Background In the past two decades, subanaesthetic doses of ketamine have been demonstrated to have rapid and sustained antidepressant effects, and accumulating research has demonstrated ketamine's therapeutic effects for a range of psychiatric conditions. Aims In light of these findings surrounding ketamine's psychotherapeutic potential, we systematically review the extant evidence on ketamine's effects in treating mental health disorders. Method The systematic review protocol was registered in PROSPERO (identifier CRD42019130636). Human studies investigating the therapeutic effects of ketamine in the treatment of mental health disorders were included. Because of the extensive research in depression, bipolar disorder and suicidal ideation, only systematic reviews and meta-analyses were included. We searched Medline and PsycINFO on 21 October 2020. Risk-of-bias analysis was assessed with the Cochrane Risk of Bias tools and A Measurement Tool to Assess Systematic Reviews (AMSTAR) Checklist. Results We included 83 published reports in the final review: 33 systematic reviews, 29 randomised controlled trials, two randomised trials without placebo, three non-randomised trials with controls, six open-label trials and ten retrospective reviews. The results were presented via narrative synthesis. Conclusions Systematic reviews and meta-analyses provide support for robust, rapid and transient antidepressant and anti-suicidal effects of ketamine. Evidence for other indications is less robust, but suggests similarly positive and short-lived effects. The conclusions should be interpreted with caution because of the high risk of bias of included studies. Optimal dosing, modes of administration and the most effective forms of adjunctive psychotherapeutic support should be examined further.
Background: Obesity and depression co-occur in a significant proportion of the population. Mechanisms linking the two disorders include the immune and the endocrine system, psychological and social mechanisms. The aim of this systematic review was to ascertain whether weight loss through dietary interventions has the additional effect of ameliorating depressive symptoms in obese patients. Methods: We systematically searched three databases (Pubmed, Medline, Embase) for longitudinal clinical trials testing a dietary intervention in people with obesity and depression or symptoms of depression. Results: Twenty-four longitudinal clinical studies met the eligibility criteria with a total of 3244 included patients. Seventeen studies examined the effects of calorie-restricted diets and eight studies examined dietary supplements (two studies examined both). Only three studies examined people with a diagnosis of both obesity and depression. The majority of studies showed that interventions using a calorie-restricted diet resulted in decreases in depression scores, with effect sizes between ≈0.2 and ≈0.6. The results were less clear for dietary supplements. Conclusions: People with obesity and depression appear to be a specific subgroup of depressed patients in which calorie-restricted diets might constitute a promising personalized treatment approach. The reduction of depressive symptoms may be related to immunoendocrine and psychosocial mechanisms.
Anorexia nervosa (AN) is a highly complex disorder to treat, especially in severe and enduring cases. Whilst the precise aetiology of the disorder is uncertain, malnutrition and weight loss can contribute to reductions in grey and white matter of the brain, impairments in neuroplasticity and neurogenesis and difficulties with cognitive flexibility, memory and learning. Depression is highly comorbid in AN and may be a barrier to recovery. However, traditional antidepressants are often ineffective in alleviating depressive symptoms in underweight patients with AN. There is an urgent need for new treatment approaches for AN. This review gives a conceptual overview for the treatment of AN with ketamine. Ketamine has rapid antidepressant effects, which are hypothesised to occur via increases in glutamate, with sequelae including increased neuroplasticity, neurogenesis and synaptogenesis. This article provides an overview of the use of ketamine for common psychiatric comorbidities of AN and discusses particular safety concerns and side effects. Potential avenues for future research and specific methodological considerations are explored. Overall, there appears to be ample theoretical background, via several potential mechanisms, that warrant the exploration of ketamine as a treatment for adults with AN.
Introduction The factors that contribute to the maintenance of anorexia nervosa (AN) are not fully understood, although it is generally accepted that depression is a core feature and contributes to poor prognosis. Individuals with depression tend to have difficulties in producing specific details of autobiographical memories and future episodes. Our aim was to investigate autobiographical memory and episodic future thinking (EFT) in individuals with AN (n = 46), people recovered from AN (recAN; n = 40), and non-affected controls (n = 35). Method Using a remotely administered computerised version of the autobiographical memory test and episodic future thinking task, we measured six aspects of memory retrieval and EFT generation: specificity, detailedness, difficulty in remembering/imagining, positivity, vividness and realism. Memory and EFT cue valence was manipulated; cues were either positive, neutral, or disorder-related/negative. As the production of EFTs is theoretically linked to the ability to retrieve autobiographical memories, the relationship between autobiographical memory specificity and EFT specificity was explored. To investigate whether autobiographical memory and EFT performance were independent of performance on other forms of cognition, working memory, verbal fluency and cognitive flexibility were measured. Results People with AN had difficulties retrieving specific details of autobiographical memories and rated autobiographical memories as less positive overall, and less vivid when primed by positive cues. People with a lifetime diagnosis (currently ill or recovered) reported greater difficulty in retrieving memories. The AN group generated less positive EFTs, particularly to positive and neutral cues. Comorbid depressive symptoms had some contribution to the observed findings. Lastly, in all groups autobiographical memory specificity predicted EFT specificity. Discussion Problems with retrieving specific details of autobiographical memories and simulating positive EFTs may be a state feature of AN. Treatments targeted at alleviating depressive symptoms, as well those targeted towards facilitating memory retrieval or reconsolidation, and the construction of positive EFTs, may contribute to hope for recovery and strengthen the sense of self beyond the disorder.
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