Serotonin syndrome

Sir: Mir and Taylor's review of serotonin syndrome (Psychiatric Bulletin, December 1999, 23, 742-747) stated that in practice lithium was well tolerated in combination with a selective serotonin reuptake inhibitor (SSRI), but mentioned four individual reports where problems had been experienced. Two of these involved the emergence of serotonin syndrome after the addition of lithium to the treatment regime of a patient already taking an SSRI without side-effects. I would like to add to these a further case seen as an emergency referral to our Affective Disorders Clinic in May 2000.

Mr B is a 53 year old professional white male who has been suffering with recurrent depressive episodes for the last 18 months. He had been treated with various antidepressants during this time. At the time of his urgent referral he had been taking paroxetine 60 mg daily for over 3 months, to which lithium 400 mg daily had been added 2 weeks previously.

On presentation Mr B described profound nausea with the addition of five of Sternbach's diagnostic criteria for serotonin syndrome: agitation, myoclonus, shivering, tremor and incoordination. Serum lithium levels at this time were within normal limits. Lithium was discontinued and the paroxetine was reduced slowly over the next 6 weeks. Within a week Mr B's symptoms had improved and on 3 week review he was symptom-free with regard to the serotonin syndrome.

The above case of serotonin syndrome was attributed to the addition of lithium to the SSRI. This was because he was side-effect-free on treatment with paroxetine and the symptoms developed shortly after commencing lithium. The symptoms disappeared after lithium treatment was terminated, despite the continuation of high, but reducing, doses of paroxetine. Muly et al (1993) describe a similar case in which lithium was used in addition to fluoxetine. Similar to the case described here, the symptoms resolved by withdrawal of lithium, despite continuation of antidepressant treatment. This can be explained by the hypothesis that lithium acts to enhance serotoninergic function as described expansively by Price et al (1990) in their review article of a large body of clinical evidence. In conclusion, it is important to remember that, while lithium is generally a well tolerated drug, there have been increasing reports demonstrating that on addition to a stable SSRI regime, mindfulness of the possibility of serotonin syndrome is essential.