Are withdrawal symptoms known in connection with citalopram treatment?/nA 57-year-old woman with a

Fråga: Are withdrawal symptoms known in connection with citalopram treatment? A 57-year-old woman with a painful shoulder condition was successfully treated with citalopram 60 mg daily (together with a non-steroidal anti-inflammatory drug) for six months. The dose has now been tapered to 10 mg daily. Further dose reduction results in severe symptoms of nausea, dizziness, headache and sweating. The patient has previously been informed that she is an ultrarapid metaboliser of debrisoquine.

Sammanfattning: Withdrawal symptoms have been described with all selective serotonin reuptake inhibitors, most frequently with paroxetine and apparently less frequently with fluoxetine, which may depend on the long half-life of this compound. To prevent abstinence, the drug should be tapered very slowly.

Svar: The question concerning selective serotonin reuptake inhibitors (SSRIs) and withdrawal symptoms has been discussed in several earlier Drugline documents, including one case where a woman with fibromyalgia experienced pain, insomnia and itching when citalopram treatment was stopped (1-4). Withdrawal symptoms like dizziness, nausea, headache and sweating seem to be fairly common, especially with paroxetine treatment, where approximately 5 percent of patients have complaints (4). There are reports concerning withdrawal symptoms with all SSRIs (citalopram, paroxetine, fluvoxamine, sertraline and fluoxetine) in the files of WHO, whereas the files of the Swedish Adverse Drug Reactions Advisory Comittee contain only 5 reports in connection with paroxetine treatment.

In the WHO material, the reporting rate has been found to be the highest for paroxetine and lowest for fluoxetine (5). This relation has also been seen in a comparative study (6). It has been proposed that the shorter half-life of paroxetine (and absence of active metabolites) is responsible for the higher incidence of withdrawal symptoms, as compared with fluoxetine (7).

This patient had earlier volunteered for a clinical trial at the Department of Clinical Pharmacology at Huddinge Hospital. She was then phenotyped for drug metabolising capacity with a debrisoquine/hydroxydebrisoquine ratio of 0.15, which indicates ultra-rapid metabolism. (Genotyping showed no gene amplification). Citalopram has an active metabolite, desmethylcitalopram, which is metabolised by CYP2D6 (debrisoquine hydroxylase). In the present case, it can be speculated on whether rapid metabolism predisposes the patient to withdrawal symptoms.