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Current Psychiatry Reports Jul 2022Identifying medications that may be used as therapeutic agents for eating disorders is a longstanding focus of research, with varying degrees of success. The present... (Review)
Review
PURPOSE OF REVIEW
Identifying medications that may be used as therapeutic agents for eating disorders is a longstanding focus of research, with varying degrees of success. The present review consolidates the most recent findings on pharmacological treatment of three eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED).
RECENT FINDINGS
Recent research suggests that olanzapine demonstrates positive effects on weight gain among outpatients with AN. There are fewer recent advances in psychopharmacological treatment for BN and BED, likely due to the relative success of prior medication trials. Olanzapine is the first medication to safely promote weight gain among individuals with AN. Fluoxetine is FDA-approved for BN treatment, and lisdexamfetamine is FDA-approved for BED treatment. BN and BED also generally respond well to SSRIs prescribed off-label. Research on psychopharmacological treatments for other eating disorders, such as avoidant-restrictive food intake disorder and other specified feeding and eating disorders, are sorely needed.
Topics: Anorexia Nervosa; Binge-Eating Disorder; Bulimia Nervosa; Feeding and Eating Disorders; Humans; Olanzapine; Weight Gain
PubMed: 35576089
DOI: 10.1007/s11920-022-01340-5 -
Brain and Behavior Feb 2022Anorexia nervosa (AN) is a severe psychiatric disorder characterized by starvation and malnutrition, a high incidence of coexisting psychiatric conditions, and treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by starvation and malnutrition, a high incidence of coexisting psychiatric conditions, and treatment resistance. The effect of pharmacotherapy has been controversial.
METHOD
A systematic review was conducted for evidence of an effect of olanzapine versus placebo in adults or its effect as adjuvant treatment of AN in adolescents.
RESULTS
A total of seven articles (304 patients with AN) were identified. There were four double-blind, randomized studies examining the effect of olanzapine in the treatment of AN. The mean difference in body mass index (BMI) at the end of treatment between olanzapine and placebo was 0.67 kg/m (95% confidence interval (CI) 0.15-1.18 kg/m ; p = 0.01; I = 0%, p for heterogeneity < 0.79). The olanzapine groups showed a significant increase in BMI of 0.68 kg/m (95% CI 0.22-1.13 kg/m ; p < 0.001; I = 0%, p for heterogeneity = 0.74) compared to the placebo groups. Only two studies examined the effect of olanzapine as adjuvant treatment in adolescents and showed an increase in BMI of 0.66 kg/m (95% CI -0.36 to 1.67 kg/m ; p = 0.21; I = 11%, p for heterogeneity = 0.32).
DISCUSSION
Olanzapine showed efficacy in the treatment of AN with an increased BMI at the end of treatment in adults. The effect of olanzapine as adjuvant treatment in adolescents remains unclear.
Topics: Adolescent; Adult; Anorexia Nervosa; Benzodiazepines; Body Mass Index; Double-Blind Method; Humans; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35020271
DOI: 10.1002/brb3.2498 -
Molecular Psychiatry Feb 2022A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Female; Haloperidol; Humans; Lithium; Male; Mania; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Tamoxifen; Valproic Acid
PubMed: 34642461
DOI: 10.1038/s41380-021-01334-4 -
Acta Psychiatrica Scandinavica Oct 2022Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and meta-analysis aimed to synthesise the evidence of efficacy, acceptability and tolerability of treatments for individuals with rapid cycling bipolar disorder (RCBD).
METHOD
A systematic search was conducted to identify randomised controlled trials assigning participants with RCBD to pharmacological and/or non-pharmacological interventions. Study inclusion and data extraction were undertaken by two reviewers independently. The primary outcome was continuous within-subject RCBD illness severity before and after treatment. Pre-post random effects meta-analyses were conducted for each outcome/intervention arm studied, generating a standardised effect size (hedge's g) and 95% confidence interval (CI).
RESULTS
A total of 34 articles describing 30 studies were included. A total of 16 separate pharmacological treatments were examined in contrast to 1 psychological therapy study. Only quetiapine and lamotrigine were assessed in >5 studies. By assessing 95% CI overlap of within-subject efficacy effects compared to placebo, the only interventions suggesting significant depression benefits (placebo g = 0.60) were olanzapine (with/without fluoxetine; g = 1.01), citalopram (g = 1.10) and venlafaxine (g = 2.48). For mania, benefits were indicated for quetiapine (g = 1.01), olanzapine (g = 1.19) and aripiprazole (g = 1.09), versus placebo (g = 0.33). Most of these effect sizes were from only one trial per treatment. Heterogeneity between studies was variable, and 20% were rated to have a high risk of bias.
