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Adverse drug reaction of the month: Nicholas K Perry Venlafaxine-induced serotonin syndrome with relapse following amitriptyline Postgrad Med J 2000; 76: 254 [Abstract] [Full text] [PDF]

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Serotonin toxicity

P Ken Gillman   (30 June 2004)

Serotonin toxicity 30 June 2004
P Ken Gillman, Dr Pioneer Valley Private Hospital Send letter to journal: Re: Serotonin toxicity kg{at}matilda.net.au P Ken Gillman	Dear Editor This is a most complex subject. It is difficult to make adequate and constructive comment about this case without going into lengthy details concerning the latest research on serotonin syndrome, which letter space will not allow. [1,2] It will be helpful for your readers to appreciate that this report cannot reasonably be upheld to represent serotonin syndrome (better referred to as serotonin toxicity), nor to instruct anyone usefully about serotonin toxicity or what combinations of drugs cause it. It is a reminder of the pitfalls of case reports and the difficulties involved in brief reviews of complex topics. I have commented on similar reports previously and noted that they reflect, at least in part, the demands that editors and referees face in discharging their role as guardians of publishing standards.[3-5] Box 2 contains several drugs (nefazodone, trazodone and amitriptyline) that decades of intensive use demonstrate to do not provoke serotonin toxicity, either by themselves, or if combined with monoamine oxidase inhibitors.[6] The inclusion of these drugs perpetuates myths and inaccuracies that are common in this field and are repeated in supposedly authoritative publications, including the British National formulary.[1] Professor Whyte's studies of large numbers of patients with serotonin toxicity have now elucidated the typical symptoms clearly; I refer readers to his seminal papers.[7-9] A more recent summary of most aspects of serotonin toxicity is contained in a recent book chapter 1 and more detailed and comprehensive data, that is more up-to-date, is contained in my web based summary document.[2] That covers all aspects of these complex interactions that may lead to serotonergic toxicity. The simple and important concept that is likely to be useful for general physicians is an appreciation that there is a spectrum, going from serotonergic side effects and progressing to toxicity. Toxicity can be life threatening, but that only occurs with co-administration of MAOIs with SRIs. Serotonergic side effects occurring with monotherapy do not cause life- threatening reactions. It therefore seems to us that using the term serotonin syndrome for cases such as this is unhelpful and suggests the potential for a fatal outcome. In reality all that is being described is exaggerated side effects. References 1. Gillman P, Whyte I. Serotonin syndrome. In: Haddad P, Dursun S, Deakin B, editors. Adverse Syndromes and Psychiatric drugs. Oxford: Oxford University Press, 2004. 2. Gillman PK. Serotonin toxicity (serotonin syndrome): A current analysis. Psychopharmacology Update Notes [Online]: Available at: www.psychotropical.com/SerotoninToxicity.doc, 2003. 3. Gillman PK. Mirtazapine: unable to induce serotonin toxicity? Clinical Neuropharmacology 2003;26:288-289. 4. Gillman P. The spectrum concept of serotonin toxicity. Pain Medicine 2004; 5:[in press]. 5. Gillman PK. Comments on "Serotonin syndrome during treatment with paroxetine and risperidone". Journal of Clinical Psychopharmacology 2001; 21(3):344-5. 6. Gillman PK. Serotonin Syndrome: History and Risk. Fundamental and Clinical Pharmacology 1998;12(5):482-491. 7. Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. Quarterly Journal of Medicine 2003;96(5):369-74. 8. Isbister G, Hackett L, Dawson A, Whyte I, Smith A. Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. British Journal of Clinical Pharmacology 2003;56:441-450. 9. Dunkley E, Isbister G, Sibbritt D, Dawson A, Whyte I. Hunter Serotonin Toxicity Criteria: a simple and accurate diagnostic decision rule for serotonin toxicity. Quarterly Journal of Medicine 2003;96:635-642.