- Email: [email protected]
5-HT2A antagonism does not affect catalepsy in rats
356 intake on olanzapine. With treatment, there was an increase in fasting insulin, C-peptide, triglycerides and leptin (p<0.05), but not glucose, total cholesterol, HDL, LDL, prolactin, or TSH. Conclusions: Olanzapine use was associated with an increase in body weight and fat mass. This change was associated with an increase in insulin and triglyceride levels suggesting the development of insulin resistance. The changes in energy intake and resting energy expenditure were not dramatic enough to explain the significant increase in body weight. The shift in nutrient utilization away from fatty acids towards carbohydrates is interesting and may be related to the increase in insulin levels. "Supported in part by a grant from the NIH to the University of North Carolina General Clinical Research Center (RR00046), and to the Clinical Nutrition Research Unit (DK56350). Support is also from an unrestricted educational grant from Eli Lilly.
PLASMA LEPTIN IN TREATED PATIENTS WITH SCHIZOPHRENIA D. W. Haupt,* J. A. Schweiger, A. K. Melson, M. Charepoo, E Fahnestock, J. W. N e w c o m e r
Psychiatry, Washington Univeristy School of Medicine, St. Louis, MO, USA Leptin, the ob gene product, is known to regulate fat metabolism and appetite via activation of hypothalamic leptin receptors. Interest in mechanisms regulating weight gain induced by antipsychotic treatment has considered the role of leptin, In humans, as in mice, leptin is secreted by adipocytes, with plasma leptin levels highly correlated with total body adiposity. Other factors regulating leptin levels in rodents and humans include insulin, ~-adrenergic agonists and glucocorticoids. The effects of schizophrenia or antipsychotic medication on leptin secretion and metabolism in humans are less clear, except for predictable adiposity-related leptin increases. Leptin levels and adiposity (body mass index, BMI, kg/m2) were measured in healthy human subjects (n= 168) and in schizophrenia and schizoaffective patients receiving treatment with either olanzapine (n=25), clozapine (n=8), risperidone (n=23) or typical antipsychotics (n=20). While BMI strongly predicts plasma leptin, ANCOVA detects a significant interaction between BMI and either subject (schiz vs control: F[1,240]=4.35, p=0.04) or treatment condition (olanzapine, clozapine, risperidone, typical, vs controls: F[4,234]=2.64, p=0.03), consistent with a smaller effect of BMI on leptin levels in the patient groups. Using close one-to-one matching of patients (n=6 l) and controls (n=61) for BMI, minimally lower plasma leptin was observed in patients compared to controls (F[1,120]=2.93, p=0.09, effect size-0.3 S.D.). The results do not support previous reports that plasma leptin may be elevated in treated patients compared to adipositymatched controls. MH01510, MH53363, MH63985, NARSAD, USPHS 5MOI RR00036, P30 DK56341 and P60-DK20579.
