Pharmacotherapy for post traumatic stress disorder (PTSD).

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment. OBJECTIVES: To assess the effects of medication for reducing PTSD symptoms in adults with PTSD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020. SELECTION CRITERIA: All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD. DATA COLLECTION AND ANALYSIS: Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity. MAIN RESULTS: We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis.  For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence.  For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events. AUTHORS' CONCLUSIONS: The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.

HIV-associated cognitive disorders in perinatally infected children and adolescents: a novel composite cognitive domains score.

Accurate assessment of HIV-associated cognitive disorders in perinatally infected children and adolescents is challenging. Assessments of general intellectual functioning, or global cognition, may not provide information regarding domain-specific strengths and weaknesses, and may therefore fail to detect, impaired trajectories of development within particular cognitive domains. We compare the efficacy of global cognitive scores to that of composite cognitive domain scores in detecting cognitive disorders in a sample of perinatally HIV-infected children, and a demographically matched HIV negative control group, drawn from the Cape Town Adolescent Antiretroviral Cohort (CTAAC) study. All children were administered a comprehensive neuropsychological test battery. Using data from that test battery, we created ten separate composite cognitive domains: general intellectual functioning, attention, working memory, visual memory, verbal memory, language, visual spatial ability, motor coordination, processing speed and executive function. Within each domain, each test bore a high level of association with each of the other tests in that domain (Cronbach's α ≥ .70 for all domains). We found that composite domain scores calculated on whole-sample data were significantly higher than those calculated using control-sample data. Our comparison of a global cognitive score to composite domain scores suggested that the latter provided more detailed information (regarding strengths, weaknesses, areas of impairment), and when compared to global scores, were more sensitive in detecting HIV-associated cognitive disorders, and were able to distinguish HIV-infected patients from uninfected controls. Hence, we recommend using this method of composite cognitive domains scores, rather than global aggregate scores, when assessing cognitive function in paediatric HIV. This method provides a convenient and relatively accurate assessment that might help with cross-cultural and cross-region comparisons as researchers try to detect cognitive impairment patterns in HIV-infected children and adolescents globally.

Motivation levels and white matter microstructure in children living with HIV.

Central nervous system involvement in HIV infection leads to neurobehavioural sequelae. Although apathy is a well-recognised symptom in adults living with HIV linked to alterations in brain structure, there is scarce research examining motivation in children living with HIV (CLWH). We used the Children's Motivation Scale (CMS; normative mean = 50, SD = 10) to assess motivation levels in 76 CLWH aged 6-16 years (63 on antiretroviral therapy [ART]; 13 ART-naïve slow progressors) in South Africa. Overall, CLWH scored low on the CMS (mean = 35.70 [SD = 5.87]). Motivation levels were significantly reduced in children taking ART compared to ART-naïve slow progressors (p = 0.02), but were not correlated with markers of HIV disease (CD4 + cell count or viral load), or neurocognitive function (p > 0.05). CMS scores were correlated with diffusion tensor imaging metrics of white matter microstructure in specific frontostriatal brain regions (p < 0.05). On multiple regression, associations with the anterior limb of the internal capsule, a subcortical white matter region, remained significant after adjusting for potential confounders. These findings suggest that reduced motivation may be an important neurobehavioural symptom in CLWH and may reflect changes in white matter microstructure of frontostriatal brain regions.

Linking Women Experiencing Incarceration to Community-Based HIV Pre-Exposure Prophylaxis Care: A Qualitative Study.

Women experiencing incarceration (WEI) in the United States are disproportionately impacted by HIV, yet HIV pre-exposure prophylaxis (PrEP) is underutilized by women in the United States. In order to inform an intervention to promote PrEP initiation during incarceration and facilitate linkage to PrEP care following release from incarceration, we conducted individual, semistructured qualitative interviews with WEI (N = 21) and key stakeholders (N = 14). While WEI had little or no previous knowledge about PrEP, they viewed it as something that would benefit women involved in the criminal justice system. Participants stated that HIV-related stigma and underestimation of HIV risk might serve as barriers to PrEP initiation during incarceration. Participants reported that competing priorities, difficulty scheduling an appointment, and lack of motivation could interfere with linkage to PrEP care in the community. Further, cost, substance use, and difficulty remembering to take the medication were cited most commonly as likely barriers to adherence.

