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Topiramate in the treatment of refractory bipolar mood disorder
P6 Other topics Previous cognitive studies have shown that cholinergic agonists (e.g., scopolamine) impair working memory and attention whereas the central cholinergic nicotinic agonist nicotine enhances working memory and attention. The present study presents the results of programmatic research in which nicotinic and muscarinic agonists and antagonists are systematically administered and changes in IT performance observed. The results indicate an important role for the cholinergic system and in particular, nicotinic receptors in a model of information processing speed and intelligence.
References [1] Deary, I. J., & Stough, C. (1996). Intelligence and Inspection Time: Achievements, Prospects, and Problems, American Psychologist, 51,599-608. [2] Stough, C., Mangan, G., Bates, T., Frank, N., Kerkin, 13. & Pellett, O. (1995). Effects of nicotine on perceptual speed? Psychopharmacology, 107, 305-310. [3] Stough, C. (1998). Nicotine and information processing: recent studies. Brain Topography Today, Koga, Y., Nagata, K., & Hirata (Eds). 799-802.
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Prellmlnary, open-label study of toplramate in rapid cycling bipolar women
V. Kusumakar, L. Yatham, S. Kutcher, C. O'Donovan. Department
of Psychiatry, Dalhousie University, IWK-Grace Health Centre, 5850 University Avenue, Halifax, NS B3J 3G9, Canada Objective: To investigate the effect of topiramate in female patients with refractory rapid cycling bipolar disorder (DSM-IV) and significant weight gain from previous treatment. Method: Nineteen female outpatients (aged 18-52 years) refractory to previous mood stabiliser therapies were included in the study. Nine patients had Bipolar I disorder and 10 patients had Bipolar II disorder. The average age of onset of illness was 18.7 years and the average duration of illness was 14.2 years (range, 7-38 years). During the 16week study phase, open-label topiramate (25 mg/day) was added to existing therapy (lithium or divalproex) and titrated by weekly increments of 25 mg/day to response. The average maximum dose of topiramate was 105.2 mg/day. Lorazepam (up to 4 mg/day) was permitted during the study for anxiety or insomnia. Outcome measures included assessment of mood (severity and cycle length), sleep and weight loss. Patients were evaluated weekly for the first 8 weeks and biweekly thereafter. Results: Fifteen patients completed the study. Mood stability was achieved in 8 (53%) patients, and 2 (13%) patients showed a significant improvement in mood. The improvement in mood stability was observed in all subjects on or before week 10. Weight loss of >5% was experienced by 5 (33%) patients, while 2 (21%) subjects experienced a reduction of 1-4%. Four patients discontinued treatment (drowsiness, ataxia and confusion (n = 2), and re-emergence of psychosis). All events leading to withdrawal occurred on or before week 3. One of the patients with ataxia and confusion experienced a significant improvement in mood stability before discontinuing at week 3. Conclusion: These preliminary observations suggest that topiramate is an effective mood stabiliser in rapid cycling bipolar disorder. Reduced titration rate or lowering of other medications may be needed if side effects occur. Future double blind studies with adequate numbers of subjects are needed to confirm the validity of these findings.
References [1] Calabrese, J.R. et al. (1998) Topiramate in severe trealment-refractory mania [Poster]. XXI Congress of the Collegium Internationale NeuroPsychopharmacologicum(CINP), Glasgow, Scotland.
