scholarly journals Efficacy and acceptability of mood stabilisers in the treatment of acute bipolar depression: systematic review

2010 ◽  
Vol 196 (4) ◽  
pp. 266-273 ◽  
Author(s):  
Ryan J. Van Lieshout ◽  
Glenda M. MacQueen
Keyword(s):  
Systematic Review ◽  
Bipolar Depression ◽  
Antidepressant Treatment ◽  
Meta Analysis ◽  
Number Needed To Treat ◽  
Mood Stabiliser ◽  
Double Blind ◽  
Manic State ◽  
Gain Switching ◽  
Drug Classes

BackgroundAlthough people with bipolar disorder spend more time in a depressed than manic state, little evidence is available to guide the treatment of acute bipolar depression.AimsTo compare the efficacy, acceptability and safety of mood stabiliser monotherapy with combination and antidepressant treatment in adults with acute bipolar depression.MethodSystematic review and meta-analysis of randomised, double-blind controlled trials.ResultsEighteen studies with a total 4105 participants were analysed. Mood stabiliser monotherapy was associated with increased rates of response (relative risk (RR) = 1.30, 95% CI 1.16–1.44, number needed to treat (NNT) = 10, 95% CI 7–18) and remission (RR = 1.51, 95% CI 1.27–1.79, NNT = 8, 95% CI 5–14) relative to placebo. Combination therapy was not statistically superior to monotherapy. Weight gain, switching and suicide rates did not differ between groups. No differences were found between individual medications or drug classes for any outcome.ConclusionsMood stabilisers are moderately efficacious for acute bipolar depression. Extant studies are few and limited by high rates of discontinuation and short duration. Further study of existing and novel agents is required.

scholarly journals The efficacy of transcranial magnetic stimulation (TMS) for negative symptoms in schizophrenia: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Rasmus Lorentzen ◽  
Tuan Dang Nguyen ◽  
Alexander McGirr ◽  
Fredrik Hieronymus ◽  
Soren Dinesen Ostergaard
Keyword(s):  
Systematic Review ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Negative Symptoms ◽  
Meta Analysis ◽  
Preliminary Evidence ◽  
Pooled Analysis ◽  
P Value ◽  
Number Needed To Treat ◽  
Double Blind

Several trials have shown preliminary evidence for efficacy using Transcranial Magnetic Stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature using a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The standardized mean difference (SMD, Cohen's d) with 95% confidence intervals (CI) was calculated for each study (TMS vs. sham) and pooled across studies using an inverse variance random effects model. We identified 56 studies with a total of 2550 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD=0.37, 95%CI: 0.23; 0.52, p-value <0.00001), corresponding to a number needed to treat of 4.85. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex, using a stimulation frequency >1 Hz, and a stimulation intensity at or above the motor threshold, was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters have yet to be resolved.

A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes

2014 ◽  
Vol 45 (4) ◽  
pp. 693-704 ◽  
Author(s):  
A. McGirr ◽  
M. T. Berlim ◽  
D. J. Bond ◽  
M. P. Fleck ◽  
L. N. Yatham ◽  
...  
Keyword(s):  
Clinical Remission ◽  
Bipolar Depression ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Number Needed To Treat ◽  
Major Depressive ◽  
Double Blind ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Rapid Treatment

BackgroundThere is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. We aimed to assess the efficacy of ketamine in major depressive episodes.MethodWe searched EMBASE, PsycINFO, CENTRAL, and Medline from 1962 to January 2014 to identify double-blind, randomized controlled trials with allocation concealment evaluating ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The primary outcome measure was clinical remission at 24 h, 3 days and 7 days post-treatment. Analyses employed a random-effects model.ResultsData were synthesized from seven RCTs employing an intravenous infusion and one RCT employing intranasal ketamine, representing 73 subjects in parallel arms and 110 subjects in cross-over designs [n = 34 with bipolar disorder (BD), n = 149 with major depressive disorder (MDD)]. Ketamine was associated with higher rates of clinical remission relative to comparator (saline or midazolam) at 24 h [OR 7.06, number needed to treat (NNT) = 5], 3 days (OR 3.86, NNT = 6), and 7 days (OR 4.00, NNT = 6), as well as higher rates of clinical response at 24 h (OR 9.10, NNT = 3), 3 days (OR 6.77, NNT = 3), and 7 days (OR 4.87, NNT = 4). A standardized mean difference of 0.90 in favor of ketamine was observed at 24 h based on depression rating scale scores, with group comparisons revealing greater efficacy in unipolar depression compared to bipolar depression (1.07 v. 0.68). Ketamine was associated with transient psychotomimetic effects, but no persistent psychosis or affective switches.ConclusionOur meta-analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. Additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.

