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AbstractNonalcoholic fatty liver disease (NAFLD) is a complex metabolic-inflammatory disease associated with poor outcomes and decreased quality of life. NAFLD is overrepresented in patients with psychiatric disorders like depression, bipolar disorder, and schizophrenia; however, a comprehensive review on NAFLD and psychiatric disorders remains to be delineated. This review endeavors to investigate the association of NAFLD with psychiatric disorders, including shared pathogenesis and future clinical derivatives. Extant literature suggests that patients with psychiatric disorders (in particular, mood disorders) are more susceptible to the development of NAFLD due to multiple reasons, including but not limited to hypothalamic–pituitary–adrenal axis dysregulation, metabolic syndrome, and chronic perceived stress. Moreover, the clinical manifestations of mood disorders (e.g., anhedonia, psychomotor retardation, lifestyle modification, etc.), and potentially long-term treatment with weight-gaining agents, differentially affect these patients, making them more prone to NAFLD. Considering the increased morbidity associated with both mood disorders and NAFLD, our review recommends regular screenings for NAFLD in select patients with mood disorders exhibiting signs of increased risk (i.e., obesity, metabolic syndrome, diabetes, or family history of NAFLD) for better diagnosis and holistic care of both potentially interrelated conditions.

AbstractObjectiveMore than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal among patients with MDD. We conducted a systematic review and network meta-analysis to evaluate the efficacy of pharmacological treatments on self-rated functional outcomes using the Sheehan Disability Scale in adults with MDD in randomized clinical trials.MethodsPubMed, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched from inception to December 10, 2019. Summary statistics are reported as weighted mean differences with 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking probabilities.ResultsWe included 42 randomized controlled trials (RCTs) (n = 18 998) evaluating the efficacy of 13 different pharmacological treatments on functional outcomes, as measured by the Sheehan Disability Scale (SDS). Duloxetine was the most effective pharmacological agent on functional outcomes, followed by (ranked by efficacy): paroxetine, levomilnacipran, venlafaxine, quetiapine, desvenlafaxine, agomelatine, escitalopram, amitriptyline, bupropion, sertraline, vortioxetine, and fluoxetine. Serotonin and norepinephrine reuptake inhibitors were more effective than other drug classes. Additionally, the comparison-adjusted funnel plot suggested the publication bias between small and large studies was relatively low.ConclusionsOur results indicate that there may be differences across antidepressant agents and classes with respect to self-reported functional outcomes. Validation and replication of these findings in large-scale RCTs are warranted. Our research results will be clinically useful for guiding psychiatrists in treating patients with MDD and functional impairment. PROSPERO registration number CRD42018116663.

AbstractCognitive impairment is common in bipolar disorder and is emerging as a therapeutic target to enhance quality of life and function. A systematic search was conducted on PubMed, PsycInfo, Cochrane, clinicaltrials.gov, and Embase databases for blinded or open-label randomized controlled trials evaluating the pro-cognitive effects of pharmacological, neurostimulation, or psychological interventions for bipolar disorder. Twenty-two trials were identified, evaluating a total of 16 different pro-cognitive interventions. The methodological quality of the identified trials were assessed using the Cochrane Risk of Bias tool. Currently, no intervention (i.e., pharmacologic, neurostimulation, cognitive remediation) has demonstrated robust and independent pro-cognitive effects in adults with bipolar disorder. Findings are preliminary and methodological limitations limit the interpretation of results. Methodological considerations including, but not limited to, the enrichment with populations with pre-treatment cognitive impairment, as well as the inclusion of individuals who are in remission are encouraged. Future trials may also consider targeting interventions to specific cognitive subgroups and the use of biomarkers of cognitive function.

AbstractBackgroundHigher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD).MethodsAdults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith–Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35).ResultsSimilar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P= .261). In addition, categorical partial response (P= .149), response (P= .526), and remission (P= .232) rates were similar between the four BMI groups.ConclusionsThe findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.

AbstractBackgroundBenzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.MethodsCross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.ResultsTotal 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P= 0 .745, partial η2< 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P< 0.001, partial η2= 0.001 and F(1, 125 459) = 349.704, P< 0.001, partial η2= 0.013, respectively.ConclusionsMale prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.

AbstractBackgroundPatients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.MethodsThis retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith–Hamilton Pleasure Scale (SHAPS).ResultsFollowing four infusions, both cohorts reported a significant reduction in QIDS-SR16Total Score (F(4, 648) = 73.4, P< .001), SI (F(4, 642) = 28.6, P< .001), GAD-7 (F(2, 265) = 53.8, P< .001), and SHAPS (F(2, 302) = 45.9, P< .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.ConclusionIV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) mixed features specifier provides a less restrictive definition of mixed mood states, compared to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), including mood episodes that manifest with subthreshold symptoms of the opposite mood state. A limited number of studies have assessed the efficacy of treatments specifically for DSM-5–defined mixed features in mood disorders. As such, there is currently an inadequate amount of data to appropriately inform evidence-based treatment guidelines of DSM-5 defined mixed features. However, given the high prevalence and morbidity of mixed features, treatment recommendations based on the currently available evidence along with expert opinion may be of benefit. This article serves to provide these interim treatment recommendations while humbly acknowledging the limited amount of evidence currently available. Second-generation antipsychotics (SGAs) appear to have the greatest promise in the treatment of bipolar disorder (BD) with mixed features. Conventional mood stabilizing agents (ie, lithium and divalproex) may also be of benefit; however, they have been inadequately studied. In the treatment of major depressive disorder (MDD) with mixed features, the comparable efficacy of antidepressants versus other treatments, such as SGAs, remains unknown. As such, antidepressants remain first-line treatment of MDD with or without mixed features; however, there are significant safety concerns associated with antidepressant monotherapy when mixed features are present, which merits increased monitoring. Lurasidone is the only SGA monotherapy that has been shown to be efficacious specifically in the treatment of MDD with mixed features. Further research is needed to accurately determine the efficacy, safety, and tolerability of treatments specifically for mood episodes with mixed features to adequately inform future treatment guidelines.

Mood episodes with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)–defined mixed features are highly prevalent in bipolar disorder (BD), affecting ~40% of patients during the course of illness. Mixed states are associated with poorer clinical outcomes, greater treatment resistance, higher rates of comorbidity, more frequent mood episodes, and increased rates of suicide. The objectives of the current review are to identify, summarize, and synthesize studies assessing the efficacy of treatments specifically for BD I and II mood episodes (ie, including manic, hypomanic, and major depressive episodes) with DSM-5–defined mixed features. Two randomized controlled trials (RCTs) and 6 post-hoc analyses were identified, all of which assessed the efficacy of second-generation antipsychotics (SGAs) for the acute treatment of BD mood episodes with mixed features. Results from these studies provide preliminary support for SGAs as efficacious treatments for both mania with mixed features and bipolar depression with mixed features. However, there are inadequate data to definitively support or refute the clinical use of specific agents. Conventional mood stabilizing agents (eg, lithium and divalproex) have yet to have been adequately studied in DSM-5–defined mixed features. Further study is required to assess the efficacy, safety, and tolerability of treatments specifically for BD mood episodes with mixed features.