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Expert Review of Clinical Pharmacology 2023Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have... (Review)
Review
INTRODUCTION
Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have been performed to identify factors contributing to the variability and thus facilitate individualized dosing. This review aims to provide a comprehensive overview of published population pharmacokinetic studies and explore potential covariates.
METHODS
We systematically searched PubMed, Web of Science, and EMBASE databases from their inception to 31 December 2022. Information on the study design, characteristics, and final parameter estimates was summarized and compared. Monte Carlo simulations provided visual predictive distributions to compare eligible studies. Forest plots were constructed to explore the effects of covariates on olanzapine pharmacokinetics.
RESULTS
A total of 10 population pharmacokinetic and three population pharmacokinetic/pharmacodynamic studies involving infants, children, adolescents, and adults were finally included. The median apparent clearance was 0.253 L/h/kg in adults, 27-43% lower than that of infants and children. Men and smokers increased the apparent clearance of olanzapine by 32% and 34%, respectively. The concentration required to achieve half of the maximum effect for the Positive and Negative Syndrome Scale total score was 24.80 ng/mL, comparable with 22.32 ng/mL for dopamine D receptor occupancy.
CONCLUSIONS
A higher dosage may be required for men or heavy smokers than for women or nonsmokers to reach the same exposure. Moreover, further population studies are essential to be conducted to clarify the dose-exposure-response relationship of olanzapine.
PROSPERO REGISTRATION
CRD42022368637.
Topics: Male; Adult; Child; Infant; Adolescent; Humans; Female; Olanzapine; Antipsychotic Agents; Schizophrenia; Research Design; Models, Biological
PubMed: 37231707
DOI: 10.1080/17512433.2023.2219055 -
Indian Journal of Psychological Medicine Jan 2024United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse... (Review)
Review
BACKGROUND AND OBJECTIVE
United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse events (weight gain) in adult patients with schizophrenia and bipolar disorder. To opine about the safety and efficacy of OLZSAM, authors performed a systematic review and meta-analysis to convene justifiable evidence.
METHODS
A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, from inception to September 2022, with the keywords: 'olanzapine and samidorphan' and schizophrenia; and "ALKS3831" and "lybalvi." Clinical trials published in English that analyzed the efficacy and safety of OLZSAM were included. The significant outcomes included in this study were change from baseline (CFB) in Positive and Negative Syndrome Scale (PANSS) at the end of the study, the proportion of patients with weight gain at the end of the study, the proportion of patients with at least one adverse event, and the incidence of drug discontinuation due to adverse events.
RESULTS
The change in PANSS score at the end of the study was comparable among groups receiving OLZSAM and olanzapine alone: standardized mean difference (SMD) = 0.04; 95% CI = -0.09 to 0.17; = 0.57. The OLZSAM group reported less incidence of weight gain: risk ratio (RR) = 0.91; 95% CI = 0.62-1.34; = 0.63, and any adverse event: RR = 0.99; 95% CI = 0.90-1.09; = 0.81. Drug discontinuation incidence was higher in the OLZSAM group: RR = 1.22; 95% CI = 0.84-1.79; = 0.30.
CONCLUSIONS
The combination OLZSAM showed comparable efficacy to olanzapine alone in schizophrenia patients, with relatively less incidence of weight gain and adverse events; however, the drug discontinuation due to adverse events was more in the OLZSAM group.
PubMed: 38524957
DOI: 10.1177/02537176231201326 -
The Psychiatric Quarterly Dec 2023Aripiprazole is an atypical antipsychotic medication, and its use in treating borderline personality disorder (BPD) is debatable because it is not FDA-approved for... (Review)
Review
Aripiprazole is an atypical antipsychotic medication, and its use in treating borderline personality disorder (BPD) is debatable because it is not FDA-approved for treating BPD. This study aimed to investigate the efficacy and safety of aripiprazole in patients with BPD. On July 2, 2021, the protocol (CRD42021256647) was registered in PROSPERO. PubMed, Scopus, Web of Science, Ovid-Medline, Embase, PsycINFO, and Cochrane (CENTRAL) were searched without regard for language or publication date. We also searched trial registries on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Randomized clinical trials with adult patients diagnosed with BPD met the inclusion criteria. The Cochrane risk of bias for randomized trials (RoB-2) method was used to assess the quality of the included studies. We included two previously published randomized clinical trials. There were 76 patients with BPD, with 38, 12, and 26 assigned to the aripiprazole, olanzapine, and placebo groups, respectively. Most patients (88.16%) were females, with ages ranging from 22.1 to 28.14 yr. Aripiprazole has been proven to reduce anxiety, depression, anger, hostility, clinical severity, and obsessive-compulsive behavior, insecurity, melancholy, anxiety, aggressiveness/hostility, phobic anxiety, paranoid thinking, psychoticism, and somatization. The adverse effects were headache, insomnia, restlessness, tremor, and akathisia. The risk of bias was considerable in both trials, which is somewhat problematic considering that prejudice can lead to incorrect outcomes and conclusions. Aripiprazole has demonstrated encouraging outcomes in the treatment of patients with BPD. More randomized controlled studies are needed.
