Criteria for the diagnosis of the serotonin syndrome:
(1) 3 or more of the following are present:
(1a) confusion, hypomania or other mental status change
(1b) agitation, restlessness (akathisia)
(1c) frightened, diaphoretic hyperarousal state
(1d) myoclonus
(1e) hyperreflexia
(1f) diaphoresis
(1g) shivering, may be uncontrollable
(1h) tremor
(1i) diarrhea
(1j) incoordination
(1k) oculogyric crisis
(1l) fever
(2) onset of symptoms coincident with the addition or increase in a drug with serotonergic activity
(3) a neuroleptic (antipsychotic agent) was not started or increased in dosage prior to the onset of symptoms
(4) other etiologies (infectious, metabolic, drug abuse, withdrawal syndrome, poisoning) have been excluded
Agents potentially causing the serotonin syndrome (after Table 2, Mills, 1995):
(1) increase in serotonin synthesis
(1a) L-tryptophan
(2) decrease in serotonin metabolism, resulting in accumulation to toxic levels
(2a) mono-amine oxidase (MAO) inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine)
(3) increase serotonin release
(3a) amphetamines
(3b) cocaine
(3c) fenfluramine
(3d) reserpine (initially)
(4) inhibition of serotonin uptake
(4a) tricyclic antidepressants (TCA): amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline
(4b) selective serotonin reuptake inhibitors (SSRI): fluvoxamine, fluoxetine, paroxetine, nefazodone, sertaline, trazodone
(4c) amphetamines
(4d) cocaine
(4e) dextromethorphan
(4f) meperidine
(4g) venlafaxine
(5) direct serotonin receptor agonists
(5a) buspirone
(5b) LSD
(5c) sumatriptan
(6) nonspecific increase in serotonin activity
(6a) lithium
(6b) electroconvulsive therapy
(7) dopamine agonists
(7a) amantadine
(7b) bromocriptine
(7c) bupropion
(7d) levodopa
Differential diagnosis:
(1) neuroleptic malignant syndrome – This shows muscle rigidity.
(2) anticholinergic syndrome
Management:
(1) discontinue medication(s) with serotonergic activity
(2) supportive care
(3) consider administration of a nonselective serotonin receptor antagonist (methysergide, cyproheptadine or propranolol)