Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials

CNS Spectrums ◽  
2016 ◽  
Vol 21 (5) ◽  
pp. 403-418 ◽  
Author(s):  
Marco Solmi ◽  
Nicola Veronese ◽  
Leonardo Zaninotto ◽  
Marc L. M. van der Loos ◽  
Keming Gao ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Adverse Effects ◽  
Bipolar Depression ◽  
Meta Analysis ◽  
Antidepressant Activity ◽  
Unipolar Depression ◽  
Mood Stabilizers ◽  
Controlled Trials ◽  
Bipolar Patients ◽  
Extreme Outlier

ObjectivesTo meta-analytically summarize lamotrigine’s effectiveness and safety in unipolar and bipolar depression.MethodsWe conducted systematic PubMed and SCOPUS reviews (last search =10/01/2015) of randomized controlled trials comparing lamotrigine to placebo or other agents with antidepressant activity in unipolar or bipolar depression. We performed a random-effects meta-analysis of depression ratings, response, remission, and adverse effects calculating standardized mean difference (SMD) and risk ratio (RR) ±95% confidence intervals (CIs).ResultsEighteen studies (n=2152, duration=9.83 weeks) in patients with unipolar depression (studies=4, n=187; monotherapy vs lithium=1, augmentation of antidepressants vs placebo=3) or bipolar depression (studies=14, n=1965; monotherapy vs placebo=5, monotherapy vs lithium or olanzapine+fluoxetine=2, augmentation of antidepressants vs placebo=1, augmentation of mood stabilizers vs placebo=3, augmentation of mood stabilizers vs trancylpromine, citalopram, or inositol=3) were meta-analyzed. Lamotrigine’s efficacy for depressive symptoms did not differ significantly in monotherapy vs augmentation studies (vs. placebo: p=0.98, I2=0%; vs active agents: p=0.48, I2=0%) or in unipolar vs bipolar patients (vs placebo: p=0.60, I2=0%), allowing pooling of each placebo-controlled and active-controlled trials. Lamotrigine outperformed placebo regarding depressive symptoms (studies=11, n=713 vs n=696; SMD=–0.15, 95% CI=–0.27, –0.02, p=0.02, heterogeneity: p=0.24) and response (after removing one extreme outlier; RR=1.42, 95% CI=1.13–1.78; p=0.003, heterogeneity: p=0.08). Conversely, lamotrigine did not differ regarding efficacy on depressive symptoms, response, or remission from lithium, olanzapine+fluoxetine, citalopram, or inositol (studies=6, n=306 vs n=318, p-values=0.85–0.92). Adverse effects and all-cause/specific-cause discontinuation were similar across all comparisons.ConclusionsLamotrigine was superior to placebo in improving unipolar and bipolar depressive symptoms, without causing more frequent adverse effects/discontinuations. Lamotrigine did not differ from lithium, olanzapine+fluoxetine, citalopram, or inositol.

Prevalence of Bipolar Depression

CNS Spectrums ◽  
2003 ◽  
Vol 8 (S12) ◽  
pp. 2-3
Author(s):  
Robert M. Post
Keyword(s):  
Bipolar Disorder ◽  
Bipolar Depression ◽  
Unipolar Depression ◽  
The United States ◽  
Mood Stabilizers ◽  
Positive Screen ◽  
Specificity And Sensitivity ◽  
Academic Settings ◽  
Mood Disorder Questionnaire ◽  
Bipolar Patients

Recent data indicate that bipolar illness is underdiagnosed and therefore undertreated in the community (Slide 1). A recent survey of >85,000 households in the United States found a 3.7% positive screen for prominent bipolar symptomatology. Using the Mood Disorder Questionnaire, which has good specificity and sensitivity in outpatient clinics, the study also found that the prevalence was higher, 9.3%, among patients 18–24 years of age. However, most disappointing was that only 20% of the positive screens were diagnosed as bipolar, and among those, most were not treated with mood stabilizers. In addition, 31% of patients had been diagnosed with unipolar depression. Several studies have shown that approximately 20% to 40% of presumptively unipolar patients actually have bipolar II or bipolar disorder not otherwise specified. Combined, the data show that bipolar disorder, bipolar depression in particular, is highly prevalent and often misdiagnosed or unrecognized.Two recent studies found virtually the same data showing that depression is the predominant problem in naturalistically treated bipolar outpatients. Judd and colleagues found that depression was three times more prevalent than mania in bipolar patients. This is exactly what was found in the Stanley Foundation bipolar outpatient follow-up study, which rated the study's first 258 patients every day for 1 year (Slide 2). The study found that patients were ill almost 50% of the time; they were depressed 33% of the days in the year, and hypomanic or manic 10.8% of the days. This occurred despite aggressive treatment with a variety of agents, such as mood stabilizers, antidepressants, and benzodiazepines in 50% of the patients, and typical or atypical neuroleptics in almost 50% of the patients. Thus, even bipolar patients who are intensively treated in academic settings have a very substantial degree of morbidity, particularly depression.

