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Antidepressant pharmacology
An antidepressant is chosen by the side-effect profile that suits the patient — an SSRI as first line, mirtazapine when sleep and appetite are wanted, bupropion when sexual function or smoking is the issue — while remembering three dangers: serotonin syndrome, TCA toxicity and discontinuation syndrome.
Why it matters in the exam
Exam questions present a patient with depression and a comorbid condition and ask which drug suits or is forbidden. Bupropion does not impair sexual function and helps smoking cessation, but is forbidden in epilepsy and eating disorders. Mirtazapine improves sleep and appetite but raises weight — suitable for a thin older person with insomnia. Duloxetine suits neuropathic pain. Venlafaxine may raise blood pressure. Paroxetine causes a marked discontinuation syndrome and has an anticholinergic effect. Citalopram prolongs the QT. Trazodone may cause priapism.
Danger states recur in questions: TCA toxicity — reduced consciousness, seizures, anticholinergic features and QRS widening on the ECG, treated with sodium bicarbonate; serotonin syndrome from drug combinations (an MAOI with an SSRI, tramadol, linezolid) — clonus, fever and diarrhoea; and hypertensive crisis in a patient on an MAOI who has eaten tyramine-rich food. Quiet effects are asked too: hyponatraemia (SIADH) with SSRIs in older people, bleeding when SSRIs are combined with NSAIDs or anticoagulants, and a warning about suicidal thoughts under age 25 in the first weeks. Antidepressants are stopped gradually, and when switching from an MAOI wait two weeks (5 weeks after fluoxetine).
Key points
- SSRI first line; choose by side effects.
- Bupropion: no sexual dysfunction; forbidden in epilepsy and eating disorders.
- Mirtazapine: sleep and appetite; weight gain.
- TCA toxicity: wide QRS → sodium bicarbonate.
- MAOI: tyramine and serotonin syndrome; two-week washout.
Summary table
| Drug or class | Advantage | Main side effects | Exam notes |
|---|---|---|---|
| SSRI (sertraline, escitalopram, fluoxetine) | First line, relatively safe | Nausea, sexual dysfunction, hyponatraemia, bleeding | Citalopram — QT; paroxetine — discontinuation syndrome |
| SNRI (venlafaxine, duloxetine) | Duloxetine for neuropathic pain | Raised blood pressure, discontinuation syndrome | Venlafaxine — check blood pressure |
| Mirtazapine | Sleep and appetite; little sexual dysfunction | Weight gain, sedation | Suits a thin older person with insomnia |
| Bupropion | No sexual dysfunction; smoking cessation | Seizure risk | Forbidden in epilepsy and eating disorders |
| TCA (amitriptyline) | Chronic pain | Anticholinergic, orthostatic hypotension, conduction disorders | In toxicity: wide QRS → sodium bicarbonate |
| MAOI | Resistant or atypical depression | Hypertensive crisis with tyramine | Serotonin syndrome in combinations; two-week washout |
A free exam question
מטופל עם דיכאון עמיד לטיפול מקבל שילוב של SSRI ,עם תרופה נוספת ומפתח היפרתרמיה קלונוס, היפר- ?רפלקסיה ובלבול. איזו תרופה סביר ביותר שהוספה (the question as examined, in Hebrew)
- א. Bupropion
- ב. Lithium
- ג. Aripiprazole
- ד. Quetiapine
Example question from the licensing exam (IMLE)
A 50-year-old male presents to the clinic with his family. He says he is sure his wife is cheating on him with several neighbors. There is no functional impairment and the psychiatric status evaluation is normal except for these thoughts. His family have tried to talk to him about it several times, but he thinks they are collaborating against him in this matter. What is true about this disorder?
- A. The affect is impaired in this disorder.
- B. It is also common to have auditory hallucinations in this disorder.
- C. The treatment of choice for the disorder is antidepressant medications.
- D. The disorder is stable over a long period of time.
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Sources
- Maudsley Prescribing Guidelines in Psychiatry, 14th edition (2021) — Antidepressants: choice, adverse effects, switching
- CANMAT Clinical Guidelines for the Management of Adults with Major Depressive Disorder, 2023 update — Pharmacological treatments
- American Geriatrics Society Beers Criteria, 2023 — Potentially inappropriate medication use in older adults
- Kaplan and Sadock's Synopsis of Psychiatry, 12th edition (2021) — Psychopharmacology: antidepressants
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.