Life engagement represents a holistic concept that encompasses outcomes reflecting life-fulfilment, well-being and participation in valued and meaningful activities, which is recently gaining attention and scientific interest. Despite its conceptual importance and its relevance, life engagement represents a largely unexplored domain in schizophrenia. The aims of the present study were to independently assess correlates and predictors of patient life engagement in a large and well-characterized sample of schizophrenia patients.

To assess the impact of different demographic, clinical, cognitive and functional parameters on life engagement in a large sample of patients with schizophrenia, data from the social cognition psychometric evaluation project were analyzed.

Overall schizophrenia and depressive symptom severity, premorbid IQ, neurocognitive performance, social cognition performance both in the emotion processing and theory of mind domains, functional capacity, social skills performance and real-world functioning in different areas all emerged as correlates of patient life engagement. Greater symptom severity and greater impairment in real-world interpersonal relationships, social skills, functional capacity and work outcomes emerged as individual predictors of greater limitations in life engagement.

Life engagement in people living with schizophrenia represents a holistic and complex construct, with several different clinical, cognitive and functional correlates. These features represent potential treatment targets to improve the clinical condition and also facilitate the process of recovery and the overall well-being of people living with schizophrenia.

Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day.

Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery–Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day).

After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day.

Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.

In patients with bipolar disorder, depression symptoms are associated with greater reduction in function and quality of life than hypomania/mania symptoms. Lumateperone (LUMA), is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder.

In a recent phase 3 clinical trial (Study 404, NCT03249376) in people with bipolar depression, LUMA 42 mg monotherapy significantly improved symptoms of depression compared with placebo (PBO). This analysis of Study 404 investigated the effects of LUMA on functional disability and quality of life as measured using the secondary outcome measure, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF).

Patients (18–75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score ≥4) were randomized to LUMA 42 mg or PBO orally, once daily in the evening for 6 weeks. The primary endpoint was the change from baseline to Day 43 in MADRS Total score, analyzed using a mixed-effects model for repeated measures (MMRM) approach in the intent-to-treat population (ITT). This post hoc analysis evaluated the mean change from baseline to Day 43 in the Q-LES-Q-SF individual item scores using an analysis of covariance with last observation carried forward (ANCOVA-LOCF) in the ITT. Categorical shifts in individual items were also analyzed.

The ITT comprised 376 patients (LUMA 42 mg, 188; PBO, 188). Patients in the LUMA 42 mg group had significantly greater improvement on MADRS Total score change from baseline to Day 43 compared with PBO (least squares mean difference vs PBO [LSMD], −4.585; 95% CI, −6.344 to −2.826; effect size vs PBO [ES], −0.56; P<.0001). LUMA 42 mg treatment significantly improved Q-LES-Q-SF Total score from baseline to Day 43 compared with PBO (LSMD, 2.9; 95% CI, 1.15 to 4.59; P=.001).

The Q-LES-Q-SF items with the lowest mean scores at baseline in both groups were mood, leisure time activities, and sexual drive, interest, and/or performance. By Day 43, LUMA 42 mg treatment significantly improved 8 of the 14 items in the Q-LES-Q-SF (P<0.05). Overall life satisfaction also significantly improved with LUMA treatment (P=.0016). The largest improvements with LUMA 42 mg compared with PBO (ES>0.3,) were seen for the ability to function in daily life, family relationships, household activities, leisure time activities, and mood (all LSMD=0.3; all P<.01).

In patients with bipolar depression, treatment with LUMA 42 mg compared with PBO significantly improved patient quality of life and functional impairment. These results support LUMA 42 mg as treatment of MDEs associated with bipolar I or bipolar II disorder in adults.

Intra-Cellular Therapies, Inc.

Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months. This 32-week trial evaluated the safety, pharmacokinetics, and efficacy of multiple-dose administration of Ari 2MRTU 960 in clinically stable adults with schizophrenia or BP-I, versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole and maintenance monotherapy treatment of BP-I [indication varies by country]). Safety and efficacy outcomes in the subpopulation of patients with BP-I are reported here.