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clinically significant effect of topiramate on haloperidol plasma concentration
D.R. Doose, K.A. Kohl, D. Desai-Krieger, J. Natarajan, D.P. van Kammen. Clinical Drug Metabolism and Clinical Research and Development,
The R. W..Johnson Pharmaceutical Research Institute, Spring House, PA, USA The anticonvulsant drag, topiramate, may have therapeutic utility in bipolar disorder. Haloperidol therapy is used in treatment of manic patients with psychotic symptoms. Therefore, it is prudent to investigate the effect of topiramate on haloperidol pharmacokinetics. In an openlabel, sequential crossover study design, the comparative single dose pharmacokinetics of haloperidol before and during multiple oral daily topiramate dosing was evaluated in 12 healthy adult volunteers. Subjects received a single 2 mg dose of haloperidol before (Day l) and during multiple daily topiramate administration (Day 14). Topiramate dosing began on Day 8 (50 mg ql2h), followed by titration to 75 mg ql2h on Day 9, and 100 mg ql2h on Days 10-16. Serial blood samples were obtained for 72 hours following haloperidol dosing before and during topiramate administration for comparison of haloperidol plasma pharmacokinetic parameters. Haloperidol was quantified in plasma by a validated assay method. Pharmacokinetic parameters were estimated by model independent methods. Topiramate slightly increased single dose haloperidol plasma concentrations. Mean haloperidol Cmax and AUC increased 5% and 15%, respectively. Differences in Cmax were not statistically significant. Differences in AUC were statistically significant, but 90% confidence intervals for the ratio of means were within bioequivalence limits. Individual subject Cmax and AUC ratios (during/before topiramate) deviated from unity by less than 20% for 8 and 7, respectively, of the 12 subjects. The greatest increase in haloperidol AUC during topiramate dosing was 28%. The observed modest change in mean haloperidol plasma pharmacokinetic parameters is likely not of clinical significance. However, the possibility of an enhanced pharmacodynamic response to haloperidol with the addition of topiramate exists. Therefore, consideration of haloperidol dosage adjustment should primarily take into consideration clinical status.
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Topiramate in the treatment of refractory bipolar mood disorder
G. Sachs, M. Sambur, C. Demopulous, S. Ghaemi. Massachusetts General Hospital, Department of Psychiatry, Boston, Massachusetts, USA Background: Topiramate (TPM) is a novel anticonvulsant, which has been reported to have psychotropic properties. Methods: Chart review was conducted at the Massachusetts General Hospital Bipolar Clinic to identify all bipolar patients who received treatment with TPM and had at least one followup visit. Data was harvested from the systematic prospective assessments routinely made at each follow-up visit including the SCID current mood modules, Clinical Global Impression (CGI), Global Assessment of Functioning Scales (GAF), and adverse effects. Results: Chart review identified 14 TPM treated patients (BP I = 11, BP I1 = 3, female = 11). In this group, eight met criteria for rapid cycling, and thirteen met criteria for at least one comorbid condition. Clinicians reported a range of target indications for TPM including rapid cycling (n = 7), hypomania/mania (n = 4), mixed episode (n = 1), depression (n = 1), and obesity (n = 1). All but one (treated for obesity) of these bipolar patients were considered highly refractory to standard treatments. On average, TPM was added to 3 4- 0.39 other medications. TPM was started at a mean dose of 50 4- 27.4 mg, and the mean duration of TPM use at the time of data harvest was 22.4 4- 22.0 weeks. Five patients discontinued TPM due to adverse effects (rash = 2, parasthesia = 1, cognitive impairment = 1, sedation = 1) and two other subjects discontinued TPM on their own after less than 2 weeks due to lack of efficacy. Of the 11 patients remaining on treatment longer than 2 weeks,
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P..6 Other topics
four experienced a decrease in severity of Bipolar illness of one or more CGI point, and eight experienced a clinically significant improvement in their primary comorbid condition as measured by the CGI-I (Anorexia nervosa = 1, Bulimia = 3, Obesity = 1, OCD = 1, PTSD = 1, Tourettes = 1). Patients with a BMI > 28 (n = 4) experienced a mean weight loss of 29.75 ± 16.29 pounds while on TPM (range 5-75 pounds). Five patients deferred discussion of their weight as they had comorbid eating disorders. Conclusion: Based on the benefit observed in these highly refractory patients, TPM appears to be a promising agent for the treatment of bipolar disorder as well as common comorbid psychiatric conditions and obesity.
