Is there any risk for drug interaction between citalopram and bupropion?/nA patient is being treate

Fråga: Is there any risk for drug interaction between citalopram and bupropion?<br><br>A patient is being treated with citalopram (20 mg daily) and treatment with bupropion for smoking cessation is considered.

Sammanfattning: No reports on drug interactions between bupropion and citalopram were found in the literature. Citalopram and bupropion mainly have different mechanisms of action and do not appear to interfere with each other´s metabolism. Therefore, the risk for pharmcodynamic or pharmacokinetic drug interactions should be low.

Svar: A thorough literature search did not reveal any reports on interactions between bupropion and citalopram.<br><br>Bupropion is an antidepressant and non-nicotine aid to smoking cessation that acts by weakly inhibiting the reuptake of dopamine and noradrenalin (1,2). Bupropion has only minimal effect on the reuptake of serotonin (1). Hence, the risk for a pharmacodynamic interaction with selective serotonin reuptake inhibitors (SSRIs), such as citalopram, should be low. In addition, bupropione and SSRI combination therapy has been proposed to be effective in the treatment of refractory depression in patients who have not responded to monotherapy (3,4).<br><br>Also the risk of clinically relevant metabolic drug interactions between bupropion and citalopram should be low. The substances are mainly metabolised by different enzymes and should not inhibit or induce each other´s metabolism. Bupropion has been shown to be metabolised to the active metabolite hydroxybupropion by cytochrome P450 isoenzyme CYP2B6 in human liver microsomes (5), whereas CYP3A4 has been reported not to contribute significantly to the metabolism (6). The Summary of Product Characteristics (SPC) states that bupropion and hydroxybupropion are weak inhibitors of CYP2D6 (1). However, there are studies indicating that bupropion and hydroxybupropion have low inhibitory potential of CYP2D6 in vitro (5) and that bupropion does not inhibit CYP2D6 in vivo (7). Citalopram is mainly metabolised by the CYP3A4 and CYP2C19 and to a minor extent by CYP2D6 (8). The fact that citalopram is metabolised by more than one CYP-enzymes suggests that inhibition of its biotransformation by other drugs is less likely.<br><br>It has been suggested that there is a theoretical risk for serotonin syndrome if citalopram is administred in combination with bupropion since bupropion is a weak inhibitor of neuronal serotonin reuptake (9). However, this risk is probably low and so far not supported by any clinical data.<div id="referenser" style="display:none;">1 Zyban. Summary product characteristics. Medical Product Agency homepage (www.mpa.se)<br>2 Cooper BR, Wang CM, Cox RF, Norton R, Shea V, Ferris RM. Evidence that the acute behavioral and electrophysiological effects of bupropion (Wellbutrin) are mediated by a noradrenergic mechanism. Neuropsychopharmacol 1994;11:133-41.<br>3 Bodkin JA, Lasser RA, Wines JD Jr, Gardner DM, Baldessarini RJ. Combining serotonin reuptake inhibitors and bupropion in partal responders to antidepressant monotherapy. J Clin Psychiatry 2000;61:61-2.<br>4 Nelson JC. Augmentation strategies with serotonergic-noradrenergic combinations. J Clin Psychiatry 1998;59(Suppl 5):65-8.<br>5 Hesse LM, Venkatakrishnan K, Court MH, von Moltke LL, Duan SX, Shader RI, Greenblatt DJ. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos 2000;28:17776-83.<br>6 Faucette SR, Hawke RL, Shord SS, Lecluyse EL, Lindley CM. Evaluation of the contribution of cytochrome P4503A4 to human liver microsomal bupropion hydroxylation. Drug Metab Dispos 2001;29:1123-9.<br>7 Pollock. BG, Sweet RA, Kirshner M, Reynolds CF 3rd. Bupropion plasma levels and CYP2D6 phenotype. Ther Drug Monit 1996;18:581-5.<br>8 Brosen K, Naranjo CA. Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram. Eur Neuropsychopharmacol 2001;11:275-83.<br>9 Drugline no 17378 (year 2000)</div>