Metabolic outcomes in patients attending a Clozapine clinic — ASN Events

Metabolic outcomes in patients attending a Clozapine clinic (#377)

Christopher Muir 1 , Rhonda Beach 1 , Yolinda Assur 1 , Irina Piatkov 1 , Roger Bartrop 1 , Sue Lynn Lau 1 2 , Mark McLean 1 2 , Dorgival Caetano 1
  1. Blacktown Hospital, Blacktown, NSW, Australia
  2. University of Western Sydney, Sydney

Background: Adverse metabolic outcomes from antipsychotic therapy are frequent, but patterns and predictors are poorly understood. No clear relationship between drug dose/levels and adverse metabolic effect exists. Norclozapine, a major metabolite, may play a role. Methods: We conducted an audit of all patients attending an outpatient clozapine clinic in May 2013 for 3 months or more. Demographic and lifestyle data, anthropometry, clozapine dose, serum biochemistry and clozapine/norclozapine levels were examined cross-sectionally. Retrospective chart review identified body-weight at 3, 6, 12 months and subsequent years of therapy. PASW statistics 18.0 was used to compare means (t-test) and perform correlations. Results: The average age (±SD) of 182 clinic-attendees was 39(±11) years. 62% male, 61% Caucasian, 12% Pacific Islander, 10% Asian, 5% Aboriginal, 5% Middle-Eastern and 5% Subcontinental. Of 65 patients with fasting BGL>6.1mmol/L, only 39% had a known diagnosis of diabetes. 10 of 32 patients with fasting BGL>7.0mmol were undiagnosed. 77% had total cholesterol >5.2mmol/L and/or triglycerides >1.7mmol/L, but only 14% received statins/fibrates. Mean duration of clozapine treatment was 368 (±259) weeks. Weight-gain on clozapine was highly variable. In 117 patients, the average weight-gain between months 3 to 12 of therapy was 2.1kg (range -17kg to +24kg, normally distributed). Weight-gain between 3-12 months did not reliably predict weight-change in subsequent years. There was greater mean weight-gain in smokers (3.8 vs 0.52kg, p=0.03) and a trend to greater weight-gain in women (3.5 vs 1.1kg, p=0.09). There was no difference in mean 3-12 month weight-gain according to Caucasian/non-Caucasian ancestry, physical activity score or BMI. There was no correlation between weight-gain and clozapine dose or level, but clozapine/norclozapine ratio was weakly inversely correlated with weight-gain (r=-0.28, p=0.007). Clozapine/norclozapine ratios were higher in those who lost vs gained weight (p=0.06), non-smokers (p=0.008) and in people of non-Caucasian descent (p=0.01). Conclusion: Metabolic disease is under-recognised in patients on clozapine. Factors affecting drug metabolism may predict susceptibility.

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