SSRIs and SNRIs: choosing, adverse effects and recognizing serotonin syndrome

Where SSRIs fit

SSRIs are the usual first-line medication for major depressive disorder and for generalized anxiety, panic disorder, social anxiety, obsessive-compulsive disorder and PTSD. They are chosen mainly by side-effect profile, interactions, prior response, and what has worked for a family member.

Counsel patients early. Benefit takes weeks, some patients feel worse or activated at first, and young adults need close monitoring for suicidal thoughts in the first weeks and after dose changes because of the boxed warning.

Adverse effects to pair with the drug

• ·All SSRIs: nausea, diarrhea, headache, insomnia or somnolence, sexual dysfunction, and a small increase in bleeding risk, particularly with NSAIDs or anticoagulants.
• ·Hyponatremia (SIADH), especially in older adults and with diuretics. Check sodium if confusion or falls appear.
• ·Citalopram: dose-dependent QT prolongation. Do not exceed 40 mg a day, and 20 mg a day in people over 60 or with certain liver or CYP2C19 issues.
• ·Paroxetine: more anticholinergic effects, weight gain, and the worst discontinuation syndrome. Avoid in pregnancy where alternatives exist.
• ·Fluoxetine: long half-life, so a slower washout, and a strong CYP2D6 inhibitor.
• ·Venlafaxine and other SNRIs: dose-related blood pressure elevation, so monitor blood pressure.
• ·Bupropion: lowers the seizure threshold and is contraindicated in seizure and eating disorders; little sexual dysfunction.

Recognizing serotonin syndrome

Think of it as a triad: mental status, autonomic instability and neuromuscular findings.

1. 01

   Mental status

   Agitation, restlessness, confusion, anxiety.

2. 02

   Autonomic

   Fever, sweating, tachycardia, diarrhea, dilated pupils, blood pressure changes.

3. 03

   Neuromuscular

   Tremor, hyperreflexia, and clonus (inducible or ocular). Clonus and hyperreflexia are the findings that most favor serotonin syndrome.

4. 04

   Treat

   Stop all serotonergic agents, give supportive care with fluids and cooling, and benzodiazepines for agitation. Cyproheptadine, a serotonin antagonist, is used for moderate to severe cases. Severe hyperthermia needs intensive care.

Combinations that carry the risk

• ·MAOIs with SSRIs, SNRIs, tricyclics, meperidine, tramadol or dextromethorphan
• ·Linezolid (a weak MAOI) with serotonergic drugs
• ·Triptans, St John's wort and some opioids, in combination with serotonergic antidepressants
• ·Switching from fluoxetine to an MAOI needs about 5 weeks. Most other SSRIs need about 2 weeks before starting an MAOI, and an MAOI needs 2 weeks off before starting an SSRI.