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Lamotrigine: Spectrum of antidepressant activity in bipolar disorder
?I Affectiue disorders and antidepressants
s144 Ip.1.0311
The impact of a primary care information program for patients with depression
exchange
K.M. Beusterien, P.N. Schrammel, D.P. Buesching’, A.B. Steinwald, T.F. GOSS. Couance Health Economics and Outcomes Services Inc. Washington, DC: Eli Lil& and Co., Inc., Indianapolis,
IN, USA
Background: Depression imposes a substantial burden on society, affecting one in eight persons over a lifetime. Providing information to patients or providers has been demonstrated to influence behavior in the management of depression. The present study was undertaken to evaluate the effects of an information exchange program on patients diagnosed with major depressive disorder (MDD). The program was designed to provide feedback to patients and their doctors based on data periodically collected from patients on their behaviors and experiences coping with depression. Objective: This study was undertaken to determine whether primary care depression patients enrolled in an educational program experienced better treatment outcomes than patients receiving usual care. Specific outcomes evaluated include severity of depression, health-related quality of life (HQL), satisfaction with care, and medical resource utilization. Methods: We performed a prospective, multicenter, evaluation in the primary care setting. Patients were randomized at the physician level to minimize crossover effects from the intervention (the program and fluoxetine therapy) to control (fluoxetine therapy and usual care). Patients were screened for MDD using the 5-item MHI scale from the SF36 Health Survey. Diagnosis of MDD was confirmed using a simple checklist administered by the physician to derive a DSM IV diagnosis. Patient self-completed questionnaires were administered at baseline, 3, 6, and 12 months. HQL measures included the SF-36, health outlook, and work productivity scales. Depression severity was measured with the Beck Depression Inventory. Satisfaction with care was measured with the Group Health Association of America Consumer Satisfaction Survey. All patients who completed a baseline and at least one follow-up questionnaire were included in the intervention effects analysis. Analysis of covariance (ANCOVA) was performed to compare endpoint scores between intervention and control patients adjusting for baseline scores. Results: Of the 18,728 questionnaires completed, 2,820 (15 percent) screened positive on the MHI-5 (score 552). Of those who screened positive, 1,917 (68 percent) met DSM IV criteria for major depressive disorder. A total of 212 patients met all eligibility criteria and enrolled in the study (13 1 intervention, 81 control). At baseline, SF-36 scores were significantly lower compared to U.S. population norms in all eight health dimensions (p < 0.05). Baseline demographics, BDI, and HQL scale scores were equivalent between groups. There were 5 1 intervention and 38 control patients included in the intervention effects analysis. The median time to follow-up was comparable between groups (5.8 months). Over this period, patients in both groups improved in both physical and mental health domains, confirming the known benefits of antidepressant therapy. The mean BDI score was significantly lower (improved) at endpoint in intervention patients (mean = 10) compared to control patients (mean = 14), (p < 0.05). Conclusion: Depression causes substantial decrements in HQL. Educational intervention programs, such as this one, may provide clinical benefits in addition to those observed with usual care alone.
Ip.1.0321
Lamotrigine: Spectrum in bipolar disorder
of antidepressant
activity
D. Rudd, J. Ascher, R. Huffian, A. Laurenza, C. Astbury, C. Watson, G. Evoniuk. Glaxo Wellcome Inc., Research Triangle Park, NC, USA Optimal therapy for bipolar depression remains a priority to the treating physician due to the significant morbidity and mortality associated with this condition. Moreover, depression is the phase of the illness associated with highest risk of suicide, poorest psychosocial functioning and most chronic course [l]. Most frequently used pharmacologic treatments include the various classes of antidepressants (including both selective
and non-selective types) as well as the mood stabilizers such as lithium, carbamazepine and valproate. The former may often be useful in alleviating depressive symptoms, but may also elicit switching into mania, especially when given as monotherapy. The latter have questionable efficacy in eating episodes of acute depression, slow onset of effect when efficacy is detected, and are associated with significant side effects. As a result polypharmacy has become common in the attempt to manage bipolar disorder effectively [2]. Lamotrigine is a novel anticonvulsant compound which has been shown to be effective in the treatment of a variety of seizure types. Initial uncontrolled studies have suggested that lamotrigine may have a bimodal spectrum of efficacy (antidepressant and antimanic activity) in the treatment of bipolar disorder. Results from controlled studies are now providing further evidence regarding antidepressant activity. Study 602 was the first controlled multicenter study of lamotigine to study bipolar depression. A total of 192 outpatients were randomized to one of three parallel treatment groups: placebo, lamotrigine 50 mg and Iamotrigine 200 mg for 7 weeks. For the active treatment groups, dosing was initiated at 25 mg/day with escalation to 50 mg at week 3, 100 mg at week 4, and 200 mg at week 5, as applicable. All subjects had an initial DSM-IV diagnosis of Bipolar I Disorder, current episode depressed with HAM-D (17-item) total scores of at least 18. In this study, lamotrigine monotherapy showed evidence of antidepressant efficacy on various measures including HAM-D, MADRS and CGI. Significant improvement was noted on some measures as early as week 3. Analysis using the Beth HDS subscale suggested strong activity on core depressive symptoms [3]. Results of these analyses as well as other clinical data will be reviewed in order to assess the potential clinical spectrum of activity of lamotrigine in the treatment of depression. References
[I] Keller MB, Lavori P, &yell W, Andreasen NC, Endicott J, Clayton PJ, and others. Differential outcome of pure manic, mixedkycliig, and pure depressive episodes in patients with bipolar illness. JAMA 1986; 255: 313842. [2] Nichol MB, Stimmel GL, Lange SC: Factors predicting the use of multiple psychotropic medications. J Clin Psychiatry 1995; 56: 6066. [3] Beth P, Allernp P, Reisby N and Gram LM. Assessment of symptom change from improvement cnrves on the Hamilton depression scale in trials with antidepressants. Psychopharmacology 1984; 84: 276281.
