Haloperidol versus placebo for schizophrenia

Irving, Claire B; Adams, Clive E; Lawrie, Stephen M.

doi:10.1002/14651858.cd003082.pub2

Cited by 35 publications

(19 citation statements)

References 99 publications

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“…3,6,[15][16][17][18][19] We then searched the Cochrane Schizophrenia Group's specialised register (compiled by regular systematic searches of numerous databases, clinical trial registers, hand searches, and conference proceedings 20 available up to August, 2009), Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search terms were the generic names of the antipsychotic drugs as well as QT*, electrocard*, arrhythm*, ecg, and prolactin* (appendix pp 70-76).…”

Section: Search Strategy and Selection Criteriamentioning

confidence: 99%

Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis

Leucht

Cipriani

Spineli

et al. 2014

FOC

329

503

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Background: The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence.We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. Methods: We did a Bayesian-framework, multipletreatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. Findings: We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73-1·03; amisulpride 0·66, 0·53-0·78; olanzapine 0·59, 0·53-0·65; risperidone 0·56, 0·50-0·63; paliperidone 0·50, 0·39-0·60; zotepine 0·49, 0·31-0·66; haloperidol 0·45, 0·39-0·51; quetiapine 0·44, 0·35-0·52; aripiprazole 0·43, 0·34-0·52; sertindole 0·39, 0·26-0·52; ziprasidone 0·39, 0·30-0·49; chlorpromazine 0·38, 0·23-0·54; asenapine 0·38, 0·25-0·51; lurasidone 0·33, 0·21-0·45; and iloperidone 0·33, 0·22-0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from 20·09 for the best drug (haloperidol) to 20·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to 21·30 192 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to 20·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in metaregressions and sensitivit...

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Section: Search Strategy and Selection Criteriamentioning

confidence: 99%

Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis

Leucht

Cipriani

Spineli

et al. 2014

FOC

329

503

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“…The exact mechanism by which FGAs calm agitated patients is still an active area of research, but butyrophenones such as haloperidol and droperidol are potent antagonists at the D2 receptor (6,7). Although the D2 receptor, and in particular, the dopamine system, is not the only neurotransmitter implicated in psychosis, interruption of dopamine transmission nonetheless relieves psychotic symptoms in agitated patients (8)(9)(10)(11). Given this, FGAs such as haloperidol and droperidol have a long tradition of use in the ED, and may be safer than some second-generation antipsychotics in alcoholpositive patients (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, FGAs are known to cause both cardiac-related side effects and movement-related side effects such as tardive dyskinesia or dystonia (8,9,(17)(18)(19). Given the black box warning by the U.S. Food and Drug Administration (FDA) issued in 2001, the safety profile of droperidol remains a controversial topic in ED literature, with several studies suggesting its safety in everyday clinical use (19)(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

First-generation Antipsychotics Are Often Prescribed in the Emergency Department but Are Often Not Administered with Adjunctive Medications

Campillo¹,

Castillo

Vilke

et al. 2015

The Journal of Emergency Medicine

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, Abstract-Background: Although first-generation antipsychotics (FGAs) have long been used in the emergency department (ED) to treat acute agitation, little is known about how these medications are used in modern clinical practice. In particular, little work has been published about whether ED clinicians administer FGAs with adjunctive medications in accordance with expert guidelines or the prescribing practices of FGAs over time. Objectives: 1) To provide a comparison of the frequency with which FGAs are administered with adjunctive benzodiazepines or anticholinergic medications. 2) To analyze the prescribing trends for FGAs over time, particularly in the years after the U.S. Food and Drug Administration (FDA) black-box warning for droperidol. Methods: This is a structured review of a retrospective cohort of patients receiving haloperidol or droperidol in two EDs over a 7-year period. Results: Haloperidol or droperidol was administered on 2833 patient visits during the study period, with haloperidol being administered most often. Adjunctive medications are administered less than half of the time. The use of droperidol has remained relatively static, whereas the use of haloperidol has increased. Conclusions: First-generation antipsychotics are still widely utilized in the ED. When administered, these medications are used with adjunctive medications that may decrease side effects less than half of the time. Droperidol use has remained unchanged in the years after the FDA black-box warning, whereas use of haloperidol has continued to rise. Ó 2015 Elsevier Inc.

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“…Large effect sizes a Symptoms and relapse Combined pharmaceutical and psychosocial treatment programmes reduce symptoms (Bird et al 2010) and relapse rates (Alvarez-Jimenez et al 2011) in psychotic patients, and prevent transition to psychosis in people at ultra-high risk (Preti & Cella, 2010) Other outcomes Social skills training improves social interactions (Pfammatter et al 2006;Kurtz & Mueser, 2008) Medium effect sizes a Symptoms and relapse Antipsychotics improve overall symptoms and reduce relapse rates more than placebo (Mota et al 2002;Duggan et al 2005;Irving et al 2006;Adams et al 2007;Nussbaum & Stroup, 2008;Rattehalli et al 2010;Belgamwar & El-Sayeh, 2011;Leucht et al 2012a, b) Second-generation antipsychotics (particularly risperidone or olanzapine in various doses) have less extrapyramidal side effects than first-generation antipsychotics (particularly haloperidol in various doses) in patients with first-episode psychosis ( Small effect sizes a Symptoms and relapse Symptoms are reduced with adjunctive lithium (Leucht et al 2007a), NMDA receptor modulators (when not adjunctive to clozapine) (Singh & Singh, 2011) and electroconvulsive therapy (Tharyan & Adams, 2005) Other outcomes Processing speed, verbal fluency, learning, motor skills and global cognition ability are improved in patients taking second-generation antipsychotics compared with patients taking first-generation antipsychotics (Woodward et al 2005) Moderate-quality evidence Medium effect sizes a Symptoms and relapse Adjunctive non-steroidal anti-inflammatory drugs improve symptoms, particularly positive symptoms ) Clozapine improves symptoms more than typical antipsychotics for treatment-resistant patients, with fewer extrapyramidal effects (Chakos et al 2001;Moncrieff, 2003) Adjunctive Ginkgo biloba reduces negative symptoms, particularly in patients taking first-generation antipsychotics (Singh et al 2010a) Music therapy improves global state (Gold et al 2009;Mössler et al 2011) Results…”

Section: High-quality Evidencementioning

confidence: 99%

How much do we know about schizophrenia and how well do we know it? Evidence from the Schizophrenia Library

2014

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Haloperidol versus placebo for schizophrenia

Cited by 35 publications

References 99 publications

Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis

Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis

First-generation Antipsychotics Are Often Prescribed in the Emergency Department but Are Often Not Administered with Adjunctive Medications

How much do we know about schizophrenia and how well do we know it? Evidence from the Schizophrenia Library

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