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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 -
The Cochrane Database of Systematic... Nov 2018Delirium is defined as a disturbance in attention, awareness and cognition with reduced ability to direct, focus, sustain and shift attention, and reduced orientation to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Delirium is defined as a disturbance in attention, awareness and cognition with reduced ability to direct, focus, sustain and shift attention, and reduced orientation to the environment. Critically ill patients in the intensive care unit (ICU) frequently develop ICU delirium. It can profoundly affect both them and their families because it is associated with increased mortality, longer duration of mechanical ventilation, longer hospital and ICU stay and long-term cognitive impairment. It also results in increased costs for society.
OBJECTIVES
To assess existing evidence for the effect of preventive interventions on ICU delirium, in-hospital mortality, the number of delirium- and coma-free days, ventilator-free days, length of stay in the ICU and cognitive impairment.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, Latin American Caribbean Health Sciences Literature, CINAHL from 1980 to 11 April 2018 without any language limits. We adapted the MEDLINE search for searching the other databases. Furthermore, we checked references, searched citations and contacted study authors to identify additional studies. We also checked the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and CenterWatch.com (all on 24 April 2018).
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of adult medical or surgical ICU patients receiving any intervention for preventing ICU delirium. The control could be standard ICU care, placebo or both. We assessed the quality of evidence with GRADE.
DATA COLLECTION AND ANALYSIS
We checked titles and abstracts to exclude obviously irrelevant studies and obtained full reports on potentially relevant ones. Two review authors independently extracted data. If possible we conducted meta-analyses, otherwise we synthesized data narratively.
MAIN RESULTS
The electronic search yielded 8746 records. We included 12 RCTs (3885 participants) comparing usual care with the following interventions: commonly used drugs (four studies); sedation regimens (four studies); physical therapy or cognitive therapy, or both (one study); environmental interventions (two studies); and preventive nursing care (one study). We found 15 ongoing studies and five studies awaiting classification. The participants were 48 to 70 years old; 48% to 74% were male; the mean acute physiology and chronic health evaluation (APACHE II) score was 14 to 28 (range 0 to 71; higher scores correspond to more severe disease and a higher risk of death). With the exception of one study, all participants were mechanically ventilated in medical or surgical ICUs or mixed. The studies were overall at low risk of bias. Six studies were at high risk of detection bias due to lack of blinding of outcome assessors. We report results for the two most commonly explored approaches to delirium prevention: pharmacologic and a non-pharmacologic intervention.Haloperidol versus placebo (two RCTs, 1580 participants)The event rate of ICU delirium was measured in one study including 1439 participants. No difference was identified between groups, (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.87 to 1.17) (moderate-quality evidence). Haloperidol versus placebo neither reduced or increased in-hospital mortality, (RR 0.98, 95% CI 0.80 to 1.22; 2 studies; 1580 participants (moderate-quality evidence)); the number of delirium- and coma-free days, (mean difference (MD) -0.60, 95% CI -1.37 to 0.17; 2 studies, 1580 participants (moderate-quality of evidence)); number of ventilator-free days (mean 23.8 (MD -0.30, 95% CI -0.93 to 0.33) 1 study; 1439 participants, (high-quality evidence)); length of ICU stay, (MD 0.18, 95% CI -0.60 to 0.97); 2 studies, 1580 participants; high-quality evidence). None of the studies measured cognitive impairment. In one study there were three serious adverse events in the intervention group and five in the placebo group; in the other there were five serious adverse events and three patients died, one in each group. None of the serious adverse events were judged to be related to interventions received (moderate-quality evidence).Physical and cognitive therapy interventions (one study, 65 participants)The study did not measure the event rate of ICU delirium. A physical and cognitive therapy intervention versus standard care neither reduced nor increased in-hospital mortality, (RR 0.94, 95% CI 0.40 to 2.20, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of delirium- and coma-free days, (MD -2.8, 95% CI -10.1 to 4.6, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of ventilator-free days (within the first 28/30 days) was median 27.4 (IQR 0 to 29.2) and 25 (IQR 0 to 28.9); 1 study, 65 participants; very low-quality evidence, length of ICU stay, (MD 1.23, 95% CI -0.68 to 3.14, I² = 0; 1 study, 65 participants; very low-quality evidence); cognitive impairment measured by the MMSE: Mini-Mental State Examination with higher scores indicating better function, (MD 0.97, 95% CI -0.19 to 2.13, I² = 0; 1 study, 30 participants; very low-quality evidence); or measured by the Dysexecutive questionnaire (DEX) with lower scores indicating better function (MD -8.76, 95% CI -19.06 to 1.54, I² = 0; 1 study, 30 participants; very low-quality evidence). One patient experienced acute back pain accompanied by hypotensive urgency during physical therapy.