Topics: Adult; Female; Humans; Male; Aripiprazole; Borderline Personality Disorder; Antipsychotic Agents; Olanzapine; Anxiety Disorders
PubMed: 37566261
DOI: 10.1007/s11126-023-10045-8 -
Expert Opinion on Pharmacotherapy 2016The prevalence of panic disorder (PD) in the population is high and these patients have work impairment, high unemployment rates, seek medical treatment more frequently... (Review)
Review
INTRODUCTION
The prevalence of panic disorder (PD) in the population is high and these patients have work impairment, high unemployment rates, seek medical treatment more frequently and have more hospitalizations than people without panic symptoms. Despite the availability of pharmacological, psychological and combined treatments, approximately one-third of all PD patients have persistent panic attacks and other PD symptoms after treatment.
AREAS COVERED
MEDLINE/Pubmed, CENTRAL, PsycINFO and Web of Science databases were searched for clinical trials in treatment-resistant PD. Only studies published between 1980 and 2015, in English, with human subjects, considered "journal articles" and clinical trial were included. We included trials recruiting only adult subjects with treatment-resistant PD, consistent with criteria from DSM-III to DSM5. We included all prospective experimental studies. Case, case series, retrospective studies or studies with <10 PD subjects were not included.
EXPERT OPINION
Only 11 articles were included in this review. There were few quality studies, only two were randomized, controlled and double blind. Augmentation of the pharmacological treatment with cognitive-behavioral therapy demonstrated some short-term efficacy in treatment-resistant PD. There were also preliminary evidences of efficacy for monotherapy with reboxetine and olanzapine, and augmentation with pindolol, divalproex sodium, aripiprazole and olanzapine in short-term treatment.
Topics: Antidepressive Agents; Antipsychotic Agents; Cognitive Behavioral Therapy; Combined Modality Therapy; Humans; Panic Disorder; Prospective Studies; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 26635099
DOI: 10.1517/14656566.2016.1109628 -
The Cochrane Database of Systematic... Oct 2019Bipolar disorder is a severe and common mental disorder where patients experience recurrent symptoms of elevated or irritable mood, depression, or a combination of both.... (Review)
Review
BACKGROUND
Bipolar disorder is a severe and common mental disorder where patients experience recurrent symptoms of elevated or irritable mood, depression, or a combination of both. Treatment is usually with psychiatric medication, including mood stabilisers, antidepressants and antipsychotics. Valproate is an effective maintenance treatment for bipolar disorder. However, evidence assessing the efficacy of valproate in the treatment of acute mania is less robust, especially when comparing it to some of the newer antipsychotic agents. This review is an update of a previous Cochrane Review (last published 2003) on the role of valproate in acute mania.
OBJECTIVES
To assess the efficacy and tolerability of valproate for acute manic episodes in bipolar disorder compared to placebo, alternative pharmacological treatments, or a combination pharmacological treatments, as measured by the treatment of symptoms on specific rating scales for individual episodes in paediatric, adolescent and adult populations.
SEARCH METHODS
We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 28 September 2018. We had also conducted an earlier search of these databases in the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all years to 6 June 2016). We also searched the World Health Organization (WHO) trials portal (ICTRP) and clinicaltrials.gov in September 2018, to identify any additional unpublished or ongoing studies.
