Reactions 851 - 12 May 2001

Clomipramine

Serotonin syndrome after clozapine withdrawal?:case report

A 44-year-old man with undifferentiated schizophrenia andobsessive-compulsive disorder experienced possibleserotonin syndrome after clozapine was withdrawn from hisregimen of clomipramine and clozapine.

The man was initially treated with clomipramine, andclozapine was started 2 months later. He received clozapine600 mg/day with the dosage reduced to 500 mg/day after 2years, and he received this lower dosage with clomipramine200 mg/day for 1 year. Clomipramine was then reduced to 50mg/day over a period of 10 days. However, his clomipraminedosage was increased to 150 mg/day over 14 days due toworsening symptoms. At the same time, clozapine wastapered and discontinued over 19 days.

The day after clozapine was discontinued, the man becameanxious, agitated and resistant to care, and he was sweatingexcessively. Three days later, he was very confused, agitated,sweating profusely, shivering and pallid. He was tense andcould not understand simple instructions. His WBC count andcreatine kinase level were slightly increased. At that time, hisdosage of clomipramine had been increased to 200 mg/dayand he was also receiving clonazepam.

It was suspected that the man had serotonin syndrome andclomipramine was withheld for 1 day, and then tapered andstopped over 3 days. His sweating, tremor and confusionresolved over the next 10 days. Clomipramine 25 mg/day wasrestarted 2 days later and clozapine was restarted 8 days afterthat. At 4 months’ follow-up, he had not experienced anyfurther symptomatology suggestive of serotonin syndrome. Atthat time, he was maintained on clozapine 450 mg/day,clomipramine 100 mg/day and valproic acid.

Author comment: ‘Clinicians should be aware thatremoving a 5-HT2a antagonist from a treatment regimenincluding an agent that increases serotonin in the synaptic cleftmay contribute to withdrawal symptoms or potentially causeserious adverse drug reactions, including serotonin syndrome.’Zerjav-Lacombe S, et al. Possible serotonin syndrome associated withclomipramine after withdrawal of clozapine. Annals of Pharmacotherapy 35:180-182, Feb 2001 - Canada 800860868

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Reactions 12 May 2001 No. 8510114-9954/10/0851-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved