Ecstasy Fluoxetine

The psychological effects of ecstasy (MDMA, methylenedi-oxymethamfetamine) may be reduced if citalopram has previously been given. It seems likely that other SSRIs will also reduce or block some of the effects of ecstasy, but increased serotonin effects may, in theory, also be possible. An isolated report describes a neurotoxic reaction in a man taking citalopram when he took unknown amounts of ecstasy. Fluoxetine and paroxetine may decrease the metabolism of ecstasy. 

Treatment of psychiatric complications should generally be along standard lines for the respective conditions. Some syndromes appear to be brief and self-limiting once ecstasy use stops, but a more chronic course may also be seen, with cases in the literature of psychoses which prove resistant to treatment (Vecellio et al. 2003). Whichever psychiatric syndrome occurs, there is possibly a theoretical indication for specific serotonergic re-uptake inhibitors such as fluoxetine, sertraline or citalopram, given the effect of ecstasy in reducing serotonin transmission. This would purely be a pragmatic approach which has not yet been properly tested, and it may be that the transmission abnormalities are not amenable to this kind of enhancement. 

As recreational use of ecstasy has dramatically increased in recent years, deaths related to its use have been reported. In a retrospective review of all violent deaths from 1992 to 1997 in South Australia, six deaths were associated with ecstasy abuse aU occurred after September 1995. Three victims had documented hyperthermia and there was evidence of hyperthermia in another. The authors suggested that individual susceptibility to MDMA may be caused by impaired metabolism by CYP2D6 or through genetically poor metabolism (seen in 5-9% of Caucasians). One woman, who died with a cerebral hemorrhage, had fluoxetine (a CYP2D6 inhibitor) present in her blood. Furthermore, toxicology identified paramethoxyamfetamine (PMA) in all the cases, amfetamine/metamfetamine in four cases, and... 

SLC6A4 (SERT) SERT plays a role in the reuptake and clearance of serotonin in the brain. Like the other SLC6A family members, SERT transports its substrates in a Na+-dependent fashion and is dependent on CL and possibly on the countertransport of K+. Substrates of SERT include serotonin (5-HT), various tryptamine derivatives, and neurotoxins such as 3,4-methylene-dioxymethamphetamine (MDMA ecstasy) and fenfluramine. SERT is the specific target of the selective serotonin reuptake inhibitors (e.g., fluoxetine and paroxetine) and one of several targets of tricyclic antidepressants e.g., amitriptyline). Genetic variants of SERT have been associated with an array of behavioral and neurological disorders. The precise mechanism by which a reduced activity of SERT, caused by either a genetic variant or an antidepressant, ultimately affects mood and behavior is not known. 

The study of ecstasy with citalopram was primarily undertaken to find out how eestasy works, but on the basis of these results and animal studies it seems likely that patients already taking citalopram may not be able to get as high on usual doses of ecstasy, and some adverse effects may also be redueed. Furthermore, if the proposed mechanism of interaction is correct, the same is also likely to be true if they are taking any other SSRI and some cases have been reported. However, be aware of possible pharmaeokinetie interaetions with some SSRIs that are potent CYP2D6 inhibitors (e.g. fluoxetine, paroxetine), which may increase ecstasy levels. There is also a risk of increased serotonergic activity and there have been a few reports of interaetions involving other sympathomimetics and SSRIs or related drugs, see Phentermine + Fluoxetine , p.205. 

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