Zur Vorlage Bei der Versicherungsanstalt Wien, am 29. 10. 2002 Betrifft: Antrag auf Kur zur Gewichtsreduktion bei Neuroleptika induzierter Adipositas des Patienten HANS BERNHARD, Geb. 23.7.1973 Sehr geehrter Frau Kollegin, Sehr geehrter Herr Kollege, Bei meinem Patienten , Herrn HANS BERNHARD kam es anfang 2002 zu einer Erstmanifestation einer Manische Depressiven Erkrankung (ICD 10 F 31.2). Ihm Rahmen der akuten und subakuten Behandlung erhielt der Pat. Zyprexa (Olanzapin) verschrieben auf welches der Pat sehr gut respondierte. Im Rahmen dieser Behandlung wurde natuerlich jeweils versucht die niedrigst moegliche Dosis zu finden. Trotz dieses Versuchs sowie Aufklaerungsma§nahmen und eines baldigen Ausschleichens der Medikation kam es dennoch zu einer massiven Gewichtszunahme. Diese Gewichtzunahme unter Zyprexa (Olanzapin) ist in der Literatur gut bekannt (Gupta, Droney et al. 1998; Gupta, Droney et al. 1999; Osser, Najarian et al. 1999; Karagianis 2000; Sacchetti, Guarneri et al. 2000; Ball, Coons et al. 2001; Baptista and Beaulieu 2001; Basson, Kinon et al. 2001; Eder, Mangweth et al. 2001; Floris, Lejeune et al. 2001; Ganguli, Brar et al. 2001; Haapasalo-Pesu and Saarijarvi 2001; Kinon, Basson et al. 2001; Gothelf, Falk et al. 2002; Malyuk, Gibson et al. 2002; Meyer 2002; Poyurovsky, Pashinian et al. 2002; Ramankutty 2002; Ratzoni, Gothelf et al. 2002; Riccitelli and Baker 2002; Virkkunen, Wahlbeck et al. 2002). So wie in der Literatur beschrieben, wurde der Patient ueber die Nebenwirkung aufgeklaert. In der Akutphase der Behandlung wurde versucht noch waehrend des stationaeren Aufenthalts eine Reduktionskost zu verordnen. Nach Entlassung aus der stationaeren Pflege erfolgte eine Besprechung der Moeglichkeiten mit den durch Zyprexa verstaerkten Hungergefuehlen umzugehen. Der Pat. erhielt eine Broschuere (speziell zu diesem Zweck von Lilly herausgegeben) und diese wurde gemeinsam besprochen. Au§erdem begann der Pat regelmae§ig Bewegung sowie Ausdauersport (Inline Skaten um die Gelenke nicht zu ueberlasten) zu machen. Nachdem es trotz Information weiterhin zu einer Gewichtszunahme kam, wurde die Dosis so schnell wie psychiatrisch moeglich weiter reduziert und der Pat. gebeten ein Esstagebuch zu fuehren. Aufgrund der Daten des Tagebuches erfolgten weitere Schulungen und Gespraeche. Zu diesem Zeitpunkt kam es zwar zu einer deutlichen Verlangsamung der Gewichtszunahme die jedoch erst nach voelligem Ausschleichen der Therapie sistierte. Insgesamt kam es jedoch zwischen Maerz 2002 Aufnahmegewicht von 90 Kg bei 175 cm Koerpergroe§e (BMI 29.4) zu einer Gewichtszunahme von 25kg mit einem Maximalgewicht von 115 Kg. (BMI 37.6) und somit zu einer manifesten behandlungsbeduerftigen Adipositas im Juni 2002. Trotz bereits durchgefuehrter Schulungen, des Bewegungsprogramms gelang es dem Pat bis jetzt (29.10.2002) nicht das Gewicht wesentlich zu reduzieren, dieses Pendelt trotz Gegenma§nahmen zwischen 111 und 114 Kg. Dies bedeutet, dass es im Rahmen der notwendigen psychiatrischen Behandlung, trotz Aufklaerung, Bewegungsprogrammen und diaetischer Einschraenkungen zu einer massiven Gewichtzunahme kam. Nachdem diese Gewichtszunahme als Folge der notwendigen Behandlung der MDK anzusehen ist, und es dem Pat. bis jetzt nicht gelungen ist sein Gewicht wieder zu normalisieren, empfehle ich fuer Hrn. HANS BERNHARD einen Kuraufenthalt wo er die notwenigen Verhaltensaenderungen und weitergehenden Informationen erlernen kann, um sie in weiterer Folge anzuwenden. Aufgrund der guten Kognitiven Faehigkeiten des Patienten und seiner bisherigen guten Erfahrungen bei der Befolgung von konkreten aerztlichen Anweisungen, sehe ich einen Kuraufenthalt zum Erlernen einer gesunden fettarmen, kohlenhydratreichen Ernaehrungsweise und eines gesunden Lebensstils als sinnvoll und indiziert. In der Hoffnung Ihnen mit diesen Informationen gedient zu haben, verbleibe ich mit freundlichen Gruessen. Sollten Sie noch weiter Fragen haben zoegern Sie nicht mit mir unter Tel: 77- 7777 7777 Kontakt aufzunehmen. Hochachtungsvoll OA.Dr. S. D. Schindler Leiter der Ambulanz Anhang: Literaturliste teilweise. mit Abstakt zu Gewichtzunahme unter Olanzapin Literaturliste: Ball, M. P., V. B. Coons, et al. (2001). "A program for treating olanzapine-related weight gain." Psychiatr Serv 52(7): 967-9. This study evaluated the effectiveness of a Weight Watchers program for patients with schizophrenia who had olanzapine-related weight gain and ascertained whether