Effect of clozapine-quetiapine combination therapy on weight and glycaemic control - Preliminary findings

Objective: The purpose of this open-label, non-randomised, 10-month, retrospective comparative study was to assess changes in weight and diabetes status for patients initially treated with clozapine who developed diabetes and who were then switched to clozapine-quetiapine combination therapy. Methods: Sixty-five clinic charts were reviewed. All patients were from longterm care facilities. Bodyweight data were collected for this group of 65 randomly selected schizophrenic patients who were on clozapine initially (200 to 800 mg/day for 6 months) and then had quetiapine ('Seroquel') added to their therapy. Clozapine dosages were reduced as quetiapine was added proportionally: 25% of the clozapine dose was changed to quetiapine, using a ratio of exactly 1mg clozapine to 2mg of quetiapine. The quetiapine dosages ranged from 200 to 800 mg/day. This means that each patient received 6 months of clozapine therapy followed by 10 months of combination treatment with clozapine-quetiapine. Weights were recorded monthly, and diabetes status was also performed for patients who developed the condition during clozapine monotherapy. Results: Changes in weight and the status of diabetes were determined in patients switched from a 6-month clozapine therapy to the 10-month combination clozapine-quetiapine treatment. All changes were statistically significant (p < 0.001). Use of this combination therapy in the management of weight gain and diabetes resulted in a 100% satisfactory response. All 65 patients showed weight loss ranging from 0.22 to 10.5kg (0.5 to 23lb) [mean 1.8kg (3.98lb)] after the first month of combination therapy, and the improvement continued through the study duration (10 months). Marked total weight loss ranged from 0.45 to 18.6kg (1 to 41lb), with a mean loss of 4.2kg (9.2lb) over the 10-month study period. 20% of patients (13 patients) who developed diabetes during the 6-month clozapine monotherapy showed significant improvement of disease status with addition of quetiapine. Compliance with medication was 100% and no significant adverse events were observed. The most common adverse event reported by patients was drowsiness. However, this did not contribute a valid reason for discontinuation of clozapine-quetiapine therapy and could be corrected by dosage adjustment at any time of the report of this adverse effect by patients. Conclusion: An unexpected, yet welcome, clinical effect of quetiapine is its apparent propensity to induce weight loss and improve glycaemic control in patients who gain weight and develop diabetes on clozapine therapy. The results of this retrospective study support the safety and tolerability of clozapine-quetiapine combination therapy.