Serotonin Syndrome & SSRI Side-Effects
Overview of serotonin syndrome:
- Background:
- Not an idiopathic reaction, but results from excess serotonergic agonism
- Onset is typically rapid, within 24 hours of medication intake
- Occurs in 15% of SSRI overdoses
- Offending drugs: many agents can cause this, particularly if used in combination (e.g. Libby Zion case)
- Antidepressants: SSRI, TCA, SNRI, MAOI
- Neuroleptics: valproic acid, lithium
- Opiates: meperidine, fentanyl, tramadol, dextromethorphan
- Antiemetics: ondansetron, metoclopramide
- Antimigraines: triptans
- OTC: St. John's wort
- Illicits: LSD, ecstasy, cocaine, amphetamines
- Diagnosis: made on clinical grounds, as serotonin levels do not correlate with toxicity
- Signs/symptoms: classic triad of AMS, autonomic hyperactivity, neuromuscular abnormalities - like many classic findings, not sensitive
- Mental status: agitation, delirium, restlessness, agitation
- Autonomic dysregulation: diaphoresis, hyperthermia, tachycardia, hypertension, diarrhea
- Neurologic changes: tremor, rigidity, hyperreflexia/clonus (most pronounced in LEs), mydriasis
- Rigidity can make diagnosis of hyperreflexia difficult
- Lab findings: metabolic acidosis, leukocytosis, rhabdomyolysis, DIC, AKI
- Signs/symptoms: classic triad of AMS, autonomic hyperactivity, neuromuscular abnormalities - like many classic findings, not sensitive
- Differential diagnosis: When considering serotonin syndrome, should always also consider NMS, malignant hyperthermia, and anticholinergic toxicity
- NMS: Sluggish neuro findings and reflexes (as opposed to hyperactive) and time of onset more protracted
- Malignant hyperthermia: Rigidity is very severe, and time of onset is rapid after administration of anesthesia
- Anticholinergic toxicity: Neuro exam normal, and characterized by hypoactive BS (as opposed to diarrhea)
- Management:
- Discontinue serotonergic agents
- Supportive care for autonomic derangements in monitored setting, as decompensation can occur rapidly
- Can sedate with benzodiazepenes to blunt neurologic hyperactivity
- If hyperthermia is persistent, may require paralysis and intubation
- If severe refractory symptoms, can consider serotonin antagonism with cyproheptadine (antihistamine with antiserotonergic properties)
- Determine ultimate need for serotonergic agent, and if necessary, reintroduce slowly in monitored setting
SSRI side effects:
- SSRIs are typically well-tolerated, but have some characteristic SEs to be aware of:
- Decreased libido
- SIADH
- Bleeding from impaired platelet aggregation due to decreased intraplatelet serotonin concentrations
- While citalopram has the fewest cytochrome p450 interactions, in overdose, it can cause seizures and arrhythmias from QT prolongation
(Christopher Woo MD, 12/6/10)