Patients with BP-I were randomized to receive Ari 2MRTU 960 every 56±2 days or AOM 400 every 28±2 days. Safety and tolerability assessments included adverse event (AE) reporting, Visual Analogue Scale (VAS) scores (scale range: 0–100) for patient-reported injection site pain, and extrapyramidal symptom (EPS) monitoring. Efficacy was assessed at Week 32 by Clinical Global Impression – Improvement (CGI-I), Clinical Global Impression – Bipolar Version (CGI-BP), Subjective Well-being under Neuroleptic Treatment – Short Form (SWN-S), Montgomery–Åsberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS).

Study completion rate was 72.5% (29/40 patients) in the Ari 2MRTU 960 group and 70.7% (29/41 patients) in the AOM 400 group. Demographics and baseline disease characteristics were generally well balanced between treatment groups. Treatment-emergent AE (TEAE) incidence was 82.5% with Ari 2MRTU 960 and 87.8% with AOM 400. The most frequent TEAEs were increased weight (Ari 2MRTU 960, 25.0%; AOM 400, 26.8%) and injection site pain (Ari 2MRTU 960, 25.0%; AOM 400, 7.3%). Mean (standard deviation [SD]) VAS score for pain after last injection was 1.2 (2.07) with Ari 2MRTU 960 and 1.3 (2.19) with AOM 400. Minimal change was seen in EPS in either group. At Week 32, mean (SD) CGI-I score was 3.1 [1.2] with Ari 2MRTU 960 and 3.2 [1.5] with AOM 400, and there was minimal mean (SD) change from baseline in CGI-BP score (Ari 2MRTU 960, -0.2 [1.0]; AOM 400, -0.6 [1.2]). Mean (SD) change from baseline in SWN-S Total score was 10.3 (16.1) with Ari 2MRTU 960 and 3.4 (21.4) with AOM 400. There was no clinically meaningful difference between the groups in MADRS Total score or YMRS Total score (difference of least squares mean change from baseline [95% confidence interval]: MADRS Total score -2.1 [-6.3, 2.1], p=0.3185; YMRS Total score 0.1 [-1.8, 2.1], p=0.8995).

In patients with BP-I, Ari 2MRTU 960 was generally well tolerated, and clinical stability was maintained during the study.

Otsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).

Treatments for MDD that can improve both overall depressive and anhedonic symptoms are urgently needed.

AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.

To evaluate the effect of AXS-05 in improving anhedonic symptoms in MDD.

GEMINI (N=327) was a randomized, double-blind, placebo-controlled, 6-week study, which randomized adults with MDD to AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) or placebo, twice daily. The primary endpoint was change from baseline in the MADRS total score at Week 6. A post-hoc analysis was conducted to determine the impact of AXS-05 versus placebo on the 5-item MADRS anhedonia subscale (MAS).

Baseline MAS scores were 19.8 and 19.6 in the AXS-05 and placebo group, respectively. At Week 1, AXS-05 treatment resulted in a significant mean reduction from baseline in the MAS score of 4.44 versus 2.69 points for placebo (p< 0.001). At Week 6, the mean reduction from baseline in the MAS was 9.70 for AXS-05 compared to 7.22 for placebo (p=0.001). Response rates (≥ 50% MAS improvement) were significantly greater for AXS-05 compared to placebo at Week 1 (p< 0.001) and at every time point thereafter.

Treatment with AXS-05 was generally safe and well tolerated. The most common adverse events being dizziness, nausea, headache, diarrhea, somnolence, and dry mouth.

Treatment with AXS-05 rapidly and significantly reduced anhedonic symptoms as well as overall depressive symptoms.

Axsome Therapeutics

Childhood maltreatment is an established risk factor for incident unipolar disorder and bipolar disorder. It is separately observed that affective disorders (AD) are also associated with higher nucleoside damage by oxidation. Childhood maltreatment may induce higher levels of nucleoside damage by oxidation and thus contribute to the development of AD; however, this relation is only sparsely investigated.