LOW PROARRHYTHMIC POTENTIAL OF THE ANTIPSYCHOTIC SERTINDOLE IN ANIMAL MODELS OF TORSADE DE POINTES W. Haverkamp,* L. Eckhardt, T. Mow, J. Matz
Dept. of Cardiology and Angiology, Hospital of'the Westfiilische Wilhelms-University, Miinster, Miinstel; Germany The new generation (atypical), non-sedating antipsychotic drug sertindole (Serdolect) blocks the IKx channel. IKr channel blockade is associated with QT interval prolongation and linked to a possible increased risk of the rare ventricular tachym'rhythmia, Torsade de
22. Drug Side Effects & Tardive Dyskinesia Pointes (TdP). Using rabbit proarrhythmia models, we have investigated the propensity of sertindole to induce TdP under very aggressive study conditions. In vitro studies were carried out in isolated, perfused, atrioventricular node ablated rabbit hearts. Sertindole (0.5, 1.0 and 1.5 microM) and the positive control sotalol (10 microM) were administered via the peffusate and the cardiac cycle length (CL) varied from 300 to 900 ms after 30 rain of drug exposure. The hearts were in periods of 5 min exposed to severe hypokalaemia (1.5 mmol). Eight monophasic action potentials and a 6-lead volume conduced ECG continuously recorded all cardiac electrical events. In an in vivo study, clofilium and the al-agonist methoxamine were administered in combination with and without sertindole (0.5 mg&g i.v.) to alphachloralose anaesthetised rabbits. ECGs were continuously recorded. Sertindole caused QT interval prolongation, which at 1.5 microM was of a similar magnitude to that of sotalol (18 vs 21%, respectively; CL of 900 ms). However, the QT prolongation by sertindole was not rate use-dependent, neither did sertindole increase transmural dispersion over the left ventricular wall. In contrast to sertindole, sotalol produced a bradycardia-dependent increase in QT prolongation and a 2-3 fold increase in transmural dispersion. During hypokalaemia, TdPs occured with sotalol in 6 of 8 hearts, but not with sertindole (n=10). The in vivo results demonstrated TdPs in 8 of 10 hearts infused with cloflium+methoxamine. In rabbits pretreated with sertindole, this frequency was lowered to 2 of 10 rabbits. We conclude that sertindole, despite QT prolongation, does not display the typical proarrhythmic potential of other IKr blockers such as sotalol. The al-adrenoceptor property of sertindole protects from clofilium+methoxamine-inducedTdR This illustrates that drugs with QT prolonging potential need to be evaluated individually for their potential risk of ventricular arrhythmias.
5-HT2A ANTAGONISM DOES NOT AFFECT CATALEPSY IN RATS R B. Hicks,* J. L. Browning, M. H. Schubert, K. A. Young
Neuropsychiatry Research Plvgram, Central Texas Veterans Health Care System, Waco, TX, USA The second-generation antipsychotics are distinguished primarily by their lack of extrapyramidal side effects. All of these compounds, except for clozapine, were developed based on their high affinities for both the 5-HT2A and D2 receptors. There has been much discussion about the role of 5-HT2A receptors in the low extrapyramidal risk associated with these compounds. One of the best predictors of the risk of extrapyramidal side effects in humans is the induction of catalepsy in rats. Prior attempts to assess the effect of the 5-HT2A receptor on catalepsy were equivocal with catalepsy reported to increase (Wadenberg et al., Pharm Biochem Behav 68: 363-370, 2001), decrease (Ninan and Kulkarni, Methods Find Exp Clin Pharmaco121: 603-608, 1999) and be unaffected by 5-HT2A antagonists (Kulikov et al., Pharmacol Biochem Behav 50: 383-387, 1995; Rearill et al, Br J Pbarmacol 126: 572-574, 1999). To clarify the effect of 5-HT2A receptor antagonism in the decreased risk of extrapyramidal side effects of second-generation antipsychotics, we evaluated the induction of catalepsy in adult male Sprague-Dawley rats. Rats were treated systemically (S.C.) with haloperidol (0, 0.1, 0.5 or l mg/kg) and 90 minutes later were given either vehicle or the 5-HT2A receptor antagonist M11,939 (2 mg/kg). Rats (N = 6/group) were tested for the presence of catalepsy at 30-minute intervals by both the bar and grid methods. 5-HT2A receptor antagonism did not affect the catalepsy induced by haloperidol at any of the doses tested. Prior studies indicate that 5-HT2A receptor antagonism augments the antipsychotic potential in the rat conditioned avoidance behavior
International Congress on Schizophrenia R~search 2003
22. Drug Side Effects & Tardive Dyskinesia model (Wadenberg et al., Biol Psychiatry 44: 508-515, 1998). The current findings suggest that second-generation antipsychotics have fewer side effects because 5-HT2A receptor antagonism increases the likelihood of being efficacious without increasing the risk of extrapyramidal side effects. Supported by The Department of Veterans Affairs VA Merit Review (K.A.Y.)
