Delayed-Onset Hypothesis of Antipsychotic Action
Bibliographic record
Abstract
CONTEXT: To understand the mechanism of action of antipsychotic drugs, it is critical to recognize the time course over which these medications take effect. Current models of antipsychotic action presume a "delayed onset" of action. OBJECTIVE: To test the delayed-onset hypothesis of antipsychotic action via a meta-analytic study. DATA SOURCES AND STUDY SELECTION: Double-masked studies that reported results from active or placebo-controlled trials of antipsychotic response during the first 4 weeks of treatment were selected. These studies were identified by searching MEDLINE, 1996 to 2001; the Cumulative Index to Nursing and Allied Health, 1982 to 2001; EMBASE, 1980 to 2001; the ACP Journal Club; the Cochrane Database of Systematic Reviews; and the Database of Abstracts of Reviews of Effectiveness. Leads from these sources were followed up by manual searches. DATA SYNTHESIS: Forty-two published studies, including 7450 patients and 119 independent response vs time curves, were identified. Reductions in total scores on the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale were 13.8% during week 1, 8.1% during week 2, 4.2% during week 3, and 4.7% during week 4. This pattern of "early-onset" improvement was present even after the estimated effect of placebo treatment was removed and when results were restricted to the psychotic subscales of the scales. CONCLUSIONS: This analysis rejects the commonly held hypothesis that antipsychotic response is delayed. Rather, these findings suggest that the antipsychotic response starts in the first week of treatment and accumulates over time. Furthermore, greater improvement occurs in the first 2 treatment weeks than in the subsequent 2 treatment weeks. Proposed mechanisms of action of antipsychotic drugs need to account for this early-onset antipsychotic effect.
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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 | 0.097 | 0.137 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.016 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.000 | 0.003 |
| Scholarly communication | 0.003 | 0.006 |
| Open science | 0.007 | 0.002 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.011 | 0.001 |
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".