AUTHORS' CONCLUSIONS
There is probably little or no difference between haloperidol and placebo for preventing ICU delirium but further studies are needed to increase our confidence in the findings. There is insufficient evidence to determine the effects of physical and cognitive intervention on delirium. The effects of other pharmacological interventions, sedation, environmental, and preventive nursing interventions are unclear and warrant further investigation in large multicentre studies. Five studies are awaiting classification and we identified 15 ongoing studies, evaluating pharmacological interventions, sedation regimens, physical and occupational therapy combined or separately, and environmental interventions, that may alter the conclusions of the review in future.
Topics: Aged; Antipsychotic Agents; Cognition Disorders; Cognitive Behavioral Therapy; Delirium; Female; Haloperidol; Humans; Intensive Care Units; Male; Middle Aged; Physical Therapy Modalities; Randomized Controlled Trials as Topic
PubMed: 30484283
DOI: 10.1002/14651858.CD009783.pub2 -
The Cochrane Database of Systematic... Jun 2018Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence.
OBJECTIVES
Our primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects.
SEARCH METHODS
We searched MEDLINE, Embase, Cochrane EBM Reviews, CINAHL, Thomson Reuters Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) from their respective inception dates until July 2017. We also searched the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database, Web of Science ISI Proceedings, and other grey literature.
SELECTION CRITERIA
We included randomised and quasi-randomised trials comparing 1) antipsychotics to nonantipsychotics or placebo and 2) typical to atypical antipsychotics for the treatment of delirium in adult hospitalised (but not critically ill) patients.
DATA COLLECTION AND ANALYSIS
We examined titles and abstracts of identified studies to determine eligibility. We extracted data independently in duplicate. Disagreements were settled by further discussion and consensus. We used risk ratios (RR) with 95% confidence intervals (CI) as a measure of treatment effect for dichotomous outcomes, and between-group standardised mean differences (SMD) with 95% CI for continuous outcomes.
MAIN RESULTS
We included nine trials that recruited 727 participants. Four of the nine trials included a comparison of an antipsychotic to a nonantipsychotic drug or placebo and seven included a comparison of a typical to an atypical antipsychotic. The study populations included hospitalised medical, surgical, and palliative patients.No trial reported on duration of delirium. Antipsychotic treatment did not reduce delirium severity compared to nonantipsychotic drugs (standard mean difference (SMD) -1.08, 95% CI -2.55 to 0.39; four studies; 494 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (SMD -0.17, 95% CI -0.37 to 0.02; seven studies; 542 participants; low-quality evidence). There was no evidence antipsychotics resolved delirium symptoms compared to nonantipsychotic drug regimens (RR 0.95, 95% CI 0.30 to 2.98; three studies; 247 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (RR 1.10, 95% CI 0.79 to 1.52; five studies; 349 participants; low-quality evidence). The pooled results indicated that antipsychotics did not alter mortality compared to nonantipsychotic regimens (RR 1.29, 95% CI 0.73 to 2.27; three studies; 319 participants; low-quality evidence) nor was there a difference between typical and atypical antipsychotics (RR 1.71, 95% CI 0.82 to 3.35; four studies; 342 participants; low-quality evidence).No trial reported on hospital length of stay, hospital discharge disposition, or health-related quality of life. Adverse event reporting was limited and measured with inconsistent methods; in those reporting events, the number of events were low. No trial reported on physical restraint use, long-term cognitive outcomes, cerebrovascular events, or QTc prolongation (i.e. increased time in the heart's electrical cycle). Only one trial reported on arrhythmias and seizures, with no difference between typical or atypical antipsychotics. We found antipsychotics did not have a higher risk of extrapyramidal symptoms (EPS) compared to nonantipsychotic drugs (RR 1.70, 95% CI 0.04 to 65.57; three studies; 247 participants; very-low quality evidence); pooled results showed no increased risk of EPS with typical antipsychotics compared to atypical antipsychotics (RR 12.16, 95% CI 0.55 to 269.52; two studies; 198 participants; very low-quality evidence).
AUTHORS' CONCLUSIONS
There were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Haloperidol; Hospitalization; Humans; Male; Olanzapine; Placebo Effect; Randomized Controlled Trials as Topic; Risperidone
PubMed: 29920656
DOI: 10.1002/14651858.CD005594.pub3 -
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 -
Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y -
The American Journal of Emergency... Jan 2022Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most optimal agent(s) for rapid tranquilization of the severely agitated patient in the emergency department (ED).
