PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. Serotonin Syndrome - SSRIs compared.

PsychoTropicalResearch, serotonin and serotonin syndrome research.

Serotonin Syndrome - SSRIs compared

Serotonin Syndrome - SSRIs compared

Date Created: 23/06/1999   Last Modified: 23/10/2000   Last Checked: 21/10/2002

Australian research in ‘toxico-epidemiology’ is leading the field. Associate Professor Ian Whyte and his colleagues in Newcastle (www.hypertox.com) have recently presented the most recent analysis of their unique prospectively gathered data set on overdoses (European Association of Poison Control Centers and Clinical Toxicologists Scientific meeting: in Dublin, June 1999). The numbers of overdoses are large (over 500) so the conclusions drawn are very likely to be reliable; this is data from which one can profit greatly by studying carefully.

It clearly demonstrates that about 10% of all patients who have taken an overdose of a single serotonergic drug (including moclobemide) will present with ‘serotonin syndrome’ (but note the limitations of the term serotonin syndrome, see other notes). The relative frequency of serotonin syndrome is about the same for :- paroxetine, sertraline, fluoxetine and moclobemide (the newer drugs- fluvoxamine and citalopram and nefazodone- are not represented in sufficient numbers to analyse as yet). But venlafaxine almost certainly produces a higher incidence of both seizures and serotonin syndrome than other drugs, including TCAs.

These figures require a slight revision of our view of the medical sequelae of over-doses of SSRIs; they may not be as harmless as has been presumed. It is also noteworthy that the indications are that serotonin syndrome is about as frequent with over-doses of moclobemide (a ‘RIMA’ type MAOI) as it is with SSRIs; however the interesting and slightly surprising finding is that clomipramine is ten times less likely to cause serotonin syndrome than the SSRIs. This is probably explained by the fact that it has significant activity as a 5-HT2A blocker.

There is a significant possibility of life-endangering serotonin syndrome if moclobemide (even as a small overdose of only 1000-2000 mg) is taken in combination with any serotonin reuptake inhibitor (that is, any ‘SSRI’, and also clomipramine, venlafaxine etc -- also see other notes). As more patients have several drugs in succession the chances of such mixed over-doses will probably increase and some morbidity may well result.

It may be worthwhile for GPs to try to ensure that patients do not have both of these sorts of drugs (ie RIMAs and SSRIs) in their homes simultaneously; computerised drug monitoring systems may be modified to give warnings alerting doctors to such eventualities.