the severity of patients' psychiatric symptoms was correlated with the patients' success in losing weight. Seven men and four women who had been treated with olanzapine and who had gained at least 7 percent of their pretreatment body weight attended Weight Watchers meetings and were offered supervised exercise sessions. The patients' weight, body mass index, and psychiatric symptoms were assessed and were compared with those of a matched comparison group who did not attend the Weight Watchers program. Only the men experienced significant weight loss. No correlation was found between weight loss and exercise or change in psychiatric symptoms. Baptista, T. and S. Beaulieu (2001). "Body weight gain, insulin, and leptin in olanzapine-treated patients." J Clin Psychiatry 62(11): 902-4. Basson, B. R., B. J. Kinon, et al. (2001). "Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone." J Clin Psychiatry 62(4): 231-8. OBJECTIVE: Clinical factors predicting weight change in patients with schizophrenia and related disorders during acute treatment with the antipsychotic drugs olanzapine, risperidone, and haloperidol were sought through retrospective analyses. METHOD: Six-week body-weight data from 2 trials, study 1 comparing olanzapine and haloperidol (N = 1,369) and study 2 olanzapine and risperidone (N = 268), were analyzed. Effects of 8 clinically relevant covariates--therapy, clinical outcome (Brief Psychiatric Rating Scale), baseline body mass index (BBMI), increased appetite, age, gender, race, and dose--on weight were compared. RESULTS: In study 1, olanzapine (vs. haloperidol) therapy, better clinical outcome, lower BBMI, and nonwhite race significantly affected weight gain. Effects of increased appetite and male gender on weight gain were significant for olanzapine but not for haloperidol. In study 2, better clinical outcome, lower BBMI, and younger age significantly affected weight gain. Increased appetite was more frequent during olanzapine treatment than during haloperidol, but not significantly different from risperidone. Significant differences in effect on weight change were found between olanzapine and haloperidol but not between olanzapine and risperidone. No evidence was found that lower antipsychotic drug doses were associated with lower weight gain. CONCLUSION: This report identifies predictive factors of acute weight change in patients with schizophrenia. Similar factors across antipsychotic drugs in predicting greater weight gain included better clinical outcome, low BBMI, and nonwhite race. Factors differing between conventional (haloperidol) and atypical (olanzapine) agents included increased appetite and gender. Choice of atypical antipsychotic drug (olanzapine vs. risperidone) was of minor importance with regard to influence on acute weight gain. Eder, U., B. Mangweth, et al. (2001). "Association of olanzapine-induced weight gain with an increase in body fat." Am J Psychiatry 158(10): 1719-22. OBJECTIVE: The goal of this study was to explore the pathophysiology of weight gain during treatment with olanzapine for schizophrenia. METHOD: The authors used a prospective, controlled, open study comparing body weight, body mass index, and related biological measures in mentally and physically healthy volunteers and olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin serum levels, body mass index, and body composition were assessed over an 8-week observation period. RESULTS: A significant increase in body weight, leptin serum levels, and percentage of body fat was seen in patients treated with olanzapine, but the drug-free comparison group did not show any significant changes. The weight gain during antipsychotic treatment with olanzapine was mainly attributable to an increase in body fat; patients' lean body mass did not change. CONCLUSIONS: In addition to the original finding that an increase in body fat is mainly responsible for olanzapine-induced weight gain, these findings confirm results obtained in other studies showing increases in body weight and serum leptin levels during treatment with second-generation antipsychotics. Floris, M., J. Lejeune, et al. (2001). "Effect of amantadine on weight gain during olanzapine treatment." Eur Neuropsychopharmacol 11(2): 181-2. Patients treated with olanzapine may gain weight, especially in the first months of therapy. Amantadine (100-300 mg/day) was started in 12 patients having a mean weight gain of 7.3 kg during olanzapine treatment. The