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Topiramate as adjunctive treatment in bipolar disorder
K.N.R, Chengappa1,2,3, D. Rathore2, J. Levine1,3, R. Atzert 1'2,3, L. Solai 1, H. Parepally 1'2. 1Western Psychiatric Institute & Clinic, University of Pittsburgh Medical Center; 2Special Studies Center, Mayview State Hospital; 3Stanley Center for the Innovative Treatment of Bipolar Disorder, Pittsburgh, PA, USA Objective: To investigate the efficacy and tolerability of topiramate as adjunctive therapy in patients with bipolar disorders refractory to previous treatments. Method: Fourteen patients with DSM-IV bipolar I disorder and two patients with schizoaffective disorder (bipolar type), who had failed to respond to standard psychotropic regimens, were included in the study. The mean age of the study population was 44 (range, 21-67) years and 10 (62.5%) subjects were female. All patients were manic (n = 13) or mixed (n = 3). Topiramate (25 mg/day) was added to existing therapy and increased by 25-50 mg every 3-7 days to a target dose of 100300 mg/day. The dosage of other psychotropic medications, including conventional mood stabilizers and atypical antipsychotics, remained constant during the 6-week study phase. Improvement was rated weekly using the Young Mania Rating Scale (YMRS), the 21-item Hamilton Depression Rating Scale (Ham-D), and the Clinical Global Impression Scale - bipolar version (CGI-BP). Results: Following 6 weeks of treatment, nine (56%) subjects were 'responders' to topiramate (_>50% reduction in the YMRS and a CGI score of 'much/very much improved'). The time to response ranged from 2 to 5 weeks. On the CGI-BP, two patients were 'minimally improved', four showed no change, and one patient was 'minimally worse'. Treatment with topiramate appeared well tolerated. All adverse events occurred singly or in combination in eight patients and were related to the CNS or gastrointestinal system. The most commonly reported adverse effect was paresthesia (n = 5). All adverse events were transient and resolved spontaneously. All patients lost weight during the 6-week study period. The mean decrease in weight was 10.3 lb. A significant reduction in average body mass index was also observed for the study population (34.4 before treatment versus 31.8 at Week 6, p = 0.001). Conclusion: These preliminary findings indicate that topiramate appears to be effective for the manic and mixed phases of bipolar illness. If these early benefits of topiramate are replicated in controlled trials, then topiramate is likely to be a significant addition to the available treatments for bipolar and related disorders.
References [1] Calabrese, J.R. et al. (1998) Pilot study of topiramate in severe treatmentrefractory mania [Abstract]. 151 st Annual Meeting of the American Psychiatric Association, Toronto, Canada.
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Development of a model to estimate the clinical and economic Impact of mood stabilizer treatment for Bipolar I disorder
L. Bryant-Comstock 1, P.E. Keck Jr.2, D.B. Mather 1, E. Bell3, S.D. Sullivan3. tGlaxo Wellcome Inc., RTP, NC; 2University of Cincinnati, Cincinnati, OH; 3University of Washington, Seattle, WA, USA Mood stabilizers play an important therapeutic role in the treatment of bipolar disorder. However, the costs and consequences of individual and combination therapies have not been comprehensively examined across the broad spectrum of conditions experienced by patients. To estimate the clinical and economic impact of treatment, we constructed a diseasebased simulation model characterizing the current patterns of treatment of bipolar I disorder among adult, non-institutionalized patients receiving mood-stabilizers. Information obtained fromthe literature and interviews with clinical psychiatrists were utilized to develop a discrete-state transition model of seven health states (acute mania, depression and mixed states; continuation mania, depression and mixed states; and prophylaxis). A treatment algorithm was developed to model the use of four mood stabilizers (carbamazepine, divalproex, lamotrigine and lithium), alone or in combination therapy. The algorithm changes mood stabilizer treatment in response to various transitions occurring within the model (ie, response, inadequate response, relapse, recurrence or adverse events leading to a change in therapy). Patients are expelled from the simulation after experiencing a specified number of treatment failures or exhausting treatment alternatives. Direct medical costs include those attributable to emergency department visits, hospitalizations, office visits, laboratory tests, diagnostic procedures and drug therapy. Resource consumption is calculated as a function of the mood stabilizer treatment and the duration of time spent in the various health states. Simulation duration, cohort size and initial health state can all be varied, allowing a number of assumptions to be tested. All base case estimates can be modified to reflect a diversity of clinical and economic data and practice patterns. Alternative treatments and treatment algorithms can be incorporated as treatment patterns and practices change. A detailed report of clinical and economic outcomes can be generated from each simulation run. Summary reports from multiple simulation runs can be presented together to compare and contrast various mood stabilizer treatments and clinical scenarios. Utilizing this discrete-state model, data from numerous sources can be combined to estimate the clinical outcomes and economic consequences of using one or more mood stabilizers in various health states experienced by patients with bipolar I disorder.
