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fluoxetine combination improves long-term quality of life in bipolar depression
s212
PI.
Affective
disorders
that i) extracellular levels of 5-HT in the forebraiu are iucreased by chrouic fluoxetiue aud chrouic flatteued glucocorticoid rhythm alone, but uot by fluoxetiue treatment in the presence of flatteued glucocorticoid rhythm; ii) the termiual release of 5-HT is uormal(ised) followiug chrouic fluoxetiue treatment, but is decreased wheu chrouic fluoxetiue treatment occurs in the presence of flatteued glucocorticoid rhythm; iii) 5-HTt* autoreceptors are deseusitized by chrouic fluoxetiue aud flatteuiug of the glucocorticoid rhythm alone, aud in combination Thus, despite deseusitisatiou of 5-HTt* autoreceptors, coucurreut flatteued glucocorticoid rhythm compromises the ability of au SSRI to elevate forebraiu 5-HT. These fiudiugs suggest that autidepressaut efficacy of SSRIs may be reduced in those patients with glucocorticoid abnormalities. References
[l] Wang et al. (2000) Pmc Nat1 Acad Sci USA 97, 325-330. [2] Leitch et al. (2003) Neuropsychopharmacology 28, 119-125. [3] Blier (2001) J Clin Psychiatry 62 S15, 12-17
mP 1 089
Analysis of treatment-emergent olanzapinelfluoxetine combination
P. Keck’ , S. Corya2, S. Briggs3, ’ University of Cincinnati Hospital, Cincinnati, i2S.A.; 2Eli Lilly and Laboratories, Indianapolis, i2S.A.;
mania
with
M. Case2, M. Tohen2. Department of Psychiatry, Company, Lilly Research 3A4edFocus, Illinois, i2S.A.
Objective: Treatment-emergeut mama is ofteu associated with bipolar depression in patients treated with autidepressauts without mood stabilizers1,2. This study compares treatment-emergeut mama rates in bipolar depressed patients treated with olauzapiueifluoxetiue combiuatiou (OFC), olauzapiue, or placebo. Methods: In this S-week, double blind treatment, patients (11~833) with bipolar depression (baseline MADRS total scores >20) were randomized to OFC (6125, 6150, or 12150 “g/day, 11=86), olauzapiue (5520 “g/day, 11=370), or placebo (11~377). 562 subjects also participated in au optional 6-mouth, open-label exteusiou phase where olauzapiue or OFC could be giveu at auy time. Treatment-emergeut mama was evaluated with the YMRS. Results: In the acute phase, treatment-emergeut mama (baseline YMRS 115 aud >15 at auy subsequent visit) did uot differ betweeu groups (OFC 6.4%, olauzapiue 5.7%, placebo 6.7%, p=.861). Subjects ou OFC (-1.38 +5.59 SD) aud olauzapiue (-0.55 +5.91 SD) had greater decreases in YMRS thau those ou placebo (0.57 +6.09 SD)(p=.027 aud pi.001, respectively). In the exteusiou phase (OFC 11=404), OFC subjects’ treatment-emergeul mama rate was 4.7% (11=19) at auytime, aud ouly 4.0% (11~16) of OFC patients met treatment-emergeut mama criterion at eudpoiut. YMRS meau chauge from baseline (3.51 +3.69 SD) to eudpoiut (0.03 +5.42 SD) for OFC was uot significant. Conclusions: Neither OFC uor olauzapiue had a greater risk of acute treatment-emergeut mama thau placebo. The rate of treatment-emergeut mama for OFC was low during a 6-mouth, open-label extension Data suggest OFC does uot present a risk of treatment-emergeut mama in bipolar depression References
[l]
Goodwin, F.K., Jamison, K.R., 1990. Manic-Depressive Illness. Oxford, New York. [2] Peet M., 1994. Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants. BL J. Psychiatry 164, 549-550.
and antidepressants
Olanzapinelfluoxetine long-term quality
of life
combination in bipolar
M. Toheu’, L. Shi’, C. Vallariuo2, V Prabhakar’, M. Namjoshi’. ‘Eli Lilly and Company, Lilly Laboratories, Indianapolis, i2S.A.; 2A4edFocus, US.A.
