Objectives
To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice ...guidelines for mood disorders (MDcpg2020).
Methods
To develop the MDcpg2020, the mood disorders committee conducted an extensive review of the available literature to develop evidence‐based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg2020, these recommendations sit alongside consensus‐based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on major depression. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of major depression.
Results
The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of electroconvulsive therapy (ECT), and discusses how to approach non‐response.
Conclusions
The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg2020. The recommendations are informed by research evidence in conjunction with clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians, but will be of interest to all clinicians and carers involved in the management of patients with depressive disorders.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Neurocognitive deficits are demonstrated in major depressive disorder (MDD) and most likely contribute to the functional impairment experienced by affected individuals. We systematically reviewed the ...evidence on neurocognitive deficits and their relationship(s) to psychosocial functioning in MDD.
English-language literature was searched in MEDLINE, EMBASE, Science Direct, and PsycInfo databases for the years 1980-October 15, 2013, with the following terms: (depressive disorder or depressive disorder, major) and permutations of (cognitive, neurocognitive, neuropsych*) with (impairment, deficit, performance, test) and (quality of life; functional outcomes; outcome assessment, health care) or (assessment, outcomes; assessment, patient outcomes; outcomes assessment; outcomes assessments, patient).
Inclusion criteria were (1) nongeriatric adults (< 60 years) with a primary diagnosis of MDD by DSM-IV, ICD-9, or ICD-10 criteria; (2) use of neuropsychological tests; and (3) use of a specific measure of social, occupational, or daily functioning. Of 488 articles identified in the initial search, 10 met the inclusion criteria.
Two independent appraisers assessed eligibility of the studies. Substantial heterogeneity in the samples and methods precluded a quantitative meta-analysis, so we performed a narrative descriptive review.
The included studies employed a variety of neurocognitive tests and assessments of psychosocial functioning. Overall, depressed samples had neurocognitive deficits in various domains that were associated with different measures of psychosocial functioning. However, these findings were constrained by methodological limitations of studies.
The limited evidence base suggests that neurocognitive functioning appears to be broadly associated with functional impairment in individuals with MDD, but the quality of evidence is weak. Further studies to clarify the relationship(s) between neurocognitive and psychosocial functioning in MDD will benefit from larger and more homogeneous samples, prospective designs with multivariate analyses, and use of comprehensive assessments of psychosocial functioning that are validated in depressed populations.
Cariprazine, a dopamine D
/D
and 5-HT
receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the ...efficacy, safety, and tolerability of cariprazine in bipolar I depression.
In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.5 mg/day (N=157) or 3.0 mg/day (N=165). The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score and Clinical Global Impressions severity (CGI-S) score, respectively. Least squares mean differences were estimated using a mixed model for repeated measures, and p values were adjusted for multiplicity.
Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms (reducing MADRS total score); the least squares mean differences were -2.5 (95% CI=-4.6, -0.4) for cariprazine at 1.5 mg/day and -3.0 (95% CI=-5.1, -0.9) for cariprazine at 3.0 mg/day. Both cariprazine dosages were associated with lower CGI-S scores compared with placebo, but the differences did not reach statistical significance after adjustment for multiplicity (least squares mean difference, -0.2 95% CI=-0.5, 0.0 for the 1.5 mg/day group and -0.3 95% CI=-0.5, 0.0 for the 3.0 mg/day group). Common treatment-emergent adverse events (in at least 5% of participants in either cariprazine treatment group and twice the rate of the placebo group) were nausea, akathisia, dizziness, and sedation. Mean changes in weight and metabolic parameters were relatively small and comparable across groups.
Cariprazine, at both 1.5 mg/day and 3.0 mg/day, was effective, generally well tolerated, and relatively safe in reducing depressive symptoms in adults with bipolar I depression.
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. “Complementary and Alternative Medicine Treatments” is the fifth of six sections of the 2016 guidelines.
Results:
Evidence-informed responses were developed for 12 questions for 2 broad categories of complementary and alternative medicine (CAM) interventions: 1) physical and meditative treatments (light therapy, sleep deprivation, exercise, yoga, and acupuncture) and 2) natural health products (St. John’s wort, omega-3 fatty acids; S-adenosyl-L-methionine SAM-e, dehydroepiandrosterone, folate, Crocus sativus, and others). Recommendations were based on available data on efficacy, tolerability, and safety.