ARE ANTIPSYCHOTICS ASSOCIATED WITH LOW BONE MINERAL DENSITY? O. D. Howes,* L. Simpson, A. Meaney, V. O'Keane, R. Mmxay, S. Smith Division of Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, United Kingdom a)To determine whether antipsychotics are associated with low bone mineral density and osteoporosis, and whether this is related to prolactin levels. Hyperprolactinaemia due to pituitary pathology is linked to reduced bone mineral density and osteoporosis 1. It is established that most antipsychotics can cause chronic hyperprolactinaemia, although some have little effect on prolactin secretion (clozapine, quetiapine, olanzapine) 2. There are strong theoretical grounds to support the hypothesis that antipsychotic treatment will be associated with bone mineral density toss and osteoporosis. No published studies have tested this hypothesis, b)The study used a case-control design. Subjects were consecutive clinic attendees taking an antipsychotic for >2 years, and controls were a local population reference sample. Main outcome measures were DX absorptiometry (DXA) scan of lumbar spine, and prolactin levels. DXA scans are reported as t-scores, that is bone mineral density relative to a young adult reference range. The WHO defines osteoporosis as a t-score >2.5 standard deviations (SD) below the mean, and osteopenia as a t-score between 1 to 2.5 SD below the mean. c)82 subjects were assessed (mean age 47y, SD_+12.6, 54%male, mean medication dose 26ling chlorpromazine equivalent, SD_+280). Mean spinal t score: -0.67 (SD_+I.4, p<0.001), prolactin 858 mU/L (SD_+127, upper limit of reference range 450mU/L). 37.8% of subjects showed spinal osteoporosis or osteopenia, d)The data indicate that spinal bone mineral density is significantly lower than expected, and mean prolactin levels are higher than normal. This supports an association between autipsychotic treatment and reduced trabecular bone mineral density, which is the pattern of bone change associated with hyperprolactinaemia associated with pituitary pathology. If replicated these results have major implications for the health of patients taking long-term antipsychotics. 1. Schlechte JA, Sherman B, Martin R. Bone density in amenorrheic women with and without hyperprolactinemia. J Clin Endocrinol Metab. 1983;56:1120-1123.2. Petty RG. Prolactin and antipsychotic medications: mechanism of action. Schizophr Res. 1999;35 Suppl:S67-S73.
OSTEOPOROSIS IN PATIENTS SUFFERING FROM SCHIZOPHRENIA M. H u m m e r , * R Malik, R. Gasser, G. K e m m l e r , M. Oehl, A. Hofer, E M o n c a y o , W. W. F l e i s c h h a c k e r
Dept. of Biological Psychiatry, Innsbruck University Hospital, Innsbruck, Austria Despite the fact that osteoporosis is regularly mentioned as a risk factor of treatment with polactin increasing antipsychotics, little is known about the prevalence and the degree of loss of bone mineral density in patients suffering from schizophrenia. In a cross-sectional study, we investigated bone mineral density of 75 in- and outpa-
357 tients suffering from schizophrenia. All patients were treated with antipsychotics for at least one year. Only patients between 19 and 50 years were studied in order to exclude patients with age related idiopathic osteoporosis. We determined bone mineral density (BMD) by dual-photon-absorptiometry (DXA). In males but not females, BMD was significantly reduced in the lumbar region (p<0.001), when compared to age and sex-matched normal data. A comparison of loss of BMD in male and female patients showed significant differences between sexes. Negative symptoms and PANSS total score were correlated negatively, while 25-hydroxy-vitamine D3 deficiency and BMI were correlated positively with BMD in male patients but not exposure to prolactin increasing antipsychotics. In summary male patients with schizophrenia in our study suffered from low bone density. Despite the fact, that there is no universally accepted policy for screening to identify individuals at high risk, this study and other reports lend support to directing more attention to bone metabolism in schizophrenia patients.