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Risperidone In children with conduct disorder
R.L. Findling. Department of Psychiatry, Case Western Reserve University/University Hospitals of Cleveland, 11100 Eulcid Avenue, Cleveland, Ohio, USA
Objective: A double-blind study was conducted to determine whether risperidone was superior to placebo in reducing aggressive symptoms in children with conduct disorder. Aggression is the most common target symptom for which youths are prescribed antipsychotics. Methods: Twenty patients without mental retardation aged 5-15 years, meeting DSM-IV criteria for conduct disorder and with a score of_>3 on the Rating of Aggression Against People and/or Property (RAAPP) scale, indicating at least moderately aggressive symptoms, were randomized to receive risperidone or placebo. Doses of risperidone were increased over a 10-week period up to maximum doses of either 1.5 or 3.0 mg/day (based on patient weight). Results: The mean ages of the patients in the risperidone and placebo groups were 10.7 and 8.2 years, respectively (p = 0.06); baseline RAAPP scores were 3.9 and 3.7 (p = 0.34). The study was completed by 6 of the 10 patients assigned to risperidone and 3 of the 10 assigned to placebo. The most common reasons for discontinuation was lack of
References [1] Deary, I. J., & Stough, C. (1996). Intelligence and Inspection Time: Achievements, Prospects, and Problems, American Psychologist, 51,599-608. [2] Stough, C., Mangan, G., Bates, T., Frank, N., Kerkin, 13. & Pellett, O. (1995). Effects of nicotine on perceptual speed? Psychopharmacology, 107, 305-310. [3] Stough, C. (1998). Nicotine and information processing: recent studies. Brain Topography Today, Koga, Y., Nagata, K., & Hirata (Eds). 799-802.
•
Prellmlnary, open-label study of toplramate in rapid cycling bipolar women
V. Kusumakar, L. Yatham, S. Kutcher, C. O'Donovan. Department
of Psychiatry, Dalhousie University, IWK-Grace Health Centre, 5850 University Avenue, Halifax, NS B3J 3G9, Canada Objective: To investigate the effect of topiramate in female patients with refractory rapid cycling bipolar disorder (DSM-IV) and significant weight gain from previous treatment. Method: Nineteen female outpatients (aged 18-52 years) refractory to previous mood stabiliser therapies were included in the study. Nine patients had Bipolar I disorder and 10 patients had Bipolar II disorder. The average age of onset of illness was 18.7 years and the average duration of illness was 14.2 years (range, 7-38 years). During the 16week study phase, open-label topiramate (25 mg/day) was added to existing therapy (lithium or divalproex) and titrated by weekly increments of 25 mg/day to response. The average maximum dose of topiramate was 105.2 mg/day. Lorazepam (up to 4 mg/day) was permitted during the study for anxiety or insomnia. Outcome measures included assessment of mood (severity and cycle length), sleep and weight loss. Patients were evaluated weekly for the first 8 weeks and biweekly thereafter. Results: Fifteen patients completed the study. Mood stability was achieved in 8 (53%) patients, and 2 (13%) patients showed a significant improvement in mood. The improvement in mood stability was observed in all subjects on or before week 10. Weight loss of >5% was experienced by 5 (33%) patients, while 2 (21%) subjects experienced a reduction of 1-4%. Four patients discontinued treatment (drowsiness, ataxia and confusion (n = 2), and re-emergence of psychosis). All events leading to withdrawal occurred on or before week 3. One of the patients with ataxia and confusion experienced a significant improvement in mood stability before discontinuing at week 3. Conclusion: These preliminary observations suggest that topiramate is an effective mood stabiliser in rapid cycling bipolar disorder. Reduced titration rate or lowering of other medications may be needed if side effects occur. Future double blind studies with adequate numbers of subjects are needed to confirm the validity of these findings.
