Nutrient imbalances in depressive disorders. Possible brain mechanisms.
We examined the utility of d-fenfluramine, a serotonin-releasing drug previously shown to diminish carbohydrate craving and weight gain in obese people, in treating patients with seasonal affective disorder (SAD), a variant of depression that occurs each fall and winter and is usually associated with hyperphagia and carbohydrate craving. Eighteen patients participated in a double-blind, placebo-controlled study in 1986-1987, each receiving, in random order, d-fenfluramine (15 mg p.o. twice daily) or a placebo for four weeks, separated by a two-week washout period. Symptoms of SAD were assessed before and after each treatment period using clinical interviews by a psychiatrist, and the Hamilton Depression Rating Scale (HDS) with a special SAD addendum (ADD). Subjects were also weighed. Patients' depression scores (mean +/- SEM) were identical before treatment with drug (20.9 +/- 1.3, HDS: 13.3 +/- 0.8 ADD) or placebo (21.4 +/- 1.2, HDS; 13.2 +/- 0.6 ADD). During placebo treatment, HDS scores declined by 22.6% (p less than 0.02) and ADD scores by 9% (p greater than 0.2). During d-fenfluramine treatment, HDS scores fell by 71% (p less than 0.0001) and ADD scores by 73% (p less than 0.0001). Thirteen of the subjects (72%) demonstrated complete reversal of their abnormal test scores on d-fenfluramine. In two others, test scores fell to normal levels with both the drug and its placebo; one subject responded only to placebo; and two failed to show therapeutic responses to either drug or placebo treatment. The group as a whole lost weight (1.2 kg) on d-fenfluramine (p less than 0.033) but not on placebo. A subsequent study on nine of the responders showed that improvements persisted for the full three-month duration of the SAD season. These results indicate that d-fenfluramine, a drug not previously identified as an antidepressant, may be useful in treating SAD. Moreover, since d-fenfluramine acts specifically to enhance serotonin-mediated neurotransmission, the data further suggest that serotonin is involved in both the affective and appetitive symptoms of SAD. Indeed, the carbohydrate craving of these patients may constitute a kind of substance abuse in which the nutrient is eaten precisely for its serotonin-mediated psychotropic effects.
Wurtman
R J
RJ
Clinical Research Center, Massachusetts Institute of Technology, Cambridge 02139.
O'Rourke
D
D
Wurtman
J J
JJ
D000328:Adult; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D004040:Dietary Carbohydrates / Q000378:metabolism*; D004311:Double-Blind Method; D004435:Eating / Q000187:drug effects; D005260:Female; D005277:Fenfluramine / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012621:Seasons; D012701:Serotonin / Q000502:physiology*; D015430:Weight Gain / Q000187:drug effects
D004040:Dietary Carbohydrates; D010919:Placebos; D005277:Fenfluramine; D012701:Serotonin