Agomelatine 25mg tablets

BackgroundAntidepressants induce physiological alterations; however, the degree to which these occur in treatment with various antidepressants is unclear. We aimed to compare and rank antidepressants based on physiological side-effects by synthesising data from randomised controlled trials (RCTs).MethodsWe searched MEDLINE, EMBASE, PsycINFO, ClinicalTrials.gov, and the US Food and Drug Administration (FDA) website from database inception to April 21, 2025. We included single-blinded and double-blinded RCTs comparing antidepressants and placebo in acute monotherapy of any psychiatric disorder. We did frequentist random-effects network meta-analyses to investigate treatment-induced changes in weight; total cholesterol; glucose; heart rate; systolic and diastolic blood pressure; corrected QT interval (QTc); sodium; potassium; aspartate transferase (AST); alanine transaminase (ALT); alkaline phosphatase (ALP); bilirubin; urea; and creatinine. We did meta-regressions to examine study-level associations between physiological change and age, sex, and baseline weight. We estimated the correlation between depressive symptom severity change and metabolic parameter change.FindingsOf 26 252 citations, 151 studies and 17 FDA reports met inclusion criteria. The overall sample included 58 534 participants, comparing 30 antidepressants with placebo. Median treatment duration was 8 weeks (IQR 6·0-8·5). We observed clinically significant differences between antidepressants in terms of metabolic and haemodynamic effects, including an approximate 4 kg difference in weight-change between agomelatine and maprotiline, over 21 beats-per-minute difference in heart rate change between fluvoxamine and nortriptyline, and over 11 mmHg difference in systolic blood pressure between nortriptyline and doxepin. Paroxetine, duloxetine, desvenlafaxine, and venlafaxine were associated with increases in total cholesterol and, for duloxetine, glucose concentrations, despite all drugs reducing bodyweight. There was strong evidence of duloxetine, desvenlafaxine, and levomilnacipran increasing AST, ALT, and ALP concentrations, although the magnitudes of these alterations were not considered clinically significant. We did not find strong evidence of any antidepressant affecting QTc, or concentrations of sodium, potassium, urea, and creatinine to a clinically significant extent. Higher baseline bodyweight was associated with larger antidepressant-induced increases in systolic blood pressure, ALT, and AST, and higher baseline age was associated with larger antidepressant-induced increases in glucose. We did not observe an association between changes in depressive symptoms and metabolic disturbance.InterpretationWe found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters. Treatment guidelines should be updated to reflect differences in physiological risk, but choice of antidepressant should be made on an individual basis, considering clinical presentation and preferences of patients, carers, and clinicians.FundingNational Institute for Health Research, Maudsley Charity, Wellcome Trust, Medical Research Council.

Abstract licence: CC BY

BackgroundAntidepressants are effective for depression, but most evidence excludes individuals with comorbid physical conditions.AimsTo assess antidepressants' efficacy and tolerability in individuals with depression and comorbid physical conditions.MethodsSystematic review and network meta-analysis of randomised controlled trials (RCTs). Co-primary outcomes were efficacy on depressive symptoms and tolerability (participants dropping out because of adverse events). Bias was assessed with the Cochrane Risk-of-Bias 2 tool and certainty of estimates with the Confidence in Network Meta-Analysis approach. A study protocol was registered in advance (https://osf.io/9cjhe/).ResultsOf the 115 included RCTs, 104 contributed to efficacy (7714 participants) and 82 to tolerability (6083 participants). The mean age was 55.7 years and 51.9% of participants were female. Neurological and cardiocirculatory conditions were the most represented (26.1% and 18.3% of RCTs, respectively). The following antidepressants were more effective than placebo: imipramine, nortriptyline, amitriptyline, desipramine, sertraline, paroxetine, citalopram, fluoxetine, escitalopram, mianserin, mirtazapine and agomelatine, with standardised mean differences ranging from -1.01 (imipramine) to -0.34 (escitalopram). Sertraline and paroxetine were effective for the largest number of ICD-11 disease subgroups (four out of seven). In terms of tolerability, sertraline, imipramine and nortriptyline were less tolerated than placebo, with relative risks ranging from 1.47 (sertraline) to 3.41 (nortriptyline). For both outcomes, certainty of evidence was 'low' or 'very low' for most comparisons.ConclusionAntidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit-risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo.

