-
Frontiers in Psychiatry 2021To compare the efficacy and tolerability of different administration strategies of aripiprazole. We searched MEDLINE, EMBASE, the Cochrane Central, Web of Science,...
Dose-Dependent Efficacy of Aripiprazole in Treating Patients With Schizophrenia or Schizoaffective Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
To compare the efficacy and tolerability of different administration strategies of aripiprazole. We searched MEDLINE, EMBASE, the Cochrane Central, Web of Science, China National Knowledge Infrastructure(CNKI), and Wanfang Data Knowledge Service Platform(Wanfang) for randomized controlled trials (RCTs) of aripiprazole, using the terms: (aripiprazole) AND (schizophr OR schizoaff) AND ("syndrome scale" OR PANSS) AND (clini OR trial). We retrieved study design, participant characteristics, comparison groups, and outcomes from each study. In total, nine RCTs were selected for meta-analysis, which covered ~1,187 participants. We defined two treatment groups that represent different treatment strategies: (1) the high-dose group (the high-dose strategy) rapidly increased to doses higher than 15 mg/day in 2 weeks or began with doses higher than 15 mg/day, otherwise the group was defined as (2) the low-dose group (the low-dose strategy). If the initial or target doses of aripiprazole in a study were all higher than 15 mg/day, the high- and low-dose groups were created based on the relative level of the dose. The high-dose group showed significantly greater reductions in Positive and Negative Syndrome Scale (PANSS) total scores (standardized mean differences = -8.31, 95% confidence interval [CI] = -16.48, -0.13; < 0.01; = 96%) than the low-dose group. The high-dose group showed superior effects compared with the low-dose group in long-term studies (more than 8 weeks) (standardized mean differences = -13.81, 95% CI = -25.07, -2.55; < 0.01; = 96%). With exception of somnolence, we did not find significant differences in side effects or discontinuation due to adverse events. Sensitivity analyses produced similar results. The high-dose treatment strategy of aripiprazole for patients with schizophrenia or schizoaffective disorder may bring more benefits without obvious side effects.
PubMed: 34456770
DOI: 10.3389/fpsyt.2021.717715 -
Journal of Psychopharmacology (Oxford,... Aug 2021Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD include increasing antidepressant dose, combining antidepressants, adding adjunctive agents, or using nonpharmacological treatments. Their efficacy and tolerability remain inadequately tested. In particular, the value and safety of increasingly employed second-generation antipsychotics (SGAs) and new esketamine, compared to lithium as antidepressant adjuncts remain unclear.
METHODS
We reviewed randomized, placebo-controlled trials and used random-effects meta-analysis to compare odds ratio (OR) versus placebo, as well as numbers-needed-to-treat (NNT) and to-harm (NNH), for adding SGAs, esketamine, or lithium to antidepressants for major depressive episodes.
RESULTS
Analyses involved 49 drug-placebo pairs. By NNT, SGAs were more effective than placebo (NNT = 11 [CI: 9-15]); esketamine (7 [5-10]) and lithium (5 [4-10]) were even more effective. Individually, aripiprazole, olanzapine+fluoxetine, risperidone, and ziprasidone all were more effective (all NNT < 10) than quetiapine (NNT = 13), brexpiprazole (16), or cariprazine (16), with overlapping NNT CIs. Risk of adverse effects, as NNH for most-frequently reported effects, among SGAs versus placebo was 5 [4-6] overall, and highest with quetiapine (NNH = 3), lowest with brexpiprazole (19), 5 (4-6) for esketamine, and 9 (5-106) with lithium. The risk/benefit ratio (NNH/NNT) was 1.80 (1.25-10.60) for lithium and much less favorable for esketamine (0.71 [0.60-0.80]) or SGAs (0.45 [0.17-0.77]).
CONCLUSIONS
Several modern antipsychotics and esketamine appeared to be useful adjuncts to antidepressants for acute major depressive episodes, but lithium was somewhat more effective and better tolerated.
LIMITATIONS
Most trials of adding lithium involved older, mainly tricyclic, antidepressants, and the dosing of adjunctive treatments were not optimized.
