Review of Fenfluramine in the Treatment of the Developmental Disabilities

Repetitive behavior disorders in autism

“…Fenfluramine, which acts by increasing 5-HT release and inhibiting its uptake, has been studied in children with autism and appears to result in improvement in stereotypies [Aman and Kern, 1989]. It should be noted, however, that there has been considerable debate concerning the possible neurotoxic effects of fenfluramine.…”

A Double-blind Comparison of Clomipramine, Desipramine, and Placebo in the Treatment of Autistic Disorder

“…However, the effects of clomipramine on central serotonergic function remain unclear,32 and fenfluramine hydrochloride, which in¬ creases central nervous system serotonin activity through increased release, reuptake inhibition, and weak receptor agonist action but depletes brain serotonin with high doses or long-term use,33"36 has been extensively studied in au¬ tism, with equivocal results. 37 Serotonin-dopamine interactions or direct effects on dopamine neurotransmission may play a role in the dif¬ ferential response of autism to clomipramine therapy, con¬ sistent with the results of previous studies showing im¬ provement in autistic symptomatology with haloperidol, a potent dopamine blocking agent.26 Serotonergic neu¬ rons are believed to exert an inhibitory influence on dopa¬ minergic function.38"40 Clomipramine, for example, po¬ tentiates the cataleptic effect of haloperidol in a dosedependent manner in rats, whereas methysergide, a serotonin antagonist, reduced haloperidol's cataleptic effect.38 Clo¬ mipramine has also been shown to have direct dopamine blocking effects, as demonstrated by its extensive binding to postsynaptic receptors of dopamine antagonists in stud¬ ies of 3H-spiperidol binding to rat striatal membranes in vitro, a property not shared by desipramine. 41 It must be kept in mind that other treatments for autism, including behavior therapy, may exert their ef¬ fects through serotonergic and/or dopamine-blocking mech¬ anisms similar to those of clomipramine, as has been shown for fluoxetine and behavior therapy in obsessivecompulsive disorder.…”

Abnormal serotonergic development in a mouse model for the Smith–Lemli–Opitz syndrome: implications for autism

“…Abnormally high brain levels of serotonin (5-HT), altered developmental dynamics of 5-HT synthesis, genetic polymorphisms in the serotonin transporter, dissymmetry of serotonergic pathways, and an increase in whole blood 5-HT levels have been reported in studies of autistic individuals (Chugani et al, 1997(Chugani et al, , 1999Betancur et al, 2002). Effective pharmacological therapies for treating autistic symptoms include drugs that impact the serotonergic system (August et al, 1984;Aman and Kern, 1989;Carlsson, 1998;McDougle et al, 1998McDougle et al, , 2000.…”