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Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Pharmacological Treatments" is the third of six sections of the 2016 guidelines. With little new information on older medications, treatment recommendations focus on second-generation antidepressants.Results: Evidence-informed responses are given for 21 questions under 4 broad categories: 1) principles of pharmacological management, including individualized assessment of patient and medication factors for antidepressant selection, regular and frequent monitoring, and assessing clinical and functional outcomes with measurement-based care; 2) comparative aspects of antidepressant medications based on efficacy, tolerability, and safety, including summaries of newly approved drugs since 2009; 3) practical approaches to pharmacological management, including drug-drug interactions and maintenance recommendations; and 4) managing inadequate response and treatment resistance, with a focus on switching antidepressants, applying adjunctive treatments, and new and emerging agents.Conclusions: Evidence-based pharmacological treatments are available for first-line treatment of MDD and for management of inadequate response. However, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient. [ABSTRACT FROM AUTHOR]

Background: Evidence from preclinical and human studies indicates the presence of reduced dopamine-1 receptor (D1R) signaling in the cortex, where D1Rs predominate, in patients with schizophrenia (SCZ), which may contribute to their cognitive deficits. Furthermore, studies in nonhuman primates (NHP) have suggested that intermittent administration of low doses of D1R agonists produce long-lasting reversals in cognitive deficits. The purpose of this trial was to test whether a similar design, involving subacute intermittent administration of low doses of a full, selective agonist at D1Rs, DAR-0100A, would improve cognitive deficits in SCZ.Methods: We randomized 49 clinically stable individuals with SCZ to three weeks of intermittent treatment with 0.5 mg or 15 mg of DAR-0100A, or placebo (normal saline). Functional magnetic resonance imaging (fMRI) BOLD was used to evaluate the effects of drug administration on brain activity during a working memory (WM) task. Effects on cognition were also assessed using the MATRICS and the N-back task as primary endpoints. The CogState battery was used as a secondary endpoint.Results: There were no observed treatment effects on either the BOLD fMRI signal during WM tasks or the WM domains of the MATRICS. Moderate improvement was detected on the CogState battery and on the attention domain of the MATRICS.Conclusion: These results suggest that low doses of D1 agonists that do not result in measureable occupancy of the D1R do not reliably improve cognition in SCZ, unlike the observations in NHP. As this drug is limited by its pharmacokinetic profile, better D1R agonists that can achieve adequate levels of D1R occupancy are needed to test the efficacy of this mechanism for cognitive enhancement in SCZ. [ABSTRACT FROM AUTHOR]

The role of cholinergic abnormalities in autism was recently evidenced and there is a growing interest in cholinergic modulation, emerging for targeting autistic symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. This study aimed to evaluate the possible effects of galantamine as an augmentative therapy to risperidone, in autistic children. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 outpatients aged 4–12 years whom had a diagnosis of autism (DSM IV-TR) and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale were equally randomized to receive either galantamine (up to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10 weeks. We rated participants by ABC-C and a side effects checklist, at baseline and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients showed significantly greater improvement in the Irritability (P = 0.017) and Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. The difference between the two groups in the frequency of side effects was not significant. In conclusion, galantamine augmentation was shown to be a relatively effective and safe augmentative strategy for alleviating some of the autism-related symptoms. [ABSTRACT FROM PUBLISHER]