improves depression R. Juarez’, Research Des Plaines,
Purpose: To determine long-term effects of olauzapiue (OLZ) aud olauzapiueifluoxetiue combiuatiou (OFC) ou health-related quality of life (HRQL) in bipolar depressed patients. Methods: Bipolar depressed patients were randomized to OLZ (5520 mgiday, 11=370), OFC (6125, 6150, or 12150 “g/day, 11=86), aud PBO (11=377), up to 8 weeks, followed by 1 week of opeulabel OLZ treatment, theu followed by 6 mouths of open-label OLZ or OFC treatment. Of the open-label patients for HRQL analysis, OLZ group (ii=1 0 1) was treated ouly ou open-label OLZ while OFC group patients (11=194) ouly ou open-label OFC after 1 week of open-label OLZ treatment. Switchers group (11=128) were exuosed to both oueu-label OFC aud OLZ treatments. HROL improvemeut was measured by the last-observation-carried-forward (LOCF) chauges in the SF-36 scores from the last acute assessmeut to the cud of open-label periods. Results: The open-label patients exhibited long-tenn improvemeut in all SF-36 dimeusious (all p-values 1.05) over open-label periods. Each individual group significantly improved several SF36 dimeusious [OLZ group: general health, meutal health, aud social fuuctiouiug; OFC group: 7 of 8 dimeusious except rolephysical; switchers group: 6 of 8 dimeusious except general health aud physical fuuctiouiug] Conclusions: Long-tenn OLZ or OFC treatment improved HRQL in bipolar depressed patients. References
[l]
Shi, L., Namjoshi, M., Yu, X., Baker, R.W., Tohen, M., Breier, A. Olanzapine alone and olanzapine in combination with fluoxetine improve health-related quality of life in patients with bipolar depression. Presented at: Collegiate of International Neuropsychopharmacology 23rd Congress, June 23-27, 2002, Montreal, Canada.
IP.1.091I
Olanzapine’s efficacy for relapse prevention bipolar disorder: A randomized double-blind placebo-controlled 12-month clinical trial
in
M. Toheu’, C. Bowdeu2, .I. Calabrese3, .I. Chou4, T. Jacobs’, R. Baker’, D. Williamson’, A. Evaus’. ‘Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, i2S.A.; 2 University of Texas Health Science Centel; Department of Psychiatry, San Antonio, i2S.A.; 3 University Hospitals of Cleveland, Department of Psychiatry, Case Western Reserve U, Cleveland, US.A.; 4NYU School of Medicine, New York, US.A. Purpose: Placebo-controlled trials have showu olauzapiue’ s efficacy for treating acute bipolar mama aud acute bipolar depression aud olauzapiue’ s efficacy in relapse preveutiou was suggested by a recent year-long lithium-controlled study. Efficacy for relapse preveutiou is further tested in this placebo-controlled study. Methods: Patients in acute manic or mixed episodes of bipolar I disorder were treated openly with olauzapiue for 6612 weeks. Patients achieving symptomatic remission (defined as YMRS total score <12 aud HAMD-21 total score <8) were randomized to
PI.
Affective
disorders
that i) extracellular levels of 5-HT in the forebraiu are iucreased by chrouic fluoxetiue aud chrouic flatteued glucocorticoid rhythm alone, but uot by fluoxetiue treatment in the presence of flatteued glucocorticoid rhythm; ii) the termiual release of 5-HT is uormal(ised) followiug chrouic fluoxetiue treatment, but is decreased wheu chrouic fluoxetiue treatment occurs in the presence of flatteued glucocorticoid rhythm; iii) 5-HTt* autoreceptors are deseusitized by chrouic fluoxetiue aud flatteuiug of the glucocorticoid rhythm alone, aud in combination Thus, despite deseusitisatiou of 5-HTt* autoreceptors, coucurreut flatteued glucocorticoid rhythm compromises the ability of au SSRI to elevate forebraiu 5-HT. These fiudiugs suggest that autidepressaut efficacy of SSRIs may be reduced in those patients with glucocorticoid abnormalities. References
[l] Wang et al. (2000) Pmc Nat1 Acad Sci USA 97, 325-330. [2] Leitch et al. (2003) Neuropsychopharmacology 28, 119-125. [3] Blier (2001) J Clin Psychiatry 62 S15, 12-17
mP 1 089
Analysis of treatment-emergent olanzapinelfluoxetine combination
P. Keck’ , S. Corya2, S. Briggs3, ’ University of Cincinnati Hospital, Cincinnati, i2S.A.; 2Eli Lilly and Laboratories, Indianapolis, i2S.A.;
