Is there any risk of an interaction between fluoxetine or alprazolam and amfetamine or gammahydroxy

Fråga: Is there any risk of an interaction between fluoxetine or alprazolam and amfetamine or gammahydroxybutyrate (GHB)?

It concerns an 18-year-old man with depressive illness who is being treated with Fontex (fluoxetine) 40 mg x1 and Xanor depot (alprazolam) 2 mg x1. The patient is suspected to abuse amfetamine and/or gammahydroxybutyrate (GHB).

Sammanfattning: We found some reports describing an interaction between fluoxetine and amfetamine. GHB and alprazolam can theoretically potentiate each others sedative effects. No reports of interactions between GHB and fluoxetine or between amfetamine and alprazolam were found.

Svar: A question concerning an interaction between fluoxetine and amfetamine has previously been answered in Drugline (1). The conclusion from this document is that neither a pharmacokinetic nor a pharmacodynamic interaction between the two substances can be ruled out. In an updated literature search two case-reports (2) were found. The first case was a man who had taken a small, unspecified, but previously tolerated dose of amfetamine who developed signs of amfetamine overdose (restlessness, agitation and hyperventilation) while taking 60 mg of fluoxetine daily. The other case concerned a man who developed schizophrenia-like symptoms after taking two unspecified doses of amfetamine while taking 20 mg fluoxetine daily. No drug determinations were reported (2). The postulated reason for this interaction is a metabolic interaction between fluoxetine and amfetamine (3). Amfetamine is metabolised in part by CYP2D6 (3,4), while fluoxetine and its metabolite, norfluoxetine are potent inhibitors of this enzyme (5).

We did not find any reports of interactions between GHB and fluoxetine or between amfetamine and alprazolam. However, GHB has been reported to increase the effects of benzodiazepines (6). Like benzodiazepines, GHB has both anxiolytic and sedative effects (6). Thus, a potentiating effect between GHB and alprazolam cannot be excluded. 1 Drugline no 13700 (year 1996) 2 Barrett J, Meehan O, Fahy T: SSRI and sympathomimetic interaction. Br J Psychiatry 1996; 168: 253 3 Blue P: SSRI and sympathomimetic interaction. Br J Psychiatry 1996; 169: 116 4 Sills TL, Greenshaw AJ, Baker GB, Fletcher PJ: The potentiating effect of sertraline and fluoxetine on amphetamine-induced locomotor activity is not mediated by serotonin. Psychopharmacology 1999; 143: 426-432 5 Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE: The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 1992; 34: 262-265 6 Maitre M: The gamma-hydroxybutyrate signalling system in brain: organization and functional implications. Prog Neurobiol 1997; 51: 337-361