patients' weight stabilised and over 3-6 months they lost an average of 3.5 kg. No clinical deterioration occurred and no adverse effects were reported. These observations merit confirmation in randomised, controlled trials. Ganguli, R., J. S. Brar, et al. (2001). "Weight gain over 4 months in schizophrenia patients: a comparison of olanzapine and risperidone." Schizophr Res 49(3): 261-7. Weight gain frequently accompanies treatment with antipsychotics. In order to determine whether newer antipsychotic agents differ from each other with respect to weight gain, we compared two cohorts of patients with DSM-IV schizophrenia who had newly started treatment with either risperidone or olanzapine. After obtaining informed consent, data regarding body weight and height were culled from existing medical records of 100 patients (50 patients in each treatment group). Baseline body weight, close to the time of starting the new medication, and body mass index [BMI = weight (kg)/height (m) squared] were compared to the body weight and BMI following 4 months of treatment. There was no significant change in mean body weight or BMI in the group treated with risperidone (baseline weight = 83.1 kg +/- 20.5, follow-up = 82.8 kg +/- 19.9; matched pair t = 0.66, P = n.s.; baseline BMI = 29.6 +/- 9.4, follow-up = 29.5 +/- 9.1; matched pair t = 0.79, P = n.s.). However, in the group treated with olanzapine, there was a significant increase in both mean body weight and BMI (baseline weight = 84.9 kg +/- 25.0, follow-up = 87.1 kg +/- 25.1; matched pair t = 4.62, P < 0.001; baseline BMI = 29.5 +/- 7.4, follow-up = 30.3 +/- 7.5; matched pair t = 4.43, P < 0.001). In this naturalistic study, treatment with olanzapine was associated with a mean weight gain of about 2 kg from baseline, in patients with schizophrenia, while treatment with risperidone was associated with no mean weight change. Gothelf, D., B. Falk, et al. (2002). "Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine." Am J Psychiatry 159(6): 1055-7. OBJECTIVE: The authors studied weight gain mechanisms and energy balance in patients treated with olanzapine. METHOD: The body mass index of male schizophrenic adolescent inpatients treated with olanzapine (N=10) and of 10 matched patients treated with haloperidol (N=10) were measured at baseline and after 4 weeks of treatment. For the patients treated with olanzapine, caloric intake, resting energy expenditure, and physical activity (determined through accelerometry and heart rate monitoring) were assessed at baseline and after 4 weeks of treatment. RESULTS: Body mass index significantly increased in those treated with olanzapine but not in those given haloperidol. The increase in body mass index was due to an increase in caloric intake without change in diet composition. Olanzapine had no significant effect on resting energy expenditure. Daily energy expenditure was very low before and after treatment. CONCLUSIONS: Olanzapine-induced weight gain is associated with a general increase in caloric intake. Gupta, S., T. Droney, et al. (1998). "Olanzapine-induced weight gain." Ann Clin Psychiatry 10(1): 39. Gupta, S., T. Droney, et al. (1999). "Olanzapine: weight gain and therapeutic efficacy." J Clin Psychopharmacol 19(3): 273-5. Haapasalo-Pesu, K. M. and S. Saarijarvi (2001). "Olanzapine induces remarkable weight gain in adolescent patients." Eur Child Adolesc Psychiatry 10(3): 205-8. We present here clinical case reports of three adolescents, aged 14-17 years, who were treated with olanzapine. The daily dose was 10 mg. Prior to olanzapine, the patients were unsuccessfully treated with other antipsychotic drugs. The response to olanzapine for psychotic symptoms was clinically significant in all three patients. The major adverse effect was excessive weight gain. The increases in body mass index (BMI) were 9, 8 and 5 kg/m2. One of the patients later lost the additional weight. Especially in adolescents obesity is a serious side effect and potential consequences include numerous health problems. Karagianis, J. (2000). "Olanzapine and weight gain." Can J Psychiatry 45(5): 493. Kinon, B. J., B. R. Basson, et al. (2001). "Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia." J Clin Psychiatry 62(2): 92-100. BACKGROUND: Weight change and the weight-related health factors of nonfasting serum glucose, serum cholesterol, and diastolic blood pressure levels were analyzed in patients with DSM-III-R schizophrenia and related