This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Koniari, I. Articles by Apostolakis, E. Search for Related Content PubMed Articles by Koniari, I. Articles by Apostolakis, E. Related Collections Related Article

eComment: Serotonin syndrome: pharmacogenomics and treatment

Cardiothoracic Surgery Department, University Hospital of Patras, 22500 Rion Patras, Greece

Serotonin syndrome following cardiac surgery

Your article is very interesting [1] as it elucidates a potentially life-threatening syndrome caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors [2]. The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system. All drugs that directly or indirectly increase central serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A (5-HT1A) and 5-hydroxytryptamine 2A (5-HT2A) can produce serotonin syndrome. Pharmacological mechanisms leading to increased central serotonin transmission include augmentation of serotonin synthesis, increased serotonin release, inhibition of serotonin uptake, inhibition of serotonin metabolism and direct stimulation of postsynaptic serotonin receptors [3].

Serotonin syndrome is not an idiopathic drug reaction but a predictable consequence of excess serotonergic agonism. However, Fox et al. [4] investigate a possible genetic contribution to individual vulnerability to the serotonin syndrome. In particular, they describe a rodent serotonin syndrome model, induced by serotonin-enhancing drugs, including SSRIs, monoamine oxidase inhibitors (MAOIs) and serotonin precursor 5-hydroxy-l-tryptophan (5-HTP). The administration of these drugs in different combinations produces a distinctive behavior profile. Knockout mice with a targeted disruption of the serotonin transporter (SERT) displayed some of these behaviors spontaneously, in the absence of drugs. The administration of such drugs in SERT –/– mice produced a markedly exaggerated serotonin syndrome behavior, relative to SERT +/+, with an intermediate SERT +/– phenotype. Serotonin syndrome behaviors in mice are at least in part mediated by postsynaptic 5-HT1A receptors. Therefore, it is possible that human SERT polymorphism that reduced SERT function creates a genetic explanation for humans with increased risk for developing serotonin syndrome.

A large number of drugs have been associated with serotonin syndrome. These include MAOIs, tricyclic antidepressants, SSRIs, opiate analgesics, over-the-counter cough medicines, antibiotics, weight-reduction agents, antiemetics, antimigraine agents, drugs of abuse and herbal products. The treatment of serotonin syndrome should begin with the discontinuation of all serotonergic agents. Generally, supportive care is the treatment of choice for most cases, but specific therapies depend on the severity of the syndrome. Specifically, mild cases are usually managed by removal of precipitating agents, as well as supportive care including intravenous fluids for hydration and to facilitate diuresis and treatment with benzodiazepines to prevent agitation. Moderate cases appear to benefit from administration of 5-HT2A antagonists, such as cyproheptadine, a histamine-1 receptor antagonist with anticholinergic and antihistaminergic characteristics, as well as chlorpromazine, a 5-HT1A and 5-HT2 receptor antagonist neuroleptic. Severe cases complicated by hyperthermia (temperature >41.1) are treated with the above therapies, as well as possible intubation, paralysis and sedation [3]. It is notable that benzodiazepines are central to the control of agitation, regardless of syndrome severity. While, several studies support the use of beta-blockers, which block 5-HT1A receptors [5].

	References

Top References

 

1. Shanmugam G, Kent B, Kirby S, Roger Baskett R. Serotonin syndrome following cardiac surgery. Interact CardioVasc Thorac Surg 2008;7:656–658.[Abstract/Free Full Text]
2. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112–1120.[Free Full Text]
3. Dvir Y, Smallwood P. Serotonin syndrome: a complex but easily avoidable condition. Gen Hosp Psychiatry 2008;30:284–287.[CrossRef][Medline]
4. Fox MA, Jensen CL, Gallagher PS. Receptor mediation of exaggerated responses to serotonin-enhancing drugs in serotonin transporter (SERT)-deficient mice. Neuropharmacology 2007;53:643–656.[CrossRef][Medline]
5. Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434–441.[Abstract/Free Full Text]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Koniari, I. Articles by Apostolakis, E. Search for Related Content PubMed Articles by Koniari, I. Articles by Apostolakis, E. Related Collections Related Article