CONCLUSIONS
While many interventions appeared efficacious, there was a lack of robust evidence for most treatments. Given the limited and heterogeneous evidence base, the optimal treatment strategies for people with RCBD are yet to be established.
Topics: Aripiprazole; Bipolar Disorder; Citalopram; Fluoxetine; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Venlafaxine Hydrochloride
PubMed: 35778967
DOI: 10.1111/acps.13471 -
The International Journal of... Apr 2020Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term... (Comparative Study)
Comparative Study Randomized Controlled Trial
Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone.
BACKGROUND
Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.
METHOD
From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy.
RESULTS
The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea.
CONCLUSIONS
Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.
Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Female; Follow-Up Studies; Haloperidol; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Young Adult
PubMed: 31974576
DOI: 10.1093/ijnp/pyaa004 -
Drugs & Aging Jan 2023Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to... (Review)
Review
Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to psychosis, irritability, impulsivity and agitation. These symptoms are associated with significant distress to the patient and caregivers, as well as more rapid progression of dementia, institutionalisation and higher mortality. The first-line management of the neuropsychiatric symptoms of dementia should be non-pharmacological. If medications are required, antipsychotics are commonly chosen. Second-generation antipsychotics such as risperidone, olanzapine, quetiapine and aripiprazole are prescribed more often than first-generation antipsychotics, such as haloperidol. The aim of this review is to provide an update on findings on adverse outcomes and clinical implications of antipsychotic use in dementia. These medications may increase mortality and can be associated with adverse events including pneumonia, cerebrovascular events, parkinsonian symptoms or higher rates of venous thromboembolism. Risks related to antipsychotic use in dementia are moderated by a number of modifiable and non-modifiable factors such as co-prescribing of other medications, medical and psychiatric co-morbidities, and demographics such as age and sex, making individualised treatment decisions challenging. Antipsychotics have further been associated with an increased risk of reliance on long-term care and institutionalisation, and they might not be cost-effective for healthcare systems. Many of these risks can potentially be mitigated by close physical health monitoring of antipsychotic treatment, as well as early withdrawal of pharmacotherapy when clinically possible.
Topics: Humans; Aged; Antipsychotic Agents; Olanzapine; Risperidone; Psychotic Disorders; Quetiapine Fumarate; Dementia; Benzodiazepines
PubMed: 36513918
DOI: 10.1007/s40266-022-00992-5 -
Schizophrenia Bulletin May 2022Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this gap with a dose-response meta-analysis.
METHODS
We searched multiple electronic databases (last update search June 2021) for all fixed-dose studies that investigated 16 second-generation antipsychotics and haloperidol in adults with acute exacerbation of schizophrenia or with negative symptoms. We estimated the dose-response curves by conducting random-effects dose-response meta-analyses. We used the restricted cubic spline to model the dose-response relationship. The primary outcome was mean weight gain in kg from baseline to endpoint, the secondary outcome was the number of patients with clinically important weight gain.
FINDINGS
Ninety-seven studies with 333 dose arms (36 326 participants) provided data for meta-analyses. Most studies were short-term with median duration of 6 weeks (range 4 to 26 weeks). In patients with acute exacerbation, amisulpride, aripiprazole, brexpiprazole, cariprazine, haloperidol, lumateperone, and lurasidone produced mild weight gain in comparison to placebo (mean difference at any dose≤1 kg), while more significant weight gain was observed by all other drugs. For most drugs, dose-response curves showed an initial dose-related increase in weight which plateaued at higher doses, while for others there was no plateau and some even had bell-shaped curves, meaning less weight gain to be associated with higher doses.
INTERPRETATION
Second-generation antipsychotics do not only differ in their propensity to produce weight gain, but also in the shapes of their dose-response curves. This information is important for dosing decisions in clinical practice.
Topics: Adult; Antipsychotic Agents; Haloperidol; Humans; Olanzapine; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 35137229
DOI: 10.1093/schbul/sbac001