A 40-year-old woman has been treated with Seroxat (paroxetine) for several months 20 mg daily. She

Fråga: A 40-year-old woman has been treated with Seroxat (paroxetine) for several months 20 mg daily. She is also treated with Imigran (sumatriptan) (duration of treatment unknown). Now Buspar (buspirone) treatment is planned because of anxiety. Is there any known risk for the combination treatment in this case?

Sammanfattning: A literature search did not reveal any documentation about the interaction between buspirone and paroxetine or sumatriptan. Considering that buspirone probably inhibits cytochrom P450 2D6 which catalyses the metabolism of paroxetine, the possibility of an interaction between the two drugs cannot be excluded. In the present case, if buspirone is added and used concomitantly with paroxetine, low doses of buspirone might be started and the effects and side effects of paroxetine in the patient should be monitored carefully.

Svar: Seroxat (paroxetine) is an antidepressant classified as a selective serotonin reuptake inhibitor (SSRI), a new group of antidepressants (cf 1). The metabolism of paroxetine is mainly catalyzed by the hepatic isozyme CYP2D6 and paroxetine is also an inhibitor of this enzyme. Imigran (sumatriptan) is a potent and selective agonist of vascular serotonin-1 (similar to 5-HT1D) receptors which mediates constriction of the cranial blood vessels and inhibit neurogenic inflammatory responses in pial vessels. It is used in acute treatment of migraine and cluster headaches (cf 2). Buspar (buspirone), a partial 5-HT1A receptor agonist, is a novel agent which has an anxiolytic effect with less potential for abuse than benzodiazepines (cf 3). Buspirone is metabolized primarily by oxidation, producing hydroxylated derivatives and a pharmacologically active metabolite, 1-(2-pyrimidinyl)piperazine. The specific enzymes catalyzing the metabolism are not known(4).

A literature search did not reveal any interaction between buspirone and paroxetine or sumatriptan. There are four previous Drugline documents concerning interactions between buspirone and other drugs, for example zimelidine, risperidone, clozapine, clonazepam and haloperidol (3,4,5,6), and the only interaction reported for buspirone is with haloperidol. It is known that the metabolism of haloperidol is catalyzed by a polymorphic enzyme (cytochrome P450 2D6). The concentration of haloperidol is increased by buspirone probably because the enzyme catalyzing the metabolism of haloperidol is inhibited by buspirone. An interaction between buspirone and paroxetine in a similar way cannot be excluded.