Linezolid (see Linezolid, [[Linezolid]]): MAO inhibitor (MAO normally degrades serotonin in the brain) and decreases serotonin reuptake
FDA Alert (7/26/11): avoid use in conjunction with SSRI’s
Methylene Blue (see Methylene Blue, [[Methylene Blue]]): reversible MAO inhibitor (MAO normally degrades serotonin in the brain) and increases serotonin release from stored vesicles
FDA Alert (7/26/11): avoid use in conjunction with SSRI’s
Moclobemide
Nialamid(e)
Pargyline
Phenelzine (Nardil) (see Phenelzine, [[Phenelzine]])
Epidemiology: possibly etiologic, when used in combination with MAO inhibitors or Selective Serotonin Reuptake Inhibitors (SSRI) (see Selective Serotonin Reuptake Inhibitors, [[Selective Serotonin Reuptake Inhibitors]])
Pharmacology: indirect neurotransmitter which moves into cytoplasmic vesicles in presynaptic adrenergic neurons –> displaces epinephrine, norepinephrine, dopamine, and serotonin into the cytosol
Methylphenidate (Ritalin) (see Methylphenidate, [[Methylphenidate]])
Pharmacology: xxx
Mirtazapine (Remeron, Avanza, Axit, Mirtaz, Mirtazon, Zispin) (see Mirtazapine, [[Mirtazapine]])
Pharmacology: tetracyclic alpha-2 adrenergic heteroreceptor blocker that increases norepinephrine and serotonin release in addition to blocking serotonin receptors
St John’s Wort (Hypericum Species) (see St John’s Wort, [[St Johns Wort]])
Pharmacology: decreases serotonin reuptake and degradation
Trazodone (Desyrel) (see Trazodone, [[Trazodone]])
Pharmacology: tetracyclic that blocks serotonin reuptake and has an antagonistic effect at the serotonin 5-HT2 receptor
Serotonin Physiology
Serotonin (5-hydroxytryptamine, 5HT) is a central and peripheral nervous system neurotransmitter
Serotonin is synthesized from L-tryptophan in the brainstem raphe nucleus and is stored in presynaptic vesicles -> released by neuronal activation
Serotonin Metabolism
Excess serotonin is taken back up into presynaptic vesicles by active transport or locally metabolized by monoamine oxidase (MAO) to 5-hydroxyindoleacetic acid
Systemic serotonin is metabolized via hepatic mixed function oxidases
Inhibition of particular mixed function oxidases by medications or other substances (grapefruit, etc) -> decreased serotonin metabolism -> increased drug effect
Serotonin Receceptors: there are 7 distinct 5HT receptors (with further specific subtypes), producing a wide variety of physiologic effects
Most central nervous system 5HT receptors are located in the brainstem raphe nuclei
The physiologic manifestations of serotonin syndrome are largely due to stimulation of 5HT1a and 5HT2 receptors
Abdominal Cramping (see Abdominal Pain, [[Abdominal Pain]]): due to the high levels of serotonin in gastric and intestinal mucosal enterochromaffin cells
Diarrhea (see Diarrhea, [[Diarrhea]]): due to the high levels of serotonin in gastric and intestinal mucosal enterochromaffin cells
Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): due to the high levels of serotonin in gastric and intestinal mucosal enterochromaffin cells
Rationale: not fully understood, and is, in part, an extrapolation from its use in TCA overdosage
In animal models, citalopram inhibits sodium/calcium cardiac channels and impairs cardiac conduction
Alkalinization may accelerate the recovery of sodium channels and alter the rate of drug unbinding
Indications
Citalopram Overdose: possible utility in other SSRI overdoses
References
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Citalopram overdose-review of cases treated in Swedish hospitals. J Toxicol Clin Toxicol. 1997;35:237-240
Citalopram in the treatment of depression and other potential uses in psychiatry. Pharmacotherapy. 1999;19:675-689
Speculations on difference between tricyclic and selective serotonin reuptake inhibitor antidepressants on their cardiac effects. Is there any? Curr Med Chem. 1999;6:469-480
An exploratory approach to the serotonin syndrome: an update of clinical phenomenology and revised diagnostic criteria. Med Hypotheses. 2000;55:218–24
QTc interval prolongation associated with citalopram overdose: a case report and literature review. Clin Neuropharmacol. 2001;24:158-162
Serotonin syndrome and atypical antipsychotics. Am J Psychiatry. 2002;159:672-3
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Cardiotoxicity and late onset seizures with citalopram overdose. J Emerg Med. 2003;25:163-166
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The serotonin syndrome. NEJM 2005;352:1112
5-Hydroxytryptamine 1A receptors in the paraventricular nucleus of the hypothalamus mediate oxytocin and adrenocorticotropin hormone release and some behavioral components of the serotonin syndrome. J Pharmacol Exp Ther. 2005;313:1324–30
Risk of serotonin syndrome with concomitant administration of linezolid and serotonin agonists. Pharmacotherapy 2006;26:1784
Serotonin toxicity caused by an interaction between fentanyl and paroxetine. Can J Anaesth. 2008 Aug;55(8):521-5 [ MEDLINE]
Linezolid and Serotonin Syndrome. Prim Care Companion J Clin Psychiatry. 2009; 11(6): 353–356
The role of methylene blue in serotonin syndrome: a systematic review. Psychosomatics. 2010 May;51(3):194-200
Serotonin syndrome precipitated by fentanyl during procedural sedation. J Emerg Med. 2010 May;38(4):477-80 [ MEDLINE]
Serotonin Syndrome in the Setting of Lamotrigine, Aripiprazole, and Cocaine Use. Case Rep Med. 2015;2015:769531. doi: 10.1155/2015/769531. Epub 2015 Aug 2 [MEDLINE]
