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Journal of Affective Disorders Oct 2023Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess the evidence for the efficacy of atypical antipsychotics in treating unipolar and bipolar depression in adolescents and young adults.
METHOD
We conducted a comprehensive systematic review and meta-analysis of randomized-control-trial studies (RCTs) of antipsychotic medications for 10- to 25-year-olds with unipolar and bipolar depression. The primary outcome of interest was change in depressive symptoms from baseline to trial endpoint.
RESULTS
No studies were identified that evaluated the use of antipsychotics in the treatment of unipolar depression. However, we identified four studies, of quetiapine, lurasidone and olanzapine/fluoxetine combination, comprising a total of 866 randomized patients, that evaluated treatment of bipolar depression. All studies used the Children's Depression Rating Scale-Revised (CDRS-R). Our meta-analysis revealed the weighted mean difference (WMD) was -4.58 (95 % CI, -6.59 to -2.57) between antipsychotic and placebo-treated groups. Response and remission rates were also significantly in favor of antipsychotic treatment.
LIMITATIONS
There were few studies, several did not address risk-of-bias domains and there was a lack of non-industry sponsored studies.
CONCLUSION
There is an absence of evidence for the use of antipsychotic medications in treatment of youth unipolar depression, and no recommendations can be made. There is some evidence for the efficacy of antipsychotics, specifically lurasidone and olanzapine/fluoxetine combination, in the treatment of young people with bipolar depression. However, this evidence is limited and more studies investigating the use of these medications in young people are needed.
Topics: Child; Adolescent; Young Adult; Humans; Antipsychotic Agents; Bipolar Disorder; Fluoxetine; Olanzapine; Lurasidone Hydrochloride
PubMed: 37467794
DOI: 10.1016/j.jad.2023.07.082 -
CNS Drugs Aug 2023Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia.... (Meta-Analysis)
Meta-Analysis
Effectiveness and Safety of Switching from Oral Antipsychotics to Once-Monthly Paliperidone Palmitate (PP1M) in the Management of Schizophrenia: A Systematic Review and Meta-Analysis.
BACKGROUND
Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia. However, the outcomes for patients who switch from oral antipsychotics (OAPs) to PP1M have not been reliably assessed. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of PP1M in the management of patients with schizophrenia with a prior history of OAP use.
METHODS
We conducted a systematic search in PubMed, EMBASE, and the Cochrane Library on 19 July 2022 to identify eligible studies. All studies that examined the effectiveness and safety of switching from OAPs to PP1M in patients with schizophrenia were included. The primary outcomes were relapse rate, hospitalisation rate, and the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score. The secondary outcomes included the changed number of inpatient visits, changed length of stay hospitalisation, change from baseline in the Clinical Global Impressions-Severity (CGI-S) score and the personal and social performance (PSP) total score, response rate, proportion of treatment discontinuation, and adverse events. We included randomised-controlled trials (RCTs), single-arm studies, and observational studies. Case reports, case series, and reviews were excluded. The quality assessment of included studies was performed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB2), the 9-point Newcastle-Ottawa Scale (NOS) instrument for non-randomised studies and cohort studies, and the 12-item National Institutes of Health (NIH) quality assessment tool for before-after (Pre-Post) study without control group. Follow-up times were reported as short- (≤ 13 weeks), medium- (14-26 weeks), and long term (≥ 27 weeks). Data were pooled using meta-analysis.
RESULTS
Fifteen studies with a total of 4740 patients were included. The long-term relapse rates and hospitalisation rates were 12% (95% CI 0.07-0.18) and 18% (95% CI 0.15-0.20), respectively. The short-, medium-, and long-term change in PANSS total score was - 21.69 (95% CI - 30.02 to -13.36), - 14.98 (95% CI - 21.45 to - 8.51) and - 17.88 (95% CI - 31.94 to -3.82), respectively. Approximately 50% of patients reported at least a 30% reduction in the PANSS score at the short-term follow-up. Improvements in CGI-S and PSP score were observed during various periods. There was a reduction in the length of stay hospitalisation and the number of inpatient visits at the medium- and long-term follow-ups. Low discontinuation and adverse event rates were reported.