Abstract licence: CC BY

The availability and use of melatonin as an over-the-counter supplement have surged significantly in recent years due to the increased prevalence of sleep-wake disorders, notably in the post-COVID-19 era. While melatonin is known for managing insomnia, its applications extend beyond that. Its anti-inflammatory, antioxidant, and analgesic properties, along with increased usage, have garnered significant interest from researchers, particularly regarding its use in migraine prophylaxis and treatment. The aim of this systematic review is to evaluate the role of melatonin as prophylactic therapy for migraine, focusing on the efficacy and side effect profile of melatonin compared to standard therapy and placebo. Six databases were searched through June 2024, identifying 735 relevant articles. Only full-text randomized control trials involving humans, written or translated into English, were included in the study. Data were extracted, screened, sought for retrieval, and assessed for quality appraisal using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). A total of seven randomized control trials involving 1,283 participants who met the eligibility criteria and passed the quality appraisal have been included in the study. All seven trials included patients diagnosed with migraine who were treated with either melatonin or agomelatine and were compared to those treated with conventional prophylactic therapy or placebo. The findings of this review suggest that melatonin significantly reduces the frequency and severity of migraines, but its dose-dependent action and benefits remain debatable. Melatonin may also have a role in weight control, warranting additional research in this direction.

Abstract licence: CC BY

Background and purposeInsomnia is a common symptom in depressive disorder, affecting up to 80% of those patients. Evidences suggest that sleep symptom improvements could alleviating depressive symptoms and reducing relapse. This article evaluated the efficacy of three antidepressants-agomelatine, mirtazapine, and trazodone-in treating insomnia symptoms in depressed patients, with a focus on polysomnographic (PSG) data, subjective sleep experience, improvement in depressive symptoms, and adverse drug reactions.MethodsA systematic search of PubMed, Cochrane Library, MEDLINE, Embase, and Web of Science was conducted for studies published from 1974 to August 2025; 30 studies (16 randomized controlled trials and 14 non-randomized controlled trials) were included. The primary outcomes were PSG measures; secondary outcomes included PSQI and HAMD scores, as well as adverse medication reactions.ResultsThe PSG results showed that agomelatine may not significantly change percentage N1 of sleep period time (N1%) and Latency of REM sleep (L-REM). Mirtazapine significantly increased total sleep time (TST), slow-wave sleep of sleep period time (SWS%), and sleep efficiency (SE%), while reducing percentage wake after sleep onset of sleep period time (WASO%). Trazodone notably improved TST, and SE%. For adverse effects, agomelatine was well-tolerated; mirtazapine commonly caused weight gain and sedation; and trazodone frequently led to dizziness, sedation, headache, nausea, and somnolence.ConclusionAll three medications significantly enhance subjective sleep perception and alleviate depressive symptoms. However, agomelatine may lack a definitive effect on improving objective sleep parameters in depressed patients. Future studies should involve larger, high-quality trials with unified methodologies to strengthen the reliability of conclusions.