SELECTION CRITERIA
Single- and double-blind, randomised controlled trials comparing valproate with placebo, alternative antimanic treatments, or a combination of pharmacological treatments. We also considered studies where valproate was used as an adjunctive treatment in combination with another agent separately from studies where it was used in monotherapy. We included male and female patients of all ages and ethnicity with bipolar disorder.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed data extraction and methodological quality assessment. For analysis, we used the odds ratio (OR) for binary efficacy outcomes and the mean difference (MD) or standardised mean difference (SMD) for continuously distributed outcomes.
MAIN RESULTS
Twenty-five trials (3252 participants) compared valproate with either placebo or alternative antimanic treatments to alleviate the symptoms of acute mania. For efficacy, our primary outcome was response rate. For tolerability, our primary outcome was the number of participants with any adverse effect. This meta-analysis included studies focusing on children, adolescents, as well as adults with a range of severity of manic symptoms. The majority of studies focused on adult men and women (aged 18 and above), were conducted in inpatient settings and completed in the US. Five studies in this review focused on children and adolescents (aged 18 and under) so that the review covers an age range from 3 - 82 years. Seven studies contained outpatient participants in some form. Nine studies included data that has been collected outside the US, namely Iran (4 studies), India (3 studies), China (1 study), or across several international countries (1 study).In adults, high-quality evidence found that valproate induces a slightly higher response compared to placebo (45% vs 29%, OR 2.05, 95% CI 1.32 to 3.20; 4 studies, 869 participants). Moderate-quality evidence found there was probably little or no difference in response rates between valproate and lithium (56% vs 62%, OR 0.80, 95% CI 0.48 to 1.35; 3 studies, 356 participants). In adults, low-quality evidence found there may be little or no difference in response rate between valproate and olanzapine (38% vs 44%, OR 0.77, 95% CI 0.48 to 1.25; 2 studies, 667 participants).In the children and adolescent population, the evidence regarding any difference in response rates between valproate and placebo was uncertain (23% vs 22%, OR 1.11, 95% CI 0.51 to 2.38; 1 study, 151 participants, very low-quality evidence). Low-quality evidence found that the response rate of participants receiving valproate may be lower compared to risperidone (23% vs 66%, OR 0.16, 95% CI 0.08 to 0.29; 1 study, 197 participants). The evidence regarding any difference in response rates between valproate and lithium was uncertain (23% vs 34%, OR 0.57, 95% CI 0.31 to 1.07; 1 study, 197 participants, very low-quality evidence).In terms of tolerability in adults, moderate-quality evidence found that there are probably more participants receiving valproate who experienced any adverse events compared to placebo (83% vs 75%, OR 1.63, 95% CI 1.13 to 2.36; 3 studies, 745 participants). Low-quality evidence found there may be little or no difference in tolerability between valproate and lithium (78% vs 86%, OR 0.61, 95% CI 0.25 to 1.50; 2 studies, 164 participants). We did not obtain primary tolerability outcome data on the olanzapine comparison.Within the children and adolescent population, the evidence regarding any difference between valproate or placebo was uncertain (67% vs 60%, OR 1.39, 95% CI 0.71 to 2.71; 1 study, 150 participants, very low-quality evidence). We did not obtain primary tolerability outcome data on the lithium or risperidone comparisons.
AUTHORS' CONCLUSIONS
There is evidence that valproate is an efficacious treatment for acute mania in adults when compared to placebo. By contrast, there is no evidence of a difference in efficacy between valproate and placebo for children and adolescents. Valproate may be less efficacious than olanzapine in adults, and may also be inferior to risperidone as a monotherapy treatment for paediatric mania. Generally, there is uncertain evidence regarding whether valproate causes more or less side effects than the other main antimanic therapies. However, evidence suggests that valproate causes less weight gain and sedation than olanzapine.
PubMed: 31621892
DOI: 10.1002/14651858.CD004052.pub2 -
Journal of Psychiatric Research Jun 2021We examined the efficacy and safety of using antipsychotic medication for schizophrenia using only randomized trials of antipsychotic for schizophrenia conducted in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We examined the efficacy and safety of using antipsychotic medication for schizophrenia using only randomized trials of antipsychotic for schizophrenia conducted in Japan to avoid the biological and environmental heterogeneities caused by pooling data from various races and ethnicities.
