Dataset Information

A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder.

ABSTRACT: OBJECTIVE:Antidepressants targeting monoaminergic neurotransmitter systems, despite their immediate effects at the synaptic level, usually require several weeks of administration to achieve clinical efficacy. The authors propose a strategy of adding creatine monohydrate (creatine) to a selective serotonin reuptake inhibitor (SSRI) in the treatment of patients with major depressive disorder. Such augmentation may lead to a more rapid onset of antidepressant effects and a greater treatment response, potentially by restoring brain bioenergetics at the cellular level. METHOD:Fifty-two women with major depressive disorder were enrolled in an 8-week double-blind placebo-controlled clinical trial and randomly assigned to receive escitalopram in addition to either creatine (5 g/day, N=25) or placebo (N=27). Efficacy was primarily assessed by changes in the Hamilton Depression Rating Scale (HAM-D) score. RESULTS:In comparison to the placebo augmentation group, patients receiving creatine augmentation showed significantly greater improvements in HAM-D score, as early as week 2 of treatment. This differential improvement favoring creatine was maintained at weeks 4 and 8. There were no differences between treatment groups in the proportion of patients who discontinued treatment prematurely (creatine: N=8, 32.0%; placebo: N=5, 18.5%) or in the overall frequency of all reported adverse events (creatine: 36 events; placebo: 45 events). CONCLUSIONS:The current study suggests that creatine augmentation of SSRI treatment may be a promising therapeutic approach that exhibits more rapid and efficacious responses in women with major depressive disorder.

SUBMITTER: Lyoo IK

PROVIDER: S-EPMC4624319 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder.

Lyoo In Kyoon IK Yoon Sujung S Kim Tae-Suk TS Hwang Jaeuk J Kim Jieun E JE Won Wangyoun W Bae Sujin S Renshaw Perry F PF

The American journal of psychiatry 20120901 9

<h4>Objective</h4>Antidepressants targeting monoaminergic neurotransmitter systems, despite their immediate effects at the synaptic level, usually require several weeks of administration to achieve clinical efficacy. The authors propose a strategy of adding creatine monohydrate (creatine) to a selective serotonin reuptake inhibitor (SSRI) in the treatment of patients with major depressive disorder. Such augmentation may lead to a more rapid onset of antidepressant effects and a greater treatment ...[more]

PMID: 22864465

Similar Datasets

Project description:BackgroundMany patients with obsessive-compulsive disorder do not respond adequately to serotonin reuptake inhibitors. Augmentation with antipsychotic drugs can be beneficial in this regard. However, since new relevant randomized controlled trials evaluating new antipsychotics were conducted, a recalculation of the effect sizes appears necessary.MethodsWe meta-analyzed all double-blind, randomized, placebo-controlled trials comparing augmentation of serotonin reuptake inhibitors with antipsychotics to placebo supplementation in treatment-resistant obsessive-compulsive disorder. The primary outcome was mean change in the Yale-Brown Obsessive-Compulsive Scale total score. Secondary outcomes were obsessions, compulsions, response rates, and attrition rates. The data collection process was conducted independently by 2 authors. Hedges's g and risks ratios were calculated as effect sizes. In preplanned meta-regressions, subgroup analyses, and sensitivity analyses, we examined the robustness of the results and explored reasons for potential heterogeneity.ResultsAltogether, 14 double-blind, randomized, placebo-controlled trials (n=491) investigating quetiapine (N=4, n=142), risperidone (N=4, n=132), aripiprazole (N=2, n=79), olanzapine (N=2, n=70), paliperidone (N=1, n=34), and haloperidol (N=1, n=34) were incorporated. Augmentation with antipsychotics was significantly more efficacious than placebo in Yale-Brown Obsessive-Compulsive Scale total reduction (N=14, n=478; Hedges's g=-0.64, 95% CI: -0.87 to -0.41; P=<.01). Aripiprazole (Hedges's g=-1.35), haloperidol (Hedges's g=-0.82), and risperidone (Hedges's g=-0.59) significantly outperformed placebo. Antipsychotics were superior to placebo in treating obsessions, compulsions, and achieving response. There was no between-group difference concerning all-cause discontinuation. The nonsignificant meta-regressions suggest no influence of the antipsychotic dose or baseline symptom severity on the meta-analytic results.ConclusionsAccording to our findings, antipsychotic augmentation of serotonin reuptake inhibitors can be regarded as an evidence-based measure in treatment-resistant obsessive-compulsive disorder.