Abstract licence: CC BY

BackgroundDepression is one of the most common mental disorders and is associated with a significant increase in the risk of mental and somatic comorbidities. The chronobiological theory of the pathogenesis of depression explains the relationship between the symptoms of depression and disturbance of circadian rhythm regulation. Disrupted circadian rhythms are also observed in other disorders such as alcohol use disorder, anxiety disorders, epilepsy, and Parkinson's disease. Therefore, there is a growing interest in the use of medications with a melatoninergic mechanism of action in the treatment of depression comorbid with the aforementioned disorders.AimThis review aims to systematically examine the evidence for the use of melatoninergic antidepressants (agomelatine and fluvoxamine) in the treatment of depression comorbid with alcohol abuse, anxiety disorders (including phobic anxiety, panic, and generalized anxiety disorders), or neuropsychiatric disorders (such as epilepsy and Parkinson's disease).MethodsThis systematic review included experimental studies, systematic reviews, and meta-analyses published in English and Russian, which examined the use of fluvoxamine and agomelatine in adult patients with recurrent depressive disorder (ICD-10) or major depressive disorder (DSM-5) comorbid with alcohol abuse, anxiety or neuropsychiatric disorders. The search was conducted in the PubMed, Cochrane Library and eLIBRARY scientific databases. The quality of the selected studies was assessed using the Cochrane Risk of Bias tool, which is used to evaluate the risk of systematic errors in clinical studies. The results were presented as a narrative synthesis and grouped by the comorbidities evaluated.ResultsA total of 20 articles were reviewed (with a pooled sample size of n=1,833 participants). The results suggest that melatoninergic antidepressants might help in reducing depressive and anxiety symptoms, improve sleep, decrease alcohol cravings, and alleviate the severity of motor symptoms in Parkinson's disease. Moreover, the use of pharmacogenetic testing to select the medication and dosage may enhance its therapeutic effectiveness.ConclusionThe review demonstrates a significant lack of clinical data and guidelines on the use of melatoninergic medications for the treatment of depression comorbid with other disorders. In this regard, it is currently difficult to draw a definitive conclusion regarding the efficacy and safety of agomelatine and fluvoxamine in the treatment of these comorbidities. Available studies suggest an improvement in the clinical manifestations of the comorbidities. Future research directions might include the development and implementation of double-blind, randomized clinical trials to study the use of melatoninergic medications in patients with depression comorbid with other disorders.

Abstract licence: CC BY

BackgroundA wide range of drugs is used to alleviate insomnia symptoms in individuals with severe mental illness (SMI), including licensed drugs and sedating drugs prescribed off-label. Yet, no review has gathered the evidence on illness-specific or transdiagnostic outcomes of pharmacological interventions for insomnia. We aimed to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) studying the efficacy and acceptability of pharmacological interventions for insomnia among individuals with SMI, defined as schizophrenia, bipolar disorder (BD) or major depressive disorder (MDD).MethodsWe searched for RCTs of pharmacological interventions for insomnia that used either placebo or another medication as inactive control or active comparator. Two independent reviewers performed the literature screening, data extraction and risk of bias assessment (RoB2). We performed random effects meta-analyses on the co-primary outcomes total sleep time (TST), sleep quality and acceptability (all-cause discontinuation) and the secondary outcomes safety and tolerability.ResultsThe search identified 3331 hits, of which 25 RCTs (n = 2476 individuals) were included, with 18 RCTs (n = 2199) in MDD, 4 RCTs (n = 162) in BD and 3 RCTs (n = 115) in schizophrenia. Of 25 RCTs, 22 had a high risk of bias. The most frequently studied drugs were agomelatine (RCTs = 3, n = 686), eszopiclone (RCTs = 3, n = 599) and zolpidem (RCTs = 3, n = 601). Compared to placebo, pharmacological interventions for insomnia were associated with improved sleep quality by a small effect size (RCTs = 8, g = 0.24, 95% CI = 0.05-0.43) and improved TST (RCTs = 10, MD = 30.82 min, 95% CI = 19.13-42.50), with similar acceptability (RCTs = 10, RR = 1.06, 95% CI = 0.90-1.25).DiscussionDespite their frequent use, many licensed and off-label pharmacological interventions for insomnia have never been investigated in patients with SMI. The studies that provided sufficient data for meta-analysis showed better efficacy with similar acceptability compared to placebo, but the generalizability of these results is limited by the high heterogeneity and low quality of the included studies. This underscores the need for high-quality RCTs to provide a better scientific basis for the pharmacological treatment of insomnia in SMI.Trial registrationCRD42023413787.

Abstract licence: CC BY-NC