Quetiapine: An Effective Antipsychotic in First-Episode Schizophrenia Despite Only Transiently High Dopamine-2 Receptor Blockade
Bibliographic record
Abstract
BACKGROUND: It has been suggested that transiently high dopamine-2 (D(2)) receptor occupancy by antipsychotic medication may be sufficient for inducing an antipsychotic response. We treated patients experiencing their first episode of schizophrenia with a single daily dose of quetiapine to achieve a transient daily peak of D(2) receptor blockade, to determine if this would lead to an antipsychotic response. METHOD: Fourteen patients with a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were treated with quetiapine titrated to a single daily dose (mean +/- SD dose at the time of the positron emission tomography [PET] scan = 427 +/- 69 mg) for 12 weeks. Peak D(2) occupancy approximately 2 hours postdose and trough D(2) occupancy approximately 20 hours postdose were determined using PET and [(11)C]raclopride. Clinical symptoms and side effects were measured at baseline and every 2 weeks during the treatment phase. RESULTS: Quetiapine administration led to a mean peak D(2) occupancy of 62% +/- 10% 2 hours postdose, which declined to 14% +/- 8% approximately 20 hours postdose. Ten (71%) of 14 patients responded to treatment with quetiapine, scoring "much improved" or greater on the Clinical Global Impressions-Improvement scale. Plasma drug levels and peak D(2) occupancy were highly correlated (r = 0.84; p =.003), as were prolactin and plasma drug levels when measured 2.5 hours after drug administration (r = 0.60; p <.05). Mean weight gain for the 10 subjects who completed the 12-week study was 4.2 +/- 4.6 kg (9.3 +/- 10.2 lb). No clinically relevant motor side effects occurred during the trial. CONCLUSION: Patients with a first episode of schizophrenia responded to treatment with a single daily dose of quetiapine despite only transiently high D(2) receptor occupancy. Our findings raise the question of whether continuously high D(2) blockade is necessary for obtaining an antipsychotic response. Future studies aimed at evaluating the relative merits of "transiently high" versus "continuously high" D(2) occupancy are warranted.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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".