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Antipsychotic adverse effects, NMS and serotonin syndrome
Antipsychotic side effects follow a timetable — acute dystonia within hours, akathisia within days, parkinsonism within weeks and tardive dyskinesia over months and years — and NMS is told apart from serotonin syndrome by the speed of onset, rigidity versus clonus, and the reflexes.
Why it matters in the exam
Exam questions present a patient who has started haloperidol, describe a movement or a state, and ask what it is and how to treat it. Acute dystonia (spasm of the neck, tongue or eyes) appears within hours to days, mainly in young men and with high-potency drugs, and is treated with an injected anticholinergic. Akathisia — inner restlessness and an urge to move — is treated by lowering the dose and with propranolol. Parkinsonism is treated by lowering the dose or with an anticholinergic. Tardive dyskinesia is treated by switching to clozapine or with VMAT2 inhibitors, and anticholinergics make it worse.
The emergencies are NMS and serotonin syndrome. NMS develops over days: high fever, "lead-pipe" rigidity, autonomic instability, altered consciousness and a very high CK; stop the drug, cool, give fluids, and when severe add dantrolene or bromocriptine. Serotonin syndrome appears within hours of combining serotonergic drugs: clonus and brisk reflexes (mainly in the legs), dilated pupils, diarrhoea and agitation; stop the drugs, give benzodiazepines and cyproheptadine. Questions also cover metabolic effects (olanzapine and clozapine), raised prolactin (risperidone), QT prolongation and the effects of clozapine.
Key points
- Dystonia in hours, akathisia in days, parkinsonism in weeks, tardive dyskinesia in months and years.
- NMS: fever, rigidity, high CK, develops over days.
- Serotonin syndrome: clonus and brisk reflexes, within hours.
- Tardive dyskinesia: clozapine or VMAT2 inhibitors; not anticholinergics.
- Metabolic monitoring: at baseline, after 12 weeks and yearly.
Summary table
| Effect | Onset | Signs | Treatment |
|---|---|---|---|
| Acute dystonia | Hours to days | Neck or tongue spasm, oculogyric crisis | Injected anticholinergic (biperiden or benztropine) or diphenhydramine |
| Akathisia | Days to weeks | Inner restlessness, need to move | Lower the dose, propranolol |
| Parkinsonism | Weeks | Tremor, rigidity, slowness | Lower the dose, anticholinergic, switch to another drug |
| Tardive dyskinesia | Months to years | Involuntary movements of the mouth and tongue | Switch to clozapine, VMAT2 inhibitors; stop anticholinergics |
| NMS | Days | Fever, lead-pipe rigidity, autonomic instability, confusion, high CK | Stop the drug, cooling, fluids; dantrolene or bromocriptine |
| Serotonin syndrome | Hours | Clonus, brisk reflexes, dilated pupils, diarrhoea | Stop the drugs, benzodiazepines, cyproheptadine |
| Clozapine | Mainly in the first months | Severe neutropenia, myocarditis, seizures, severe constipation, hypersalivation | Neutrophil monitoring; stopping smoking raises the drug level |
A free exam question
בן 15 , עם ADHD, הגיב בתופעות לוואי לתכשירים שונים. כשהרופא המטפל מציע שימוש ב- Modafinil בהתבסס על מחקרים, מנהל המחלקה לא מסכים בנימוק, שבזמנו ה- FDA פסל אותו לשימוש ב- ADHD . מה הייתה הסיבה לפסילתו? (the question as examined, in Hebrew)
- א. נדודי שינה
- ב. Steven-Jonson Syndrome
- ג. כאבי ראש
- ד. Agranulocytosis
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Sources
- APA Practice Guideline for the Treatment of Patients With Schizophrenia, 3rd edition (2020) — Management of side effects
- Maudsley Prescribing Guidelines in Psychiatry, 14th edition (2021) — Antipsychotics: adverse effects
- Boyer and Shannon, New England Journal of Medicine, 2005 — The serotonin syndrome
- Kaplan and Sadock's Synopsis of Psychiatry, 12th edition (2021) — Psychopharmacology: dopamine receptor antagonists
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-02. The text may contain errors; when in doubt, check the source.