METHODS
We searched for eligible studies on Embase, PubMed, and CENTRAL. Primary outcomes were improvement in Positive and Negative Syndrome Scale total score (PANSS-T) and all-cause discontinuation. Other outcomes were improvement in PANSS subscale scores, discontinuation due to adverse events or inefficacy, and the incidence of 16 adverse events.
RESULTS
We calculated mean difference or risk ratios and 95% credible intervals. We identified 34 RCTs (6798 patients; mean study duration, 9.0 ± 4.24 weeks; proportion of male patients, 53.7%; mean age, 43.3 years). Besides placebo, studies included aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, clocapramine (no PANSS data), clozapine (no PANSS data), haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, perospirone, quetiapine, and risperidone. Efficacy and safety profiles differed for antipsychotics used with schizophrenia in Japanese patients. All active treatments other than haloperidol and quetiapine outperformed placebo to improve PANSS-T. Asenapine, olanzapine, paliperidone, and risperidone outperformed placebo for all-cause discontinuation. Asenapine, blonanserin, blonanserin-patch, haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, and risperidone outperformed placebo to improve PANSS positive subscale scores. Aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, lurasidone, olanzapine, paliperidone, perospirone, and risperidone outperformed placebo to improve PANSS negative subscale scores. The confidence in evidence of most outcomes was low or very low.
CONCLUSION
Our results are similar to those of previous network meta-analysis involving various races and ethnicities.
Topics: Adult; Antipsychotic Agents; Humans; Japan; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 33964682
DOI: 10.1016/j.jpsychires.2021.04.032 -
The Journal of Clinical Psychiatry Jul 2023Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and...
Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and dopamine D-receptor occupancy for oral and long-acting injectable (LAI) formulations. Databases were systematically searched for randomized controlled trials (RCTs) and uncontrolled trials concerning blood olanzapine levels in relation to clinical outcomes or D-receptor occupancy using MEDLINE (PubMed), Web of Science, PsycINFO, and Cochrane Library (March 2021, updated in December 2021). We excluded articles not written in English or German and non-human data. Search terms included , , , , and . The process of study selection followed a previously published protocol and PRISMA guidelines. A total of 2,824 articles were identified through database search and 1 article via reference list check. Thirty-four studies were suitable for qualitative synthesis, and 13 studies were included in the quantitative analysis. Reviewers performed data extraction and quality assessment of the included studies independently following the review protocol. Evidence for a relationship between blood olanzapine level and efficacy/side effects (constipation) is considered low (Level C). In total, 3 studies of moderate quality consistently showed therapeutic thresholds of around 20 ng/mL for olanzapine 12 hours post-dose. This threshold is in line with findings from positron emission tomography (PET) studies that suggest optimal drug efficacy (65%-80% D-receptor occupancy) between 17 and 44 ng/mL. We suggest a therapeutic reference range of 20-40 ng/mL for olanzapine oral and LAI formulations. In this range, optimal treatment response is expected in patients with schizophrenia and schizophrenia spectrum disorders. Side effects, especially weight gain, may already occur at therapeutic levels. However, higher plasma concentrations are in general well tolerated and should not necessarily require a dose reduction in case of good response and tolerance.
Topics: Humans; Olanzapine; Antipsychotic Agents; Reference Values; Schizophrenia; Receptors, Dopamine D2; Benzodiazepines
PubMed: 37471567
DOI: 10.4088/JCP.22r14626 -
The Cochrane Database of Systematic... Sep 2018Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or radiotherapy, or whilst in the palliative phase of illness.
OBJECTIVES
To assess the efficacy and safety of olanzapine when used as an antiemetic in the prevention and treatment of nausea and vomiting related to cancer in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase for published data on 20th September 2017, as well as ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform for unpublished trials. We checked reference lists, and contacted experts in the field and study authors.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of olanzapine versus any comparator with or without adjunct therapies for the prevention or treatment, or both, of nausea or vomiting in people with cancer aged 18 years or older, in any setting, of any duration, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. We used GRADE to assess quality of evidence for each main outcome. We extracted data for absence of nausea or vomiting and frequency of serious adverse events as primary outcomes. We extracted data for patient perception of treatment, other adverse events, somnolence and fatigue, attrition, nausea or vomiting severity, breakthrough nausea and vomiting, rescue antiemetic use, and nausea and vomiting as secondary outcomes at specified time points.