mania
with
M. Case2, M. Tohen2. Department of Psychiatry, Company, Lilly Research 3A4edFocus, Illinois, i2S.A.
Objective: Treatment-emergeut mama is ofteu associated with bipolar depression in patients treated with autidepressauts without mood stabilizers1,2. This study compares treatment-emergeut mama rates in bipolar depressed patients treated with olauzapiueifluoxetiue combiuatiou (OFC), olauzapiue, or placebo. Methods: In this S-week, double blind treatment, patients (11~833) with bipolar depression (baseline MADRS total scores >20) were randomized to OFC (6125, 6150, or 12150 “g/day, 11=86), olauzapiue (5520 “g/day, 11=370), or placebo (11~377). 562 subjects also participated in au optional 6-mouth, open-label exteusiou phase where olauzapiue or OFC could be giveu at auy time. Treatment-emergeut mama was evaluated with the YMRS. Results: In the acute phase, treatment-emergeut mama (baseline YMRS 115 aud >15 at auy subsequent visit) did uot differ betweeu groups (OFC 6.4%, olauzapiue 5.7%, placebo 6.7%, p=.861). Subjects ou OFC (-1.38 +5.59 SD) aud olauzapiue (-0.55 +5.91 SD) had greater decreases in YMRS thau those ou placebo (0.57 +6.09 SD)(p=.027 aud pi.001, respectively). In the exteusiou phase (OFC 11=404), OFC subjects’ treatment-emergeul mama rate was 4.7% (11=19) at auytime, aud ouly 4.0% (11~16) of OFC patients met treatment-emergeut mama criterion at eudpoiut. YMRS meau chauge from baseline (3.51 +3.69 SD) to eudpoiut (0.03 +5.42 SD) for OFC was uot significant. Conclusions: Neither OFC uor olauzapiue had a greater risk of acute treatment-emergeut mama thau placebo. The rate of treatment-emergeut mama for OFC was low during a 6-mouth, open-label extension Data suggest OFC does uot present a risk of treatment-emergeut mama in bipolar depression References
[l]
Goodwin, F.K., Jamison, K.R., 1990. Manic-Depressive Illness. Oxford, New York. [2] Peet M., 1994. Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants. BL J. Psychiatry 164, 549-550.
and antidepressants
Olanzapinelfluoxetine long-term quality
of life
combination in bipolar
M. Toheu’, L. Shi’, C. Vallariuo2, V Prabhakar’, M. Namjoshi’. ‘Eli Lilly and Company, Lilly Laboratories, Indianapolis, i2S.A.; 2A4edFocus, US.A.
improves depression R. Juarez’, Research Des Plaines,
Purpose: To determine long-term effects of olauzapiue (OLZ) aud olauzapiueifluoxetiue combiuatiou (OFC) ou health-related quality of life (HRQL) in bipolar depressed patients. Methods: Bipolar depressed patients were randomized to OLZ (5520 mgiday, 11=370), OFC (6125, 6150, or 12150 “g/day, 11=86), aud PBO (11=377), up to 8 weeks, followed by 1 week of opeulabel OLZ treatment, theu followed by 6 mouths of open-label OLZ or OFC treatment. Of the open-label patients for HRQL analysis, OLZ group (ii=1 0 1) was treated ouly ou open-label OLZ while OFC group patients (11=194) ouly ou open-label OFC after 1 week of open-label OLZ treatment. Switchers group (11=128) were exuosed to both oueu-label OFC aud OLZ treatments. HROL improvemeut was measured by the last-observation-carried-forward (LOCF) chauges in the SF-36 scores from the last acute assessmeut to the cud of open-label periods. Results: The open-label patients exhibited long-tenn improvemeut in all SF-36 dimeusious (all p-values 1.05) over open-label periods. Each individual group significantly improved several SF36 dimeusious [OLZ group: general health, meutal health, aud social fuuctiouiug; OFC group: 7 of 8 dimeusious except rolephysical; switchers group: 6 of 8 dimeusious except general health aud physical fuuctiouiug] Conclusions: Long-tenn OLZ or OFC treatment improved HRQL in bipolar depressed patients. References
[l]
Shi, L., Namjoshi, M., Yu, X., Baker, R.W., Tohen, M., Breier, A. Olanzapine alone and olanzapine in combination with fluoxetine improve health-related quality of life in patients with bipolar depression. Presented at: Collegiate of International Neuropsychopharmacology 23rd Congress, June 23-27, 2002, Montreal, Canada.
IP.1.091I
Olanzapine’s efficacy for relapse prevention bipolar disorder: A randomized double-blind placebo-controlled 12-month clinical trial
in
M. Toheu’, C. Bowdeu2, .I. Calabrese3, .I. Chou4, T. Jacobs’, R. Baker’, D. Williamson’, A. Evaus’. ‘Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, i2S.A.; 2 University of Texas Health Science Centel; Department of Psychiatry, San Antonio, i2S.A.; 3 University Hospitals of Cleveland, Department of Psychiatry, Case Western Reserve U, Cleveland, US.A.; 4NYU School of Medicine, New York, US.A. Purpose: Placebo-controlled trials have showu olauzapiue’ s efficacy for treating acute bipolar mama aud acute bipolar depression aud olauzapiue’ s efficacy in relapse preveutiou was suggested by a recent year-long lithium-controlled study. Efficacy for relapse preveutiou is further tested in this placebo-controlled study. Methods: Patients in acute manic or mixed episodes of bipolar I disorder were treated openly with olauzapiue for 6612 weeks. Patients achieving symptomatic remission (defined as YMRS total score <12 aud HAMD-21 total score <8) were randomized to