References [1] Calabrese, J.R. et al. (1998) Topiramate in severe trealment-refractory mania [Poster]. XXI Congress of the Collegium Internationale NeuroPsychopharmacologicum(CINP), Glasgow, Scotland.
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clinically significant effect of topiramate on haloperidol plasma concentration
D.R. Doose, K.A. Kohl, D. Desai-Krieger, J. Natarajan, D.P. van Kammen. Clinical Drug Metabolism and Clinical Research and Development,
The R. W..Johnson Pharmaceutical Research Institute, Spring House, PA, USA The anticonvulsant drag, topiramate, may have therapeutic utility in bipolar disorder. Haloperidol therapy is used in treatment of manic patients with psychotic symptoms. Therefore, it is prudent to investigate the effect of topiramate on haloperidol pharmacokinetics. In an openlabel, sequential crossover study design, the comparative single dose pharmacokinetics of haloperidol before and during multiple oral daily topiramate dosing was evaluated in 12 healthy adult volunteers. Subjects received a single 2 mg dose of haloperidol before (Day l) and during multiple daily topiramate administration (Day 14). Topiramate dosing began on Day 8 (50 mg ql2h), followed by titration to 75 mg ql2h on Day 9, and 100 mg ql2h on Days 10-16. Serial blood samples were obtained for 72 hours following haloperidol dosing before and during topiramate administration for comparison of haloperidol plasma pharmacokinetic parameters. Haloperidol was quantified in plasma by a validated assay method. Pharmacokinetic parameters were estimated by model independent methods. Topiramate slightly increased single dose haloperidol plasma concentrations. Mean haloperidol Cmax and AUC increased 5% and 15%, respectively. Differences in Cmax were not statistically significant. Differences in AUC were statistically significant, but 90% confidence intervals for the ratio of means were within bioequivalence limits. Individual subject Cmax and AUC ratios (during/before topiramate) deviated from unity by less than 20% for 8 and 7, respectively, of the 12 subjects. The greatest increase in haloperidol AUC during topiramate dosing was 28%. The observed modest change in mean haloperidol plasma pharmacokinetic parameters is likely not of clinical significance. However, the possibility of an enhanced pharmacodynamic response to haloperidol with the addition of topiramate exists. Therefore, consideration of haloperidol dosage adjustment should primarily take into consideration clinical status.