DIFFERENTIAL RATE OF WEIGHT GAIN PRESENT AMONG PATIENTS TREATED WITH OLANAZPINE L. Jaton,* B. J. Kinon, M. Rotelli, S. Kollack-Walker, C. Kaiser
Neuroscience, Eli Lilly and Company, Indianapolis, IN, USA Weight gain is an important issue in the use of atypical antipsychotics including olanzapine. Previous studies have demonstrated a varied weight response in patients treated with olanzapine: some patients gain little to no weight or actually lose weight, others show modest weight gain, and some gain excessive amounts of weight [Basson et al., 2001 ; Kinon et al., 2001]. In those patients who gain weight, the increase occurs relatively early in treatment reaching a plateau after 39 weeks [Kinon et al., 2001]. In this study, we analyzed the rate at which patients gain weight during treatment with olanzapine. A retrospective analysis of weight gain was performed for 1189 patients diagnosed with schizophrenia or schizoaffective disorder who were treated with olanzapine over a 52-week treatment period (HGAJ study, l 189/1336 patients had complete data and were included in the analysis; average olanzapine dose was 13.2 mg). Patients were dichotomized into two main groups according to the percentage of body weight gained during the first 6 weeks of treatment with olanzapine: 1) patients who gained greater than or equal to 7% of their body weight within first 6 weeks of treatment (Rapid Weight Gain Group, RWG), and 2) patients who lost weight, gained no weight or gained less than 7% of their body weight during the first 6 weeks of treatment (NonRapid Weight Gain Group, NRWG). Results demonstrated that approximately 15% of the patient population showed rapid increases in weight (RWG group) while 85% of patients gained weight more slowly or not at all (NRWG group). Patients in the RWG group gained >2% of their body weight (approximately 4-7 pounds) within the first two weeks of treatment with olanzapine and were more likely to report an increase in appetite as compared to patients in the NRWG group. Furthermore, patients who gained weight during treatment with olanzapine also showed robust clinical improvement in psychopathology. By measuring the weight of patients during the first few weeks of olanzapine treatment and by assessing changes in appetite, clinicians may be able to predict who is likely to gain weight rapidly and who may benefit most from behavioral and pharmacologic interventions shown to be effective in limiting overall weight gain [Jones et al., 2001].
International Congress on Schizophrenia Research 2003
PLASMA LEPTIN IN TREATED PATIENTS WITH SCHIZOPHRENIA D. W. Haupt,* J. A. Schweiger, A. K. Melson, M. Charepoo, E Fahnestock, J. W. N e w c o m e r
Psychiatry, Washington Univeristy School of Medicine, St. Louis, MO, USA Leptin, the ob gene product, is known to regulate fat metabolism and appetite via activation of hypothalamic leptin receptors. Interest in mechanisms regulating weight gain induced by antipsychotic treatment has considered the role of leptin, In humans, as in mice, leptin is secreted by adipocytes, with plasma leptin levels highly correlated with total body adiposity. Other factors regulating leptin levels in rodents and humans include insulin, ~-adrenergic agonists and glucocorticoids. The effects of schizophrenia or antipsychotic medication on leptin secretion and metabolism in humans are less clear, except for predictable adiposity-related leptin increases. Leptin levels and adiposity (body mass index, BMI, kg/m2) were measured in healthy human subjects (n= 168) and in schizophrenia and schizoaffective patients receiving treatment with either olanzapine (n=25), clozapine (n=8), risperidone (n=23) or typical antipsychotics (n=20). While BMI strongly predicts plasma leptin, ANCOVA detects a significant interaction between BMI and either subject (schiz vs control: F[1,240]=4.35, p=0.04) or treatment condition (olanzapine, clozapine, risperidone, typical, vs controls: F[4,234]=2.64, p=0.03), consistent with a smaller effect of BMI on leptin levels in the patient groups. Using close one-to-one matching of patients (n=6 l) and controls (n=61) for BMI, minimally lower plasma leptin was observed in patients compared to controls (F[1,120]=2.93, p=0.09, effect size-0.3 S.D.). The results do not support previous reports that plasma leptin may be elevated in treated patients compared to adipositymatched controls. MH01510, MH53363, MH63985, NARSAD, USPHS 5MOI RR00036, P30 DK56341 and P60-DK20579.
