Serotonin syndrome

Editor, – I would like to reinforce the message about the spectrum of serotonin toxicity (Aust Prescr 2003;26:62-3). This term represents a more productive descriptive model than serotonin syndrome because there is a spectrum progressing from serotonergic adverse effects through to toxicity (hyperthermia and death). Severity is proportional to the degree of elevation of serotonin concentrations. The loose usage of the term serotonin syndrome continues to produce great confusion.^1,2 For instance, the frequently made statement 'serotonin syndrome is rare' is nonsensical because it is like saying 'poisoning is rare in those who do not ingest poisons'.

General physicians will be reassured to be reminded that life-threatening/fatal serotonin toxicity related to therapeutic drugs has been reported only when monoamine oxidase inhibitors (MAOIs) are combined with serotonin reuptake inhibitors.

I maintain a current synopsis about serotonin toxicity and implicated drugs (i.e. what drugs act as serotonin reuptake inhibitors, or MAOIs, in humans) at www.psychotropical.com/SerotoninToxicity.doc. I also draw your readers' attention to other original Australian research.³ The 'HATS' database continues to make a valuable contribution to all aspects of serotonin toxicity and the interesting deductions that ensue.⁴

Clinical advice from experts may be accessed via the toxicology services whose 24 hour telephone number in Australia is 13 11 26.

Ken Gillman
Consultant, Pioneer Valley Private Hospital
Mackay
Honorary Senior Lecturer
James Cook University, Qld

Editor, – The review of serotonin syndrome (Aust Prescr 2003;26:62-3) explores drug interactions as a cause of serotonergic toxicity. We have noticed a significant number of enquiries regarding the concomitant use of the commonly used migraine medication sumatriptan and selective serotonin reuptake inhibitors (SSRIs). The article implies that any combination of serotonergic drugs should be avoided. While sumatriptan is regarded as 'serotonergic', the isolated case reports of apparent serotonin syndrome are not convincing and do not, in our clinical practice, constitute a reason for avoiding the combination.

A review failed to locate clinical evidence supporting a contraindication for sumatriptan and SSRIs.⁵ Sumatriptan, a 5-HT agonist, does not appreciably cross the blood-brain barrier and has a significantly lower affinity for 5-HT1A than for 5-HT1D receptors, thereby limiting its intrinsic ability to mediate a serotonergic response. Nevertheless, as the Australian Prescriber article suggests, patients should be educated about the possibility of interactions between serotonergic drugs. Before starting therapy, they also need to be informed of the signs and symptoms of serotonin toxicity and what to do if an adverse reaction develops.

Felicity Prior
Director
Hunter Drug Information Service
Department of Clinical Toxicology and Pharmacology
Newcastle Mater Misericordiae Hospital, NSW

Dr M. Hall and Dr N. Buckley, the authors of the article, comment:

As stated in our original article, sumatriptan has been linked to mild serotonin syndrome in a number of case reports. We deliberately did not include it in the table of drugs implicated in severe serotonin syndrome. We do not believe that the article suggests that any combination of serotonergic medications should be avoided, but merely points out that the potential for such an interaction exists, and prompts education of the patient, and the physician, about these possibilities.