting for estimated premorbid ability, current affective symptoms, and nadir CD4 count. Secondary analyses explored neurocognitive correlates of positive BZD urine toxicology screens (TOX+) and specific BZD agents. Results: Median duration of BZD use was 24 months. Current BZD use related to higher likelihood of NCI (odds ratio = 2.13, P = 0.003) and poorer global (d = −0.28, P = 0.020), processing speed (d = −0.23, P = 0.047), and motor T-scores (d = −0.32, P = 0.008). Compared with BZD−/TOX−, BZD+/TOX+ exhibited additional decrements in executive function (d = −0.48, P = 0.013), working memory (d = −0.49, P = 0.011), and delayed recall (d = −0.41, P = 0.032). For individual agents, diazepam, lorazepam, and alprazolam were most strongly associated with NCI (odds ratios >2.31). Discussion: BZD use may elevate risk for NCI in PLWH, potentially through diffuse neurocognitive slowing and acute compromise of recall and higher-order capacities. These effects are robust to psychosocial and HIV-specific factors and occur in comparison with a tightly matched BZD− group. Prospective and interventional studies should evaluate causal associations between NCI and BZD use and explore treatment alternatives to BZDs in PLWH.

The association between benzodiazepine use and greater risk of neurocognitive impairment is moderated by medical burden in people with HIV

“…In contrast, benzodiazepine groups were comparable in rates of current and past substance use disorders and in HIV disease characteristics with the exception of a longer duration of HIV disease in benzodiazepine users versus non-users. Consistent with our previous results in a sample of PWH with and without viral suppression (Saloner et al 2019b ), we found higher rates of NCI in benzodiazepine users (49.3%) versus non-users (36.1%) ( X 2 = 4.86, p = 0.03) among ART-treated, virally suppressed PWH. Among considered covariates, BDI-II scores, lifetime MDD diagnosis, number of medications, antidepressant and antipsychotic medication use and current alcohol use disorder were associated with NCI at p ≤ 0.10 and, thus, were included in all statistical models.…”

“…Domain-specific analyses showed that the benzodiazepine use X medical burden interaction was evident in speed of information processing, verbal fluency and motor function. This is consistent with our prior study that also found an adverse effect of benzodiazepine use on speed of information processing and motor domains among PWH (Saloner et al 2019b ). A commonality among speed of information processing, motor function, and verbal fluency is that they are all speed-dependent and regulated by frontostriatal neural circuitry (Ances et al 2012 ; Hakkers et al 2017 ), which aligns with the theory that benzodiazepine causes psychomotor slowing (Rollings et al 1994 ; Stewart 2005 ; Lader 2011 ).…”

“…In contrast, benzodiazepine use was independently associated with a higher likelihood of impairments in learning, recall and working memory/attention regardless of medical burden. This finding is also consistent with our prior findings that PWH who report benzodiazepine use and are positive for benzodiazepine in a toxicology test show working memory/attention and delayed recall impairments compared to PWH without evidence of benzodiazepine use (Saloner et al 2019b ). Similarly, a recent study from the Women’s Interagency HIV Study that reported an interaction between anxiolytic use (primarily benzodiazepines) and HIV serostatus on learning performance, whereby HIV-related learning deficits were only observed among those reporting anxiolytic use (Rubin et al 2018 ).…”

Assessing the clinical utility of the severity dependence scale for benzodiazepine use disorder

“… 7 This was further highlighted by Rowan et al who proposed an increased risk in neurocognitive impairment in people living with HIV (PLWH) who use benzodiazepines. 8 …”

“…7 This was further highlighted by Rowan et al who proposed an increased risk in neurocognitive impairment in people living with HIV (PLWH) who use benzodiazepines. 8 A United States of America study highlighted that chronic benzodiazepine users are estimated at 500 000 to 1 million in the United Kingdom, 4 million in the United States of America and several Background: Benzodiazepines are often used as a part of mental health pharmacological management; however, often when prescribed for extended periods, they increase the risk of benzodiazepine use disorder (BUD). Clinical interviews are at the centre of diagnosing this disorder.…”