MAIN RESULTS
We included 14 RCTs (1917 participants) from high-, middle- and low-income countries, representing over 24 different cancers. Thirteen studies were in chemotherapy-induced nausea and vomiting. Oral olanzapine was administered during highly emetogenic (HEC) or moderately emetogenic (MEC) chemotherapy (12 studies); chemoradiotherapy (one study); or palliation (one study). Eight studies await classification and 13 are ongoing.The main comparison was olanzapine versus placebo/no treatment. Other comparisons were olanzapine versus NK1 antagonist, prokinetic, 5-HT3 antagonist or dexamethasone.We assessed all but one study as having one or more domains that were at high risk of bias. Eight RCTs with fewer than 50 participants per treatment arm, and 10 RCTs with issues related to blinding, were at high risk of bias. We downgraded GRADE assessments due to imprecision, inconsistency and study limitations.Olanzapine versus placebo/no treatmentPrimary outcomesOlanzapine probably doubles the likelihood of no nausea or vomiting during chemotherapy from 25% to 50% (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.59 to 2.47; 561 participants; 3 studies; solid tumours; HEC or MEC therapy; moderate-quality evidence) when added to standard therapy. Number needed to treat for additional beneficial outcome (NNTB) was 5 (95% CI 3.3 - 6.6).It is uncertain if olanzapine increases the risk of serious adverse events (absolute risk difference 0.7% more, 95% CI 0.2 to 5.2) (RR 2.46, 95% CI 0.48 to 12.55; 7 studies, 889 participants, low-quality evidence).Secondary outcomesFour studies reported patient perception of treatment. One study (48 participants) reported no difference in patient preference. Four reported quality of life but data were insufficient for meta-analysis.Olanzapine may increase other adverse events (RR 1.71, 95% CI 0.99 to 2.96; 332 participants; 4 studies; low-quality evidence) and probably increases somnolence and fatigue compared to no treatment or placebo (RR 2.33, 95% CI 1.30 to 4.18; anticipated absolute risk 8.2% more, 95% CI 1.9 to 18.8; 464 participants; 5 studies; moderate-quality evidence). Olanzapine probably does not affect all-cause attrition (RR 0.99, 95% CI 0.57 to 1.73; 943 participants; 8 studies; I² = 0%). We are uncertain if olanzapine increases attrition due to adverse events (RR 3.00, 95% CI 0.13 to 70.16; 422 participants; 6 studies). No participants withdrew due to lack of efficacy.We are uncertain if olanzapine reduces breakthrough nausea and vomiting (RR 0.38, 95% CI 0.10 to 1.47; 501 participants; 2 studies; I² = 54%) compared to placebo or no treatment. No studies reported 50% reduction in severity of nausea or vomiting, use of rescue antiemetics, or attrition.We are uncertain of olanzapine's efficacy in reducing acute nausea or vomiting. Olanzapine probably reduces delayed nausea (RR 1.71, 95% CI 1.40 to 2.09; 585 participants; 3 studies) and vomiting (RR 1.28, 95% CI 1.14 to 1.42; 702 participants; 5 studies).Subgroup analysis: 5 mg versus 10 mgPlanned subgroup analyses found that it is unclear if 5 mg is as effective an antiemetic as 10 mg. There is insufficient evidence to exclude the possibility that 5 mg may confer a lower risk of somnolence and fatigue than 10 mg.Other comparisonsOne study (20 participants) compared olanzapine versus NK1 antagonists. We observed no difference in any reported outcomes.One study (112 participants) compared olanzapine versus a prokinetic (metoclopramide), reporting that olanzapine may increase freedom from overall nausea (RR 2.95, 95% CI 1.73 to 5.02) and overall vomiting (RR 3.03, 95% CI 1.78 to 5.14).One study (62 participants) examined olanzapine versus 5-HT3 antagonists, reporting olanzapine may increase the likelihood of 50% or greater reduction in nausea or vomiting at 48 hours (RR 1.82, 95% CI 1.11 to 2.97) and 24 hours (RR 1.36, 95% CI 0.80 to 2.34).One study (229 participants) compared olanzapine versus dexamethasone, reporting that olanzapine may reduce overall nausea (RR 1.73, 95% CI 1.37 to 2.18), overall vomiting (RR 1.27, 95% CI 1.10 to 1.48), delayed nausea (RR 1.66, 95% CI 1.33 to 2.08) and delayed vomiting (RR 1.25, 95% CI 1.07 to 1.45).
