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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 -
Pharmacopsychiatry Sep 2022Early-onset schizophrenia (EOS) - onset before age 18 - is linked with great disease burden and disability. Decision-making for EOS pharmacological treatment may be... (Review)
Review
Early-onset schizophrenia (EOS) - onset before age 18 - is linked with great disease burden and disability. Decision-making for EOS pharmacological treatment may be challenging due to conflicting information from evidence and guidelines and unidentified care needs may remain unmet.We searched for systematic reviews, meta-analyses and umbrella reviews of EOS pharmacological treatment published in PubMed over the past 10 years and selected five clinical guidelines from Europe, North-America and Australia. Based on predefined outcomes, we critically compared the evidence supporting EOS-approved drugs in Europe and/or North-America with guidelines recommendations. We also evaluated the coverage of these outcomes to identify unmet needs.One systematic review, nine meta-analyses and two umbrella reviews (k=203 trials, N=81,289 participants, including duplicated samples across selected articles) were retrieved. Evidence supported the efficacy of aripiprazole, clozapine, haloperidol, lurasidone, molindone, olanzapine, quetiapine, risperidone and paliperidone in EOS, all of which obtained approval for EOS either in Europe and/or in North-America. Cognition, functioning and quality of life, suicidal behaviour and mortality and services utilisation and cost-effectiveness were poorly covered/uncovered.Among the antipsychotics approved for EOS, aripiprazole, lurasidone, molindone, risperidone, paliperidone and quetiapine emerged as efficacious and comparably safe options. Olanzapine is known for a high risk of weight gain and haloperidol for extrapyramidal side-effects. Treatment-resistant patients should be offered clozapine. Future long-term trials looking at cognition, functioning, quality of life, suicidal behaviour, mortality, services utilisation and cost-effectiveness are warranted. Closer multi-agency collaboration may bridge the gap between evidence, guidelines and approved drugs.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Haloperidol; Humans; Lurasidone Hydrochloride; Molindone; Olanzapine; Paliperidone Palmitate; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Systematic Reviews as Topic
PubMed: 35777418
DOI: 10.1055/a-1854-0185 -
Critical Care (London, England) Jun 2020Practice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness.... (Review)
Review
Practice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness. Dosing recommendations however are often based on strategies used in patients with normal body habitus. Recommendations specific to critically ill patients with extreme obesity are lacking. Nonetheless, clinicians must craft dosing regimens for this population. This paper is intended to help clinicians design initial dosing regimens for medications commonly used in the management of pain, agitation, and delirium in critically ill patients with extreme obesity. A detailed literature search was conducted with an emphasis on obesity, pharmacokinetics, and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided.
Topics: Analgesia; Analgesics, Non-Narcotic; Analgesics, Opioid; Benzodiazepines; Critical Illness; Deep Sedation; Delirium; Dexmedetomidine; Dose-Response Relationship, Drug; Etomidate; Haloperidol; Humans; Ketamine; Obesity; Pain Management; Quetiapine Fumarate
PubMed: 32513237
DOI: 10.1186/s13054-020-03040-z -
Annals of Internal Medicine Oct 2019Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are...
BACKGROUND
Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear.
PURPOSE
To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults.
DATA SOURCES
PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions.
STUDY SELECTION
Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms.
DATA EXTRACTION
One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers.
DATA SYNTHESIS
Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, with insufficient or no evidence for antipsychotics versus placebo. For direct comparisons of different second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for multiple other outcomes. There was little evidence demonstrating neurologic harms associated with short-term use of antipsychotics for treating delirium in adult inpatients, but potentially harmful cardiac effects tended to occur more frequently.
LIMITATIONS
Heterogeneity was present in terms of dose and administration route of antipsychotics, outcomes, and measurement instruments. There was insufficient or no evidence regarding multiple clinically important outcomes.
CONCLUSION
Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).
Topics: Antipsychotic Agents; Cognition; Delirium; Electrocardiography; Haloperidol; Heart; Hospital Mortality; Hospitalization; Humans; Length of Stay; Observational Studies as Topic; Palliative Care; Randomized Controlled Trials as Topic; Severity of Illness Index; Time Factors
PubMed: 31476770
DOI: 10.7326/M19-1860 -
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 -
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 -
Annals of Emergency Medicine Dec 2021We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation.
METHODS
We conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events.
RESULTS
Between June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]).
CONCLUSION
In ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.
Topics: Adult; Anesthetics, Dissociative; Canada; Female; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Ketamine; Male; Midazolam; Middle Aged; Psychomotor Agitation
PubMed: 34353650
DOI: 10.1016/j.annemergmed.2021.05.023