Psychotic Episode Associated With Dexfenfluramine
TO THE EDITOR: Dexfenfluramine has recently been introduced for the treatment of obesity. Dexfenfluramine exerts its anorectic effect by causing a blockade of presynaptic serotonin release and reuptake. Although other adverse central nervous system effects such as fatigue, drowsiness, impaired concentration, insomnia, and headache have been reported (1–5), a literature search revealed no cases of psychotic episodes associated with dexfenfluramine use; we report here such a case.
Mr. A was a white, 48-year-old man with major depression. He had a history of alcohol and cannabis abuse but had been sober and drug free for 2 years. He had never experienced major depression until 1 year earlier, at which time he experienced feelings of hopelessness, impaired concentration, and severe fatigue. He also gained more than 35 pounds within several months. He was placed on a regimen of doxepin, 200 mg/day, to which he responded well, without any side effects. Two months before admission to our unit, Mr. A's primary care physician had placed him on a regimen of dexfenfluramine, 30 mg/day, for treatment of obesity after several unsuccessful dieting attempts. Although he initially experienced insomnia for about 2 weeks, Mr. A's sleep pattern eventually had returned to normal.
On the day that Mr. A was admitted to the psychiatric emergency room, he had become increasingly paranoid. He blamed family members and the government for taking part in a conspiracy against him and the citizens of the United States. He eventually walked into a federal building in the neighborhood and asked to see the visitor's log. When his request was denied by the security personnel, he became violent. Mr. A's extreme agitation and combativeness at the time of admission necessitated the use of four-point restraints. He was responding to internal stimuli and blaming the medical staff for being a part of the conspiracy against him. He had pressured speech and exhibited grandiose and paranoid delusions, e.g., “I knew the truth about what happened to that airplane.” He responded well to a 5-mg intramuscular dose of droperidol that was administered shortly after admission. A urine toxicology screen and a blood alcohol test revealed that no alcohol or illicit drugs had been ingested. No electrolyte imbalance was determined from routine laboratory tests. There was no history of psychotic disorder in the family. Mr. A was given intramuscular haloperidol, 2 mg b.i.d., during the subsequent 24 hours of his hospital stay. He was discharged, and his symptoms resolved completely within 72 hours after dexfenfluramine discontinuation. He was able to go back to work within a week.
In this report we described a psychotic episode associated with dexfenfluramine use in a patient with major depression. The patient never had any psychotic disorder before the current episode. This episode could have been a rare adverse effect of dexfenfluramine alone or the result of an interaction between dexfenfluramine and doxepin, a tricyclic antidepressant agent that inhibits the reuptake of norepinephrine into the nerve terminals at the synaptic level. Considering the size and the high motivation of the target population, the pharmacologic actions, drug interactions, and adverse effect profile of dexfenfluramine need to be reevaluated. Even more important is the responsibility of all physicians to closely follow their patients after prescribing a newly approved drug.
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