LOW PROARRHYTHMIC POTENTIAL OF THE ANTIPSYCHOTIC SERTINDOLE IN ANIMAL MODELS OF TORSADE DE POINTES W. Haverkamp,* L. Eckhardt, T. Mow, J. Matz
Dept. of Cardiology and Angiology, Hospital of'the Westfiilische Wilhelms-University, Miinster, Miinstel; Germany The new generation (atypical), non-sedating antipsychotic drug sertindole (Serdolect) blocks the IKx channel. IKr channel blockade is associated with QT interval prolongation and linked to a possible increased risk of the rare ventricular tachym'rhythmia, Torsade de
22. Drug Side Effects & Tardive Dyskinesia Pointes (TdP). Using rabbit proarrhythmia models, we have investigated the propensity of sertindole to induce TdP under very aggressive study conditions. In vitro studies were carried out in isolated, perfused, atrioventricular node ablated rabbit hearts. Sertindole (0.5, 1.0 and 1.5 microM) and the positive control sotalol (10 microM) were administered via the peffusate and the cardiac cycle length (CL) varied from 300 to 900 ms after 30 rain of drug exposure. The hearts were in periods of 5 min exposed to severe hypokalaemia (1.5 mmol). Eight monophasic action potentials and a 6-lead volume conduced ECG continuously recorded all cardiac electrical events. In an in vivo study, clofilium and the al-agonist methoxamine were administered in combination with and without sertindole (0.5 mg&g i.v.) to alphachloralose anaesthetised rabbits. ECGs were continuously recorded. Sertindole caused QT interval prolongation, which at 1.5 microM was of a similar magnitude to that of sotalol (18 vs 21%, respectively; CL of 900 ms). However, the QT prolongation by sertindole was not rate use-dependent, neither did sertindole increase transmural dispersion over the left ventricular wall. In contrast to sertindole, sotalol produced a bradycardia-dependent increase in QT prolongation and a 2-3 fold increase in transmural dispersion. During hypokalaemia, TdPs occured with sotalol in 6 of 8 hearts, but not with sertindole (n=10). The in vivo results demonstrated TdPs in 8 of 10 hearts infused with cloflium+methoxamine. In rabbits pretreated with sertindole, this frequency was lowered to 2 of 10 rabbits. We conclude that sertindole, despite QT prolongation, does not display the typical proarrhythmic potential of other IKr blockers such as sotalol. The al-adrenoceptor property of sertindole protects from clofilium+methoxamine-inducedTdR This illustrates that drugs with QT prolonging potential need to be evaluated individually for their potential risk of ventricular arrhythmias.
