Clinical guidelines on long-term pharmacotherapy for bipolar disorder in children and adolescents

Bipolar disorder is a severe affective disorder which can present in adolescence, or sometimes earlier, and often requires a pharmacotherapeutic approach. The phenomenology of bipolar disorder in children and adolescents appears to differ from that of adult patients, prompting the need for specific pharmacotherapy guidelines for long-term management in this patient population. Current treatment guidelines were mainly developed based on evidence from studies in adult patients, highlighting the requirement for further research into the pharmacotherapy of children and adolescents with bipolar disorder. This review compares and critically analyzes the available guidelines, discussing the recommended medication classes, their mechanisms of action, side effect profiles and evidence bas

Evaluation of cariprazine in the treatment of bipolar I and II depression: a randomized, double-blind, placebo-controlled, phase 2 trial

This double-blind placebo-controlled, fixed/flexible-dose phase 2 trial assessed the efficacy, safety, and tolerability of cariprazine vs. placebo for depressive episodes associated with bipolar I or II disorder. Primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (baseline to week 8), and secondary endpoint was mean Clinical Global Impressions-Improvement score (week 8). Patients were randomized (N = 233) 1:1:1 to placebo, 'low-dose' 0.25-0.5 mg/day or 'high-dose' 1.5-3.0 mg/day cariprazine. Adverse events, laboratory results, vital signs, extrapyramidal symptoms, and suicide risk were monitored. Neither cariprazine group significantly separated from placebo in primary (mixed-effect model repeated measures MADRS least-squares mean differences: low-dose = −0.7, P = 0.7408; high-dose = 0.0, P = 0.9961) or secondary efficacy measures. No new safety signals with cariprazine were observed and common treatment-emergent adverse events (≥5% of cariprazine patients and twice the rate of placebo) included insomnia, akathisia, dry mouth, nausea, weight increased, diarrhea, restlessness, vomiting, musculoskeletal stiffness, migraine, and cough. Metabolic and weight changes were generally similar for cariprazine and placebo. Factors that may have affected the outcome of the trial were identified, which helped to inform the design and conduct of subsequent phase 2b/3 clinical trials of cariprazine in bipolar depression

UTILIZATION OF THE LINE-INTERCEPT METHOD TO ESTIMATE THE COVERAGE, DENSITY, AND AVERAGE LENGTH OF ROW SKIPS IN COTTON AND OTHER ROW CROPS

In row crops, a skip is a length of row within the drill where the crop has failed to establish. If the number of skips and their mean length per acre becomes too high, then considerable losses in crop yield occur. Frequently, farmers are faced with the decision to replant a crop which has row skips. To make the best decision, reliable estimates of the stand loss due to skips must be available. In making this decision, three parameters are useful: the percent of the area per acre that is skipped, the number of individual skips (that is, density) per acre, and the mean row length per skip. The line-intercept method for the sampling of two-dimensional objects (particles) can be used to obtain estimates of these parameters. The method is illustrated with an example from a cotton field

Second Generation Antipsychotic Long Acting Injections in Bipolar Disorder:Systematic review & meta-analysis

Background: Non-adherence is a significant problem in bipolar disorder. Second-generation antipsychotics (SGA) long-acting injections (LAIs) may improve adherence in bipolar disorder and may prevent relapses. However, the evidence is limited and conflicting. Objective: The objective of this study was to evaluate efficacy and safety of SGA LAIs in bipolar disorder. Method: Systematic review and meta-analysis of randomised controlled trials (RCTs) (≥6 months duration) investigating safety and efficacy of SGA LAIs for bipolar disorder. We searched Pubmed, Embase, CINAHL, Cochrane, PsycINFO, LiLACS, www.clinicaltrials.gov up to October 2016. We also contacted the manufacturers of SGA LAIs. Primary efficacy and safety outcomes were relapse rate and all-cause discontinuation respectively. Results: Total of seven RCTs (n = 1192) were included. SGA LAIs show superiority over placebo for study-defined relapse rate (RR = 0.58, 95% CI = 0.49-0.68, P < 0.00001) and all-cause discontinuation (RR = 0.72, 95% CI = 0.64-0.82, P < 0.00001). However, no significant difference was found between SGA LAIs and oral active control for relapse rate (RR = 0.92, P = 0.79) and all-cause discontinuation (RR = 1.2, P = 0.31). In terms of secondary outcomes, SGA LAIs performed better than placebo in relapse to mania/hypomania, young mania rating scales (YMRS), clinical global impression-severity (CGI-S), montgomery-asberg depression rating scale (MADRS). There was no significant difference between SGA LAIs and oral active control regarding relapse to mania/hypomania, YMRS, CGI-S, extra-pyramidal side effects (EPSEs), weight gain. However, the active control performed better than SGA LAIs in relapse to depression, MADRS, and prolactin-related AEs. Conclusions: Current evidence is very limited to support the use of SGA LAIs (compared to oral medication) in bipolar disorder. Further high-quality studies, particularly comparing SGA LAIs with active control, are warranted

Which Depressive Symptoms and Medication Side Effects Are Perceived by Patients as Interfering Most with Occupational Functioning?

Background. Major depressive disorder (MDD) is associated with significant impairment in occupational functioning. This study sought to determine which depressive symptoms and medication side effects were perceived by patients with MDD to have the greatest interference on work functioning. Methods. 164 consecutive patients with MDD by DSM-IV criteria completed a standard assessment that included a self-rated questionnaire about the degree to which symptoms and side effects interfered with work functioning. Results. The symptoms perceived by patients as interfering most with work functioning were fatigue and low energy, insomnia, concentration and memory problems, anxiety, and irritability. The medication side effects rated as interfering most with work functioning were daytime sedation, insomnia, headache, and agitation/anxiety. There were no differences between men and women in symptoms or side effects that were perceived as interfering with work functioning. Limitations. This was a cross-sectional study; only subjective assessments of work functioning were obtained; the fact that patients were using varied medications acts as a potential confound. Conclusions. Specific depressive symptoms and medication side effects were perceived by patients as interfering more with occupational functioning than others. These factors should be considered in treatment selection (e.g., in the choice of antidepressant) in working patients with MDD

Decarboxylative hydrazination of unactivated carboxylic acids by cerium photocatalysis

We report the cerium photocatalyzed radical decarboxylative hydrazination of carboxylic acids with di-tert-butylazodicarboxylate (DBAD). The operationally simple protocol provides rapid access to synthetically useful hydrazine derivatives and overcomes current scope limitations in the photoredox-catalyzed decarboxylation of carboxylic acids

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe