Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression: A Double-blind, Placebo-controlled Study (The BOLDER II Study)
Abstract
This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P <or= 0.001 vs. placebo). Therapeutic effect sizes at Week 8 were 0.61 and 0.54 for quetiapine 300 and 600 mg/d, respectively. Improvements in mean HAM-D scores were also significantly greater with both quetiapine doses than with placebo (P < 0.001) as early as Week 1 and throughout the study. The MADRS response and remission rates were also significantly greater in both quetiapine dose groups compared with placebo. Improvements in primary and secondary outcomes were observed with both 300 and 600 mg/d quetiapine without major differences between the doses. Common adverse events included dry mouth, sedation, somnolence, dizziness, and constipation. The incidence of treatment-emergent mania or hypomania was lower with quetiapine treatment than placebo. This study demonstrates that quetiapine monotherapy is an effective and well-tolerated treatment for depressive episodes in bipolar disorder, confirming the results observed from a previous study (BipOLar DEpRession [BOLDER] I).
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Aripiprazole trials excluded patients with psychotic features; bipolar II patients were only enrolled in quetiapine studies (32-34%); no trials excluded rapid cycling, which represented 18-40% of patients in studies reporting such data.
“The aripiprazole trials (Thase et al. 2008) excluded patients with psychotic features and bipolar II patients were only enrolled in the quetiapine studies (32-34 %) ; no trials excluded patients with rapid cycling, which represented 18-40 % of patients in the studies reporting such data”
From Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis (2010) · cites this paper as Thase et al. 2006
Quetiapine and olanzapine as monotherapy were significantly more efficacious than placebo, as indicated by greater reductions in MADRS scores, in the treatment of acute bipolar depression from week 1 onwards.
“Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards.”
From Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis (2010) · cites this paper as Thase et al. 2006
Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962 · see citing works
A Rating Scale for Mania: Reliability, Validity and Sensitivity
Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978) · British Journal of Psychiatry · doi:10.1192/bjp.133.5.429 · Cited by 8,744 · see citing works
The Long-term Natural History of the Weekly Symptomatic Status of Bipolar I Disorder
Judd, L. L., Akiskal, H. S., Schettler, P. J., Endicott, J., Maser, J., Solomon, D. A., Leon, A. C., Rice, J. A., & Keller, M. B. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.6.530 · Cited by 2,106 · see citing works
Calabrese, J. R., Keck, P. E., Macfadden, W., Minkwitz, M., Ketter, T. A., Weisler, R. H., Cutler, A. J., McCoy, R., Wilson, E., Mullen, J., et al. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.7.1351 · Cited by 883 · see citing works
Self-citationJudd, L. L., Akiskal, H. S., Schettler, P. J., Endicott, J., Leon, A. C., Solomon, D. A., Coryell, W., Maser, J. D., & Keller, M. B. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.12.1322 · Cited by 577 · cited 1× · see citing works
“Depressive symptoms are associated with equal if not greater psychosocial dysfunction, as manic symptoms and subsyndromal depressive symptoms are associated with significant impairment in patients with bipolar I or II disorder.(4) Moreover, the bouts of depression—not mania—ultimately account for the high lifetime rat…”
BackgroundYatham, L. N., Kennedy, S. H., O'Donovan, C., Parikh, S., MacQueen, G., McIntyre, R., Sharma, V., Silverstone, P., Alda, M., Baruch, P., et al. (2005) · Bipolar Disorders · doi:10.1111/j.1399-5618.2005.00219.x · Cited by 388 · see citing works
Müller, M. (2003) · Journal of Affective Disorders · doi:10.1016/s0165-0327(02)00120-9 · Cited by 282 · see citing works
Divalproex in the treatment of bipolar depression: a placebo-controlled study
Davis, L. L., Bartolucci, A., & Petty, F. (2005) · Journal of Affective Disorders · doi:10.1016/j.jad.2004.09.009 · Cited by 181 · see citing works
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Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., et al. (2018) · Bipolar Disorders · doi:10.1111/bdi.12609 · Cited by 1,852 · see citing works
Self-citationDiazgranados, N., Ibrahim, L., Brutsche, N. E., Newberg, A., Kronstein, P., Khalife, S., Kammerer, W. A., Quezado, Z., Luckenbaugh, D. A., Salvadore, G., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.90 · Cited by 963 · see citing works
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Bak, M., Fransen, A., Janssen, J., van Os, J., & Drukker, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094112 · Cited by 490 · see citing works
Grunze, H., Vieta, E., Goodwin, G. M., Bowden, C., Licht, R. W., Möller, H.-J., Kasper, S., & WFSBP Task Force On Treatment Guidelines For Bipolar Disorders (2010) · The World Journal of Biological Psychiatry · doi:10.3109/15622970903555881 · Cited by 399 · see citing works
McElroy, S. L., Weisler, R. H., Chang, W., Olausson, B., Paulsson, B., Brecher, M., Agambaram, V., Merideth, C., Nordenhem, A., Young, A. H., et al. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.08m04942gre · Cited by 328 · see citing works
Self-citationACOG Committee on Clinical Practice Guidelines–Obstetrics (2023) · Obstetrics & Gynecology · doi:10.1097/aog.0000000000005202 · Cited by 252 · see citing works
Thase, M. E., Jonas, A., Khan, A., Bowden, C. L., Wu, X., McQuade, R. D., Carson, W. H., Marcus, R. N., & Owen, R. (2008) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181618eb4 · Cited by 251 · see citing works
Self-citationVieta, E., Suppes, T., Eggens, I., Persson, I., Paulsson, B., & Brecher, M. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.06.001 · Cited by 227 · see citing works
Self-citationDurgam, S., Earley, W., Lipschitz, A., Guo, H., Laszlovszky, I., Németh, G., Vieta, E., Calabrese, J. R., & Yatham, L. N. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15020164 · Cited by 209 · see citing works
Self-citationBandelow, B., Chouinard, G., Bobes, J., Ahokas, A., Eggens, I., Liu, S., & Eriksson, H. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145709990423 · Cited by 142 · see citing works
Bahji, A., Ermacora, D., Stephenson, C., Hawken, E. R., & Vazquez, G. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.03.030 · Cited by 139 · see citing works
Millan, M. J., Goodwin, G. M., Meyer-Lindenberg, A., & Ove Ögren, S. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.01.016 · Cited by 132 · see citing works
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Bond, D. J., Lam, R. W., & Yatham, L. N. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.11.008 · Cited by 122 · see citing works
Cruz, N., Sanchez-Moreno, J., Torres, F., Goikolea, J. M., Valentí, M., & Vieta, E. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145709990344 · Cited by 121 · see citing works
Coplan, J. D., Gopinath, S., Abdallah, C. G., & Berry, B. R. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00189 · Cited by 90 · see citing works
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Berk, M., Ng, F., Wang, W. V., Calabrese, J. R., Mitchell, P. B., Malhi, G. S., & Tohen, M. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2007.06.011 · Cited by 85 · see citing works
Self-citationKadakia, A., Dembek, C., Heller, V., Singh, R., Uyei, J., Hagi, K., Nosaka, T., & Loebel, A. (2021) · BMC Psychiatry · doi:10.1186/s12888-021-03220-3 · Cited by 79 · see citing works
Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder
Fountoulakis, K. N., Vieta, E., Siamouli, M., Valenti, M., Magiria, S., Oral, T., Fresno, D., Giannakopoulos, P., & Kaprinis, G. S. (2007) · Annals of General Psychiatry · doi:10.1186/1744-859x-6-27 · Cited by 76 · see citing works
Suppes, T., Hirschfeld, R. M., Vieta, E., Raines, S., & Paulsson, B. (2008) · The World Journal of Biological Psychiatry · doi:10.1080/15622970701317265 · Cited by 73 · see citing works
Self-citationQuetiapine for the treatment of bipolar mania in older adults
Sajatovic, M., Calabrese, J. R., & Mullen, J. (2008) · Bipolar Disorders · doi:10.1111/j.1399-5618.2008.00614.x · Cited by 70 · see citing works
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Sheehan, D. V., McElroy, S. L., Harnett-Sheehan, K., Keck, P. E., Janavs, J., Rogers, J., Gonzalez, R., Shivakumar, G., & Suppes, T. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.10.005 · Cited by 69 · see citing works
Efficacy of bright light therapy in bipolar depression
Yorguner Kupeli, N., Bulut, N. S., Carkaxhiu Bulut, G., Kurt, E., & Kora, K. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2017.12.020 · Cited by 51 · see citing works
Gjerden, P., Bramness, J. G., Tvete, I. F., & Slørdal, L. (2017) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-017-2281-8 · Cited by 48 · see citing works
Young, A. H., McElroy, S. L., Olausson, B., Paulsson, B., (D1447C00001), O. B. O. T. E. I., & Embolden II (D1447C00134) Investigators (2014) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2012.665177 · Cited by 46 · see citing works
