Adjunctive cariprazine for major depressive disorder: a systematic review and meta-analysis.

Converging evidence has suggested that treatment augmentation with a second-generation atypical antipsychotic (SGA) may improve treatment outcomes in major depressive disorder (MDD) patients after an incomplete response to a first-line antidepressant. Cariprazine is a recently approved SGA for MDD augmentation. Herein, we evaluate both continuous (ie, change in depressive symptom severity scores over time) and categorical (ie, remission and response rates) outcomes. Following a full-text review, four randomized controlled trials (RCTs) were included in our meta-analysis, while five studies were included for a qualitative review. Risk ratios (RRs) were calculated for all included randomized controlled studies to determine the relative response and remission rates of cariprazine compared to placebo augmentation. The RR for all-cause dropout was also determined as a proxy for overall acceptability. Two studies found a statistically significant treatment response using cariprazine augmentation. One study observed depressive symptom remission for cariprazine compared to placebo. Our random-effects model revealed moderate antidepressant effects of cariprazine, with a standardized mean difference (SMD) in Montgomery-Åsberg Depression Rating Scale (MADRS) scores of -1.79 (95% CI): -2.89, -0.69). Our pooled response RR and remission RR were calculated as 1.21 (95% CI: 1.05, 1.39, P=0.008) and 0.99 (95% CI: 0.84, 1.17, P=0.91), respectively. The RR for response was statistically significant (P<0.05). However, the RR for remission was not statistically significant. The findings from our meta-analysis include a variable magnitude of effects. Evidence suggests cariprazine may be an effective treatment for MDD; however, further results are needed to clarify this relation.

Associations of substance use, psychosis, and mortality among people living in precarious housing or homelessness: A longitudinal, community-based study in Vancouver, Canada.

BACKGROUND: The "trimorbidity" of substance use disorder and mental and physical illness is associated with living in precarious housing or homelessness. The extent to which substance use increases risk of psychosis and both contribute to mortality needs investigation in longitudinal studies. METHODS AND FINDINGS: A community-based sample of 437 adults (330 men, mean [SD] age 40.6 [11.2] years) living in Vancouver, Canada, completed baseline assessments between November 2008 and October 2015. Follow-up was monthly for a median 6.3 years (interquartile range 3.1-8.6). Use of tobacco, alcohol, cannabis, cocaine, methamphetamine, and opioids was assessed by interview and urine drug screen; severity of psychosis was also assessed. Mortality (up to November 15, 2018) was assessed from coroner's reports and hospital records. Using data from monthly visits (mean 9.8, SD 3.6) over the first year after study entry, mixed-effects logistic regression analysis examined relationships between risk factors and psychotic features. A past history of psychotic disorder was common (60.9%). Nonprescribed substance use included tobacco (89.0%), alcohol (77.5%), cocaine (73.2%), cannabis (72.8%), opioids (51.0%), and methamphetamine (46.5%). During the same year, 79.3% of participants reported psychotic features at least once. Greater risk was associated with number of days using methamphetamine (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.05-1.24, p = 0.001), alcohol (aOR 1.09, 95% CI 1.01-1.18, p = 0.04), and cannabis (aOR 1.08, 95% CI 1.02-1.14, p = 0.008), adjusted for demographic factors and history of past psychotic disorder. Greater exposure to concurrent month trauma was associated with increased odds of psychosis (adjusted model aOR 1.54, 95% CI 1.19-2.00, p = 0.001). There was no evidence for interactions or reverse associations between psychotic features and time-varying risk factors. During 2,481 total person years of observation, 79 participants died (18.1%). Causes of death were physical illness (40.5%), accidental overdose (35.4%), trauma (5.1%), suicide (1.3%), and unknown (17.7%). A multivariable Cox proportional hazard model indicated baseline alcohol dependence (adjusted hazard ratio [aHR] 1.83, 95% CI 1.09-3.07, p = 0.02), and evidence of hepatic fibrosis (aHR 1.81, 95% CI 1.08-3.03, p = 0.02) were risk factors for mortality. Among those under age 55 years, a history of a psychotic disorder was a risk factor for mortality (aHR 2.38, 95% CI 1.03-5.51, p = 0.04, adjusted for alcohol dependence at baseline, human immunodeficiency virus [HIV], and hepatic fibrosis). The primary study limitation concerns generalizability: conclusions from a community-based, diagnostically heterogeneous sample may not apply to specific diagnostic groups in a clinical setting. Because one-third of participants grew up in foster care or were adopted, useful family history information was not obtainable. CONCLUSIONS: In this study, we found methamphetamine, alcohol, and cannabis use were associated with higher risk for psychotic features, as were a past history of psychotic disorder, and experiencing traumatic events. We found that alcohol dependence, hepatic fibrosis, and, only among participants <55 years of age, history of a psychotic disorder were associated with greater risk for mortality. Modifiable risk factors in people living in precarious housing or homelessness can be a focus for interventions.

Social and structural factors associated with substance use within the support network of adults living in precarious housing in a socially marginalized neighborhood of Vancouver, Canada.

BACKGROUND: The structure of a social network as well as peer behaviours are thought to affect personal substance use. Where substance use may create health risks, understanding the contribution of social networks to substance use may be valuable for the design and implementation of harm reduction or other interventions. We examined the social support network of people living in precarious housing in a socially marginalized neighborhood of Vancouver, and analysed associations between social network structure, personal substance use, and supporters' substance use. METHODS: An ongoing, longitudinal study recruited 246 participants from four single room occupancy hotels, with 201 providing social network information aligned with a 6-month observation period. Use of tobacco, alcohol, cannabis, cocaine (crack and powder), methamphetamine, and heroin was recorded at monthly visits. Ego- and graph-level measures were calculated; the dispersion and prevalence of substances in the network was described. Logistic mixed effects models were used to estimate the association between ego substance use and peer substance use. Permutation analysis was done to test for randomness of substance use dispersion on the social network. RESULTS: The network topology corresponded to residence (Hotel) with two clusters differing in demographic characteristics (Cluster 1 -Hotel A: 94% of members, Cluster 2 -Hotel B: 95% of members). Dispersion of substance use across the network demonstrated differences according to network topology and specific substance. Methamphetamine use (overall 12%) was almost entirely limited to Cluster 1, and absent from Cluster 2. Different patterns were observed for other substances. Overall, ego substance use did not differ over the six-month period of observation. Ego heroin, cannabis, or crack cocaine use was associated with alter use of the same substances. Ego methamphetamine, powder cocaine, or alcohol use was not associated with alter use, with the exception for methamphetamine in a densely using part of the network. For alters using multiple substances, cannabis use was associated with lower ego heroin use, and lower ego crack cocaine use. Permutation analysis also provided evidence that dispersion of substance use, and the association between ego and alter use was not random for all substances. CONCLUSIONS: In a socially marginalized neighborhood, social network topology was strongly influenced by residence, and in turn was associated with type(s) of substance use. Associations between personal use and supporter's use of a substance differed across substances. These complex associations may merit consideration in the design of interventions to reduce risk and harms associated with substance use in people living in precarious housing.