5-HT2A ANTAGONISM DOES NOT AFFECT CATALEPSY IN RATS R B. Hicks,* J. L. Browning, M. H. Schubert, K. A. Young
Neuropsychiatry Research Plvgram, Central Texas Veterans Health Care System, Waco, TX, USA The second-generation antipsychotics are distinguished primarily by their lack of extrapyramidal side effects. All of these compounds, except for clozapine, were developed based on their high affinities for both the 5-HT2A and D2 receptors. There has been much discussion about the role of 5-HT2A receptors in the low extrapyramidal risk associated with these compounds. One of the best predictors of the risk of extrapyramidal side effects in humans is the induction of catalepsy in rats. Prior attempts to assess the effect of the 5-HT2A receptor on catalepsy were equivocal with catalepsy reported to increase (Wadenberg et al., Pharm Biochem Behav 68: 363-370, 2001), decrease (Ninan and Kulkarni, Methods Find Exp Clin Pharmaco121: 603-608, 1999) and be unaffected by 5-HT2A antagonists (Kulikov et al., Pharmacol Biochem Behav 50: 383-387, 1995; Rearill et al, Br J Pbarmacol 126: 572-574, 1999). To clarify the effect of 5-HT2A receptor antagonism in the decreased risk of extrapyramidal side effects of second-generation antipsychotics, we evaluated the induction of catalepsy in adult male Sprague-Dawley rats. Rats were treated systemically (S.C.) with haloperidol (0, 0.1, 0.5 or l mg/kg) and 90 minutes later were given either vehicle or the 5-HT2A receptor antagonist M11,939 (2 mg/kg). Rats (N = 6/group) were tested for the presence of catalepsy at 30-minute intervals by both the bar and grid methods. 5-HT2A receptor antagonism did not affect the catalepsy induced by haloperidol at any of the doses tested. Prior studies indicate that 5-HT2A receptor antagonism augments the antipsychotic potential in the rat conditioned avoidance behavior
International Congress on Schizophrenia R~search 2003
22. Drug Side Effects & Tardive Dyskinesia model (Wadenberg et al., Biol Psychiatry 44: 508-515, 1998). The current findings suggest that second-generation antipsychotics have fewer side effects because 5-HT2A receptor antagonism increases the likelihood of being efficacious without increasing the risk of extrapyramidal side effects. Supported by The Department of Veterans Affairs VA Merit Review (K.A.Y.)
ARE ANTIPSYCHOTICS ASSOCIATED WITH LOW BONE MINERAL DENSITY? O. D. Howes,* L. Simpson, A. Meaney, V. O'Keane, R. Mmxay, S. Smith Division of Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, United Kingdom a)To determine whether antipsychotics are associated with low bone mineral density and osteoporosis, and whether this is related to prolactin levels. Hyperprolactinaemia due to pituitary pathology is linked to reduced bone mineral density and osteoporosis 1. It is established that most antipsychotics can cause chronic hyperprolactinaemia, although some have little effect on prolactin secretion (clozapine, quetiapine, olanzapine) 2. There are strong theoretical grounds to support the hypothesis that antipsychotic treatment will be associated with bone mineral density toss and osteoporosis. No published studies have tested this hypothesis, b)The study used a case-control design. Subjects were consecutive clinic attendees taking an antipsychotic for >2 years, and controls were a local population reference sample. Main outcome measures were DX absorptiometry (DXA) scan of lumbar spine, and prolactin levels. DXA scans are reported as t-scores, that is bone mineral density relative to a young adult reference range. The WHO defines osteoporosis as a t-score >2.5 standard deviations (SD) below the mean, and osteopenia as a t-score between 1 to 2.5 SD below the mean. c)82 subjects were assessed (mean age 47y, SD_+12.6, 54%male, mean medication dose 26ling chlorpromazine equivalent, SD_+280). Mean spinal t score: -0.67 (SD_+I.4, p<0.001), prolactin 858 mU/L (SD_+127, upper limit of reference range 450mU/L). 37.8% of subjects showed spinal osteoporosis or osteopenia, d)The data indicate that spinal bone mineral density is significantly lower than expected, and mean prolactin levels are higher than normal. This supports an association between autipsychotic treatment and reduced trabecular bone mineral density, which is the pattern of bone change associated with hyperprolactinaemia associated with pituitary pathology. If replicated these results have major implications for the health of patients taking long-term antipsychotics. 1. Schlechte JA, Sherman B, Martin R. Bone density in amenorrheic women with and without hyperprolactinemia. J Clin Endocrinol Metab. 1983;56:1120-1123.2. Petty RG. Prolactin and antipsychotic medications: mechanism of action. Schizophr Res. 1999;35 Suppl:S67-S73.