Self-citationSheehan, D. V., Harnett-Sheehan, K., Hidalgo, R. B., Janavs, J., McElroy, S. L., Amado, D., & Suppes, T. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.07.016 · Cited by 42 · see citing works
Kemp, D. E., Gao, K., Fein, E. B., Chan, P. K., Conroy, C., Obral, S., Ganocy, S. J., & Calabrese, J. R. (2012) · Bipolar Disorders · doi:10.1111/bdi.12013 · Cited by 39 · see citing works
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Frye, M. A., Prieto, M. L., Bobo, W. V., Kung, S., Veldic, M., Alarcon, R. D., Moore, K. M., Choi, D.-S., Biernacka, J. M., & Tye, S. J. (2014) · Journal of Affective Disorders · doi:10.1016/s0165-0327(14)70005-9 · Cited by 36 · see citing works
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Young, A. H., Calabrese, J. R., Gustafsson, U., Berk, M., McElroy, S. L., Thase, M. E., Suppes, T., & Earley, W. (2013) · International Journal of Bipolar Disorders · doi:10.1186/2194-7511-1-10 · Cited by 35 · see citing works
Self-citationDatto, C., Pottorf, W. J., Feeley, L., LaPorte, S., & Liss, C. (2016) · Annals of General Psychiatry · doi:10.1186/s12991-016-0096-0 · Cited by 32 · see citing works
Effects of quetiapine on DNA methylation in neuroblastoma cells
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Nunez, N. A., Singh, B., Romo‐Nava, F., Joseph, B., Veldic, M., Cuellar‐Barboza, A., Cabello Arreola, A., Vande Voort, J. L., Croarkin, P., Moore, K. M., et al. (2020) · Bipolar Disorders · doi:10.1111/bdi.12859 · Cited by 31 · see citing works
McElroy, S. L., Martens, B. E., Winstanley, E. L., Creech, R., Malhotra, S., & Keck (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.11.014 · Cited by 27 · see citing works
Kim, W. S. H., Dimick, M. K., Omrin, D., Mitchell, R. H. B., Riegert, D., Levitt, A., Schaffer, A., Belo, S., Iazzetta, J., Detzler, G., et al. (2023) · Bipolar Disorders · doi:10.1111/bdi.13288 · Cited by 24 · see citing works
Lydiard, R. B., Culpepper, L., Schiöler, H., Gustafsson, U., & Paulsson, B. (2009) · The Primary Care Companion to The Journal of Clinical Psychiatry · doi:10.4088/pcc.08m00659 · Cited by 23 · see citing works
Self-citationLamotrigine plus Quetiapine Combination Therapy in Treatment-Resistant Bipolar Depression
Ahn, Y. M., Nam, J. Y., Culver, J. L., Marsh, W. K., Bonner, J. C., & Ketter, T. A. (2011) · Annals of Clinical Psychiatry · doi:10.1177/104012371102300104 · Cited by 23 · see citing works
Is there a ‘weight neutral’ second-generation antipsychotic for bipolar disorder?
Fang, F., Wang, Z., Wu, R., Calabrese, J. R., & Gao, K. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2016.1276284 · Cited by 18 · see citing works
Self-citationCai, L., Chen, G., Yang, H., & Bai, Y. (2023) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000449 · Cited by 11 · see citing works
Loebel, A., Siu, C., Rajagopalan, K., Pikalov, A., Cucchiaro, J., & Ketter, T. A. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.07.033 · Cited by 11 · see citing works
Jeong, J.-H., Bahk, W.-M., Woo, Seo, Hong, Jon, Min, & Yoon (2013) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s41081 · Cited by 9 · see citing works
- Authors
- Thase, M. E., Macfadden, W., Weisler, R. H., Chang, W., Paulsson, B., Khan, A., & Calabrese, J. R.
- Affiliations
- University of Pittsburgh (US)
- AstraZeneca (United Kingdom) (GB)
- University of North Carolina at Chapel Hill (US)
- AstraZeneca (Sweden) (SE)
- University Hospitals of Cleveland (US)
- Corresponding author
- Thase, Michael E.
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2006-12
- Volume
- 26
- Issue
- 6
- Pages
- 600-609
- ISSN
- 0271-0749 (ISSN-L)
- OpenAlex
- W1995358122
- Cited by
- 559
- References
- 9
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 11 · 2023: 13 · 2022: 8 · 2021: 13 · 2020: 17 · 2019: 19 · 2018: 12 · 2017: 19 · 2016: 15 · 2015: 41 · 2014: 36 · 2013: 38 · 2012: 38
- FWCI
- 32.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- quetiapine, bipolar depression, bipolar I disorder, bipolar II disorder, monotherapy, antidepressant efficacy, tolerability, treatment-emergent mania, hypomania, dose comparison, adverse events
- MeSH terms
- Quetiapine Fumarate, Adolescent, Adult, Aged, Analysis of Variance, Anxiety Disorders, Bipolar Disorder, Dibenzothiazepines, Double-Blind Method, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Quality of Life, Severity of Illness Index, Time Factors, Antipsychotic Agents, United States, Least-Squares Analysis, Treatment Outcome, Diagnostic and Statistical Manual of Mental Disorders
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