Low doses of insulin as a treatment of tardive dyskinesia: conjuncture or conjecture?
Tardive dyskinesia (TD) induced by antipsychotic drugs represents a great concern for patients and psychiatrists. Considering its pathophysiological mechanisms, there exists a convergence towards the development of postsynaptic dopaminergic hypersensitivity as a possible cause of TD. Hypersensitivity following receptor blockade is the consequence of an increased number of receptors and such a synthesis is energy-dependent. In the brain, under normal conditions, energy is almost exclusively provided by glucose utilization. We thus hypothesized that, if glucose availability were reduced, the metabolically hyperactive structures should represent the best functional target of a reduction in fuel availability. Twenty chronic schizophrenic outpatients (13 males, 7 females), aged 20-67 (mean: 38.3), accepted to participate in this double-blind, placebo-controlled study. They were randomly assigned to either the insulin treatment group (10 patients) or to the insulin-placebo group (10 patients). They received a subcutaneous injection of 10 units of standard insulin or placebo at 10 a.m. From day 1 to day 15, injections were performed daily and, thereafter, every other week for 5 weeks totalizing 20 injections in 90 days. At day 7, the insulin treatment group showed a sharp decrease in the intensity of TD symptoms which persisted throughout the duration of the study. By contrast, no change in TD symptomatology was observed in the insulin-placebo-treated group. Although a direct effect on DA neurones, or at least the participation of such an effect, cannot be excluded, our data favor a role of decreased glucose availability in reversing receptor hypersensitivity.
Mouret
J
J
Unité Clinique de Psychiatrie Biologique (UCPB), CHS Le Vinatier, Lyon-Bron, France.
Khomais
M
M
Lemoine
P
P
Sebert
P
P
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011954:Receptors, Dopamine / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy
D001786:Blood Glucose; D007328:Insulin; D011954:Receptors, Dopamine