disorders who received treatment with olanzapine for up to 3 years, and comparisons were made to patients treated with haloperidol. Baseline body mass index (BBMI; kg/m2) and dose (mg/day) were investigated as predictors of long-term weight change experienced during olanzapine treatment. METHOD: This analysis retrospectively examined 573 patients receiving olanzapine and 103 patients receiving haloperidol for 39 weeks or more from a study of 1,996 patients randomly assigned 2:1 to either olanzapine, 5 to 20 mg/day, or haloperidol, 5 to 20 mg/day. After 6 weeks of acute therapy, patients continued for 1 year or more with either double-blind or open-label olanzapine therapy or double-blind haloperidol therapy. RESULTS: Mean weight gain for olanzapine-treated patients observed for a median of 2.54 years trended toward a plateau after the first 39 weeks of treatment with a last-observation-carried-forward mean weight change of 6.26 kg (13.8 lb) and a median of 5.90 kg (13.0 lb). This was significantly higher than that for haloperidol-treated patients, whose mean weight gain was 0.69 kg (1.5 lb) after 1.15 years (p < .001). Patients with higher BBMI (> 27.6) gained significantly less weight during treatment with olanzapine than their lighter counterparts (BBMI < 27.6) (p < .001). The effect of olanzapine dose on weight was not significant (p > or = . 183). Median serum glucose at endpoint was not significantly associated (p = .096) with weight change for olanzapine. Median serum cholesterol and diastolic blood pressure for olanzapine- treated patients at endpoint showed a relationship with weight change that was statistically (p < or = .001) but not clinically significant. The difference in incidence of elevated serum glucose, cholesterol, or diastolic blood pressure between olanzapine and haloperidol therapy groups was not different (p > .05). CONCLUSION: Mean weight gain during olanzapine treatment trended toward a plateau after the initial 39 weeks of treatment with no further significant gain out to 3 years. Higher BBMI was predictive of a lower long-term weight gain, while dose was not a significant predictor of greater longer term weight change. The relationship between weight change and glucose was not statistically significant. The association between weight change and changes in cholesterol as well as changes in diastolic blood pressure was statistically significant but not considered clinically relevant based on the ranges observed. Malyuk, R., B. Gibson, et al. (2002). "Olanzapine associated weight gain, hyperglycemia and neuroleptic malignant syndrome: case report." Int J Geriatr Psychiatry 17(4): 326-8. We describe here a case of olanzapine associated weight gain, hyperglycemia and neuroleptic malignant syndrome in a 64 year-old woman with a significant medical history. Eighteen weeks after initiating olanzapine, Mrs X lost glycemic control, exhibited signs and symptoms consistent with neuroleptic malignant syndrome and gained 8.9 kg. We suggest that utilization of olanzapine in the less medically stable geriatric patient be implemented with vigilant monitoring for such complications mentioned above. Meyer, J. M. (2002). "A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: metabolic outcomes after 1 year." J Clin Psychiatry 63(5): 425-33. BACKGROUND: Metabolic side effects have been increasingly noted during therapy with novel antipsychotics, but there is a dearth of comprehensive comparative data in this area. The goal of this retrospective study was to examine the changes in weight parameters, fasting glucose, and fasting lipids in long-term inpatients treated with either risperidone or olanzapine. METHOD: A retrospective study was performed by reviewing charts of patients at Oregon State Hospital, Salem, who were treated during July and August 1999, comparing metabolic outcomes during the first year of therapy with either risperidone or olanzapine. Data were analyzed also by age, sex, and concurrent use of lithium or valproate. Included for analysis were patients at least 18 years old with baseline weights obtained within 3 weeks of drug initiation, and baseline fasting triglycerides, cholesterol, and glucose obtained within 3 months prior to drug initiation and at 1 year of treatment (+/- 4 weeks). The patients meeting these criteria in each drug cohort (risperidone, N = 47; olanzapine, N = 47) included 1 patient with diagnosed diabetes mellitus prior to onset of treatment. RESULTS: Among those patients under 60 years old, olanzapine patients (N = 37) experienced significantly greater increases at 1 year in all metabolic parameters than the risperidone group (N = 39), except for weight variables: triglycerides +104.8 mg/dL (olanzapine) versus +31.7 mg/dL (risperidone) (p = .037); cholesterol +30.7 mg/dL (olanzapine) versus +7.2 mg/dL (risperidone) (p = .004); glucose +10.8 mg/dL (olanzapine) versus +0.74 mg/dL (risperidone) (p = .030). Patients under 60 years of age with concurrent use of lithium or valproate were associated with greater weight gain in both drug groups, but this difference was statistically significant only for the olanzapine cohort. Neither weight change nor use of lithium or valproate was associated with increases in glucose or lipids among those under 60 years old for either drug. CONCLUSION: Olanzapine therapy is associated with significantly greater increases in fasting glucose and lipid levels for nongeriatric adult patients than risperidone, and the increases are not correlated with changes in weight parameters. Appropriate monitoring of fasting glucose and serum lipid levels should be considered during extended treatment with atypical antipsychotics. Osser, D. N., D. M. Najarian, et al. (1999). "Olanzapine increases weight and serum triglyceride levels." J Clin Psychiatry 60(11): 767-70. BACKGROUND: Previous studies have suggested that clozapine is associated with increases in both weight and serum triglyceride (but not cholesterol) levels. Because of the pharmacologic similarities between clozapine and olanzapine, we decided to evaluate if olanzapine use was associated with an increase in triglycerides. METHOD: Twenty- five inpatients (21 men, 4 women) were treated with olanzapine, and their outcomes were tracked prospectively in a medication utilization evaluation study. RESULTS: After 12 weeks on a mean +/- SD dose of 13.8+/-4.4 mg/day, weight increased a mean of 12 lb (5.4 kg; from 190+/- 37 lb [85.5+/-16.7 kg] to 202+/-30 lb [90.9+/-13.5 kg]), while fasting triglycerides increased a mean of 60 mg/dL (from 162+/-121 mg/dL to 222+/-135 mg/dL). Both increases were significant at p < .05. Fasting total cholesterol did not increase. The triglyceride increase was even larger when we excluded 8 patients who received various interventions to lower lipid levels (e.g., pravastatin, low-fat diet) during the olanzapine trial. There was a strong association between weight change and triglyceride change (p < .02); after controlling for weight, analysis of covariance showed no independent increase in triglycerides. CONCLUSION: These results suggest olanzapine has significant effects on weight and serum triglyceride levels. Clinical implications are discussed. Poyurovsky, M., A. Pashinian, et al. (2002). "Olanzapine-induced weight gain in patients with first-episode schizophrenia: a double-blind, placebo-controlled study of fluoxetine addition." Am J Psychiatry 159(6): 1058-60. OBJECTIVE: Since olanzapine-induced weight gain may be attributable to the antagonistic activity of olanzapine at the serotonin-2C receptor, the authors hypothesized that it might be attenuated by addition of the selective serotonin reuptake inhibitor fluoxetine. METHOD: First- episode hospitalized schizophrenia patients (N=30) were randomly assigned in an 8-week double-blind study of olanzapine, 10 mg/day, coadministered with either fluoxetine, 20 mg/day (N=15), or placebo (N=15). RESULTS: The group receiving olanzapine plus fluoxetine showed significantly less improvement in positive and disorganized symptom dimensions than the group receiving olanzapine plus placebo. The two groups demonstrated similar and substantial gradual weight gains. CONCLUSIONS: These results suggest that fluoxetine coadministration is clinically ineffective and cannot attenuate olanzapine-induced weight gain. Ramankutty, G. (2002). "Olanzapine-induced destabilization of diabetes in the absence of weight gain." Acta Psychiatr Scand 105(3): 235-6; discussion 236-7. OBJECTIVE: To provide evidence that olanzapine can cause glucose dysregulation by a mechanism other than weight gain. METHOD: I report a case of a diabetic patient who developed glucose dysregulation soon after initiation of olanzapine treatment, occurring in the absence of weight gain. I compare this case to previous case reports. RESULTS: Our patient developed persistent hyperglycaemia within 3 weeks of initiating treatment with olanzapine. Weight