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Adolescent inpatients with schizophrenia treated with olanzapine: Further results from an ongoing multicenter study
i8. Therapeutics: Treatment Trials
281
PERCEPTIONS OF SEXUAL FUNCTIONING, PROLACTIN LEVELS AND PSYCHOPATHOLOGY IN AN OLANZAPINE SWITCH TRIAL R. A. D i c k s o n , * W. M. Glazer, G. J. R e m i n g t o n , E. Stip, D. J. Walker, M. Luther, B. Jones
Research & Development Division, Eli Lilly Canada Inc., Toronto, ON, Canada Objective: To assess perceptions of antipsychotic-induced sexual side effects in schizophrenia spectrum patients switched to olanzapine from previous antipsychotics as well as correlations with changes in prolactin levels, and improvement in depression, BPRS scores, mad cognitive abilities. Methods: The DGSFi, a gender-keyed, computerized self-report instrument designed to assess sexual functioning and perceptions of antipsychotic-induced sexual side effects, the BPRS, a cognitive battery, and the Calgary Depression Scale were administered at baseline, 4 weeks and 8 weeks during this open-label olanzapine switch trial. 15"olactin levels were also obtained at these time points. Results: Both men and women perceived improvement in sexual satisfaction. Males (n=86) were significantly less bothered (p<.006) by sexual side effects and there was a significant decrease in the perception that the prescribed antipsychotic medication caused erectile dysfunction (p<.001 ) and ejaculatory problems (p<.05). For females (n=49), the perception in the frequency of sexual thoughts (p<.005) and in the ability to achieve orgasm (p<.001) significantly increased at weeks 4 and 8. In males, improvement in sexual satisfaction and erectile ability correlated with reduction in prolactin levels. Correlations with psychopathology, depression and cognition were also explored. Conclusions: Switching to olanzapine significantly reduced prolactin levels in men and women and correlations were found with some but not all of the reported improvements in perceptions of sexual functioning. Improvement in some phases of sexual functioning was found in both men and women and overall perceptions that the antipsychotic medication impaired sexual satisfaction decreased by week 4 and were sustained at week 8.
ADOLESCENT INPATIENTS WITH SCHIZOPHRENIA TREATED WITH OLANZAPINE: FURTHER RESULTS FROM AN ONGOING MULTICENTER STUDY R. W. D i t t m a n n , * U. H a g e n a h , J. J u n g h a n g , A. Maestele, C. Mehler, E. Meyer, M. Pitzer, H. R e m s c h m i d t , D. S c h l a m p , M. Schulte-Markwort, O. W e i f f e n b a c h
Psychosomatic Department, Children's Hospital, University of Hamburg, LD, Germany Objective: To present the results from an ongoing olanzapine (OLA) study in adolescent inpatients with schizophrenia. Background: 1) Most psychotropic compounds do not have the regulatory approval for ages <18 years; 2) Efficacy and safety data on these drugs, including OLA, are scarce for this age group. Methods: This is an ongoing multicenter trial of OLA (5-20 mg/day) in pats. (12-21 years of age) with DSM-IV schizophrenia (last patient visit: Oct. 2002). BPRS and CGI scales were used to assess the efficacy of OLA (response criterion: ->30% in BPRS reduction). Safety of OLA was determined by using the modified SAS, and by assessing spontaneous adverse events (AEs), weight gain, and laboratory analytes. According to the protocol, an interim analysis of safety data (up to Week 6) was performed as soon as 50 pats. finished 6 weeks of OLA therapy (or dropped out). Results: 1. So far, 99 pats. have entered the study; 31 of them have completed the 6 months observation period
of the study. The response rate was 59/78 (75.6%) at Week 6. 2. As to the safety sample (analysed so far): N = 51, N = 33 male, mean age 15.9 years. Mean length of OLA treatment: 95 days, mean maximum dose: 16.5 mg/d. There were two pats. with 'serious' AEs (rehospitalization). Most common treatment-emergent AEs: Weight gain (N = 11; 22 %), tremor (N = 9; 18%), headache (N = 8, 16%), akathisia (N = 6; 12%); increases of hepatic enzymes (N = 10; 20%), of prolactin (N = 7; 14%), of creatine kinase (N = 6; 12%), and leucopenia (N = 2; 4%), neutropenia (N = 1; 2%). Labs: leukocytes min: 3.7 (1/Ill), neutrophils min: 29%; prolactin: above normal at baseline in 26% of pats., at last observation in 63%, max. single value: 104 microg/1. Minimal changes (baseline to endpoint) in blood pressure, heart rate, and body temperature. Mean weight gain: 4.4 kg, BMI increase: 1.5, inversely related to baseline BMI. Mean change in SAS score: -0.6. Efficacy and safety results from the full sample will be presented in the future. Conclusions: Data fi'om this carefully monitored trial (as to ICH) in this age revealed: 1. Interim safety results were acceptable for the review board and allowed for study continuation, 2. Data provide valuable information on the feasibility of psychopharmacology trials in adolescents, 3. The full data set from this relatively large, carefully studied sample will offer solid information for routine antipsychotic treatment of adolescent patients with schizophrenia.