Contraception as a Potential Gateway to Pre-Exposure Prophylaxis: US Women's Pre-Exposure Prophylaxis Modality Preferences Align with Their Birth Control Practices.

Addressing women's low uptake of HIV pre-exposure prophylaxis (PrEP) requires improved understanding of their product preferences. Such preferences should be contextualized according to other aspects of their reproductive health, including their contraception practices. We investigated women's preferences across 10 PrEP modalities currently available or under study and examined associations between PrEP modality preferences and contraception practices. Heterosexually active women recently engaged in care at Connecticut Planned Parenthood centers (n = 563) completed an online survey. Participants were presented with images and descriptions of 10 PrEP modalities and asked to indicate their preference and specify their reasoning in an open-response format. Participants also reported prior and current use of 16 contraception modalities along with relationship, sexual health, and sociodemographic characteristics. The sample included women ages 18-45 (45.3% 25 or younger) who were predominantly non-Hispanic black (35.7%) or white (33.7%). All PrEP modalities presented were preferred by at least some women, with daily pills (24.9%), injections (24.3%), and invisible implants (14.9%) preferred most commonly. Across all modalities, associated reasoning often centered around ease of use and comfort. Coincidence with contraception modality was the third-most common reason underlying women's preferences. Women currently using the analogous contraception modality versus never having used it had higher odds of preferring PrEP daily pills [adjusted odds ratio (AOR) = 2.03], injections (AOR = 8.45), invisible implants (AOR = 11.63), and vaginal rings (AOR = 8.66). Diversification of available PrEP modalities and prioritization of those coinciding with popular contraception practices-especially daily pills, injections, and implants-could optimize PrEP acceptability, encourage PrEP uptake, and ultimately reduce HIV incidence among women.

Screening for HIV-associated neurocognitive disorders in perinatally infected adolescents: youth-International HIV Dementia Scale validation.

CONTEXT: Perinatal HIV infection has adverse cognitive consequences into adolescence. However, there are no screening tools that assess risk for HIV-associated neurocognitive disorders in adolescent populations. Such screening tools are needed urgently for clinical care in resource-poor settings with a high prevalence of HIV. OBJECTIVE: To investigate the performance of the International HIV Dementia Scale (IHDS) as a screening tool for HIV-associated neurocognitive disorders in perinatally adolescents. DESIGN: The current study is a quantitative, quasiexperimental design. METHODS: Perinatally HIV-infected adolescents aged 9-12 years were recruited from community health clinics into the Cape Town Adolescent Antiretroviral Cohort; matched HIV-negative controls from the same communities were enrolled. Each participant completed the IHDS and a comprehensive neuropsychological battery. The adult version of the IHDS was performed, except for two minor modifications. We evaluated the diagnostic validity of this modified instrument, the youth-IHDS (y-IHDS), using a four-step process that included sensitivity and specificity calculations, and generating receiver operating characteristic curves. Validity was measured against the youth HIV-associated diagnostic criteria. RESULTS: At a cut-off score of 10 or less, the y-IHDS demonstrated good sensitivity (94%) but poor specificity (24%) for detecting all forms of neurocognitive disorders, with an acceptable area under the curve value of 0.695. CONCLUSION: The y-IHDS requires minimal resources and is based on a screening tool for adult HIV-associated cognitive disorders that is already widely used globally. Hence, this brief, cost-efficient, and valid screening tool may be a useful addition for clinicians working in resource-poor contexts in which adolescent HIV is highly prevalent.