Topics: Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Ketamine; Lithium Compounds; Randomized Controlled Trials as Topic
PubMed: 34238049
DOI: 10.1177/02698811211013579 -
The Primary Care Companion For CNS... Jun 2021To assess the long-term efficacy and safety of aripiprazole as an augmentation strategy for major depressive disorder (MDD). Ovid MEDLINE, PsycInfo, and Embase... (Meta-Analysis)
Meta-Analysis
To assess the long-term efficacy and safety of aripiprazole as an augmentation strategy for major depressive disorder (MDD). Ovid MEDLINE, PsycInfo, and Embase databases were systematically searched for clinical studies of adult patients with MDD on long-term aripiprazole augmentation. Long-term follow-up was defined as ≥ 6 months. Primary outcome was remission from depression. Secondary outcome was incidence of adverse effects. Four open-label studies were included in this review. Random effects meta-analysis of 3 studies (n = 2,117) revealed a weighted average remission proportion of 0.33 (0.16-0.51), showing trend of improved response with duration of treatment. Three studies (n = 2,231) provided adverse effects data. Medically significant weight gain (25%-28% participants) was higher in studies with patients receiving doses ≥ 5 mg and lower (3.5%) in a study using doses < 5 mg. Akathisia (15%-16%), insomnia (12%-17%), somnolence (14%), and fatigue (18%) were common adverse effects. Tardive dyskinesia risk was low (< 1%) at 1-year follow-up. All included studies were open-label, noncontrolled studies, with longest follow-up of 52 weeks, limiting efficacy and safety conclusions. Aripiprazole augmentation may be an effective long-term strategy for treatment of refractory MDD. Lower maintenance doses (2-5 mg) of aripiprazole may be effective and have fewer side effects compared to larger doses (> 5 mg-10 mg).
Topics: Adult; Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Tardive Dyskinesia
PubMed: 34167174
DOI: 10.4088/PCC.20r02799 -
NPJ Schizophrenia May 2021Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose... (Review)
Review
Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D receptor (DR) partial agonists and DR antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare DR partial agonists with DR antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified DR partial agonist, and was not significantly different from pooled DR antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled DR antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation DR antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole's efficacy did not differ substantially from DR antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other DR partial agonists with DR antagonists in early stages of schizophrenia.
PubMed: 34035313
DOI: 10.1038/s41537-021-00158-z -
BMC Psychiatry May 2021While clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled... (Meta-Analysis)
Meta-Analysis
BACKGROUND
While clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled trials (RCT's) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of AAP monotherapy in adults with bipolar depression.
METHODS
Efficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement - Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated.
RESULTS
Eighteen RCT's met inclusion criteria of the systematic literature review. On change in MADRS, lurasidone (- 4.71 [95% Crl - 6.98, - 2.41]), quetiapine (- 4.80 [- 5.93, - 3.72]), olanzapine (- 4.57 [- 5.92, - 3.20]), and cariprazine (- 2.29 [- 3.47, - 1.09]) were more efficacious than placebo. Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to cariprazine (1.78 [95% Crl 1.08, 2.77]), aripiprazole (2.38 [1.38, 3.85]), and ziprasidone (2.47 [1.41, 3.98]), but was similar to olanzapine (1.68 [0.99,2.65]) and quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score, lurasidone was significantly better than cariprazine (- 0.38 [95% Crl - 0.66,-0.10]) and ziprasidone (- 0.58 [- 0.91,-0.26]), but similar to quetiapine (- 0.08 [- 0.36, 0.19])and olanzapine (- 0.04 [- 1.41, 1.46]). Lurasidone (0.34 kg [95% Crl - 0.22, 0.89]) and aripiprazole (0.20 kg [- 0.59, 1.00]) had a similar weight change compared to placebo, but olanzapine (2.88 kg [2.40, 3.36]), quetiapine (1.17 kg [0.84, 1.49]), and cariprazine (0.65 kg [0.34, 0.96]) were associated with greater weight gain. The NNT for response was the lowest for lurasidone (NNT = 5) followed by quetiapine (NNT = 6), olanzapine (NNT = 10) and cariprazine (NNT = 12).
CONCLUSIONS
In this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.
Topics: Adult; Antipsychotic Agents; Bayes Theorem; Bipolar Disorder; Depression; Humans; Network Meta-Analysis; Quetiapine Fumarate; Treatment Outcome
PubMed: 33975574
DOI: 10.1186/s12888-021-03220-3 -
Advances in Therapy May 2021To assess the risk of occurrence and potential determinants of metabolic disorders in adult patients treated with second-generation antipsychotics (SGAs) under...
Real-World Data on the Adverse Metabolic Effects of Second-Generation Antipsychotics and Their Potential Determinants in Adult Patients: A Systematic Review of Population-Based Studies.
INTRODUCTION
To assess the risk of occurrence and potential determinants of metabolic disorders in adult patients treated with second-generation antipsychotics (SGAs) under real-world practice conditions.
