Association of Antidepressant Use With Drug-Related Extrapyramidal Symptoms
Bibliographic record
Abstract
BACKGROUND: Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study. METHODS: A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, calendar time, and age through density-based sampling. Rate ratios were computed using conditional logistic regression adjusting for other covariates. RESULTS: We identified 3,838 subjects with EPSs compared with 38,380 age-matched control subjects. Rate ratios with respect to EPSs were as follows: duloxetine, 5.68 (95% confidence interval [CI], 4.29-7.53); mirtazapine, 3.78 (95% CI, 1.71-8.32); citalopram, 3.47 (95% CI, 2.68-4.50); escitalopram, 3.23 (95% CI, 2.44-4.26); paroxetine, 3.07 (95% CI, 2.15-4.40); sertraline, 2.57 (95% CI, 2.02-3.28); venlafaxine, 2.37 (95% CI, 1.71-3.29); bupropion, 2.31 (95% CI, 1.67-3.21); and fluoxetine, 2.03 (95% CI, 1.48-2.78). CONCLUSIONS: This observational study demonstrates a harmful association between the incidence of Parkinson disease or associated EPSs and use of the antidepressants duloxetine, mirtazapine, citalopram, escitalopram, paroxetine, sertraline, venlafaxine, bupropion, and fluoxetine.
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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 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".