Side Effects of Fenfluramine in Autistic Children

Piggott, Leonard R.; Gdowski, Charles L.; Villanueva, David; Fischhoff, Joseph; Frohman, Charles F.

doi:10.1016/s0002-7138(09)60241-7

Cited by 19 publications

(4 citation statements)

References 5 publications

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“…Although some studies have suggested improved social relatedness, reduced stereotypic behavior, decreased overactivity, and improved attention span, results have been conflicting and most improvements were relative to the baseline placebo rather than postfenfluramine placebo period. Fenfluramine was associated with side effects in some subjects, including lethargy, decreased appetite, and irritability (Piggott et al, 1986). Because of possible neurotoxicity (Schuster et al, 1986?, fenfluramine does not appear to have a role in the treatment of most autistic children, but the response of some children may provide direction for further research.…”

Section: Clinical Pharmacological Trialsmentioning

confidence: 99%

Autism: Review of neurochemical investigation

Cook

1990

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171

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The neurochemistry of autism, the most well-validated childhood neuropsychiatric disorder, has been studied extensively over the past three decades. Autism is of interest neurochemically because it represents a relatively homogeneous disorder with a triad of social, communicative, and intellectual developmental disturbance. Because a sufficient animal model has been lacking and relatively few diagnosed people with autism have died, most investigation has been of peripheral fluids and tissues. The most consistent finding has been that over 25% of autistic children and adolescents are hyperserotonemic. However, after 29 years of investigation, the mechanism of hyperserotonemia has not been determined. Hyperserotonemia has been found to be familial. Elevated plasma norepinephrine has also been a replicated finding. Cerebrospinal fluid (CSF) opiate activity has been found to be elevated in two studies. Plasma cyclic adenosine monophosphate (cAMP) has been found to be elevated in autistic children. A high rate of nonsuppression after dexamethasone and blunted or delayed growth hormone response to L-dopa have been found. Abnormal cell-mediated immunity has been replicated consistently in autism. Although several pharmacological trials have been conducted and shown promise in initial open trials, only "typical" antipsychotic drugs have shown replicable chronic ameliorating effects in double-blind trials. However, chronic neurotoxicity (tardive dyskinesia) has also been revealed. Findings of morphological changes in the cerebellum have been replicated. Findings in need of replication include diminished platelet function, increased baseline CSF homovanillic acid, decreased nerve cell adhesion molecule serum fragment, blunted prolactin response to fenfluramine, amelioration of symptoms by naltrexone and bromocriptine, reduced electroretinographic (ERG) b-wave amplitude, and morphological changes in the hippocampus, amygdala, and septal nuclei. In addition to refining and replicating past findings, future directions that may be fruitful include investigation of neurochemical aspects of platelet function, of interactions between monoaminergic systems, of phosphatidylinositides, and of pharmacological response to "atypical" antipsychotic agents and relatively selective serotonin receptor subtype agonists or antagonists.

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Section: Clinical Pharmacological Trialsmentioning

confidence: 99%

Autism: Review of neurochemical investigation

Cook

1990

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171

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“…A 67.3% rise of serotonin after drug discontinuation was reported in only a few children (Klykylo et aI., 1985). Although two reports list numerous untoward effects associated with fenfluramine administration, information on untoward effects during the 2-month placebo period is lacking (Piggott et al, 1986;Realmuto et al, 1986). In the current study, more children had untoward effects on fenfluramine than on placebo.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Fenfluramine in Autistic Children

Campbell

Adams

Small

et al. 1988

Journal of the American Academy of Child & Adolescent Psych

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“…The serotonin receptor blocker clomipramine was found to be superior to placebo and to desipramine in autistic disorder (17). However, the use of fluoxetine led to hyperactivity and insomnia (18), and the side-effect profile of fenfluramine (including lethargy and an increase in stereotypic behavior) limited its use (19).…”

Section: Introductionmentioning

confidence: 99%