In total, 860 participants (468 patients with AD, 151 unaffected first-degree relatives, and 241 healthy control persons) completed the Childhood Trauma Questionnaire (CTQ). The association between CTQ scores and markers of systemic DNA and RNA damage by oxidation as measured by urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) levels, respectively, was investigated.

In multiple regression models adjusted for sex- and age, 8-oxodG and 8-oxoGuo levels were found to be higher in individuals who had experienced more childhood maltreatment. These associations persisted in models additionally adjusted for body mass index, alcohol, and current smoking status. Emotional abuse, sexual abuse, and emotional neglect were principally responsible for the foregoing associations.

Our findings of an association between childhood maltreatment and oxidative stress markers suggest that childhood maltreatment overall, notably emotional abuse and emotional neglect, is associated with enhanced systemic damage to DNA and RNA in adulthood. Further, individuals with AD reported a higher prevalence of childhood maltreatment, which may induce higher levels of nucleoside damage by oxidation in adulthood, possibly leading to increased risk of developing AD. Longitudinal studies are needed to clarify this relationship further.

The endogenous opioid system affects metabolism, including weight regulation. Evidence from preclinical and clinical studies provides a rationale for targeting this system to mitigate weight-related side effects of antipsychotics. This review describes the role of the opioid system in regulating weight and metabolism, examines the effects of opioid receptor antagonism on those functions, and explores the use of opioid antagonists to mitigate antipsychotic-associated weight gain and/or metabolic effects.

A PubMed literature search was conducted to identify representative opioid antagonists and associated preclinical and clinical studies examining their potential for the regulation of weight and metabolism.

The mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR) types have overlapping but distinct patterns of central and peripheral expression, and each contributes to the regulation of body weight and metabolism. Three representative opioid antagonists (eg, naltrexone, samidorphan, and LY255582) were identified for illustration. These opioid antagonists differed in their receptor binding and pharmacokinetic profiles, including oral bioavailability, systemic clearance, and half-life, and were associated with varying effects on food intake, energy utilization, and metabolic dysregulation.

Preclinical and clinical data suggest that antagonism of the endogenous opioid system is a mechanism to address antipsychotic-associated weight gain and metabolic dysregulation. However, evidence suggests that the differing roles of MOR, DOR, and KOR in metabolism, together with the differences in receptor binding, pharmacokinetic, and functional activity profiles of the opioid receptor antagonists discussed in this review, likely contribute to their differential pharmacodynamic effects and clinical outcomes observed regarding antipsychotic-associated weight gain.

To investigate the effect of cariprazine on cognitive symptom change across bipolar I disorder and schizophrenia.

Post hoc analyses of 3- to 8-week pivotal studies in bipolar I depression and mania were conducted; one schizophrenia trial including the Cognitive Drug Research System attention battery was also analyzed. Outcomes of interest: Montgomery-Åsberg Depression Rating Scale [MADRS], Functioning Assessment Short Test [FAST], Positive and Negative Syndrome Scale [PANSS]). LSMDs in change from baseline to end of study were reported in the overall intent-to-treat population and in patient subsets with specified levels of baseline cognitive symptoms or performance.

In patients with bipolar depression and at least mild cognitive symptoms, LSMDs were statistically significant for cariprazine vs placebo on MADRS item 6 (3 studies; 1.5 mg=−0.5 [P<.001]; 3 mg/d=−0.2 [P<.05]) and on the FAST Cognitive subscale (1 study; 1.5 mg/d=−1.4; P=.0039). In patients with bipolar mania and at least mild cognitive symptoms, the LSMD in PANSS Cognitive subscale score was statistically significant for cariprazine vs placebo (3 studies; −2.1; P=.001). In patients with schizophrenia and high cognitive impairment, improvement in power of attention was observed for cariprazine 3 mg/d vs placebo (P=.0080), but not for cariprazine 6 mg/d; improvement in continuity of attention was observed for cariprazine 3 mg/d (P=.0012) and 6 mg/d (P=.0073).