CONCLUSION
Based on our findings, this study may support the efficacy and safety of switching from OAPs to PP1M for the treatment of patients with schizophrenia. Future large-scale studies are warranted to confirm our findings.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Schizophrenia; Administration, Oral; Recurrence; Chronic Disease
PubMed: 37490267
DOI: 10.1007/s40263-023-01028-1 -
Scientific Reports Nov 2023Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in augmentation with selective serotonin reuptake inhibitors (SSRIs) in the treatment of moderate to severe obsessive-compulsive disorder: a systematic review and meta-analysis of randomized clinical trials.
Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its pharmacological treatment. About 40-60% of the cases are treatment-refractory, and this makes searching for second-line treatment necessary. 5-Hydroxytryptamine-3 (5-HT3) antagonists are among the many medications that have been used in augmentation with SSRIs. In this systematic review and meta-analysis, we assessed the efficacy and safety of 5-HT3 receptor antagonists in augmentation with SSRIs in treating moderate to severe OCD. We searched PubMed, Web of Science, Scopus, Cochrane library, and Google Scholar for relevant trials published up to December 2022. The effect size was the mean difference in Yale-Brown obsessive compulsive scale (Y-BOCS) scores before and after receiving 5-HT3 receptor antagonist drugs in augmentation with SSRIs in moderate to severe OCD patients. We included 6 randomized-controlled trails (RCTs) with 334 patients assessing the effect of the augmentation of SSRIs with ondansetron, granisetron, and tropisetron on treating moderate to severe OCD. Our results were in favor of the experimental group in total (Z = 8.37, P < 0.00001), in the compulsion subgroup (Z = 5.22, P < 0.00001), and in the obsession subgroup (Z = 8.33, P < 0.00001). They are well-tolerated, and have mild side effects and do not result in withdrawal. Augmentation of 5-HT3 antagonists with SSRIs can be beneficial in treating moderate to severe OCD. Further multi-center trials under adequate conditions in longer periods are needed to help come up with a comprehensive action plan.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Serotonin; Receptors, Serotonin, 5-HT3; Treatment Outcome; Randomized Controlled Trials as Topic; Obsessive-Compulsive Disorder; Drug Therapy, Combination
PubMed: 38012263
DOI: 10.1038/s41598-023-47931-x -
Journal of Psychiatric Research Nov 2023The benefits of serotonin 3 receptor antagonists (5-HT3R-As) in obsessive-compulsive disorder (OCD) treatment remain unclear. Thus, this study aimed to perform a... (Meta-Analysis)
Meta-Analysis
The benefits of serotonin 3 receptor antagonists (5-HT3R-As) in obsessive-compulsive disorder (OCD) treatment remain unclear. Thus, this study aimed to perform a systematic review and a random-effects meta-analysis, including double-blind, randomized, placebo-controlled trials (DBRPCTs). The outcomes include the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score (primary), Y-BOCS obsession subscale score, Y-BOCS compulsive subscale score, treatment response, remission rate, all-cause discontinuation, and incidence of individual adverse events (nervousness/restlessness/anxiety, insomnia, headache, dizziness/lightheadedness, decreased appetite, constipation, nausea/vomiting, diarrhea, dry mouth, sweating/increased perspiration, itching/pruritus, tremor, and sexual dysfunction/decreased libido). The mean differences (MD) for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals (CIs) were calculated. Our study included 10 DBRPCTs (n = 628). Pooled 5-HT3R-As outperformed placebo regarding Y-BOCS total score (MD = -5.08, 95% CI = -7.04, -3.12, N = 9, n = 560), Y-BOCS obsession subscale score, Y-BOCS compulsive subscale score, treatment response, and remission rate. Individually, all 5-HT3R-As outperformed placebo regarding Y-BOCS total score (granisetron: MD = -5.59, 95% CI = -8.79, -2.39, N = 3, n = 178, ondansetron: MD = -5.72, 95% CI = -8.06, -3.37, N = 6, n = 331, tropisetron: MD = -2.87, 95% CI = -5.19, -0.550, N = 1, n = 96). However, all-cause discontinuation and incidence of individual adverse events between pooled 5-HT3R-As and placebo were not significantly different. In conclusion, our meta-analysis suggested 5-HT3R-As as efficacious for symptom improvement in individuals with OCD. However, the number of individuals included in each study was small; thus, a replication randomized trial of 5-HT3R-As should be conducted using a larger sample size.