Project description:Previous neuroimaging studies have shown that serotonin-norepinephrine reuptake inhibitor antidepressants alter functional activity in large expanses of brain regions. However, it is not clear how these regions are systemically organized on a connectome level with specific topological properties, which may be crucial to revealing neural mechanisms underlying serotonin-norepinephrine reuptake inhibitor treatment of persistent depressive disorder. To investigate the effect of serotonin-norepinephrine reuptake inhibitor antidepressants on brain functional connectome reconfiguration in persistent depressive disorder and whether this reconfiguration promotes the improvement of clinical symptoms, we combined resting-state functional magnetic resonance imaging (fMRI) scans acquired in two randomized, double-blind, placebo-controlled trial studies of serotonin-norepinephrine reuptake inhibitor antidepressant treatment of patients with persistent depressive disorder. One was a randomized, double-blind, placebo-controlled trial of 10-week duloxetine medication treatment, which included 17 patients in duloxetine group and 17 patients in placebo group (ClinicalTrials.gov Identifier: NCT00360724); the other one was a randomized, double-blind, placebo-controlled trial of 12-week desvenlafaxine medication treatment, which included 16 patients in desvenlafaxine group and 15 patients in placebo group (ClinicalTrials.gov Identifier: NCT01537068). The 24-item Hamilton Depression Rating Scale was used to measure clinical symptoms, and graph theory was employed to examine serotonin-norepinephrine reuptake inhibitor antidepressant treatment effects on the topological properties of whole-brain functional connectome of patients with persistent depressive disorder. We adopted a hierarchical strategy to examine the topological property changes caused by serotonin-norepinephrine reuptake inhibitor antidepressant treatment, calculated their small-worldness, global integration, local segregation and nodal clustering coefficient in turn. Linear regression analysis was used to test associations of treatment, graph properties changes and clinical symptom response. Symptom scores were more significantly reduced after antidepressant than placebo administration (η 2 = 0.18). There was a treatment-by-time effect that optimized the functional connectome in a small-world manner, with increased global integration and increased nodal clustering coefficient in the bilateral thalamus (left thalamus η 2 = 0.21; right thalamus η 2 = 0.23). The nodal clustering coefficient increment of the right thalamus (ratio = 29.86; 95% confidence interval, -4.007 to -0.207) partially mediated the relationship between treatment and symptom improvement, and symptom improvement partially mediated (ratio = 21.21; 95% confidence interval, 0.0243-0.444) the relationship between treatment and nodal clustering coefficient increments of the right thalamus. Our study may indicate a putative mutually reinforcing association between nodal clustering coefficient increment of the right thalamus and symptom improvement from serotonin-norepinephrine reuptake inhibitor antidepressant treatments with duloxetine or desvenlafaxine.

Project description:Depressive episodes are a major cause of morbidity and dysfunction in individuals suffering from bipolar disorder. Currently available treatments for this condition have limited efficacy and new therapeutic options are needed. Extensive research in the pathophysiology of bipolar disorder points to the existence of mitochondrial and bioenergetic dysfunction. We hypothesized that creatine monohydrate, a nutraceutical that works as a mitochondrial modulator, would be effective as an adjunctive therapy for bipolar depression. We conducted a double-blind trial in which 35 patients with bipolar disorder type I or II in a depressive episode by DSM-IV criteria and in use of regular medication for the treatment of this phase of the disease were randomly allocated into two adjunctive treatment groups for 6 weeks: creatine monohydrate 6 g daily (N = 17) or placebo (N = 18). Primary efficacy was assessed by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS). We did not find a statistically significant difference in the comparison between groups for the change in score on the MADRS after 6 weeks in an intention-to-treat (ITT) analysis (p = 0.560; Cohen's d = 0.231). However, we found significant superiority of creatine add-on vs. placebo when we considered the remission criterion of a MADRS score ? 12 at week 6 analyzing the outcome of the 35 randomized patients on ITT (52.9% remission in the creatine group vs. 11.1% remission in the placebo group) and of the 23 completers (66.7% remission in the creatine group vs. 18.2% remission in the placebo group) (p = 0.012; OR = 9.0 and p = 0.036; OR = 9.0, respectively). Two patients who received creatine switched to hypomania/mania early in the trial. No clinically relevant physical side-effects were reported or observed. This proof-of-concept study, aiming to restore brain bioenergetics using an adjunctive mitochondrial modulator, is not conclusive on the efficacy of creatine add-on for bipolar depression, but suggests that this compound may have a role in the adjunctive treatment of this phase of the illness. Further investigation through randomized controlled trials with larger samples should be conducted to verify the efficacy of creatine supplementation for bipolar depression and also for subsyndromal depressive symptoms.

Project description:BackgroundThis randomized, double-blind, placebo-controlled study evaluated dose-response relationships of lisdexamfetamine dimesylate when used as augmentation for major depressive disorder in individuals exhibiting inadequate responses to antidepressant monotherapy.MethodsEligible adults (18-65 years) were assigned to antidepressant monotherapy (escitalopram or venlafaxine extended-release) plus lisdexamfetamine dimesylate-matching placebo during an eight-week single-blind lead-in phase. Participants meeting randomization criteria were randomized (1:1:1:1:1) to eight weeks of lisdexamfetamine dimesylate (10, 30, 50, or 70 mg) or placebo while maintaining antidepressant therapy. Dose-responses for changes from augmentation baseline to week 16/early termination for Montgomery-Åsberg Depression Rating Scale total score (primary efficacy endpoint) and vital signs (systolic and diastolic blood pressure and pulse) were assessed using multiple comparisons procedures with modeling.ResultsFor Montgomery-Åsberg Depression Rating Scale total score change, no significant dose-responses were observed for any candidate dose-response curve (all p>0.10). In the dose-response evaluable population, least squares mean (90% confidence interval) treatment differences versus placebo for Montgomery-Åsberg Depression Rating Scale total score change at week 16 were -1.4 (-3.9, 1.2), 0.1 (-2.5, 2.7), -0.7 (-3.4, 2.0), and -0.9 (-3.5, 1.6) with 10, 30, 50, and 70 mg lisdexamfetamine dimesylate, respectively. For all vital sign parameters, lisdexamfetamine dimesylate exhibited significant dose-responses for all candidate dose-response curves (all p<0.10), with increases observed as lisdexamfetamine dimesylate dose increased; a linear relationship provided the best fit. Mean±standard deviation changes from augmentation baseline for systolic and diastolic blood pressure and pulse at week 16/early termination were -0.7±9.90 and -0.3±7.24 mm Hg and 0.2±10.57 bpm with placebo and were 1.9±9.47 and 0.8±7.40 mm Hg and 3.6±9.74 bpm with lisdexamfetamine dimesylate (all doses combined). The safety and tolerability profile of lisdexamfetamine dimesylate was consistent with previous studies.ConclusionsLisdexamfetamine dimesylate augmentation did not provide benefit over placebo in adults with inadequate responses to antidepressant monotherapy based on the assessed efficacy measures.

Dataset Information

A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder.

Publications

A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets