Centrally acting appetite suppressant drugs used in the treatment of obesity fall into 2 broad pharmacological categories; those which act via brain catecholamine pathways and those which act via serotonin pathways. Of the former group, amphetamine and phenmetrazine are no longer recommended because of their stimulant properties and addictive potential. The remaining drugs in this class include amfepramone (diethylpropion), phentermine, mazindol and phenylpropanolamine. All have been shown to reduce appetite and lower food intake, thereby helping obese patients more easily keep to a low-calorie diet and lose weight. They all have some sympathomimetic and stimulant properties. Anorectic drugs which promote serotonin neurotransmission have no such stimulant or sympathomimetic properties. They are fenfluramine, together with its recently introduced dextrorotatory stereoisomer dexfenfluramine, and fluoxetine. They reduce appetite and food intake and are effective in the treatment of obesity. Anorectic drugs should be reserved for those who are clinically at risk from being overweight, and then only as part of a comprehensive weight-reducing programme including regular dietary counselling. Although current licensing regulations only allow their use over a relatively short period (12 to 16 weeks), clinical trials have shown them to be effective over longer periods, particularly in preventing weight regain. Of the compounds currently indicated for use in obesity, dexfenfluramine appears to have the most suitable pharmacological profile, although it should not be given to patients with a history of depression. When used appropriately, appetite suppressants can be of real therapeutic benefit, and pose little risk.

SynopsisBecause of the practical difficulties which arise in studying manic patients, a reproducible model for mania using human subjects would be a valuable adjunct to research in this condition. Dextroamphetamine, given as a single oral 20 mg dose, fulfils the criteria for such a model in that there are very close similarities between the changes which occur after dextroamphetamine and those which have been observed in mania in terms of subjective experience, physiological and endocrine changes, and response to pharmacological agents.

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A 12-month double-blind trial of carbamazepine vs lithium, given as sole treatment for the prophylaxis of bipolar affective disorder, was carried out in 31 patients. All were previously stable on lithium; 15 were switched over to carbamazepine and 16 remained on lithium. Although the overall relapse rate was similar in the 2 groups (6 on carbamazepine, 8 on lithium), nearly all the relapses in carbamazepine occurred in the first month, probably precipitated by lithium withdrawal. Two patients on carbamazepine developed a rash and were withdrawn. More side effects were noted during the early stages on carbamazepine. Patients on lithium tended to gain weight (+4 kg) compared with carbamazepine (-3.1 kg). It is concluded that carbamazepine is as effective as lithium in the prophylaxis of bipolar affective disorder; changeover from lithium to carbamazepine should be done slowly.

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This study investigated the role of the 5-HT2/1C receptor antagonist ritanserin on d-fenfluramine (d-FF) induced changes in food intake, prolactin (PRL) secretion and oral temperature in 12 healthy male volunteers. The study was double blind and placebo controlled. Food intake was measured using an automated food dispenser. d-FF (30 mg) significantly reduced fat intake. While ritanserin (5 mg) had no effect when given alone it abolished the d-FF induced reduction in fat intake. In addition, ritanserin abolished the d-FF induced rise in PRL and oral temperature. The results suggest that 5-HT2 or 5-HT1C receptors mediate the effects of d-fenfluramine on appetite, prolactin secretion and temperature in humans.

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