AUTHORS' CONCLUSIONS
There is moderate-quality evidence that oral olanzapine probably increases the likelihood of not being nauseous or vomiting during chemotherapy from 25% to 50% in adults with solid tumours, in addition to standard therapy, compared to placebo or no treatment. There is uncertainty whether it increases serious adverse events. It may increase the likelihood of other adverse events, probably increasing somnolence and fatigue. There is uncertainty about relative benefits and harms of 5 mg versus 10 mg.We identified only RCTs describing oral administration. The findings of this review cannot be extrapolated to provide evidence about the efficacy and safety of any injectable form (intravenous, intramuscular or subcutaneous) of olanzapine.
Topics: Adult; Antiemetics; Antineoplastic Agents; Benzodiazepines; Chemoradiotherapy; Dexamethasone; Disorders of Excessive Somnolence; Fatigue; Humans; Metoclopramide; Nausea; Neoplasms; Olanzapine; Quality of Life; Randomized Controlled Trials as Topic; Vomiting
PubMed: 30246876
DOI: 10.1002/14651858.CD012555.pub2 -
Psychological Medicine Jul 2023Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy.
METHODS
A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events.
RESULTS
Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, = 4375), amisulpride [1.99 (1.55-2.55)], sulpiride [1.50 (1.03-2.17)], and quetiapine [1.48 (1.23-1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, = 8349), ziprasidone [1.80 (1.07-3.04)], risperidone [1.59 (1.19-2.14)], aripiprazole [1.54 (1.35-1.76)], brexpiprazole [1.41 (1.21-1.66)], cariprazine [1.27 (1.07-1.52)], and quetiapine [1.23 (1.08-1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior.
CONCLUSION
Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Risperidone; Depressive Disorder, Major; Amisulpride; Olanzapine; Benzodiazepines; Dibenzothiazepines
PubMed: 35510505
DOI: 10.1017/S0033291722000745 -
Therapeutic Advances in... 2023Treatment-resistant schizophrenia (TRS) affects approximately 30% of people with schizophrenia. Clozapine is the gold standard treatment for TRS but is not always... (Review)
Review
BACKGROUND
Treatment-resistant schizophrenia (TRS) affects approximately 30% of people with schizophrenia. Clozapine is the gold standard treatment for TRS but is not always suitable, with a proportion of individuals intolerant of side effects or unable to engage in necessary blood monitoring. Given the profound impact TRS can have on those affected, alternative pharmacological approaches to care are needed.
OBJECTIVES
To review the literature on the efficacy and tolerability of high-dose olanzapine (>20 mg daily) in adults with TRS.
DESIGN
This is a systematic review.
DATA SOURCES AND METHODS
We searched for eligible trials published prior to April 2022 in PubMed/MEDLINE, Scopus and Google Scholar. Ten studies met the inclusion criteria [five randomised controlled trials (RCTs), one randomised crossover trial and four open label studies]. Data were extracted for predefined primary outcomes (efficacy, tolerability).
RESULTS
Compared with standard treatment, high-dose olanzapine was non-inferior in four RCTs, three of which used clozapine as the comparator. Clozapine was superior to high-dose olanzapine in a double-blind crossover trial. Open-label studies demonstrated tentative evidence in support of high-dose olanzapine use. It was better tolerated than clozapine and chlorpromazine in two respective RCTs, and was generally well tolerated in open-label studies.
CONCLUSION
This evidence suggests high-dose olanzapine is superior for TRS when compared with other commonly used first- and second-generation antipsychotics, including haloperidol and risperidone. In comparison with clozapine, the data are encouraging for the use of high-dose olanzapine where clozapine use is problematic, but larger, better designed trials are needed to assess the comparative efficacy of both treatments. There is insufficient evidence to consider high-dose olanzapine equivalent to clozapine when clozapine is not contraindicated. Overall, high-dose olanzapine was well tolerated, with no serious side effects.
REGISTRATION
This systematic review was preregistered with PROSPERO [CRD42022312817].
PubMed: 37187727
DOI: 10.1177/20451253231168788