METHODS
The protocol for systematic review was registered (PROSPERO; CRD42020212534). We searched MEDLINE, Embase, PsycINFO, and Cochrane Database/CENTRAL from inception to June 2, 2021. We limited studies to randomized controlled trials that enrolled adult ED patients with severe agitation and compared drugs for rapid tranquilization. Predetermined outcomes were: 1) Adequate sedation within 30 min (effectiveness), 2) Immediate, serious adverse event - cardiac arrest, ventricular tachydysrhythmia, endotracheal intubation, laryngospasm, hypoxemia, hypotension (safety), and 3) Time to adequate sedation (effect onset). We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2 tool. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effects model and vague prior distribution to calculate odds ratios with 95% credible intervals for dichotomous outcomes and frequentist NMA to calculate mean differences with 95% confidence intervals for continuous outcomes. We assessed confidence in results using CINeMA. We used surface under the cumulative ranking (SUCRA) curves to rank agent(s) for each outcome.
RESULTS
Eleven studies provided data for effectiveness (1142 patients) and safety (1147 patients). Data was insufficient for effect onset. The NMA found that ketamine (SUCRA = 93.0%) is most likely to have superior effectiveness; droperidol-midazolam (SUCRA = 78.8%) is most likely to be safest. There are concerns with study quality and imprecision. Quality of the point estimates varied for effectiveness but mostly rated "very low" for safety.
CONCLUSIONS
Available evidence suggests that ketamine and droperidol have intermediate effectiveness for rapid tranquilization of the severely agitated patient in the ED. There is insufficient evidence to definitively determine which agent(s) may be safest or fastest-acting. Further, direct-comparison study of ketamine and droperidol is recommended.
Topics: Adult; Droperidol; Emergence Delirium; Emergency Service, Hospital; Humans; Ketamine; Network Meta-Analysis; Psychomotor Agitation; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 34823192
DOI: 10.1016/j.ajem.2021.11.011 -
Brain and Behavior Jun 2023Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines... (Review)
Review
INTRODUCTION
Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines for diagnosis and treatment. Resulting from Group A Beta-Hemolytic Streptococcus infection, SC presents various symptoms. This review aims to collect and evaluate available data on SC management to propose a cohesive treatment plan.
METHODS
We searched PubMed, the Cochrane Library, Google Scholar, and ClinicalTrials.gov for literature on SC management from inception until 24th July 2022. Studies were screened by titles and abstracts. Cochrane Collaboration's Risk of Bias tool (RoB-1) assessed Randomized Controlled Trials, while the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool evaluated nonrandomized studies.
RESULTS
The review includes 11 articles assessing 579 patients. Excluding one study with 229 patients, of the remaining 550 patients, 338 (61.5%) were females. Treatments used were dopamine antagonists in 118 patients, antiepileptics in 198, corticosteroids in 134, IVIG in 7, and PE in 8 patients. Dopamine antagonists, particularly haloperidol, were the primary treatment choice, while valproic acid (VPA) was favored among antiepileptics. Prednisolone, a corticosteroid, showed promising results with weight gain as the only side-effect. Our review emphasizes the importance of immunomodulators in SC, contrasting previous literature.
CONCLUSION
Despite limitations, dopamine antagonists can serve as first-line agents in SC management, followed by antiepileptics. The role of immunomodulators warrants further investigation for conclusive recommendations.
Topics: Female; Humans; Male; Chorea; Anticonvulsants; Valproic Acid; Haloperidol; Dopamine Antagonists
PubMed: 37150977
DOI: 10.1002/brb3.3035 -
The Cochrane Database of Systematic... Mar 2016Cocaine dependence is a public health problem characterised by recidivism and a host of medical and psychosocial complications. Cocaine dependence remains a disorder for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cocaine dependence is a public health problem characterised by recidivism and a host of medical and psychosocial complications. Cocaine dependence remains a disorder for which no pharmacological treatment of proven efficacy exists.
OBJECTIVES
To evaluate the efficacy and the acceptability of antipsychotic medications for cocaine dependence.
SEARCH METHODS
This review is an update of a previous Cochrane review published in 2007. We searched up to 15 July 2015 in Cochrane Drugs and Alcohol Group Specialised Register (searched in CRSLive); the Cochrane Library (including the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE)); PubMed; EMBASE; CINAHL and Web of Science. All searches included non-English language literature.