These post hoc analyses provide preliminary evidence of greater improvements for cariprazine vs placebo across cognitive measures in patients with bipolar I depression and mania, and schizophrenia, suggesting potential benefits for cariprazine in treating cognitive symptoms.

Analysis of efficacy and tolerability of vortioxetine 20 mg/day, and optimal timing of dose adjustment, in patients with major depressive disorder (MDD).

Pooled analysis of six randomized, fixed-dose studies of vortioxetine 5 to 20 mg/day. Mean change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) total score was analyzed by vortioxetine dose using a mixed model for repeated measures. Tolerability was assessed over the 8-week treatment period and from day 8 (ie, following dose increase to 20 mg/day). Data from three randomized, flexible-dose studies were examined for frequency and timing of dose adjustment.

A clear dose–response relationship for vortioxetine was confirmed in terms of improvement in MADRS total score. Significant differences vs placebo were seen for vortioxetine 20 mg/day from week 2 onwards; vortioxetine 10 mg did not separate from placebo until week 4. At week 8, mean change in MADRS total score from baseline was significantly greater for vortioxetine 20 mg/day vs 10 mg/day (difference, −1.03 points; P < .05). Incidence of adverse events was not increased in patients who received vortioxetine 20 mg/day vs 10 mg/day. In flexible-dose studies, dosage was increased to 20 mg/day after 1 week in 48.0% of patients; final dosage was 20 mg/day in 64.3% of patients.

Vortioxetine 20 mg is significantly more effective than vortioxetine 10 mg in patients with MDD, with a similar tolerability profile. In flexible-dose studies, almost half of all patients received 20 mg/day after 1 week and two-thirds received 20 mg/day as their final dosage.

Acceptance and willingness to pay for the COVID-19 vaccine are unknown.

We compared attitudes toward COVID-19 vaccination in people suffering from depression or anxiety disorder and people without mental disorders, and their willingness to pay for it.

Adults with depression or anxiety disorder (n = 79) and healthy controls (n = 134) living in Chongqing, China, completed a cross-sectional study between 13 and 26 January 2021. We used a validated survey to assess eight aspects related to attitudes toward the COVID-19 vaccines. Psychiatric symptoms were assessed by the 21-item Depression, Anxiety and Stress Scale.

Seventy-six people with depression or anxiety disorder (96.2%) and 134 healthy controls (100%) reported willingness to receive the COVID-19 vaccine. A significantly higher proportion of people with depression or anxiety disorder (64.5%) were more willing to pay for the COVID-19 vaccine than healthy controls (38.1%) (P ≤ 0.001). After multivariate adjustment, severity of depression and anxiety was significantly associated with willingness to pay for COVID-19 vaccination among psychiatric patients (P = 0.048). Non-healthcare workers (P = 0.039), health insurance (P = 0.003), living with children (P = 0.006) and internalised stigma (P = 0.002) were significant factors associated with willingness to pay for COVID-19 vaccine in healthy controls.

To conclude, psychiatric patients in Chongqing, China, showed high acceptance and willingness to pay for the COVID-19 vaccine. Factors associated with willingness to pay for the COVID-19 vaccine differed between psychiatric patients and healthy controls.

Cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, is approved for the treatment of schizophrenia and for depressive, manic, or mixed episodes associated with bipolar I disorder. Previous post hoc analyses have demonstrated that cariprazine was effective versus placebo for improving cognitive symptoms in patients with schizophrenia or bipolar depression. This post hoc analysis evaluated the effects of cariprazine on cognitive symptoms in patients with acute manic or mixed bipolar episodes.