ANTIPSYCHOTIC MAINTENANCE IN SCHIZOPHRENIA: PARTIAL COMPLIANCE AND CLINICAL OUTCOME J. Docherty,* R. M a h m o u d , A. Grogg, C. K o z m a
Weill Medical College, Cornell University, White Plains, NY, USA Antipsychotic maintenance treatment improves outcome in schizophrenia, and continuous medication maintenance is more efficacious than an intermittent (drug holiday) strategy. Continuous medication treatment is, however, difficult to achieve in practice and most patients achieve only partial adherence. Adequate data regarding the impact of this partial compliance on outcome are not available. We report results from a large (N=565) multicenter (21 sites & 17 states) effectiveness trial. Chronic schizophrenic patients with an acute exacerbation were randomized to begin treatment with either risperidone or "best choice" conventional antipsychotic. Symptoms were assessed at baseline and follow up by the PANSS, and compliance was assessed as "medication possession" from primary records of presclibed or dispensed medication.(1) Partial compliance was typical in this population with 94% of patients receiving no antipsychotic drug for varying periods (mean 112 days) with 50% of patients having medication compliance (days of medication possession/outpatient days) of 70% or less. (2) There was a highly statistically significant relationship between compliance and symptom outcome. A regression model accounting for over 25% of the variance in the PANSS score indicated a .16 point change in total PANSS for every one percent difference in medication possession. Thus, a 20% drop in compliance predicts a 3.1 point increase in the PANSS (p< .0001). The relationship between compliance and symptom outcomes was also tested by comparing higher compliance to lower compliance patients. Improvement in PANSS score was significantly greater in the higher compliance group (p < .0002). (3) Consistent with other data comparing maintenance treatment with an atypical (risperidone) versus conventional antipsychotic, patients randomized to risperidone had significantly greater improvement. Controlling for symptom severity at baseline and compliance, the regression model indicates a 4.7 point or approximately 30% greater improvement in PANSS score with risperidone (p< .0026). These results are the first
International Congress on Schizophrenia Research 2003
281
PERCEPTIONS OF SEXUAL FUNCTIONING, PROLACTIN LEVELS AND PSYCHOPATHOLOGY IN AN OLANZAPINE SWITCH TRIAL R. A. D i c k s o n , * W. M. Glazer, G. J. R e m i n g t o n , E. Stip, D. J. Walker, M. Luther, B. Jones
Research & Development Division, Eli Lilly Canada Inc., Toronto, ON, Canada Objective: To assess perceptions of antipsychotic-induced sexual side effects in schizophrenia spectrum patients switched to olanzapine from previous antipsychotics as well as correlations with changes in prolactin levels, and improvement in depression, BPRS scores, mad cognitive abilities. Methods: The DGSFi, a gender-keyed, computerized self-report instrument designed to assess sexual functioning and perceptions of antipsychotic-induced sexual side effects, the BPRS, a cognitive battery, and the Calgary Depression Scale were administered at baseline, 4 weeks and 8 weeks during this open-label olanzapine switch trial. 15"olactin levels were also obtained at these time points. Results: Both men and women perceived improvement in sexual satisfaction. Males (n=86) were significantly less bothered (p<.006) by sexual side effects and there was a significant decrease in the perception that the prescribed antipsychotic medication caused erectile dysfunction (p<.001 ) and ejaculatory problems (p<.05). For females (n=49), the perception in the frequency of sexual thoughts (p<.005) and in the ability to achieve orgasm (p<.001) significantly increased at weeks 4 and 8. In males, improvement in sexual satisfaction and erectile ability correlated with reduction in prolactin levels. Correlations with psychopathology, depression and cognition were also explored. Conclusions: Switching to olanzapine significantly reduced prolactin levels in men and women and correlations were found with some but not all of the reported improvements in perceptions of sexual functioning. Improvement in some phases of sexual functioning was found in both men and women and overall perceptions that the antipsychotic medication impaired sexual satisfaction decreased by week 4 and were sustained at week 8.
