Obesity Management

Obesity, like depression, is an extremely important and common epidemiologic condition. Overweight requires pointers as to the point when to pharmacologically intervene e.g. 20% above ideal body weight or Body Mass Index of > 27-30. Such pharmacological interventions are logical as morbidity and mortality statistics support use of the anorexigenic agents always combined with the necessary elements of calorie control, activity and change in eating habits. Such prescriptions will lower the overall risks more than the triad management of pure diet, exercise and behavioral interventions without drugs.

The link of serotonin receptors with appetite, craving and weight control is also important. Serotonin blocking agents such as cyproheptadine characteristically have been associated with weight gain and several antidepressant compounds such as the SSRI group and trazodone have at times been used in weight reduction although their effect is unpredictable. The exact receptor subtypes involved and mechanisms e.g. agonism or antagonism for weight control is unclear. Such data is confounded by approximately one third of patients with obesity having significant depressive disorder.

The development of anti-obesity agents such as dexfenfluramine (Redux) raised fascinating serotonergic links for both appetite suppression and selective carbohydrate craving and apparently markedly diminished the risks of the norepinephric / amphetamine like effects of previous compounds. Dexfenfluramine is the active isomer of fenfluramine (Pondamin) meaning that half the dose previously required could be taken with the same effect and without the extra side-effects of the levo- fenfluramine. However, unfortunately, these two drugs have been withdrawn from the USA and possibly other markets because of questions pertaining to heart valve lesions which may or may not be linked.

Because receptor subtype effects have not been well-studied the interaction of serotonin active drugs is complex and at times unclear. There are however good theoretical pointers suggesting reduced dosage with cautious combination use only with the shorter acting antidepressants that do not overflow the serotonergic bathtub but which may have significant norepinephric effects.