SELECTION CRITERIA
All randomised controlled trials and controlled clinical trials with focus on the use of any antipsychotic medication for the treatment of cocaine dependence.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 14 studies (719 participants). The antipsychotic drugs studied were risperidone, olanzapine, quetiapine, lamotrigine, aripiprazol, haloperidol and reserpine. Comparing any antipsychotic drugs versus placebo, we found that antipsychotics reduced dropout: eight studies, 397 participants, risk ratio (RR) 0.75 (95% confidence interval (CI) 0.57 to 0.97), moderate quality of evidence. We found no significant differences for any of the other primary outcomes considered: number of participants using cocaine during the treatment, two studies, 91 participants: RR 1.02 (95% CI 0.65 to 1.62); continuous abstinence, three studies, 139 participants: RR 1.30 (95% CI 0.73 to 2.32); side effects, six studies, 291 participants: RR 1.01 (95% CI 0.93 to 1.10); and craving, four studies, 240 participants: RR 0.13 (-1.08 to 1.35). For all of these comparisons we rated the quality of evidence as low.Comparisons of single drug versus placebo or versus another drug are conducted in few trials with small sample sizes, limiting the reliability of the results. Among these comparisons, only quetiapine seemed to outperform placebo in reducing cocaine use, measured by grams per week: mean difference (MD) -0.54 (95% CI -0.92 to -0.16), by US dollars spent per week: MD -53.80 (95% CI -97.85 to -9.75), and by craving: MD -1.23 (95% CI -2.19 to -0.27), but results came from one study with 60 participants.The major limitations of the studies were the high risk of attrition bias (40% of the included studies) and low quality of reporting, mainly for the risk of selection bias, performance and detection bias, that we rated as being at unclear risk for 75% to 80% of the studies. Furthermore, most of the included studies did not report results on important outcomes such as side effects, or use of cocaine during treatment and craving, which prevented the possibility of including them in statistical synthesis.
AUTHORS' CONCLUSIONS
At present, there is no evidence supporting the clinical use of antipsychotic medications in the treatment of cocaine dependence, although results come from only 14 trials, with small sample sizes and moderate to low quality of evidence.
Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cocaine-Related Disorders; Haloperidol; Humans; Lamotrigine; Olanzapine; Patient Dropouts; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Reserpine; Risperidone; Triazines
PubMed: 26992929
DOI: 10.1002/14651858.CD006306.pub3 -
The Cochrane Database of Systematic... Nov 2016Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically... (Review)
Review
BACKGROUND
Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression.
OBJECTIVES
To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015).
SELECTION CRITERIA
We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression.
DATA COLLECTION AND ANALYSIS
One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study (1 RCT, n=110, RR 1.37, CI 0.84 to 2.24, low-quality evidence). Although there were some data for the outcomes listed above, there were no data on most of the binary outcomes and none on service outcomes (use of hospital/police), satisfaction with treatment, acceptance of treatment, quality of life or economics.
AUTHORS' CONCLUSIONS
Only one study could be included and most data were heavily skewed, almost impossible to interpret and oflow quality. There were also some limitations in the study design with unclear description of allocation concealment and high risk of bias for selective reporting, so no firm conclusions can be made. This review shows how trials in this group of people are possible - albeit difficult. Further relevant trials are needed to evaluate use of haloperidol in treatment of long-term/persistent aggression in people living with psychosis.
Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Haloperidol; Humans; Middle Aged; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 27889922
DOI: 10.1002/14651858.CD009830.pub2 -
The Cochrane Database of Systematic... Apr 2005Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece, Italy, the Netherlands and the UK. Benperidol is a butyrophenone antipsychotic, with the highest neuroleptic potency in terms of D2 receptor blockade. Those taking it are therefore reputed to be at high risk of extrapyramidal side effects, but benperidol's unusual profile may render it valuable to subgroups of people with schizophrenia.
OBJECTIVES
To examine the clinical effects and safety of benperidol for those with schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's register (November 2004) for this update.
SELECTION CRITERIA
We included all randomised controlled trials that compared benperidol with other treatments for people with schizophrenia, or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We reliably selected studies, quality rated them and extracted data. We independently extracted data but excluded data if loss to follow up was greater than 50%. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis.
MAIN RESULTS
The update yielded no further studies for inclusion in the review. We identified only one unpublished poorly randomised controlled trial (N=40, duration 30 days, comparison perphenazine). Although benperidol was inferior to perphenazine (1 RCT, N=40, global state no better or worse RR 8.0 CI 2.1 to 30, NNH 1.4 CI 1 to 2) poor reporting suggests that an overestimate of effect is likely. It was not possible to report other outcomes.
AUTHORS' CONCLUSIONS
Currently, there are insufficient data from randomised trials to assess the clinical effects of benperidol. This compound merits further research interest.
Topics: Antipsychotic Agents; Benperidol; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 15846648
DOI: 10.1002/14651858.CD003083.pub2