METHODS
MEDLINE, EMBASE, and PsycInfo were searched in July 2019 from database inception. We included population-based, longitudinal, comparative studies that report the results of the outcomes of interest for adult participants, including diabetes, ketoacidosis, hyperosmolar hyperglycemic state, weight gain/obesity, dyslipidemia, hypertension, and metabolic syndrome. Two reviewers independently extracted data on the study design, study quality, and study outcomes.
RESULTS
We included 40 studies. Most studies showed that clozapine and olanzapine were associated with an increased likelihood of developing diabetes, while the results for risperidone and quetiapine were mixed. Although less well studied, ziprasidone and aripiprazole appeared to not be associated with the occurrence of diabetes. Information on antipsychotic-induced weight gain/obesity is extremely scarce. Regarding dyslipidemia, aripiprazole was not associated with an increased likelihood of developing dyslipidemia, clozapine was associated with an increased likelihood of developing dyslipidemia, and risperidone, olanzapine, quetiapine, and ziprasidone showed mixed results. Two studies suggested an association between ziprasidone and the occurrence of hypertension. Several studies found that the occurrence of a metabolic disorder acted as a risk factor for the development of other metabolic disorders. We did not find information on brexpiprazole, cariprazine, or lurasidone, and data on any long-acting SGA were lacking.
CONCLUSION
Although there are relevant differences among SGAs concerning the risk of metabolic disorders, it appears that none of the SGAs included in our review are fully devoid of these disturbances.
Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Olanzapine; Quetiapine Fumarate; Risperidone
PubMed: 33826090
DOI: 10.1007/s12325-021-01689-8 -
Journal of Psychopharmacology (Oxford,... Aug 2021OnabotulinumtoxinA is a novel therapeutic intervention whose mechanism of action is believed to modify the negative facial feedback, thus abating symptoms of depression.... (Meta-Analysis)
Meta-Analysis
Efficacy of onabotulinumtoxinA in the treatment of unipolar major depression: Systematic review, meta-analysis and meta-regression analyses of double-blind randomised controlled trials.
BACKGROUND
OnabotulinumtoxinA is a novel therapeutic intervention whose mechanism of action is believed to modify the negative facial feedback, thus abating symptoms of depression. This putative new antidepressant agent offers minimal systemic side effects and negligible risk of pharmacological interactions. We set out to examine the evidence for the use of onabotulinumtoxinA in major depression.
METHODS
A systematic search of the literature identified double-blind randomised controlled trials (RCTs) investigating the use of onabotulinumtoxinA in the treatment of major depression versus placebo. Data, reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), was combined in meta-analyses (PROSPERO registration ID: CRD42020183538).
RESULTS
The search identified five RCTs (four double-blind) comparing onabotulinumtoxinA to placebo. OnabotulinumtoxinA was more effective than placebo when administered within the 20-40 IU dose range in double-blind RCTs. The analysis was free of publication bias and significantly heterogeneous. Meta-regression analyses indicated that onabotulinumtoxinA was more efficacious in women and in higher doses in female patients and less effective with polypharmacy, especially when an increasing number of antidepressants were prescribed. The effectiveness of onabotulinumtoxinA was higher in more recently published double-blind RCTs.
CONCLUSION
The meta-analysis supports the efficacy of the intervention with the results being highly heterogeneous across studies. In view of the heterogeneity of the findings and the significant moderators of benefit (sex, year of study completion and the interaction between sex and dose), more research is required to better understand the role of onabotulinumtoxinA in the treatment of depression.
Topics: Antidepressive Agents; Botulinum Toxins, Type A; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Neuromuscular Agents; Randomized Controlled Trials as Topic; Sex Factors
PubMed: 33719696
DOI: 10.1177/0269881121991827 -
Schizophrenia Bulletin Jul 2021Obesity and adverse metabolic outcomes in patients with severe mental illness are clinically significant but potentially preventable. Importantly, the evidence for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Obesity and adverse metabolic outcomes in patients with severe mental illness are clinically significant but potentially preventable. Importantly, the evidence for switching to antipsychotics to reduce cardiometabolic burden is unclear.
METHOD
PubMED, Embase, PsycINFO, and Cochrane were searched from inception to March 8, 2020. Articles reporting weight and metabolic changes after antipsychotic switching vs staying on the previous antipsychotic were meta-analyzed both across and within group.
