Possible Interaction: Amphetamine and Fluoxetine

“One mechanism to account for these cases is a pharmacokinetic interaction between fluoxetine and amphetamine.”

“SIR: Barrett et al (1996) describe two cases of toxicity associated with the combined use of fluox etine and amphetamine.”

“ Fluoxetine treatment was shown to cause a locomotor sensitized response to a challenge dose of amphetamine (0.5 mg/kg), indicating the presence of a supersensitive dopaminergic transmission.”

“ Fluoxetine , in addition to inhibiting serotonin reuptake, inhibits hepatic mixed function oxidase, which plays an important role in the metabolic degradation of amphetamines.”

“ Subchronic fluoxetine treatment also produced an increase in the brain concentration of amphetamine when rats were challenged with amphetamine 48 h, but not 5 days, after the cessation of fluoxetine treatment.”

“The results of the present study show that 5 days of systemic treatment with fluoxetine (5 mg/kg) resulted in an augmented locomotor response to amphetamine (0.5 mg/kg).”

“This pattern of results indicates that subchronic fluoxetine potentiates the response to amphetamine within a limited time-window, and that this potentiating effect is likely to be due to the reduced metabolism of amphetamine via the inhibition of cytochrome P450 by fluoxetine and/or its metabolite norfluoxetine.”

“ Fluoxetine treatment also resulted in a higher concentration of amphetamine in the CNS.”

“Further, the results indicate that fluoxetine potentiates the effects of amphetamine by decreasing the metabolism of amphetamine, probably through inhibition of cytochrome P450 isozymes.”

“Results show that 5.0 mg/kg fluoxetine potentiated the locomotor activity induced by amphetamine (0.5–1.0 mg/ kg), and enhanced the increased dopamine overflow in the nucleus accumbens induced by amphetamine.”

“Together, these findings indicate that acute fluoxetine treatment potentiates the locomotor stimulating and dopamine activating effects of amphetamine.”

“Conclusions: The results of these experiments suggest that chronic fluoxetine treatment may induce adaptive changes in serotonergic transmission that, in themselves, do not alter the function of central reward processes, but may alter the ability of amphetamine to potentiate ICSS reward.”

“It is probable that sertraline and fluoxetine augment the locomotor stimulatory effect of amphetamine by decreasing the metabolism of amphetamine, perhaps via actions on cytochrome P450 isozymes.”

“Pretreatment with fluoxetine (2.5, 5, and 10 mg/kg), an inhibitor of serotonin reuptake, significantly decreased rates of responding maintained by amphetamine , but had no effect on responding maintained by cocaine at any of the doses tested.”

“However, if fluoxetine is given prior to amphetamine exposure for 1 day and animals are then tested for the saline response, lever pressing activity is significantly reduced.”

“Larger depletion of DA after the amphetamines had been administered in the fluoxetine pretreated animal were associated with a transient increase in the brain levels of methamphetamine and amphetamine.”

“This suggests that fluoxetine may inhibit the metabolism of amphetamines.”