OSTEOPOROSIS IN PATIENTS SUFFERING FROM SCHIZOPHRENIA M. H u m m e r , * R Malik, R. Gasser, G. K e m m l e r , M. Oehl, A. Hofer, E M o n c a y o , W. W. F l e i s c h h a c k e r
Dept. of Biological Psychiatry, Innsbruck University Hospital, Innsbruck, Austria Despite the fact that osteoporosis is regularly mentioned as a risk factor of treatment with polactin increasing antipsychotics, little is known about the prevalence and the degree of loss of bone mineral density in patients suffering from schizophrenia. In a cross-sectional study, we investigated bone mineral density of 75 in- and outpa-
357 tients suffering from schizophrenia. All patients were treated with antipsychotics for at least one year. Only patients between 19 and 50 years were studied in order to exclude patients with age related idiopathic osteoporosis. We determined bone mineral density (BMD) by dual-photon-absorptiometry (DXA). In males but not females, BMD was significantly reduced in the lumbar region (p<0.001), when compared to age and sex-matched normal data. A comparison of loss of BMD in male and female patients showed significant differences between sexes. Negative symptoms and PANSS total score were correlated negatively, while 25-hydroxy-vitamine D3 deficiency and BMI were correlated positively with BMD in male patients but not exposure to prolactin increasing antipsychotics. In summary male patients with schizophrenia in our study suffered from low bone density. Despite the fact, that there is no universally accepted policy for screening to identify individuals at high risk, this study and other reports lend support to directing more attention to bone metabolism in schizophrenia patients.
DIFFERENTIAL RATE OF WEIGHT GAIN PRESENT AMONG PATIENTS TREATED WITH OLANAZPINE L. Jaton,* B. J. Kinon, M. Rotelli, S. Kollack-Walker, C. Kaiser
Neuroscience, Eli Lilly and Company, Indianapolis, IN, USA Weight gain is an important issue in the use of atypical antipsychotics including olanzapine. Previous studies have demonstrated a varied weight response in patients treated with olanzapine: some patients gain little to no weight or actually lose weight, others show modest weight gain, and some gain excessive amounts of weight [Basson et al., 2001 ; Kinon et al., 2001]. In those patients who gain weight, the increase occurs relatively early in treatment reaching a plateau after 39 weeks [Kinon et al., 2001]. In this study, we analyzed the rate at which patients gain weight during treatment with olanzapine. A retrospective analysis of weight gain was performed for 1189 patients diagnosed with schizophrenia or schizoaffective disorder who were treated with olanzapine over a 52-week treatment period (HGAJ study, l 189/1336 patients had complete data and were included in the analysis; average olanzapine dose was 13.2 mg). Patients were dichotomized into two main groups according to the percentage of body weight gained during the first 6 weeks of treatment with olanzapine: 1) patients who gained greater than or equal to 7% of their body weight within first 6 weeks of treatment (Rapid Weight Gain Group, RWG), and 2) patients who lost weight, gained no weight or gained less than 7% of their body weight during the first 6 weeks of treatment (NonRapid Weight Gain Group, NRWG). Results demonstrated that approximately 15% of the patient population showed rapid increases in weight (RWG group) while 85% of patients gained weight more slowly or not at all (NRWG group). Patients in the RWG group gained >2% of their body weight (approximately 4-7 pounds) within the first two weeks of treatment with olanzapine and were more likely to report an increase in appetite as compared to patients in the NRWG group. Furthermore, patients who gained weight during treatment with olanzapine also showed robust clinical improvement in psychopathology. By measuring the weight of patients during the first few weeks of olanzapine treatment and by assessing changes in appetite, clinicians may be able to predict who is likely to gain weight rapidly and who may benefit most from behavioral and pharmacologic interventions shown to be effective in limiting overall weight gain [Jones et al., 2001].
International Congress on Schizophrenia Research 2003