Characterizing the clinical profile of mania without major depressive episodes: a systematic review and meta-analysis of factors associated with unipolar mania.

BACKGROUND: The diagnostic concept of unipolar mania (UM), i.e. the lifetime occurrence of mania without major depressive episodes, remains a topic of debate despite the evidence accumulated in the last few years. We carried out a systematic review and meta-analysis of observational studies testing factors associated with UM as compared to bipolar disorder with a manic-depressive course (md-BD). METHODS: Studies indexed up to July 2022 in main electronic databases were searched. Random-effects meta-analyses of the association between UM and relevant correlates yielded odds ratio (OR) or standardized mean difference (SMD), with 95% confidence intervals (CIs). RESULTS: Based on data from 21 studies, factors positively or negatively associated with UM, as compared to md-BD, were: male gender (OR 1.47; 95% CI 1.11-1.94); age at onset (SMD -0.25; 95% CI -0.46 to -0.04); number of hospitalizations (SMD 0.53; 95% CI 0.21-0.84); family history of depression (OR 0.55; 95% CI 0.36-0.85); suicide attempts (OR 0.25; 95% CI 0.19-0.34); comorbid anxiety disorders (OR 0.35; 95% CI 0.26-0.49); psychotic features (OR 2.16; 95% CI 1.55-3.00); hyperthymic temperament (OR 1.99; 95% CI 1.17-3.40). The quality of evidence for the association with previous suicide attempts was high, moderate for anxiety disorders and psychotic features, and low or very low for other correlates. CONCLUSIONS: Despite the heterogeneous quality of evidence, this work supports the hypothesis that UM might represent a distinctive diagnostic construct, with peculiar clinical correlates. Additional research is needed to better differentiate UM in the context of affective disorders, favouring personalized care approaches.

Long-acting injectable antipsychotics for the treatment of bipolar disorder: evidence from mirror-image studies.

Clinical trials and real-world data have shown that long-acting injectable antipsychotics (LAIs) might be an effective therapeutic option also for people with bipolar disorder (BD). However, complementing evidence from mirror-image studies investigating LAIs in BD is scattered and has not been systematically evaluated so far. We thus performed a review of observational mirror-image studies testing the effectiveness of LAI treatment on clinical outcomes in people with BD. Embase, MEDLINE, and PsycInfo electronic databases were systematically searched (via Ovid) up to November 2022. We included six mirror-image studies that compared relevant clinical outcomes between the 12-months after (post-treatment period) and the 12-months before (pre-treatment period) the initiation of a LAI treatment in adults with BD. We found that LAI treatment is associated with a significant reduction in days spent in hospital and number of hospitalizations. Moreover, LAI treatment seems to be associated with a significant decrease in the proportion of individuals with at least one hospital admission, even though data on this outcome were reported by just two studies. In addition, studies consistently estimated a significant reduction of hypo-/manic relapses after LAI treatment initiation, while the effect of LAIs for depressive episodes is less clear. Finally, LAI treatment initiation was associated with a lower number of emergency department visits in the year after LAI initiation. The findings of this review seem to suggest that the use of LAIs is an effective strategy to improve major clinical outcomes in people with BD. Nonetheless, additional research, based on standardized assessments of prevalent polarity and relapses, is needed to identify the clinical characteristics of individuals with BD who are most likely to benefit from a LAI treatment.

Clinical correlates of comorbid attention deficit hyperactivity disorder in adults suffering from bipolar disorder: A meta-analysis.

OBJECTIVE: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder. METHOD: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence. RESULTS: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p < 0.001) and unemployed (odds ratio = 1.45; p = 0.045), and less likely to be married (odds ratio = 0.62; p = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = -0.36; p < 0.001); more mood episodes (standardized mean difference = 0.35; p = 0.007), particularly depressive (standardized mean difference = 0.30; p = 0.011) and mixed (standardized mean difference = 0.30; p = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p = 0.024) and attempted suicides (odds ratio = 1.83; p < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p = 0.019), panic disorder (odds ratio = 1.89; p < 0.001), social phobia (odds ratio = 1.61; p = 0.017), eating disorders (odds ratio = 1.91; p = 0.007), antisocial personality disorder (odds ratio = 3.59; p = 0.004) and substance (odds ratio = 2.29; p < 0.001) or alcohol (odds ratio = 2.28; p < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate). CONCLUSION: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.

Effect of long-acting injectable antipsychotics on emergency department visits and hospital admissions in people with bipolar disorder: A retrospective mirror-image analysis from the Northern Milan Area Cohort (NOMIAC) study.

BACKGROUND: Mood recurrences in bipolar disorder (BD) are often associated with poor treatment adherence. Despite long-acting injectable antipsychotics (LAIs) may favor treatment compliance, their use in BD is still poorly explored. METHODS: This mirror-image study investigated the effect of LAIs initiation on the number of emergency department (ED) visits and days of hospitalization, among individuals with BD from the mental health services of a large area of the Metropolitan City of Milan. The mirror periods were 365 days either side of the LAI initiation. Individual medical records were retrospectively reviewed. RESULTS: Sixty-eight individuals with BD initiating a LAI over the index period were included. We estimated that LAI initiation overall reduced both ED visits (p = 0.002) and days of hospitalization (p < 0.001). This remained true only for those participants who i) continued LAI for the entire 12-month period of observation and ii) were treated with a second-generation antipsychotic LAI. In addition, LAI initiation reduced number of hospitalization days during hypo/manic (p = 0.013), but not depressive (p = 0.641) episodes, as well as compulsory admission days (p = 0.002). LIMITATIONS: Due to the retrospective design, we could not collect systematic information on symptom severity and reasons of LAI discontinuation. Moreover, the limited sample size did not allow us to estimate effectiveness of single LAI agents. CONCLUSIONS: Our study provides additional insight on the effectiveness of LAIs in BD, supporting their clinical utility for pragmatic outcomes such as ED visits and hospitalizations. Further longitudinal research is needed to clarify the real-world effectiveness of LAIs for BD clinical management.