Topics: Humans; Obsessive-Compulsive Disorder; Serotonin 5-HT3 Receptor Antagonists; Randomized Controlled Trials as Topic; Outcome Assessment, Health Care
PubMed: 37866327
DOI: 10.1016/j.jpsychires.2023.10.029 -
The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review.Journal of Psychopharmacology (Oxford,... Dec 2023Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this... (Review)
Review
BACKGROUND
Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this systematic review, we aimed to review the relationship between the 5-HT7 receptor system and mood and anxiety disorders, and to explore the pharmacology and therapeutic potential of medications that target the 5-HT7 receptor for their treatment.
METHODS
Medline, Cochrane Library, EMBASE, PsycINFO databases, the National Institute of Health website Clinicaltrials.gov, controlled-trials.com, and relevant grey literature were used to search for original research articles, and reference lists of included articles were then hand searched.
RESULTS
Sixty-four studies were included in the review: 52 animal studies and 12 human studies. Studies used a variety of preclinical paradigms and questionnaires to assess change in mood, and few studies examined sleep or cognition. Forty-four out of 47 (44/47) preclinical 5-HT7 modulation studies identified potential antidepressant effects and 20/23 studies identified potential anxiolytic effects. In clinical studies, 5/7 identified potential antidepressant effects in major depressive disorder, 1/2 identified potential anxiolytic effects in generalized anxiety disorder, and 3/3 identified potential antidepressant effects in bipolar disorders.
CONCLUSION
While there is some evidence that the 5-HT7 receptor system may be a potential target for treating mood and anxiety disorders, many agents included in the review also bind to other receptors. Further research is needed using drugs that bind specifically to 5-HT7 receptors to examine treatment proof of concept further.
Topics: Animals; Humans; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major
PubMed: 37994803
DOI: 10.1177/02698811231211228 -
Journal of Psychiatric Research Jun 2024Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and... (Review)
Review
Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and risperidone are two commonly prescribed antipsychotics, metabolized primarily through CYP2D6. Here, we aimed to provide an overview of the effect of CYP2C19 and CYP2D6 on side-effects of aripiprazole and risperidone, and expand on existing literature by critically examining methodological issues associated with pharmacogenetic studies. A PRISMA compliant search of six electronic databases (Pubmed, PsychInfo, Embase, Central, Web of Science, and Google Scholar) identified pharmacogenetic studies on aripiprazole and risperidone. 2007 publications were first identified, of which 34 were included. Quality of literature was estimated using Newcastle-Ottowa Quality Assessment Scale (NOS) and revised Cochrane Risk of Bias tool. The average NOS score was 5.8 (range: 3-8) for risperidone literature and 5 for aripiprazole (range: 4-6). All RCTs on aripiprazole were rated as high risk of bias, and four out of six for risperidone literature. Study populations ranged from healthy volunteers to inpatient individuals in psychiatric units and included adult and pediatric samples. All n = 34 studies examined CYP2D6. Only one study genotyped for CYP2C19 and found a positive association with neurological side-effects of risperidone. Most studies did not report any relationship between CYP2D6 and any side-effect outcome. Heterogeneity between and within studies limited the ability to synthesize data and draw definitive conclusions. Studies lacked statistical power due to small sample size, selective genotyping methods, and study design. Large-scale randomized trials with multiple measurements, providing robust evidence on this topic, are suggested.
Topics: Humans; Aripiprazole; Cytochrome P-450 CYP2D6; Risperidone; Cytochrome P-450 CYP2C19; Antipsychotic Agents
PubMed: 38631139
DOI: 10.1016/j.jpsychires.2024.04.001 -
Acta Psychiatrica Scandinavica Dec 2023Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging...
