A Review and Bayesian Meta-Analysis of Clinical Efficacy and Adverse Effects of 4 Atypical Neuroleptic Drugs Compared With Haloperidol and Placebo
The objective of the study was to examine the efficacy and the degree of adverse effects connected with atypical neuroleptic drugs and haloperidol by using a previously described Bayesian statistical method that includes both direct and indirect comparisons simultaneously.
The authors used the results of 30 double-blind, randomized studies including comparisons of 4 atypical neuroleptics and haloperidol, head-to-head or against placebo. We calculated the response ratios for drugs against placebo and thereafter the relative response ratios for one drug against another. With uniform priors, we calculated and ranked the posterior estimates of response ratios for antipsychotic effect, weight gain, and occurrence of extrapyramidal symptoms.
All second-generation neuroleptics analyzed are fairly effective with response ratios against placebo ranging between 1.55 (credibility interval, 1.36-1.76) and 1.99 (1.76-2.26), with clozapine being the most effective and aripiprazole the least effective among them. The risk of inducing weight gain is clearly very high for all 5 neuroleptic drugs compared with placebo with response ratios of 12.21 (10.22-15.05) for olanzapine and 11.28 (6.89-17.77) for clozapine. There is a clear increased risk of extrapyramidal adverse effects for haloperidol compared with placebo as the response ratio is 2.33 (2.03-2.49). The other drugs all have considerably less risk of extrapyramidal adverse effects.
The 4 second-generation neuroleptics included in our meta-analysis show only small differences in overall efficacy, with clozapine being the most effective and aripiprazole the least effective among them. When the risk of adverse effects is analyzed, olanzapine and clozapine are afflicted with the highest risk of inducing weight gain and haloperidol with extrapyramidal symptoms. Even aripiprazole and risperidone, however, induce considerable weight gain compared with placebo but may be acceptable alternatives when tailoring drug treatment to the individual patient.
Available from: Gabriel de Erausquin
- "It has been well established that antipsychotic drugs can lead to parkinsonism (Klemp et al., 2011; Leucht et al., 1999). However, it is worth pointing out that the presence of parkinsonism in untreated schizophrenia is not surprising or a new finding (Caligiuri et al., 1993; Chakos et al., 1992; Chatterjee et al., 1995; Honer et al., 2005; McCreadie et al., 2005). "
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ABSTRACT: We tested the hypothesis that loss of substantia nigra neurons in subjects at risk of schizophrenia (1), as reflected by midbrain hyperechogenicity (2) and parkinsonian motor impairment (3), is asymmetric and influenced by sex. We evaluated 62 subjects with never-treated chronic schizophrenia, 80 of their adult, unaffected first degree relatives and 62 healthy controls (matched by sex and age to the cases), part of an Andean population of Northern Argentina. Parkinsonism was scored blindly using UPDRS-3 (Unified Parkinson's Disease Rating Scale) on videotaped exams by 2 independent raters. Transcranial ultrasound was performed by an expert sonographist blind to subject condition with a 2.5MHz transducer through a temporal bone window. Quantification of echogenic area was carried out on saved images by a different evaluator. We found a significant difference in parkinsonian motor impairment between patients, their relatives as well as controls. All three groups showed worse parkinsonism on the left side than the right, corresponding with increased echogenicity on the right substantia nigra compared with the left. Females had significantly more right echogenicity than males, and patients and unaffected relatives were significantly more echogenic than controls on that side. On the left, only female patients had significant echogenicity. Our data supports the notion that unaffected relatives of schizophrenic subjects have increased parkinsonism and concomitant brainstem abnormalities which may represent a vulnerability to the disease. Both motor and brainstem abnormalities are asymmetric and influenced by sex.
Copyright © 2015 Elsevier B.V. All rights reserved.
Available from: Matthew Allen Butkus
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ABSTRACT: This paper explores the role of clinical mental health diagnoses, contextual diagnoses, and the ethical practice of psychotherapy. There is a tendency among professionals to align themselves with one of these two camps and subsequently dismiss the other camp as invalid, incorrect, or unethical. This is a false dichotomy that, when subscribed to very strictly, can lead to harmful and unethical practice. A case is discussed regarding Attention Deficit-Hyperactivity Disorder. A thorough analysis of the context and the DSM-IV-TR symptoms for the identified patient are provided. A discussion of ethical dilemmas and suggestions for practice follow.
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ABSTRACT: BACKGROUND: Debate continues about the comparative benefits and harms of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in treating schizophrenia. PURPOSE: To compare the effects of FGAs with those of SGAs in the treatment of adults aged 18 to 64 years with schizophrenia and related psychosis on illness symptoms, diabetes mellitus, mortality, tardive dyskinesia, and a major metabolic syndrome. DATA SOURCES: English-language studies from 10 electronic databases to March 2012, reference lists of relevant articles, and gray literature. STUDY SELECTION: Randomized trials for efficacy and cohort studies at least 2 years in duration for adverse events. DATA EXTRACTION: Two independent reviewers extracted data from 114 studies involving 22 comparisons and graded the strength of evidence for primary outcomes as insufficient, low, moderate, or high using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: Few differences of clinical importance were found for core illness symptoms; lack of precision in effect estimates precluded firm conclusions for many comparisons. Moderate-strength evidence showed a clinically important benefit of haloperidol over olanzapine for improving positive symptoms, but the benefit was scale-dependent: It was seen when the Scale for the Assessment of Positive Symptoms was used but not when the Positive and Negative Syndrome Scale (PANSS) was used. Moderate-strength evidence showed a clinically important benefit of olanzapine over haloperidol in improving negative symptoms when the PANSS and the Scale for the Assessment of Negative Symptoms were used. Low-strength evidence showed no difference in mortality for chlorpromazine verus clozapine or haloperidol versus aripiprazole, increased incidence of the metabolic syndrome for olanzapine versus haloperidol (risk differences, 2% and 22%), and higher incidence of tardive dyskinesia for chlorpromazine versus clozapine (risk differences, 5% and 9%). Evidence was insufficient to draw conclusions for diabetes mellitus. LIMITATIONS: All studies had high or unclear risk of bias. Length of study follow-up was often too brief to adequately measure adverse events. Medication comparisons, dosage, and outcome measurement were heterogenous for head-to-head comparisons. Selective patient populations limit generalizability. CONCLUSION: Clear benefits of FGAs versus SGAs for treating schizophrenia remain inconclusive because of variation in assessing outcomes and lack of clinically important differences for most comparisons. The strength of evidence on safety for major medical events is low or insufficient. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.
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