Data from 3 phase II/III, randomized, double-blind, placebo-controlled studies in patients with manic or mixed episodes associated with bipolar I disorder (NCT00488618, NCT01058096, NCT01058668) were pooled and analyzed. Patients were randomized to placebo or flexibly dosed cariprazine (3-12 mg/d, 3-6 mg/d, or 6-12 mg/d [1 study only]) for 3 weeks of double-blind treatment; all dose groups were combined for the pooled analysis. Cognitive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) Cognitive subscale (sum of PANSS items P2, N5, N7, G10, G11); a score of 15 or greater at baseline indicated the presence of cognitive symptoms. Mean changes from baseline to week 3 in PANSS cognitive subscale/item scores and Young Mania Rating Scale (YMRS) total score were evaluated in the overall intent-to-treat (ITT) population and in the subgroup of patients with baseline cognitive symptoms. A mixed-effects model for repeated measures (MMRM) was used to impute missing values.

Of the 1012 patients in the ITT population, 174 (placebo=71; cariprazine=103) had a PANSS Cognitive subscale score of 15 or greater at baseline. At week 3, the cariprazine group demonstrated significantly greater mean improvement than the placebo group on PANSS cognitive subscale scores in both the ITT population (−2.2 vs −1.3; P<.0001) and the subgroup with baseline cognitive symptoms (−4.0 vs −1.9; P=.0002). In patients with baseline cognitive symptoms, improvement was significantly greater for cariprazine- versus placebo-treated patients on YMRS total score (−16.7 vs −8.2; P<.0001) and the individual PANSS cognitive subscale items of conceptual disorganization (−1.1 vs −0.5; P=.0004), difficulty in abstract thinking (−0.8 vs −0.3; P=.0044), stereotyped thinking (−0.3 vs −0.1; P=.0350), and poor attention (−1.1 vs −0.6; P=.0043).

In patients with manic or mixed episodes associated with bipolar I disorder, cariprazine versus placebo was effective in improving cognitive symptoms in the overall patient population as well as in patients with baseline cognitive symptoms. In addition, cariprazine versus placebo also demonstrated efficacy in improving manic symptoms in patients with baseline cognitive symptoms. These results suggest that cariprazine may provide benefits for the treatment of cognitive symptoms in patients with bipolar I mania.

AbbVie Inc.

Approximately 70% of patients with bipolar disorder (BPD) are initially misdiagnosed, resulting in significantly delayed diagnosis of 7–10 years on average. Misdiagnosis and diagnostic delay adversely affect health outcomes and lead to the use of inappropriate treatments. As depressive episodes and symptoms are the predominant symptom presentation in BPD, misdiagnosis as major depressive disorder (MDD) is common. Self-rated screening instruments for BPD exist but their length and reliance on past manic symptoms are barriers to implementation, especially in primary care settings where many of these patients initially present. We developed a brief, pragmatic bipolar I disorder (BPD-I) screening tool that not only screens for manic symptoms but also includes risk factors for BPD-I (eg, age of depression onset) to help clinicians reduce the misdiagnosis of BPD-I as MDD.

Existing questionnaires and risk factors were identified through a targeted literature search; a multidisciplinary panel of experts participated in 2 modified Delphi panels to select concepts thought to differentiate BPD-I from MDD. Individuals with self-reported BPD-I or MDD participated in cognitive debriefing interviews (N=12) to test and refine item wording. A multisite, cross-sectional, observational study was conducted to evaluate the screening tool’s predictive validity. Participants with clinical interview-confirmed diagnoses of BPD-I or MDD completed a draft 10-item screening tool and additional questionnaires/questions. Different combinations of item sets with various item permutations (eg, number of depressive episodes, age of onset) were simultaneously tested. The final combination of items and thresholds was selected based on multiple considerations including clinical validity, optimization of sensitivity and specificity, and pragmatism.

A total of 160 clinical interviews were conducted; 139 patients had clinical interview-confirmed BPD-I (n=67) or MDD (n=72). The screening tool was reduced from 10 to 6 items based on item-level analysis. When 4 items or more were endorsed (yes) in this analysis sample, the sensitivity of this tool for identifying patients with BPD-I was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. These properties represent an improvement over the Mood Disorder Questionnaire, while using >50% fewer items.

This new 6-item BPD-I screening tool serves to differentiate BPD-I from MDD in patients with depressive symptoms. Use of this tool can provide real-world guidance to primary care practitioners on whether more comprehensive assessment for BPD-I is warranted. Use of a brief and valid tool provides an opportunity to reduce misdiagnosis, improve treatment selection, and enhance health outcomes in busy clinical practices.