BACKGROUND
Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging evidence suggests the clinical utility of long-acting injections (LAI) in such clinical scenarios. In this study, we aimed to describe clozapine augmentation with LAIs in an inner London hospital and explore the literature on the clinical effectiveness of this treatment modality.
METHODS
Patients prescribed clozapine, who were commenced on a LAI between 2007 and 2023 by the United Kingdom's largest mental health trust, were identified from electronic patient records. First, routine clinical data were used to describe the use, effectiveness, and safety of this augmentation strategy. Second, we conducted a literature search up to 1st June 2023 to identify published studies describing clinical outcomes after clozapine augmentation with a LAI. Clinical outcomes were collated and presented in a table, including hospitalisation rates and quantitative clinical assessments using validated scales.
RESULTS
Of the 1248 patients prescribed clozapine in SLaM, three patients (0.2%) received augmentation with the following LAIs: olanzapine embonate, paliperidone palmitate and pipotiazine palmitate. This treatment strategy was clinically effective and generally well tolerated in all three cases. Twelve published studies between 2010 and 2022 were included in the review. Eight distinct LAIs were reported (4 first and 4 second generation antipsychotics), with risperidone and paliperidone most widely studied. All the identified studies were observational including mirror-image studies, case series and case reports. Duration of follow up varied from 3 months to 3 years. There was evidence that the use of LAIs with clozapine can significantly reduce clinical symptoms, hospitalisation rates and bed days. No serious adverse effects were reported.
CONCLUSION
This preliminary evidence suggests clinical utility of LAIs in alleviating residual symptoms and subsequently reducing hospitalisation rates in patients optimised on clozapine treatment. The current study warrants further investigations including a randomised controlled study to establish the clinical efficacy, tolerability, and place in therapy of this treatment modality.
Topics: Humans; Antipsychotic Agents; Clozapine; Schizophrenia; Risperidone; Paliperidone Palmitate; Delayed-Action Preparations
PubMed: 37899506
DOI: 10.1111/acps.13621 -
British Journal of Anaesthesia Sep 2023Neuraxial opioids provide effective analgesia for Caesarean delivery, however, pruritus can be a troubling side-effect. Effective agents to prevent pruritus are needed.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuraxial opioids provide effective analgesia for Caesarean delivery, however, pruritus can be a troubling side-effect. Effective agents to prevent pruritus are needed. Our objective was to perform an updated systematic review and network meta-analysis to provide clinicians with a comparison of relative efficacy of available interventions to reduce the incidence of pruritus, induced by either intrathecal or epidural single-shot morphine, in women undergoing Caesarean delivery.
METHODS
Databases systematically searched (up to January 2022) included PubMed MEDLINE, Web of Science, EBSCO CINAHL, Embase, LILACS, and two Cochrane databases. We included randomised, controlled trials involving adult female patients undergoing Caesarean delivery. We pooled trials comparing interventions used for preventing pruritus after Caesarean delivery and performed a Bayesian model network meta-analysis.
RESULTS
The final primary network included data from comparisons of 14 distinct interventions (including placebo) used to reduce the incidence of pruritus in 6185 participants. We judged five interventions to be 'definitely superior' to placebo: propofol, opioid agonist-antagonists (neuraxial), opioid antagonists, opioid agonist-antagonists (systemic), and serotonin antagonists. For the network evaluating the incidence of severe pruritus (warranting additional therapeutic treatment of pruritus), data were available for 14 interventions (including placebo) in 4489 patients. For this outcome, we judged three interventions to be 'definitely superior' to placebo: dopamine antagonists (neuraxial) and systemic and neuraxial opioid agonist-antagonists.
CONCLUSION
Our analysis found several interventions to be effective in reducing the incidence of pruritus. Although sub-hypnotic doses of propofol appear to have an antipruritic effect, replication of this finding and further investigation of optimal dosing are warranted.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO (CRD42022367058).
