Fenfluramine Tricyclic antidepressants

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. 

Exacerbation of depression has been seen in some patients given fenfluramine and several cases of withdrawal depression have been observed in patients taking amitriptyline and fenfluramine, following episodes of severe depression. The manufacturers have advised that fenfluramine should not be used in patients with a history of depression or in those being treated with antidepressants. On the other hand it has also been claimed that fenfluramine can be used safely and effectively with tricyclic antidepressants." One report describes a rise in the plasma levels of amitriptyline when fenfluramine 60 mg daily was given to patients taking amitriptyline 150 mg daily. ... 

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