scholarly journals Breathing-focused Yoga as Augmentation for Unipolar and Bipolar Depression: A Randomized Controlled Trial: Le yoga axé sur la respiration comme traitement d’appoint pour la dépression unipolaire et bipolaire: Un essai randomisé contrôlé

2020 ◽  
pp. 070674372094053
Author(s):  
Arun V. Ravindran ◽  
Martha S. McKay ◽  
Tricia da Silva ◽  
Claudia Tindall ◽  
Tiffany Garfinkel ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Controlled Trial ◽  
Well Being ◽  
Mood Stabilizers ◽  
Adjunctive Treatment ◽  
Residual Symptoms ◽  
Significant Difference ◽  
Bipolar Patients

Objective: Patients with depression frequently experience persistent residual symptoms even with optimal interventions. These patients often use complementary treatments, including yoga, as a preferred alternative or adjunctive treatment. There is evidence for the benefit of yoga for depression, but this has not been rigorously evaluated, particularly in bipolar depression. We aimed to determine the feasibility and benefit of manualized breathing-focused yoga in comparison to psychoeducation as augmentation to pharmacotherapy for improving residual symptoms of depression in unipolar and bipolar patients. Methods: Using a randomized single-blind crossover design, 72 outpatients with unipolar or bipolar depression were augmented with the two 8-week interventions at separate times, as add-ons to current first-line antidepressants and mood stabilizers. The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS). Due to the high dropout of participants after crossover at Week 8, analysis focused on between-group comparisons of yoga and psychoeducation during the initial 8 weeks of the study. Results: There was a significant decline in depressive symptoms, as measured by the MADRS, following 8 weeks of yoga. However, there was no significant difference in MADRS ratings between intervention groups. Similar improvements in self-rated depressive symptoms and well-being were also observed across time. Conclusions: Both yoga and psychoeducation may improve residual symptoms of unipolar and bipolar depression as add-on to medications. In-class group sessions and long study durations may reduce feasibility for this population. Larger trials with parallel group design and shorter duration may be more feasible.

scholarly journals Antidepressant Treatment for Acute Bipolar Depression: An Update

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ben H. Amit ◽  
Abraham Weizman
Keyword(s):  
Bipolar Depression ◽  
Antidepressant Treatment ◽  
Cochrane Collaboration ◽  
Unipolar Depression ◽  
Mood Stabilizers ◽  
The Past ◽  
First Line Therapy ◽  
Concurrent Use ◽  
The Subject ◽  
Bipolar Patients

While studies in the past have focused more on treatment of the manic phase of bipolar disorder (BD), recent findings demonstrate the depressive phase to be at least as debilitating. However, in contrast to unipolar depression, depression in bipolar patients exhibits a varying response to antidepressants, raising questions regarding their efficacy and tolerability.Methods. We conducted a MEDLINE and Cochrane Collaboration Library search for papers published between 2005 and 2011 on the subject of antidepressant treatment of bipolar depression. Sixty-eight articles were included in the present review.Results. While a few studies did advocate the use of antidepressants, most well-controlled studies failed to show a robust effect of antidepressants in bipolar depression, regardless of antidepressant class or bipolar subtype. There was no significant increase in the rate of manic/hypomanic switch, especially with concurrent use of mood stabilizers. Prescribing guidelines published in recent years rely more on atypical antipsychotics, especially quetiapine, as a first-line therapy.Conclusions. Antidepressants probably have no substantial role in acute bipolar depression. However, in light of conflicting results between studies, more well-designed trials are warranted.

Pharmacologic Treatment of Bipolar Disorder

CNS Spectrums ◽  
2010 ◽  
Vol 15 (S3) ◽  
pp. 10-13 ◽  
Author(s):  
Claudia Baldassano
Keyword(s):  
Bipolar Disorder ◽  
Bipolar Depression ◽  
Mood Stabilizers ◽  
Controlled Trials ◽  
United States Food ◽  
Mortality Ratio ◽  
States Food ◽  
Disorder Treatment ◽  
Standardized Mortality Ratios ◽  
Bipolar Patients

Regarding the treatment of patients with bipolar disorder, positive findings have shown that patients engaged in treatment may live longer. Angst and Sellaro studied standardized mortality ratios for patients with bipolar disorder and found a significant reduction in mortality ratio in our bipolar patients who were actively in treatment (Slide 1). Data from the Collaborative Depression Study by Judd and colleagues showed that bipolar patients are quite symptomatic. Judd and colleagues followed bipolar patients over a 13-year period and found that these patients were symptomatic ~50% of the study period. What were these patients most likely to be symptomatic with: bipolar depression (Slide 2). Thus, it is important to focus on bipolar depression and examine placebo-controlled trials that were adequately powered in its treatment.Over the last decade, there have been positive trials studying lamotrigine, quetiapine, olanzapine, and olanzapine-fluoxetine combination. Two of these medications are United States Food and Drug Administration—approved in bipolar disorder treatment: quetiapine and olanzapine-fluoxetine. There are a number of negative trials in bipolar depression, including a number of antidepressant monotherapy trials and antidepressants in combination with mood stabilizers (Slide 3). However, what is the most frequent pharmacotherapy treatment used for bipolar depression? It is the use of antidepressants alone; antidepressant monotherapy is twice as commonly prescribed as mood stabilizers (Slide 4). Thus, it is necessary for clinicians to possess knowledge of the evidence and results from both positive and negative antidepressant trials for bipolar disorder.

