Early evaluation of patient risk for substantial weight gain during olanzapine treatment for schizophrenia, schizophreniform, or schizoaffective disorder.
BACKGROUND
To make well informed treatment decisions for their patients, clinicians need credible information about potential risk for substantial weight gain. We therefore conducted a post-hoc analysis of clinical trial data, examining early weight gain as a predictor of later substantial weight gain.


METHODS
Data from 669 (Study 1) and 102 (Study 2) olanzapine-treated patients diagnosed with schizophrenia, schizophreniform, or schizoaffective disorder were analyzed to identify and validate weight gain cut-offs at Weeks 1-4 that were predictive of substantial weight gain (defined as an increase of > or = 5, 7, 10 kg or 7% of baseline weight) after approximately 30 weeks of treatment. Baseline characteristics alone, baseline characteristics plus weight change from baseline to Weeks 1, 2, 3 or 4, and weight change from baseline to Weeks 1, 2, 3, or 4 alone were evaluated as predictors of substantial weight gain. Similar analyses were performed to determine BMI increase cut-offs at Weeks 1-4 of treatment that were predictive of substantial increase in BMI (1, 2 or 3 kg/m2 increase from baseline).


RESULTS
At Weeks 1 and 2, predictions based on early weight gain plus baseline characteristics were more robust than those based on early weight gain alone. However, by Weeks 3 and 4, there was little difference between the operating characteristics associated with these two sets of predictors. The positive predictive values ranged from 30.1% to 73.5%, while the negative predictive values ranged from 58.1% to 89.0%. Predictions based on early BMI increase plus baseline characteristics were not uniformly more robust at any time compared to those based on early BMI increase alone. The positive predictive values ranged from 38.3% to 83.5%, while negative predictive values ranged from 42.1% to 84.7%. For analyses of both early weight gain and early BMI increase, results for the validation dataset were similar to those observed in the primary dataset.


CONCLUSIONS
Results from these analyses can be used by clinicians to evaluate risk of substantial weight gain or BMI increase for individual patients. For instance, negative predictive values based on data from these studies suggest approximately 88% of patients who gain less than 2 kg by Week 3 will gain less than 10 kg after 26-34 weeks of olanzapine treatment. Analysis of changes in BMI suggests that approximately 84% of patients who gain less than .64 kg/m2 in BMI by Week 3 will gain less than 3 kg/m2 in BMI after 26-34 weeks of olanzapine treatment. Further research in larger patient populations for longer periods is necessary to confirm these results.
Lipkovich
Ilya
I
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. lipkovichia@lilly.com
Jacobson
Jennie G
JG
Hardy
Thomas A
TA
Hoffmann
Vicki Poole
VP
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D015992:Body Mass Index; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000453:epidemiology*; D000077152:Olanzapine; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000453:epidemiology*; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D015430:Weight Gain
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine
Am J Psychiatry. 2005 May;162(5):954-62
15863798
Schizophr Res. 2008 Jul;102(1-3):230-40
18423985
Schizophr Res. 2003 Jan 1;59(1):19-27
12413638
J Clin Psychiatry. 1999 Jun;60(6):358-63
10401912
Br J Psychiatry Suppl. 2004 Apr;47:S76-9
15056598
MMWR Morb Mortal Wkly Rep. 2006 Sep 15;55(36):985-8
16971886
J Clin Psychiatry. 2004 May;65(5):715-20
15163261
J Clin Psychiatry. 2001 Apr;62(4):231-8
11379836
Am J Psychiatry. 1997 Apr;154(4):457-65
9090331
J Psychopharmacol. 2005 Nov;19(6 Suppl):110-7
16280344
J Clin Psychiatry. 2005 Dec;66(12):1576-9
16401160
J Clin Psychopharmacol. 1997 Oct;17(5):407-18
9315992
Schizophr Bull. 2008 Nov;34(6):1163-71
18156640
N Engl J Med. 2005 Sep 22;353(12):1209-23
16172203
J Clin Psychopharmacol. 2006 Jun;26(3):316-20
16702898
BMC Psychiatry. 2005 Jan 13;5:3
15649317
J Clin Psychopharmacol. 2005 Jun;25(3):255-8
15876905
J Clin Psychiatry. 2005 Feb;66(2):205-12
15705006
J Nerv Ment Dis. 2005 Oct;193(10):641-6
16208158
Diabetes Care. 2004 Dec;27(12):2806-12
15562189
Ann Clin Psychiatry. 2006 Jul-Sep;18(3):163-7
16923654
Psychiatr Serv. 2003 Aug;54(8):1155-7
12883145
J Clin Psychiatry. 2001 Feb;62(2):92-100
11247108
J Nerv Ment Dis. 2004 Jun;192(6):421-7
15167405
Int Clin Psychopharmacol. 2005 Jul;20(4):199-205
15933480
J Clin Psychiatry. 2005 Feb;66(2):183-94; quiz 147, 273-4
15705003