Can Buspar (buspirone) in itself or combined with Cipramil (citalopram) cause enhanced and prolonge

Fråga: Can Buspar (buspirone) in itself or combined with Cipramil (citalopram) cause enhanced and prolonged menstruation? A 41-year-old woman with major depression is being treated with Cipramil since a long time without any complications. Recently, the dose of Cipramil was raised to 60 mg and two weeks later Buspar 5 mg was added. The patient had then an enhanced and prolonged menstruation, but did not have any bruises or bleedings from other mucous membranes.

Sammanfattning: Patients may be susceptible to serotonergic overstimulation when adding buspirone to citalopram treatment, but no cases of bleeding disorder due to the combination have been reported. High doses of SSRIs have been mentioned as a risk for haemorrhagic side effects. In the present case, this might be the cause of the enhanced bleeding, since the dose of Cipramil can be considered high. It can hence be of interest to monitor the plasma concentration of this drug.

Svar: The question concerning an interaction between buspirone and citalopram has been documented previously in Drugline (1). It was concluded that no documentation about such an interaction was known. An updating literature search has revealed new data. An interaction between buspirone and citalopram may result in excessive serotonergic effect. A case report describes serotonin syndrome and hyponatremia after ingestion of excessive doses of buspirone and citalopram (initial concentration of the latter was estimated to more than 1200 nmol/l) (2). However, no bleeding disorder was observed and it is not clear if the symptoms may occur in patients taking therapeutic doses.

In two studies, addition of buspirone to SSRI treatment did not result in any serious side effects. In one placebo-controlled study, 82 female and 37 male patients with major depressive episodes had buspirone (maximum 60 mg daily) or placebo added to their medication with 30 mg paroxetine or 40 mg citalopram (3). No statistically significant differences were found in the response rate or in the frequency of adverse reactions, comparing with the placebo. In the second study, 22 patients with major depression received 20 to 30 mg buspirone daily for four or five weeks in addition to their existing medication with fluoxetine, paroxetine or citalopram (4). No serious side effects, such as serotonin syndrome or bleeding complications, were observed.

Buspirone per se is known to produce dose-related adverse effects similar to the SSRIs (5). The Swedish Medical Product Agency has received three reports of haematological side effects associated with buspirone (6). These reports concern hematoma, epistaxis and increased PK-value. In addition, one observation of meno-metrorrhagia has been reported.

High doses of SSRIs, such as citalopram, have been associated with bleeding complications due to inhibition of serotonin reuptake in platelets (7, 8, 9). In the present case, this might be the cause of the enhanced bleeding, since the dose of 60 mg Cipramil can be considered high.