AbbVie Inc.

Although mania is the hallmark symptom of bipolar I disorder (BD-I), most patients initially present for treatment with depressive symptoms. Misdiagnosis of BD-I as major depressive disorder (MDD) is common, potentially resulting in poor outcomes and inappropriate antidepressant monotherapy treatment. Screening patients with depressive symptoms is a practical strategy to help healthcare providers (HCPs) identify when additional assessment for BD-I is warranted. The new 6-item Rapid Mood Screener (RMS) is a pragmatic patient-reported BD-I screening tool that relies on easily understood terminology to screen for manic symptoms and other BD-I features in <2 minutes. The RMS was validated in an observational study in patients with clinically confirmed BD-I (n=67) or MDD (n=72). When 4 or more items were endorsed (“yes”), the sensitivity of the RMS for identifying patients with BP-I was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. To more thoroughly understand screening tool use among HCPs, a 10-minute survey was conducted.

A nationwide sample of HCPs (N=200) was selected using multiple HCP panels; HCPs were asked to describe their opinions/current use of screening tools, assess the RMS, and evaluate the RMS versus the widely recognized Mood Disorder Questionnaire (MDQ). Results were reported by grouped specialties (primary care physicians, general nurse practitioners [NPs]/physician assistants [PAs], psychiatrists, and psychiatric NPs/PAs). Included HCPs were in practice <30 years, spent at least 75% of their time in clinical practice, saw at least 10 patients with depression per month, and diagnosed MDD or BD in at least 1 patient per month. Findings were reported using descriptive statistics; statistical significance was reported at the 95% confidence interval.

Among HCPs, 82% used a tool to screen for MDD, while 32% used a tool for BD. Screening tool attributes considered to be of the greatest value included sensitivity (68%), easy to answer questions (66%), specificity (65%), confidence in results (64%), and practicality (62%). Of HCPs familiar with screening tools, 70% thought the RMS was at least somewhat better than other screening tools. Most HCPs were aware of the MDQ (85%), but only 29% reported current use. Most HCPs (81%) preferred the RMS to the MDQ, and the RMS significantly outperformed the MDQ across valued attributes; 76% reported that they were likely to use the RMS to screen new patients with depressive symptoms. A total of 84% said the RMS would have a positive impact on their practice, with 46% saying they would screen more patients for bipolar disorder.

The RMS was viewed positively by HCPs who participated in a brief survey. A large percentage of respondents preferred the RMS over the MDQ and indicated that they would use it in their practice. Collectively, responses indicated that the RMS is likely to have a positive impact on screening behavior.

AbbVie Inc.

Brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity and synaptogenesis, may be decreased in bipolar disorder, but has not been systematically investigated in people with newly diagnosed bipolar disorder and unaffected first-degree relatives.

To compare BDNF levels in patients with newly diagnosed bipolar disorder, their unaffected first-degree relatives and healthy controls.

The study investigated plasma BDNF levels in patients (n = 371) with newly diagnosed bipolar disorder, their unaffected first-degree relatives (n = 98) and healthy controls (n = 200) using enzyme-linked immunosorbent assay. We further investigated associations between BDNF levels and illness-related variables and medication status.

BDNF levels were found to be 22.0% (95% CI 1.107–1.343) higher in patients with bipolar disorder compared with healthy controls (P < 0.001) and 15.6% higher in unaffected first-degree relatives compared with healthy controls (95% CI 1.007–1.327, P = 0.04), when adjusting for age and gender. Further, BDNF levels were positively associated with duration of illness at a trend level (P = 0.05), age (P = 0.001) and use of anti-epileptic medication (P = 0.05).

These findings suggest that BDNF levels are not decreased in the early stages of bipolar disorder and in unaffected first-degree relatives contrasting with prior findings during later stages of the illness.

More 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.

PubMed, 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.

We 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.

Our 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.