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Background: Reserpine is an effective antihypertensive drug, but its role in routine practice has declined such that it is rarely used. This is largely based on the assumption that reserpine causes depression. This assumption was a foundation for the original monoamine hypothesis of depression. However, there remains conflicting evidence as to whether reserpine causes depression, and no systematic review of available evidence. Aims: We systematically reviewed evidence on effects of reserpine on depressive and related symptoms (e.g. anxiety, suicidal ideation). Method: Electronic searches of MEDLINE, Embase and PsycINFO were conducted to identify studies up to 14 February 2021. Studies of any methodological design involving reserpine-treated and reserpine-untreated conditions, in any adult human population, were included and a narrative synthesis of findings was undertaken. Risk of bias (RoB) was examined using ROBINS-I. Results: Of the 35 studies meeting inclusion criteria, 9 were randomised controlled trials. Eleven studies reported some depressogenic effects, 13 reported no effect and 11 reported putative antidepressant effects. Studies identifying depressive effects were more likely to examine people without psychiatric disorders at baseline, while studies identifying a potential antidepressant effect tended to treat fewer participants for shorter durations, at higher doses. Around one-third of studies conducted in people with psychiatric disorders showed beneficial effects on depression symptoms. 30/35 studies were at high RoB. Conclusions: Associations between reserpine and depression are inconsistent and limited by a lack of high-quality evidence. Due to reserpine's apparently complex effects, we urge nuance rather than simplicity surrounding the monoamine hypothesis of depression. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a highly burdensome health condition, for which there are numerous accepted pharmacological and psychological interventions. Adjunctive treatment (augmentation/combination) is recommended for the ~50% of MDD patients who do not adequately respond to first-line treatment. We aimed to evaluate the current evidence for concomitant approaches for people with early-stage treatment-resistant depression (TRD; defined below). Methods: We systematically searched Medline and Institute for Scientific Information Web of Science to identify randomised controlled trials of adjunctive treatment of ⩾10 adults with MDD who had not responded to ⩾1 adequate antidepressant. The cochrane risk of bias (RoB) tool was used to assess study quality. Pre-post treatment meta-analyses were performed, allowing for comparison across heterogeneous study designs independent of comparator interventions. Results: In total, 115 trials investigating 48 treatments were synthesised. The mean intervention duration was 9 weeks (range 5 days to 18 months) with most studies assessed to have low (n = 57) or moderate (n = 51) RoB. The highest effect sizes (ESs) were from cognitive behavioural therapy (ES = 1.58, 95% confidence interval (CI): 1.09–2.07), (es)ketamine (ES = 1.48, 95% CI: 1.23–1.73) and risperidone (ES = 1.42, 95% CI: 1.29–1.61). Only aripiprazole and lithium were examined in ⩾10 studies. Pill placebo (ES = 0.89, 95% CI: 0.81–0.98) had a not inconsiderable ES, and only six treatments' 95% CIs did not overlap with pill placebo's (aripiprazole, (es)ketamine, mirtazapine, olanzapine, quetiapine and risperidone). We report marked heterogeneity between studies for almost all analyses. Conclusions: Our findings support cautious optimism for several augmentation strategies; although considering the high prevalence of TRD, evidence remains inadequate for each treatment option. [ABSTRACT FROM AUTHOR]

Abstract An increasing number of studies are utilizing saliva sampling as a method of assessing adrenal steroid secretion. Saliva samples have certain advantages over plasma, being non-invasive and easily collected. [...]

Abstract Sodium valproate is a commonly used anticonvulsant, particularly in the management of childhood refractory epilepsy. There is a good literature base regarding its haematological effects in this group of [...]

The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the most important breakthrough in depression research in the last 50 years. Ketamine remains an off-label treatment for treatment-resistant depression with factors that limit widespread use including its dissociative effects and abuse potential. Ketamine is a racemic mixture, composed of equal amounts of (S)-ketamine and (R)-ketamine. An (S)-ketamine nasal spray has been developed and approved for use in treatment-resistant depression in the United States and Europe; however, some concerns regarding efficacy and side effects remain. Although (R)-ketamine is a less potent N-Methyl-D-Aspartate receptor antagonist than (S)-ketamine, increasing preclinical evidence suggests (R)-ketamine may have more potent and longer lasting antidepressant effects than (S)-ketamine, alongside fewer side effects. Furthermore, a recent pilot trial of (R)-ketamine has demonstrated rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research is ongoing to determine the specific cellular and molecular mechanisms underlying the antidepressant actions of ketamine and its component enantiomers in an effort to develop future rapid-acting antidepressants that lack undesirable effects. Here, we briefly review findings regarding the antidepressant effects of ketamine and its enantiomers before considering underlying mechanisms including N-Methyl-D-Aspartate receptor antagonism, γ-aminobutyric acid-ergic interneuron inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor activation, brain-derived neurotrophic factor and tropomyosin kinase B signalling, mammalian target of rapamycin complex 1 and extracellular signal-regulated kinase signalling, inhibition of glycogen synthase kinase-3 and inhibition of lateral habenula bursting, alongside potential roles of the monoaminergic and opioid receptor systems. [ABSTRACT FROM AUTHOR]

14 Vázquez GH, Bahji A, Undurraga J, et al. (2021) Efficacy and tolerability of combination treatments for major depression: antidepressants plus second-generation antipsychotics vs. esketamine vs. lithium. Yin-To Liao and colleagues conducted a large study (5606 individuals, over period 1997-2013) to examine the increased risk in patients with bipolar disorder (BPD) of traumatic brain injury (TBI). These findings contrast with the sensitivity of working memory tests to aberrant activity in cognitively impaired compared to cognitively normal BPD patients and to changes in task-related neuronal activity with mood episodes and pro-cognitive treatments, respectively. Brexpiprazole was more efficacious in patients with impaired or no insight (predominantly EU patients) than patients with excellent insight (predominantly US patients) ([15]). [Extracted from the article]

A postscript to 'Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association for Psychopharmacology' The BAP bipolar guideline was published in the Journal of Psychopharmacology in June 2003 [...]

Abstract Bipolar affective disorders can be successfully treated with long-term use of the mood stabilizer lithium. However, discontinuation of lithium treatment is followed by a high incidence of manic episodes. [...]

Decisions about the use of psychotropic medication in pregnancy are an ongoing challenge for clinicians and women with mental health problems, owing to the uncertainties around risks of the illness itself to mother and fetus/infant, effectiveness of medications in pregnancy and risks to the fetus/infant from in utero exposure or via breast milk. These consensus guidelines aim to provide pragmatic advice regarding these issues. They are divided into sections on risks of untreated illness in pregnancy; general principles of using drugs in the perinatal period; benefits and harms associated with individual drugs; and recommendations for the management of specific disorders. [ABSTRACT FROM AUTHOR]