ADOLESCENT INPATIENTS WITH SCHIZOPHRENIA TREATED WITH OLANZAPINE: FURTHER RESULTS FROM AN ONGOING MULTICENTER STUDY R. W. D i t t m a n n , * U. H a g e n a h , J. J u n g h a n g , A. Maestele, C. Mehler, E. Meyer, M. Pitzer, H. R e m s c h m i d t , D. S c h l a m p , M. Schulte-Markwort, O. W e i f f e n b a c h
Psychosomatic Department, Children's Hospital, University of Hamburg, LD, Germany Objective: To present the results from an ongoing olanzapine (OLA) study in adolescent inpatients with schizophrenia. Background: 1) Most psychotropic compounds do not have the regulatory approval for ages <18 years; 2) Efficacy and safety data on these drugs, including OLA, are scarce for this age group. Methods: This is an ongoing multicenter trial of OLA (5-20 mg/day) in pats. (12-21 years of age) with DSM-IV schizophrenia (last patient visit: Oct. 2002). BPRS and CGI scales were used to assess the efficacy of OLA (response criterion: ->30% in BPRS reduction). Safety of OLA was determined by using the modified SAS, and by assessing spontaneous adverse events (AEs), weight gain, and laboratory analytes. According to the protocol, an interim analysis of safety data (up to Week 6) was performed as soon as 50 pats. finished 6 weeks of OLA therapy (or dropped out). Results: 1. So far, 99 pats. have entered the study; 31 of them have completed the 6 months observation period
of the study. The response rate was 59/78 (75.6%) at Week 6. 2. As to the safety sample (analysed so far): N = 51, N = 33 male, mean age 15.9 years. Mean length of OLA treatment: 95 days, mean maximum dose: 16.5 mg/d. There were two pats. with 'serious' AEs (rehospitalization). Most common treatment-emergent AEs: Weight gain (N = 11; 22 %), tremor (N = 9; 18%), headache (N = 8, 16%), akathisia (N = 6; 12%); increases of hepatic enzymes (N = 10; 20%), of prolactin (N = 7; 14%), of creatine kinase (N = 6; 12%), and leucopenia (N = 2; 4%), neutropenia (N = 1; 2%). Labs: leukocytes min: 3.7 (1/Ill), neutrophils min: 29%; prolactin: above normal at baseline in 26% of pats., at last observation in 63%, max. single value: 104 microg/1. Minimal changes (baseline to endpoint) in blood pressure, heart rate, and body temperature. Mean weight gain: 4.4 kg, BMI increase: 1.5, inversely related to baseline BMI. Mean change in SAS score: -0.6. Efficacy and safety results from the full sample will be presented in the future. Conclusions: Data fi'om this carefully monitored trial (as to ICH) in this age revealed: 1. Interim safety results were acceptable for the review board and allowed for study continuation, 2. Data provide valuable information on the feasibility of psychopharmacology trials in adolescents, 3. The full data set from this relatively large, carefully studied sample will offer solid information for routine antipsychotic treatment of adolescent patients with schizophrenia.
ANTIPSYCHOTIC MAINTENANCE IN SCHIZOPHRENIA: PARTIAL COMPLIANCE AND CLINICAL OUTCOME J. Docherty,* R. M a h m o u d , A. Grogg, C. K o z m a
Weill Medical College, Cornell University, White Plains, NY, USA Antipsychotic maintenance treatment improves outcome in schizophrenia, and continuous medication maintenance is more efficacious than an intermittent (drug holiday) strategy. Continuous medication treatment is, however, difficult to achieve in practice and most patients achieve only partial adherence. Adequate data regarding the impact of this partial compliance on outcome are not available. We report results from a large (N=565) multicenter (21 sites & 17 states) effectiveness trial. Chronic schizophrenic patients with an acute exacerbation were randomized to begin treatment with either risperidone or "best choice" conventional antipsychotic. Symptoms were assessed at baseline and follow up by the PANSS, and compliance was assessed as "medication possession" from primary records of presclibed or dispensed medication.(1) Partial compliance was typical in this population with 94% of patients receiving no antipsychotic drug for varying periods (mean 112 days) with 50% of patients having medication compliance (days of medication possession/outpatient days) of 70% or less. (2) There was a highly statistically significant relationship between compliance and symptom outcome. A regression model accounting for over 25% of the variance in the PANSS score indicated a .16 point change in total PANSS for every one percent difference in medication possession. Thus, a 20% drop in compliance predicts a 3.1 point increase in the PANSS (p< .0001). The relationship between compliance and symptom outcomes was also tested by comparing higher compliance to lower compliance patients. Improvement in PANSS score was significantly greater in the higher compliance group (p < .0002). (3) Consistent with other data comparing maintenance treatment with an atypical (risperidone) versus conventional antipsychotic, patients randomized to risperidone had significantly greater improvement. Controlling for symptom severity at baseline and compliance, the regression model indicates a 4.7 point or approximately 30% greater improvement in PANSS score with risperidone (p< .0026). These results are the first
International Congress on Schizophrenia Research 2003