Melatonin and melatonin‐agonists for metabolic syndrome components in patients treated with antipsychotics: A systematic review and meta‐analysis

Abstract

Objective: Metabolic side effects are a limiting factor in the use of antipsychotics, which remain the cornerstone of long-term management of patients with severe mental illness. There is contrasting evidence on a possible role of melatonin and melatonin-agonists in attenuating antipsychotic-induced metabolic abnormalities. Design:We conducted a systematic review (PubMed, PsycInfo, Cochrane databases, up to August 2020) and a random-effect meta-analysis of double-blind, randomized placebo-controlled trials (RCTs) involving melatonin and melatonin-agonists in the treatment of antipsychotic-induced metabolic changes. The primary outcome was the standardized mean difference (SMD) of composite metabolic outcomes built with metabolic syndrome components. Secondary outcomes were individual metabolic syndrome components, and other anthropometric, glucose metabolism, lipid profile, and psychopathology measures.Results: Out of the initial 41 studies, six documented five separate RCTs randomizing 248 patients (126 to melatonin/ramelteon, 122 to placebo) affected by schizophrenia-spectrum disorders and bipolar disorder. Melatonin/ramelteon outperformed placebo on the primary outcome (SMD −0.28, 95% CI = −0.39 ÷ −0.168), as well as on all individual components of metabolic syndrome (systolic blood

Role of Melatonin in the Management of Sleep and Circadian Disorders in the Context of Psychiatric Illness

“…Dysfunction of immune system might be related to psychiatric disorders such as schizophrenia and mood disorders [97,98]. Furthermore, melatonin may be beneficial for metabolic syndrome in patients treated with antipsychotics [99]. A recent systematic review and meta-analysis demonstrated the effects of melatonin on attenuating metabolic parameters such as fasting glucose, blood pressure, high-density lipoprotein, and triglycerides [99].…”

“…Furthermore, melatonin may be beneficial for metabolic syndrome in patients treated with antipsychotics [99]. A recent systematic review and meta-analysis demonstrated the effects of melatonin on attenuating metabolic parameters such as fasting glucose, blood pressure, high-density lipoprotein, and triglycerides [99]. These effects might be direct or due to correcting sleep or circadian rhythms.…”

Metabolic risk factors of cognitive impairment in young women with major psychiatric disorder

“…SCH, BP, and MDD are prevalent among young women (18-34 years of age) (2)(3)(4). Both MPD and complications of therapy such as drug-induced metabolic syndrome (MetS) and anticholinergic side effects impede the total functioning of these young women (3)(4)(5)(6)(7)(8). Sequelae include impaired cognition, reproductive function, and community engagement.…”

“…Sequelae include impaired cognition, reproductive function, and community engagement. Cognitive impairment poses a key barrier to recovery by reducing treatment compliance; disrupting life style; degrading community functioning; and worsening regression; thus, leading to a vicious cycle that furthers psychomorbidity and social dysfunction, ending in lifelong disability (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Against this background, interest in the mitigation of cognitive impairment has grown substantially.…”

Clozapine and the aryl hydrocarbon receptor

“…It may be important to note that AhR-induced cytochrome P450 (CYP)1b1 leads to the “backward” conversion of melatonin to N -acetylserotonin (NAS). Melatonin is produced by all cells so far investigated and is an important inhibitor of antipsychotic metabolic dysregulation (Miola et al, 2022). Melatonin inhibition will have diverse and detrimental effects across an array of cell types, while the upregulation of NAS will have trophic and proliferative effects, given that NAS in brain-derived neurotrophic factor (BDNF) mimic, via the activation of the BDNF receptor, TrkB (Jang et al, 2010).…”