Topics: Pregnancy; Adult; Humans; Female; Morphine; Analgesics, Opioid; Propofol; Network Meta-Analysis; Bayes Theorem; Cesarean Section; Pruritus
PubMed: 37455197
DOI: 10.1016/j.bja.2023.05.028 -
Schizophrenia Research Jun 2024Although uncommon, the risk of aggression and violence is greater in people with schizophrenia than in the general population. Clozapine is the "gold standard"... (Review)
Review
Although uncommon, the risk of aggression and violence is greater in people with schizophrenia than in the general population. Clozapine is the "gold standard" pharmacologic treatment for the management of persistent agitation and aggression in people with schizophrenia and is consistently recommended by guidelines and reviews for this purpose. Although clozapine is indicated for treatment-resistant schizophrenia based on its superior efficacy, studies have proposed that clozapine may have specific properties that ameliorate aggression and hostility that are distinct from its antipsychotic effects. A literature review was conducted on June 3, 2023, using the US National Library of Medicine's PubMed resource to identify articles focusing on clozapine for the treatment of aggression, violence, and/or hostility in patients with schizophrenia or schizoaffective disorder. The majority of evidence, including from randomized control trials, supports the utilization of clozapine as maintenance treatment for persistent aggressive behavior in patients with schizophrenia, and supports that its anti-aggressive effects may be independent from its antipsychotic properties (e.g. - treatment of hallucinations and delusions). Future randomized control studies evaluating clozapine and clozapine serum levels with aggression as the primary outcome would be of benefit.
Topics: Humans; Clozapine; Aggression; Psychotic Disorders; Schizophrenia; Violence; Antipsychotic Agents
PubMed: 38290941
DOI: 10.1016/j.schres.2023.11.008 -
Journal of Managed Care & Specialty... Feb 2024Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT)... (Review)
Review
A systematic review of the real-world effectiveness and economic and humanistic outcomes of selected oral antipsychotics among patients with schizophrenia in the United States: Updating the evidence and gaps.
BACKGROUND
Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT) remains the cornerstone for managing schizophrenia. However, nonadherence and high treatment failure lead to increased disease burden and medical spending. Cost-effective management of schizophrenia requires understanding the value of current therapies to facilitate better planning of management policies while addressing unmet needs.
OBJECTIVE
To review existing evidence and gaps regarding real-world effectiveness and economic and humanistic outcomes of OATs, including asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine.
METHODS
We conducted a literature search using PubMed, American Psychological Association PsycINFO (EBSCOhost), and the Cumulative Index of Nursing and Allied Health Literature from January 2010 to March 2022 as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language articles describing adults with schizophrenia receiving at least 1 of the selected OATs and reporting real-world effectiveness, direct or indirect costs, humanistic outcomes, behavioral outcomes, adherence/persistence patterns, or product switching were identified.
RESULTS
We identified 25 studies from a total of 24,190 articles. Real-world effectiveness, cost, and adherence/persistence outcomes were reported for most OATs that were selected. Humanistic outcomes and product switching were reported only for lurasidone. Behavioral outcomes (eg, interpersonal relations and suicide ideation) were not reported for any OAT. The key economic outcomes across studies were incremental cost-effectiveness ratios, cost per quality-adjusted life-years, and health care costs. In studies that compared long-acting injectables (LAIs) with OATs, LAIs had a higher pharmacy and lower medical costs, while total health care cost was similar between LAIs and OATs. Indirect costs associated with presenteeism, absenteeism, or work productivity were not reported for any of the selected OATs. Overall, patients had poor adherence to OATs, ranging between 20% and 61% across studies. Product switching did not impact the all-cause health care costs before and after treatment.
CONCLUSIONS
Our findings showed considerable gaps exist for evidence on behavioral outcomes, humanistic outcomes, medication switching, and adherence/persistence across OATs. Our findings also suggest an unmet need regarding treatment nonadherence and lack of persistence among patients receiving OATs. We identified a need for research addressing OATs' behavioral and humanistic outcomes and evaluating the impact of product switching in adults with schizophrenia in the United States, which could assist clinicians in promoting patient-centered care and help payers understand the total value of new antipsychotic drugs.
Topics: Adult; Humans; United States; Antipsychotic Agents; Schizophrenia; Lurasidone Hydrochloride; Paliperidone Palmitate; Quetiapine Fumarate
PubMed: 38308625
DOI: 10.18553/jmcp.2024.30.2.183