•
Topiramate in the treatment of refractory bipolar mood disorder
G. Sachs, M. Sambur, C. Demopulous, S. Ghaemi. Massachusetts General Hospital, Department of Psychiatry, Boston, Massachusetts, USA Background: Topiramate (TPM) is a novel anticonvulsant, which has been reported to have psychotropic properties. Methods: Chart review was conducted at the Massachusetts General Hospital Bipolar Clinic to identify all bipolar patients who received treatment with TPM and had at least one followup visit. Data was harvested from the systematic prospective assessments routinely made at each follow-up visit including the SCID current mood modules, Clinical Global Impression (CGI), Global Assessment of Functioning Scales (GAF), and adverse effects. Results: Chart review identified 14 TPM treated patients (BP I = 11, BP I1 = 3, female = 11). In this group, eight met criteria for rapid cycling, and thirteen met criteria for at least one comorbid condition. Clinicians reported a range of target indications for TPM including rapid cycling (n = 7), hypomania/mania (n = 4), mixed episode (n = 1), depression (n = 1), and obesity (n = 1). All but one (treated for obesity) of these bipolar patients were considered highly refractory to standard treatments. On average, TPM was added to 3 4- 0.39 other medications. TPM was started at a mean dose of 50 4- 27.4 mg, and the mean duration of TPM use at the time of data harvest was 22.4 4- 22.0 weeks. Five patients discontinued TPM due to adverse effects (rash = 2, parasthesia = 1, cognitive impairment = 1, sedation = 1) and two other subjects discontinued TPM on their own after less than 2 weeks due to lack of efficacy. Of the 11 patients remaining on treatment longer than 2 weeks,
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four experienced a decrease in severity of Bipolar illness of one or more CGI point, and eight experienced a clinically significant improvement in their primary comorbid condition as measured by the CGI-I (Anorexia nervosa = 1, Bulimia = 3, Obesity = 1, OCD = 1, PTSD = 1, Tourettes = 1). Patients with a BMI > 28 (n = 4) experienced a mean weight loss of 29.75 ± 16.29 pounds while on TPM (range 5-75 pounds). Five patients deferred discussion of their weight as they had comorbid eating disorders. Conclusion: Based on the benefit observed in these highly refractory patients, TPM appears to be a promising agent for the treatment of bipolar disorder as well as common comorbid psychiatric conditions and obesity.
•
Topiramate as adjunctive treatment in bipolar disorder
K.N.R, Chengappa1,2,3, D. Rathore2, J. Levine1,3, R. Atzert 1'2,3, L. Solai 1, H. Parepally 1'2. 1Western Psychiatric Institute & Clinic, University of Pittsburgh Medical Center; 2Special Studies Center, Mayview State Hospital; 3Stanley Center for the Innovative Treatment of Bipolar Disorder, Pittsburgh, PA, USA Objective: To investigate the efficacy and tolerability of topiramate as adjunctive therapy in patients with bipolar disorders refractory to previous treatments. Method: Fourteen patients with DSM-IV bipolar I disorder and two patients with schizoaffective disorder (bipolar type), who had failed to respond to standard psychotropic regimens, were included in the study. The mean age of the study population was 44 (range, 21-67) years and 10 (62.5%) subjects were female. All patients were manic (n = 13) or mixed (n = 3). Topiramate (25 mg/day) was added to existing therapy and increased by 25-50 mg every 3-7 days to a target dose of 100300 mg/day. The dosage of other psychotropic medications, including conventional mood stabilizers and atypical antipsychotics, remained constant during the 6-week study phase. Improvement was rated weekly using the Young Mania Rating Scale (YMRS), the 21-item Hamilton Depression Rating Scale (Ham-D), and the Clinical Global Impression Scale - bipolar version (CGI-BP). Results: Following 6 weeks of treatment, nine (56%) subjects were 'responders' to topiramate (_>50% reduction in the YMRS and a CGI score of 'much/very much improved'). The time to response ranged from 2 to 5 weeks. On the CGI-BP, two patients were 'minimally improved', four showed no change, and one patient was 'minimally worse'. Treatment with topiramate appeared well tolerated. All adverse events occurred singly or in combination in eight patients and were related to the CNS or gastrointestinal system. The most commonly reported adverse effect was paresthesia (n = 5). All adverse events were transient and resolved spontaneously. All patients lost weight during the 6-week study period. The mean decrease in weight was 10.3 lb. A significant reduction in average body mass index was also observed for the study population (34.4 before treatment versus 31.8 at Week 6, p = 0.001). Conclusion: These preliminary findings indicate that topiramate appears to be effective for the manic and mixed phases of bipolar illness. If these early benefits of topiramate are replicated in controlled trials, then topiramate is likely to be a significant addition to the available treatments for bipolar and related disorders.
