The effect of sertraline on depression and associations with persistent depression in survivors of HIV-related cryptococcal meningitis

Abstract

Background: Depression is a risk factor for worse outcomes in persons living with HIV/AIDS and has a prevalence more than three times as high as in the general population. Despite this, there are few randomized studies of antidepressants in HIV-infected Africans. Methods: We enrolled 460 HIV-infected Africans with cryptococcal meningitis into a randomized clinical trial of adjunctive sertraline vs placebo (2015-2017). We defined depression using depression using a Center for Epidemiologic Studies Depression Scale (CES-D) score of >15, and severe depression as >26 at one and three months after meningitis diagnosis and initiation of treatment.We evaluated the relationship between sertraline and depression, as well as associations with persistent depression, at three months. Results: At one- and three-months post meningitis diagnosis, 62% (108/174) and 44% (74/169) of all subjects had depression (CES>15), respectively. At three months, sertraline-treated subjects had consistent risk for depression as placebo-treated subjects but were significantly less likely to have severe depression (CES>26) (OR 0.335; 95%CI, 0.130-0.865). Of those with depression at one month, sertraline-treated subjects were less likely than placebo-treated subjects to be depressed at three months (p=0.05). Sertraline was the only factor we found significant in predicting persistent depression at three months among those who had depression at one month. Conclusions: Depression is highly prevalent in HIV-infected persons who have survived cryptococcal meningitis. We found that sertraline is associated with a modest reduction in depression in those with depression at baseline and a significant decrease in severe depression.

Neurocognitive outcomes of tuberculous meningitis in a primarily HIV-positive Ugandan cohort

“…As prior psychiatric illness was not assessed, we cannot determine whether premorbid depression may have also contributed to risk of advanced HIV and TBM. Given the association between depression and HIV-induced immunosuppression 14 , it is notable that unlike the significant improvement in depression reported after ART initiation in survivors of cryptococcal meningitis 17,57 , high rates of depression persisted in our cohort at six months, well after ART was initiated. Immunologic differences in the response to cryptococcal meningitis and TBM 55 , known to be important in the development and persistence of depression 58,59 , may partly explain this disparity.…”

Neurocognitive outcomes of HIV-associated tuberculous meningitis

“…As prior psychiatric illness was not assessed, we cannot determine whether premorbid depression may have also contributed to risk of advanced HIV and TBM. Given the association between depression and HIV-induced immunosuppression 14 , it is notable that unlike the significant improvement in depression reported after ART initiation in survivors of cryptococcal meningitis 17,56 , high rates of depression persisted in our cohort at six months, well after ART was initiated. Immunologic differences in the response to cryptococcal meningitis and TBM 54 , known to be important in the development and persistence of depression 57,58 , may partly explain this disparity.…”

Cryptococcal meningitis

“…Individuals with cryptococcal meningitis may initially present with psychiatric symptoms such as mania, depression, and early signs of neurocognitive impairment at the time of cryptococcal meningitis diagnosis 208 . Depression rates among survivors with HIV are high (67% at one month, 44% at three months after diagnosis) and associated with baseline altered mental status and increased distance from a healthcare center, indicating that delays in care and severe infection result in higher rates of depression 209 . Long-term data on neurological sequelae in cryptococcal meningitis are limited, and the existing literature exhibits methodological and analytical heterogeneity 40 .…”