Understanding antipsychotic “atypicality”: a clinical and pharmacological moving target
Bibliographic record
Abstract
The introduction of a number of new antipsychotics in the last decade has generated considerable excitement regarding the treatment of schizophrenia and related psychotic conditions. Clinically, it has produced changing expectations regarding treatment outcome, while academically it has encouraged a re-evaluation and expansion of theories of the pathophysiology of schizophrenia and antipsychotic activity. In this review, the development of antipsychotics is traced, beginning with chlorpromazine's introduction in the early 1950s, and followed to the present. Despite 50 years of use and a plethora of antipsychotics available worldwide, our conceptualization of their major mode of action remains essentially unchanged. It was shortly after their development that attention turned to the importance of dopamine, and in particular the dopamine D2 receptor. Current thinking has elaborated on this model, with serotonin and glutamate receiving the greatest attention most recently, but D2 antagonism remains the sine qua non of antipsychotic activity. Although the notion of "atypical" remains somewhat of a moving target, we do have at our disposal a new generation of antipsychotics that reflect a different clinical profile from their conventional counterparts. The precise degree of these differences and the underlying mechanisms remain unclear, however. The direction new antipsychotic development takes will undoubtedly hinge on answers to these questions.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".