Ip.1.0331
Sertraline treatment of major depressive in a general practice population
disorder
S. Kutcher, J. LeBlanc’, C.C. MacLaren, F! Thompson2, V Hadrava3. ‘Dalhousie University Dept. of Psychiatry, Halifar, Noua Scotia: Dalhousie University Dept. of Pediatrics, Halifax, Nova Scotia; ‘Clinical Trials Atlantic Corporation, Halifax, Nova Scotia: ‘Pjzer Canada Inc., Canada Clinical psychopharmacology studies are usually conducted at tertiary centres or involve psychiatrists as the contact physician. The results of these investigations cannot be assumed to reflect the realities of psychopharmacologic treatments conducted by primary care physicians in a general practice population. Objective: This study uses a primary care population to evaluate both
the clinical efficacy and safety profile of sertraline in the treatment of Major Depressive Disorder (MDD). Method: The fist 199 study completers of the acute phase (nine weeks) of a multicentre randomized controlled Phase IV study with a total sample size of 2.50 were evaluated in terms of their overall response to sertraline, sustained response to sertraline by final dose (50 or 100 mg), initial response to sertmline by age, sustained response to sertraline by age and the number of new adverse events reported. Sustained response is defined as a 50% reduction in Hamilton-D scores which is maintained until the end of the acute phase. The effect of a depression management program (RHYTHMS) on compliance with sertraline treatment was also evaluated. Both male and female subjects between the ages of 19 and 64 with a primary diagnosis of MDD were eligible for the study, provided that they were able to give consent. Subjects
s144 Ip.1.0311
The impact of a primary care information program for patients with depression
exchange
K.M. Beusterien, P.N. Schrammel, D.P. Buesching’, A.B. Steinwald, T.F. GOSS. Couance Health Economics and Outcomes Services Inc. Washington, DC: Eli Lil& and Co., Inc., Indianapolis,
IN, USA
Background: Depression imposes a substantial burden on society, affecting one in eight persons over a lifetime. Providing information to patients or providers has been demonstrated to influence behavior in the management of depression. The present study was undertaken to evaluate the effects of an information exchange program on patients diagnosed with major depressive disorder (MDD). The program was designed to provide feedback to patients and their doctors based on data periodically collected from patients on their behaviors and experiences coping with depression. Objective: This study was undertaken to determine whether primary care depression patients enrolled in an educational program experienced better treatment outcomes than patients receiving usual care. Specific outcomes evaluated include severity of depression, health-related quality of life (HQL), satisfaction with care, and medical resource utilization. Methods: We performed a prospective, multicenter, evaluation in the primary care setting. Patients were randomized at the physician level to minimize crossover effects from the intervention (the program and fluoxetine therapy) to control (fluoxetine therapy and usual care). Patients were screened for MDD using the 5-item MHI scale from the SF36 Health Survey. Diagnosis of MDD was confirmed using a simple checklist administered by the physician to derive a DSM IV diagnosis. Patient self-completed questionnaires were administered at baseline, 3, 6, and 12 months. HQL measures included the SF-36, health outlook, and work productivity scales. Depression severity was measured with the Beck Depression Inventory. Satisfaction with care was measured with the Group Health Association of America Consumer Satisfaction Survey. All patients who completed a baseline and at least one follow-up questionnaire were included in the intervention effects analysis. Analysis of covariance (ANCOVA) was performed to compare endpoint scores between intervention and control patients adjusting for baseline scores. Results: Of the 18,728 questionnaires completed, 2,820 (15 percent) screened positive on the MHI-5 (score 552). Of those who screened positive, 1,917 (68 percent) met DSM IV criteria for major depressive disorder. A total of 212 patients met all eligibility criteria and enrolled in the study (13 1 intervention, 81 control). At baseline, SF-36 scores were significantly lower compared to U.S. population norms in all eight health dimensions (p < 0.05). Baseline demographics, BDI, and HQL scale scores were equivalent between groups. There were 5 1 intervention and 38 control patients included in the intervention effects analysis. The median time to follow-up was comparable between groups (5.8 months). Over this period, patients in both groups improved in both physical and mental health domains, confirming the known benefits of antidepressant therapy. The mean BDI score was significantly lower (improved) at endpoint in intervention patients (mean = 10) compared to control patients (mean = 14), (p < 0.05). Conclusion: Depression causes substantial decrements in HQL. Educational intervention programs, such as this one, may provide clinical benefits in addition to those observed with usual care alone.