References [1] Calabrese, J.R. et al. (1998) Pilot study of topiramate in severe treatmentrefractory mania [Abstract]. 151 st Annual Meeting of the American Psychiatric Association, Toronto, Canada.
•
Development of a model to estimate the clinical and economic Impact of mood stabilizer treatment for Bipolar I disorder
L. Bryant-Comstock 1, P.E. Keck Jr.2, D.B. Mather 1, E. Bell3, S.D. Sullivan3. tGlaxo Wellcome Inc., RTP, NC; 2University of Cincinnati, Cincinnati, OH; 3University of Washington, Seattle, WA, USA Mood stabilizers play an important therapeutic role in the treatment of bipolar disorder. However, the costs and consequences of individual and combination therapies have not been comprehensively examined across the broad spectrum of conditions experienced by patients. To estimate the clinical and economic impact of treatment, we constructed a diseasebased simulation model characterizing the current patterns of treatment of bipolar I disorder among adult, non-institutionalized patients receiving mood-stabilizers. Information obtained fromthe literature and interviews with clinical psychiatrists were utilized to develop a discrete-state transition model of seven health states (acute mania, depression and mixed states; continuation mania, depression and mixed states; and prophylaxis). A treatment algorithm was developed to model the use of four mood stabilizers (carbamazepine, divalproex, lamotrigine and lithium), alone or in combination therapy. The algorithm changes mood stabilizer treatment in response to various transitions occurring within the model (ie, response, inadequate response, relapse, recurrence or adverse events leading to a change in therapy). Patients are expelled from the simulation after experiencing a specified number of treatment failures or exhausting treatment alternatives. Direct medical costs include those attributable to emergency department visits, hospitalizations, office visits, laboratory tests, diagnostic procedures and drug therapy. Resource consumption is calculated as a function of the mood stabilizer treatment and the duration of time spent in the various health states. Simulation duration, cohort size and initial health state can all be varied, allowing a number of assumptions to be tested. All base case estimates can be modified to reflect a diversity of clinical and economic data and practice patterns. Alternative treatments and treatment algorithms can be incorporated as treatment patterns and practices change. A detailed report of clinical and economic outcomes can be generated from each simulation run. Summary reports from multiple simulation runs can be presented together to compare and contrast various mood stabilizer treatments and clinical scenarios. Utilizing this discrete-state model, data from numerous sources can be combined to estimate the clinical outcomes and economic consequences of using one or more mood stabilizers in various health states experienced by patients with bipolar I disorder.
~
Risperidone In children with conduct disorder
R.L. Findling. Department of Psychiatry, Case Western Reserve University/University Hospitals of Cleveland, 11100 Eulcid Avenue, Cleveland, Ohio, USA
Objective: A double-blind study was conducted to determine whether risperidone was superior to placebo in reducing aggressive symptoms in children with conduct disorder. Aggression is the most common target symptom for which youths are prescribed antipsychotics. Methods: Twenty patients without mental retardation aged 5-15 years, meeting DSM-IV criteria for conduct disorder and with a score of_>3 on the Rating of Aggression Against People and/or Property (RAAPP) scale, indicating at least moderately aggressive symptoms, were randomized to receive risperidone or placebo. Doses of risperidone were increased over a 10-week period up to maximum doses of either 1.5 or 3.0 mg/day (based on patient weight). Results: The mean ages of the patients in the risperidone and placebo groups were 10.7 and 8.2 years, respectively (p = 0.06); baseline RAAPP scores were 3.9 and 3.7 (p = 0.34). The study was completed by 6 of the 10 patients assigned to risperidone and 3 of the 10 assigned to placebo. The most common reasons for discontinuation was lack of