Are there any reasons to suspect pharmacokinetic interactions between buprenorphine and fluoxetine,

Fråga: Are there any reasons to suspect pharmacokinetic interactions between buprenorphine and fluoxetine, sertraline, citalopram, mirtazapine, venlafaxine or reboxetine? Which might be the optimal antidepressant to use in a patient with heroin addiction and depression.

The question is prompted by a patient who experienced a lack of effect of buprenorphine after initiation of fluoxetine.

Sammanfattning: The most certain way of avoiding a possible pharmacokinetic interaction between buprenorphine and an antidepressant would probably be choosing citalopram, sertraline or venlafaxine. The fact that buprenorphine has an active metabolite would seem to make it less sensitive to possible interactions at the cytochrome level. Our lab offers the possibility of analysing serum concentrations of buprenorphine as well as of fluoxetine, venlafaxine, sertraline and citalopram.

Svar: No reports of pharmacodynamic or pharmacokinetic interactions between buprenorfin and the aforementioned antidepressants could be found in Medline or in the standard literature.

Buprenorphine is metabolised into its active metabolite norbuprenorphine by cytochrome P450 isoenzyme CYP3A4. The metabolite is excreted through feces and urine. At supratherapeutic concentrations, buprenorfin is an inhibitor of CYP3A4 (1).

Of the aforementioned antidepressants, fluoxetine, venlafaxine and sertraline are predominantly metabolised by CYP2D6. Mirtazapine is probably metabolised by both CYP1A2, CYP2D6 and CYP3A4. The metabolic pathways of reboxetine are unknown. Citalopram is primarily metabolised by CYP2C19 and CYP2D6. Fluoxetine is a strong inhibitor of CYP2D6 at clinical concentrations (2).

A theoretical approach in a patient with heroinism and depression would be to use methadone instead of buprenorphine. Methadone is a potent serotonin reuptake inhibitor at clinical concentrations (3). Clinical documentation for methadone as an antidepressant, however, is lacking. Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999 FASS 2003 (The Swedish catalogue of approved medical products) Gourevitch MN, Friedland GH. Interactions between methadone and medications used to treat HIV infektion: a review. Mt Sinai J Med 2000;67(5-6):429-36.