Ip.1.0321
Lamotrigine: Spectrum in bipolar disorder
of antidepressant
activity
D. Rudd, J. Ascher, R. Huffian, A. Laurenza, C. Astbury, C. Watson, G. Evoniuk. Glaxo Wellcome Inc., Research Triangle Park, NC, USA Optimal therapy for bipolar depression remains a priority to the treating physician due to the significant morbidity and mortality associated with this condition. Moreover, depression is the phase of the illness associated with highest risk of suicide, poorest psychosocial functioning and most chronic course [l]. Most frequently used pharmacologic treatments include the various classes of antidepressants (including both selective
and non-selective types) as well as the mood stabilizers such as lithium, carbamazepine and valproate. The former may often be useful in alleviating depressive symptoms, but may also elicit switching into mania, especially when given as monotherapy. The latter have questionable efficacy in eating episodes of acute depression, slow onset of effect when efficacy is detected, and are associated with significant side effects. As a result polypharmacy has become common in the attempt to manage bipolar disorder effectively [2]. Lamotrigine is a novel anticonvulsant compound which has been shown to be effective in the treatment of a variety of seizure types. Initial uncontrolled studies have suggested that lamotrigine may have a bimodal spectrum of efficacy (antidepressant and antimanic activity) in the treatment of bipolar disorder. Results from controlled studies are now providing further evidence regarding antidepressant activity. Study 602 was the first controlled multicenter study of lamotigine to study bipolar depression. A total of 192 outpatients were randomized to one of three parallel treatment groups: placebo, lamotrigine 50 mg and Iamotrigine 200 mg for 7 weeks. For the active treatment groups, dosing was initiated at 25 mg/day with escalation to 50 mg at week 3, 100 mg at week 4, and 200 mg at week 5, as applicable. All subjects had an initial DSM-IV diagnosis of Bipolar I Disorder, current episode depressed with HAM-D (17-item) total scores of at least 18. In this study, lamotrigine monotherapy showed evidence of antidepressant efficacy on various measures including HAM-D, MADRS and CGI. Significant improvement was noted on some measures as early as week 3. Analysis using the Beth HDS subscale suggested strong activity on core depressive symptoms [3]. Results of these analyses as well as other clinical data will be reviewed in order to assess the potential clinical spectrum of activity of lamotrigine in the treatment of depression. References
[I] Keller MB, Lavori P, &yell W, Andreasen NC, Endicott J, Clayton PJ, and others. Differential outcome of pure manic, mixedkycliig, and pure depressive episodes in patients with bipolar illness. JAMA 1986; 255: 313842. [2] Nichol MB, Stimmel GL, Lange SC: Factors predicting the use of multiple psychotropic medications. J Clin Psychiatry 1995; 56: 6066. [3] Beth P, Allernp P, Reisby N and Gram LM. Assessment of symptom change from improvement cnrves on the Hamilton depression scale in trials with antidepressants. Psychopharmacology 1984; 84: 276281.
Ip.1.0331
Sertraline treatment of major depressive in a general practice population
disorder
S. Kutcher, J. LeBlanc’, C.C. MacLaren, F! Thompson2, V Hadrava3. ‘Dalhousie University Dept. of Psychiatry, Halifar, Noua Scotia: Dalhousie University Dept. of Pediatrics, Halifax, Nova Scotia; ‘Clinical Trials Atlantic Corporation, Halifax, Nova Scotia: ‘Pjzer Canada Inc., Canada Clinical psychopharmacology studies are usually conducted at tertiary centres or involve psychiatrists as the contact physician. The results of these investigations cannot be assumed to reflect the realities of psychopharmacologic treatments conducted by primary care physicians in a general practice population. Objective: This study uses a primary care population to evaluate both
the clinical efficacy and safety profile of sertraline in the treatment of Major Depressive Disorder (MDD). Method: The fist 199 study completers of the acute phase (nine weeks) of a multicentre randomized controlled Phase IV study with a total sample size of 2.50 were evaluated in terms of their overall response to sertraline, sustained response to sertraline by final dose (50 or 100 mg), initial response to sertmline by age, sustained response to sertraline by age and the number of new adverse events reported. Sustained response is defined as a 50% reduction in Hamilton-D scores which is maintained until the end of the acute phase. The effect of a depression management program (RHYTHMS) on compliance with sertraline treatment was also evaluated. Both male and female subjects between the ages of 19 and 64 with a primary diagnosis of MDD were eligible for the study, provided that they were able to give consent. Subjects