scholarly journals Mindfulness-based and acceptance-based programmes in the treatment of obsessive–compulsive disorder: a study protocol for a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e050329
Author(s):  
Johannes Julian Bürkle ◽  
Johannes Caspar Fendel ◽  
Stefan Schmidt
Keyword(s):  
Systematic Review ◽  
Depressive Symptoms ◽  
Obsessive Compulsive Disorder ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

IntroductionCognitive–behavioural therapy (CBT) with exposure and response prevention is the recommended standard for the treatment of obsessive–compulsive disorder (OCD). However, a high proportion of patients refuse this treatment, do not respond or relapse shortly after treatment. Growing evidence suggests that mindfulness-based and acceptance-based programmes (MABPs) are an effective option for the treatment of OCD. This systematic review and meta-analysis will examine the effectiveness of MABPs in treating OCD. We also aimed to explore potential moderators of the programmes’ effectiveness.Methods and analysisWe will systematically search MEDLINE, Embase, PsycINFO, PSYINDEX, Web of Science, CINAHL and Cochrane Register of Controlled Trials (no language restrictions) for studies that evaluate the effect of MABPs on patients with OCD. We will conduct backward and forward citation searches of included studies and relevant reviews and contact corresponding authors. The primary outcome will be pre-post intervention change in symptom severity. A secondary outcome will be change in depressive symptoms. Two reviewers will independently screen the records, extract the data and rate the methodological quality of the studies. We will include both controlled and uncontrolled trials. Randomised controlled trials will be meta-analysed, separately assessing between-group effects. A second meta-analysis will assess the within-group effect of all eligible studies. We will explore moderators and sources of heterogeneity such as the specific programme, study design, changes in depressive symptoms, hours of guided treatment, control condition and prior therapy (eg, CBT) using metaregression and subgroup analyses. We will perform sensitivity analyses using follow-up data. A narrative synthesis will also be pursued. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of the evidence.Ethics and disseminationEthical approval is not required. Results will be published in peer-reviewed journals and presented at international conferences.

scholarly journals Cardiovascular Toxicities Secondary to Biotherapy and Molecular Targeted Therapies in Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2159
Author(s):  
Charalampos Aktypis ◽  
Maria-Eleni Spei ◽  
Maria Yavropoulou ◽  
Göran Wallin ◽  
Anna Koumarianou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Targeted Therapies ◽  
Safety Profile ◽  
Meta Analysis ◽  
Mtor Inhibitors ◽  
Risk Of Bias ◽  
Neuroendocrine Neoplasms ◽  
Controlled Trials

A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87–3.12 and OR: 3.41, 95% CI: 1.46–7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47–1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35–1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66–6.48) followed by TKIs (OR:1.51, 95% CI: 0.59–3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64–4.64) and TKIs (OR:1.64, 95% CI: 0.35–7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87–5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.

scholarly journals The Effects of Modified Simiao Decoction in the Treatment of Gouty Arthritis: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Ya-Fei Liu ◽  
Ying Huang ◽  
Cai-Yu-Zhu Wen ◽  
Jun-Jun Zhang ◽  
Guo-Lan Xing ◽  
...  
Keyword(s):  
Systematic Review ◽  
Uric Acid ◽  
Adverse Effects ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Gouty Arthritis ◽  
Mean Difference ◽  
Controlled Trials ◽  
Randomised Controlled ◽  
Anti Inflammation

The modified Simiao decoctions (MSD) have been wildly applied in the treatment of gouty arthritis in China. However, the evidence needs to be evaluated by a systematic review and meta-analysis. After filtering, twenty-four randomised, controlled trials (RCTs) comparing the effects of MSD and anti-inflammation medications and/or urate-lowering therapies in patients with gouty arthritis were included. In comparison with anti-inflammation medications, urate-lowering therapies, or coadministration of anti-inflammation medications and urate-lowering therapies, MSD monotherapy significantly lowered serum uric acid (p<0.00001, mean difference = −90.62, and 95% CI [−128.38, −52.86];p<0.00001, mean difference = −91.43, and 95% CI [−122.38, −60.49];p=0.02, mean difference = −40.30, and 95% CI [−74.24, −6.36], resp.). Compared with anti-inflammation medications and/or urate-lowering therapies, MSD monotherapy significantly decreased ESR (p<0.00001; mean difference = −8.11; 95% CI [−12.53, −3.69]) and CRP (p=0.03; mean difference = −3.21; 95% CI [−6.07, −0.36]). Additionally, the adverse effects (AEs) of MSD were fewer (p<0.00001; OR = 0.08; 95% CI [0.05, 0.16]). MSD are effective in the treatment of gouty arthritis through anti-inflammation and lowering urate. However, the efficacy of MSD should be estimated with more RCTs.

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