scholarly journals Adjunctive treatment with psychostimulants and stimulant-like drugs for resistant bipolar depression: a systematic review and meta-analysis

CNS Spectrums ◽  
2020 ◽  
pp. 1-12
Author(s):  
Evangelia Maria Tsapakis ◽  
Antonio Preti ◽  
Michael D. Mintzas ◽  
Konstantinos N. Fountoulakis
Keyword(s):  
Systematic Review ◽  
Treatment Guidelines ◽  
Bipolar Depression ◽  
Meta Analysis ◽  
Adjunctive Treatment ◽  
Number Needed To Treat ◽  
Residual Symptoms ◽  
Random Effects Models ◽  
Meta Analyses ◽  
Patients Experience

Abstract Background Depression is considered to be the most difficult to treat phase of bipolar disorder as patients experience residual symptoms causing long-term disability. This work aims to explore the role of add-on stimulant and stimulant-like medication in resistant bipolar depression patients. Methods Systematic review of add-on stimulants and stimulant-like drugs in resistant bipolar depression by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analysis was performed using the random-effects models. Heterogeneity was evaluated with Cochran’s Q and I2 statistics. Results Six randomized controlled trials of add-on modafinil, armodafinil, and lisdexamphetamine (LDX) (n = 813) vs placebo (n = 815) in the treatment of resistant bipolar depression were included. These drugs were more likely to induce remission from an episode of resistant bipolar depression (relative risk [RR] = 1.37; 95% confidence interval [CI]: 1.06-1.77; number needed to treat for an additional beneficial outcome = 16). Moreover, they did not induce more dropouts than placebo (RR = 1.04; 95% CI: 0.91-1.18), nor did they increase the risk of adverse effects (53/772 vs 41/771) at the end of treatment (RR = 1.30; 95% CI: 0.81-2.10; number needed to treat for an additional harmful outcome = 62). Suicidality and manic switch were not affected by active treatment. Heterogeneity was low (Cochran’s Q: P > .05), but sometimes with a large CI. Conclusions LDX, modafinil, and armodafinil seem to offer a reasonably well-tolerated and safe treatment in resistant bipolar depression. Treatment guidelines should, therefore, be revised to include these medications earlier in the therapeutic algorithm for resistant acute bipolar depression. Further research is, however, necessary for the elucidation of the clinical usefulness of these and other similar compounds.

scholarly journals Comparative Efficacy and Tolerability of Adjunctive Pharmacotherapies for Acute Bipolar Depression: A Systematic Review and Network Meta-analysis: Efficacité Et Tolérabilité Comparatives Des Pharmacothérapies D’appoint Pour La Dépression Bipolaire Aiguë: Une Revue Systématique Et Une Méta-Analyse De Réseau

2020 ◽  
pp. 070674372097085
Author(s):  
Anees Bahji ◽  
Dylan Ermacora ◽  
Callum Stephenson ◽  
Emily R. Hawken ◽  
Gustavo Vazquez
Keyword(s):  
Systematic Review ◽  
Bipolar Depression ◽  
Data Extraction ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Comparative Efficacy ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Augmentation Strategies ◽  
Intravenous Ketamine

Objective: We investigated the comparative efficacy and tolerability of augmentation strategies for bipolar depression. Data Sources: We conducted a systematic review and network meta-analysis of 8 electronic databases for double-blind, randomized controlled trials of adjunctive pharmacotherapies for acute bipolar depression. Data Extraction and Synthesis: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool for study quality appraisal. Two reviewers independently abstracted data. We resolved all discrepancies by consensus. Main Outcomes and Measures: Primary outcomes were response and completion of treatment. We estimated summary rate ratios (RRs) and standardized mean differences (SMDs) relative to placebo controls using frequentist random-effects network meta-analysis. Results: We identified 69 trials meeting eligibility criteria (8,007 participants, 42.8 years, 58.0% female). Adjunctive racemic intravenous ketamine, coenzyme Q10, pramipexole, fluoxetine, and lamotrigine were more effective than placebo. Summary RRs for response ranged between 1.51 (95% confidence interval [CI], 1.11 to 2.06) for fluoxetine and 12.49 (95% CI, 3.06 to 50.93) for racemic intravenous ketamine. For completion of treatment, risperidone appeared less tolerable than placebo (RR = 0.59; 95% CI, 0.38 to 0.94), while fluoxetine seemed more tolerable than placebo (RR = 1.13; 95% CI, 1.02 to 1.24). None of the investigated agents were associated with increased treatment-emergent mood switches. Conclusions and Relevance: The evidence for augmentation strategies in bipolar depression is limited to a handful of agents. Fluoxetine appeared to have the most consistent evidence base for both efficacy and tolerability. There remains a need for additional research exploring novel treatment strategies for bipolar depression, particularly head-to-head studies.

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