recorded just prior to commencement and soon after discontinuation of olanzapine were not significantly different. CONCLUSION: Controlled studies are necessary to elucidate the mechanism by which olanzapine can cause dysregulation of glucose homeostasis, and to develop guidelines for the use of olanzapine in patients with known diabetes as well as in patients with risk factors for diabetes. Ratzoni, G., D. Gothelf, et al. (2002). "Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study." J Am Acad Child Adolesc Psychiatry 41(3): 337-43. OBJECTIVE: To evaluate weight gain associated with olanzapine, risperidone, and haloperidol treatment and its clinical risk factors in adolescent patients. METHOD: The study was conducted at three adolescent psychiatric departments in two mental health centers in the Tel Aviv area. All patients were Jewish Israelis. Weight and body mass index (BMI) of hospitalized adolescents treated with olanzapine (n = 21), risperidone (n = 21), or haloperidol (n = 8) were prospectively monitored on a weekly basis for the first 12 weeks of treatment. Various clinical risk factors were tested for association with weight gain. RESULTS: The olanzapine and risperidone groups experienced significant weight gain between baseline and endpoint (p < .01), whereas the average weight of the haloperidol group did not change. Average weight gain was significantly higher for the olanzapine group (7.2 +/- 6.3 kg, 11.1% +/- 7.8%) than for the risperidone (3.9 +/- 4.8 kg, 6.6% +/- 8.6%) and haloperidol (1.1 +/- 3.3 kg, 1.5% +/- 6.0%) groups. Extreme weight gain (>7%) was recorded in 19 patients (90.5%), 9 patients (42.9%), and 1 (12.5%) patient, respectively Gender (males), low concern about gaining weight (females), low baseline BMI, and paternal BMI were positively correlated with weight gain, whereas previous neuroleptic history, neuroleptic dosage, response to treatment, and illness duration were not. CONCLUSIONS: Olanzapine and risperidone are associated with extreme weight gain in adolescents, much higher than that reported in adults. This side effect should be taken into consideration before prescribing these medications, especially in patients at high risk. Riccitelli, G. and N. Baker (2002). "Weight gain and hyperglycaemia associated with olanzapine." Aust N Z J Psychiatry 36(2): 270-1. Sacchetti, E., L. Guarneri, et al. (2000). "H(2) antagonist nizatidine may control olanzapine-associated weight gain in schizophrenic patients." Biol Psychiatry 48(2): 167-8. BACKGROUND: Olanzapine is temporally associated, in a number of patients with schizophrenia, with weight gain. H(2) antagonists, like nizatidine, have been shown to control appetite in overweight patients. METHODS: A patient with olanzapine temporally associated weight gain was treated with nizatidine as "add-on" therapy. RESULTS: Nizatidine treatment was associated with good control and subsequent reduction of weight after 4 to 5 weeks of therapy in a patient with repetitive episodes of weight gain during olanzapine treatment. Olanzapine was otherwise well tolerated and effective in controlling psychopathology. CONCLUSIONS: H(2) antagonist treatment with olanzapine may be a valid medical strategy in preventing and/or reducing weight gain in patients with schizophrenia. Controlled studies are recommended to confirm this observation. Virkkunen, M., K. Wahlbeck, et al. (2002). "Decrease of energy expenditure causes weight increase in olanzapine treatment - a case study." Pharmacopsychiatry 35(3): 124-6. The aim of this study was to evaluate the mechanisms underlying weight gain induced by the atypical antipsychotic, olanzapine. We performed euglycemic, hyperinsulinemic clamp combined with indirect calorimetry on a 48-year-old male with antisocial personality disorder, alcohol dependence and paranoid ideation before and after one month of olanzapine (10 - 15 mg/day) therapy. The patient gave his informed, written consent for this study. The results were a weight gain of 6 kg and a decrease in both basal (from 1673 to 1613 kcal/24 h) and 3-hour (from 22.8 to 20.2 cal/kg fat free mass/min) energy expenditure. Serum thyroid hormone and high-density lipoprotein cholesterol levels decreased, and the triglyceride and low-density lipoprotein cholesterol levels increased. Insulin sensitivity did not change. We conclude that decreased basal energy expenditure may contribute to weight gain in olanzapine treatment. copyright 2002 HANS BERNHARD