SSRIs & SNRIs
The AANP exam tests SSRIs and SNRIs as the front door of outpatient mental health pharmacology. SSRIs (sertraline, escitalopram, fluoxetine, paroxetine, citalopram) and SNRIs (venlafaxine, duloxetine) are first-line for major depression, generalized anxiety, panic disorder, PTSD, and OCD. Therapeutic effect takes 4–6 weeks; side effects (GI upset, sexual dysfunction, insomnia, mild weight effects) appear in days. Citalopram carries a QT warning above 40 mg (20 mg in older adults). Paroxetine is the most anticholinergic and has the worst withdrawal profile. Fluoxetine has the longest half-life and self-tapers. Duloxetine adds neuropathic-pain coverage. The danger questions are serotonin syndrome (clonus, hyperthermia, autonomic instability) when an SSRI is combined with tramadol, MAOIs, linezolid, or triptans.
📖 Overview
SSRIs (sertraline, escitalopram, fluoxetine) are first-line for major depressive disorder, generalized anxiety, panic disorder, OCD, and PTSD. SNRIs (venlafaxine, duloxetine) add norepinephrine reuptake inhibition and are often used when SSRIs fail, or for patients with concurrent neuropathic pain or fibromyalgia. All take 4–6 weeks for full effect.
⚙️ Mechanism of Action
SSRIs: block serotonin reuptake → ↑ synaptic serotonin. SNRIs: block both serotonin and norepinephrine reuptake.
💎 Board Pearls
- ⏳ Onset: 2 weeks for some effect, 4–6 weeks for full response. Counsel patients early.
- ⚠️ Black box warning: ↑ suicidal ideation <24 yrs — monitor closely first 4 weeks.
- 🔥 Serotonin syndrome: triad of mental status change + autonomic instability + neuromuscular hyperactivity (clonus, hyperreflexia). Triggered by SSRI + MAOI, tramadol, triptans, linezolid, St. John's Wort.
- ⚡ Citalopram QT black box → max 40 mg (20 mg in elderly, hepatic impairment).
- 🫤 Discontinuation syndrome: dizzy, flu-like, brain zaps — taper slowly. WORST with paroxetine + venlafaxine (short half-lives).
- 🤰 Pregnancy: sertraline preferred; paroxetine = cat D (avoid); fluoxetine OK but long t½.
- 🤕 Venlafaxine at high dose → HTN (dose-dependent NE effect).
- 🦵 Duloxetine → FDA-approved for diabetic neuropathy + fibromyalgia + chronic MSK pain.
💊 Drugs in This Class
Practice Questions
A 48-year-old man on sertraline 150 mg daily for major depressive disorder was started on tramadol 50 mg every 6 hours three days ago after a lumbar strain. He presents to the clinic with agitation, diaphoresis, tachycardia (HR 124), BP 168/98, temperature 38.6°C, dilated pupils, and spontaneous clonus in both lower extremities with hyperreflexia. Which of the following is the most likely diagnosis?
Sources
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