Antipsychotics in Adults With Schizophrenia: Comparative Effectiveness of First-Generation Versus Second-Generation Medications
Bibliographic record
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.045 | 0.096 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.013 |
| Bibliometrics | 0.005 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".