RESULTS
Of 61 identified studies, 59 were meta-analyzed (40% rated high quality). In the switch-vs-stay pairwise meta-analyses, only aripiprazole significantly reduced weight (-5.52 kg, 95% CI -10.63, -0.42, P = .03), while olanzapine significantly increased weight (2.46 kg, 95% CI 0.34, 4.57, P = .02). Switching to aripiprazole also significantly improved fasting glucose (-3.99 mg/dl, 95% CI -7.34, -0.64, P = .02) and triglycerides (-31.03 mg/dl, 95% CI -48.73, -13.34, P = .0001). Dropout and psychosis ratings did not differ between switch and stay groups for aripiprazole and olanzapine. In before-to-after switch meta-analyses, aripiprazole (-1.96 kg, 95% CI -3.07, -0.85, P < .001) and ziprasidone (-2.22 kg, 95% CI -3.84, -0.60, P = .007) were associated with weight loss, whereas olanzapine (2.71 kg, 95% CI 1.87, 3.55, P < .001), and clozapine (2.80 kg, 95% CI 0.26, 5.34, P = .03) were associated with weight gain. No significant weight or other cardiometabolic changes were observed when switching to amisulpride, paliperidone/risperidone, quetiapine, or lurasidone.
CONCLUSIONS
Switching antipsychotics to agents with lower weight gain potential, notably to aripiprazole and ziprasidone, can improve weight profile and other cardiometabolic outcomes. When choosing switch agents, both the weight gain potential of the pre- and post-switch antipsychotic must be considered. Antipsychotic switching in psychiatrically stable patients must be weighed against the risk of psychiatric worsening.
Topics: Antipsychotic Agents; Humans; Mental Disorders; Patient Acuity; Weight Gain
PubMed: 33547471
DOI: 10.1093/schbul/sbaa191 -
Therapeutic Advances in... 2021Antipsychotic agents (APS) are widely used drugs to treat psychotic symptoms and can effectively reduce both positive and negative symptoms of schizophrenia. For...
BACKGROUND
Antipsychotic agents (APS) are widely used drugs to treat psychotic symptoms and can effectively reduce both positive and negative symptoms of schizophrenia. For decades, some studies suggested that there is a relationship between using APS and the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). However, results remain inconclusive.
METHOD
This review has been registered in International Prospective Register of Systematic Reviews (PROSPERO, ID: CDR42020155620). Relevant studies were identified among observational studies published up to 1 October 2019 in the databases MEDLINE, EMBASE, and Cochrane Library. Random or fixed-effects models were used to calculate the pooled odds ratio (OR).
RESULTS
In total, 28 observational studies were included. The results showed that compared with non-users, current APS users have significantly increased risks of VTE [OR 1.55 95% confidence interval (CI) 1.36, 1.76] and PE (OR 3.68, 95% CI 1.23, 11.05). Subgroup analyses suggested that new users were associated with a higher risk of VTE (OR 2.06, 95% CI 1.81, 2.35). For individual drugs, increased risk of VTE and PE was observed in taking haloperidol, risperidone, olanzapine, prochlorperazine but not in chlorpromazine, quetiapine or aripiprazole. However, careful interpretation is needed because of high heterogeneity among studies and scarce data.
CONCLUSION
The present comprehensive meta-analysis further indicates a significantly increased risk of VTE and PE in current APS users compared with non-users. Subgroup analyses suggest that new users are more likely to develop VTE. However, due to significant heterogeneity among studies, conclusions should be considered with caution.
PubMed: 33505665
DOI: 10.1177/2045125320982720 -
European Review For Medical and... Nov 2020To describe a patient with Sjögren syndrome (SS) associated with obsessive-compulsive disorder (OCD).
OBJECTIVE
To describe a patient with Sjögren syndrome (SS) associated with obsessive-compulsive disorder (OCD).
PATIENTS AND METHODS
Case report and systematic review of the literature.
CASE REPORT
A 40-year-old female patient with a history of xerostomia and xerophthalmia initiated in 2015. She also had a history of changing her behavior, and she practices rituals, recurrent obsessions, and compulsions. She was diagnosed with OCD. She was treated with fluoxetine associated with risperidone and then was changed for aripiprazole 10 mg/day. Cognitive-behavioral therapy was also applied. She had good control of the obsessions with these drugs and psychotherapy. Laboratory tests showed positive antinuclear antibodies, anti-Ro/SS-A, and-La/SS-B antibodies. Schirmer test, break up time, and positive green lisamin were all positive. Scintigraphy and ultrasound of salivary glands were positive. A diagnosis of Sjögren syndrome was determined. She was treated with HCQ, vitamin D3 50,000 IU/week, omega-3 2 g, and artificial tears with a good response. Currently, 5 years later, the patient is asymptomatic and has OCD under adequate control even without drugs.
CONCLUSIONS
This case illustrates a rare case of a patient with SS who evolved with OCD.
Topics: Adult; Cognitive Behavioral Therapy; Female; Humans; Obsessive-Compulsive Disorder; Sjogren's Syndrome
PubMed: 33275251
DOI: 10.26355/eurrev_202011_23836