Conclusions:
For MDD of mild to moderate severity, exercise, light therapy, St. John’s wort, omega-3 fatty acids, SAM-e, and yoga are recommended as first- or second-line treatments. Adjunctive exercise and adjunctive St. John’s wort are second-line recommendations for moderate to severe MDD. Other physical treatments and natural health products have less evidence but may be considered as third-line treatments. CAM treatments are generally well tolerated. Caveats include methodological limitations of studies and paucity of data on long-term outcomes and drug interactions.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abstract Brain-derived neurotrophic factor (BDNF) plays a central role in synaptic plasticity and neurogenesis. Bipolar disorder (BD) is among the most disabling of all psychiatric disorders and is ...associated with poor outcomes. Some studies suggest that BDNF levels decrease during mood states and remain normal during euthymia, but other studies have contradicted this paradigm. Therefore, the aim of this study was to perform a meta-analysis of all studies that measured peripheral BDNF levels in adults with BD. We conducted a systematic review using electronic databases. Inclusion criteria were studies that measured BDNF in plasma or serum in vivo in adult patients with BD. The resulting studies were compiled to measure the effect sizes (ESs) of the differences in BDNF levels between BD patients in different mood states and controls. Thirteen studies were included with a total of 1113 subjects. The BDNF levels were decreased in both mania and depression when compared to controls (ES −0.81, 95% CI −1.11 to −0.52, p < 0.0001 and ES −0.97, 95% CI −1.79 to −0.51, p = 0.02, respectively). The BDNF levels were not different in euthymia when compared to controls (ES −0.20, 95% CI −0.61 to 0.21, p = 0.33). Meta-regression analyses in euthymia showed that age ( p < 0.0001) and length of illness ( p = 0.04) influenced the variation in ES. There was also an increase in BDNF levels following the treatment for acute mania (ES −0.63, 95% CI −1.11 to −0.15, p = 0.01). In conclusion, BDNF levels are consistently reduced during manic and depressive episodes and recover after treatment for acute mania. In euthymia, BDNF decreases with age and length of illness. These data suggest that peripheral BDNF could be used as a biomarker of mood states and disease progression for BD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective:The authors evaluated the efficacy, safety, and tolerability of cariprazine, an atypical antipsychotic candidate, in adult patients with acute bipolar I depression.Method:This was an 8-week ...multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in adult patients with bipolar I disorder experiencing a current major depressive episode. Patients were randomly assigned (1:1:1:1) to receive placebo or cariprazine at 0.75, 1.5, or 3.0 mg/day. The primary and secondary efficacy parameters were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions severity subscale (CGI-S), respectively, analyzed using a mixed-effects model for repeated measures on the modified intent-to-treat population.Results:The intent-to-treat population comprised 571 patients (141 in the placebo group and 140, 145, and 145 in the cariprazine 0.75-, 1.5-, and 3.0-mg/day groups). Cariprazine at 1.5 mg/day showed significantly greater improvement on MADRS total score change from baseline to week 6 compared with placebo; the least squares mean difference was −4.0 (95% CI=−6.3, −1.6; significant after adjustment for multiple comparisons). Cariprazine at 3.0 mg/day showed greater MADRS score reduction than placebo (−2.5, 95% CI=−4.9, −0.1; not significant when adjusted for multiple comparisons). The 0.75 mg/day dosage was similar to placebo. A similar pattern for significance was observed on the CGI-S (1.5 mg/day: least squares mean difference=−0.4, 95% CI=−0.6, −0.1; 3.0 mg/day: −0.3, 95% CI=−0.5, −0.0). The most common adverse events (≥10%) in cariprazine-treated patients were akathisia and insomnia; weight gain was slightly higher with cariprazine than with placebo.Conclusions:Cariprazine at 1.5 mg/day demonstrated consistent efficacy compared with placebo across outcomes and was generally well tolerated, suggesting efficacy for the treatment of bipolar I depression.
Cariprazine treats acute manic and depressive episodes in bipolar I disorder (BP-I), but its efficacy in preventing relapse of mood episode remains unknown.
In this phase 3b, double-blind, ...placebo-controlled study, patients with BP-I with acute manic or depressive episodes (each with/without mixed features), were treated with cariprazine 3.0 mg/day during a 16-week open-label treatment period; those who achieved stable remission within 8 weeks and remained stable for at least another 8 weeks were randomized to receive cariprazine 1.5 or 3.0 mg per day or placebo in the double-blind treatment period for up to 39 weeks. The primary efficacy endpoint was time to relapse of any mood episode. Adverse events (AEs) were assessed.
Patients (440/896) enrolled in the open-label treatment period achieved stability criteria and were randomized to receive cariprazine 3.0 mg/day (n = 148), cariprazine 1.5 mg/day (n = 147), or placebo (n = 145) in the double-blind treatment period. Relapse rates were 17.9%, 16.8%, and 19.7% in the cariprazine 3.0 mg/day, cariprazine 1.5 mg/day, and placebo groups, respectively. Neither dose of cariprazine was more effective than placebo on the primary outcome (3.0 mg/day: HR = 0.89, 95% CI: 0.5, 1.5; 1.5 mg/day: HR = 0.83, 95% CI 0.5, 1.4). The most frequently reported AEs (≥5%) were akathisia, headache, insomnia, and nausea in the open-label treatment period and increased weight and insomnia in the double-blind treatment period. In the open-label and double-blind treatment periods, 7.5% and 1.6% of patients experienced an AE leading to discontinuation.
Cariprazine was not superior to placebo in the prevention of relapses in this study. Relapse rates were unusually low in the placebo group. Cariprazine was well-tolerated.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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