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Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial
Open accessAbstract
Background Treatment-resistant major depression is common and potentially life-threatening in elderly people, in whom little is known about the benefits and risks of augmentation pharmacotherapy. We aimed to assess whether aripiprazole is associated with a higher probability of remission than is placebo.Methods We did a randomised, double-blind, placebo-controlled trial at three centres in the USA and Canada to test the efficacy and safety of aripiprazole augmentation for adults aged older than 60 years with treatment-resistant depression (Montgomery Asberg Depression Rating Scale [MADRS] score of ≥15). Patients who did not achieve remission during a pre-trial with venlafaxine extended-release (150-300 mg/day) were randomly assigned (1:1) to the addition of aripiprazole (target dose 10 mg [maximum 15 mg] daily) daily or placebo for 12 weeks. The computer-generated randomisation was done in blocks and stratified by site. Only the database administrator and research pharmacists had knowledge of treatment assignment. The primary endpoint was remission, defined as an MADRS score of 10 or less (and at least 2 points below the score at the start of the randomised phase) at both of the final two consecutive visits, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00892047.Findings From July 20, 2009, to Dec 30, 2013, we recruited 468 eligible participants, 181 (39%) of whom did not remit and were randomly assigned to aripiprazole (n=91) or placebo (n=90). A greater proportion of participants in the aripiprazole group achieved remission than did those in the placebo group (40 [44%] vs 26 [29%] participants; odds ratio [OR] 2·0 [95% CI 1·1-3·7], p=0·03; number needed to treat [NNT] 6·6 [95% CI 3·5-81·8]). Akathisia was the most common adverse effect of aripiprazole (reported in 24 [26%] of 91 participants on aripiprazole vs 11 [12%] of 90 on placebo). Compared with placebo, aripiprazole was also associated with more Parkinsonism (15 [17%] of 86 vs two [2%] of 81 participants), but not with treatment-emergent suicidal ideation (13 [21%] of 61 vs 19 [29%] of 65 participants) or other measured safety variables.Interpretation In adults aged 60 years or older who do not achieve remission from depression with a first-line antidepressant, the addition of aripiprazole is effective in achieving and sustaining remission. Tolerability concerns include the potential for akathisia and Parkinsonism.Funding National Institute of Mental Health, UPMC Endowment in Geriatric Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, National Center for Advancing Translational Sciences, and the Campbell Family Mental Health Research Institute.
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“This remission rate is comparable with those seen in our previous bilateral rTMS trial (33%)7 and deep rTMS trial (40%)32 and comparable with the remission rate seen with aripiprazole augmentation in older adults with TRD.33”
In the citing paper
“The largest published randomized controlled trial to date amongst older adults (“IRL GREY”) – a multi‐site, double‐blind, placebo‐controlled trial of aripiprazole augmentation of primary pharmacotherapy with venlafaxine – demonstrated efficacy for augmentation, yielding a 44% remission rate versus 29% with placebo (number needed to treat: 6.6) 222 .”
From Mental health care for older adults: recent advances and new directions in clinical practice and research (2022) · cites this paper as [222]
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“Aripiprazole was well tolerated in analyses of both cardiometabolic and neurological outcomes, and led to a reduction in the prevalence and severity of suicidal ideation.”
From Mental health care for older adults: recent advances and new directions in clinical practice and research (2022) · cites this paper as [222]
In the citing paper
“Augmentation of antidepressants with either lithium131 or with the aripiprazole132 have been found effective in late-life major depression unresponsive to an antidepressant.”
From Mechanisms and treatment of late-life depression (2019) · cites this paper as [132]
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Citations
Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817
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
SF-36 health survey: Manual and interpretation guide
Ware, J. (2003) · Medical Entomology and Zoology · Cited by 11,424
Whiteford, H. A., Degenhardt, L., Rehm, J., Baxter, A. J., Ferrari, A. J., Erskine, H. E., Charlson, F. J., Norman, R. E., Flaxman, A. D., Johns, N., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61611-6 · Cited by 6,006
Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia
Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Keefe, R. S. E., Davis, S. M., Davis, C. E., Lebowitz, B. D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051688 · Cited by 5,892
Assessment of suicidal intention: The Scale for Suicide Ideation.
Beck, A. T., Kovacs, M., & Weissman, A. (1979) · Journal of Consulting and Clinical Psychology · doi:10.1037//0022-006x.47.2.343 · Cited by 3,419
Randolph, C., Tierney, M. C., Mohr, E., & Chase, T. N. (1998) · Journal of Clinical and Experimental Neuropsychology · doi:10.1076/jcen.20.3.310.823 · Cited by 2,519
Miller, M. D., Paradis, C. F., Houck, P. R., Mazumdar, S., Stack, J. A., Rifai, A. H., Mulsant, B., & Reynolds, C. F. (1992) · Psychiatry Research · doi:10.1016/0165-1781(92)90005-n · Cited by 1,990
Self-citationLingjærde, O., Ahlfors, U. G., Bech, P., Dencker, S. J., & Elgen, K. (1987) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1987.tb10566.x · Cited by 1,705
(2018) · Sage eBooks · doi:10.4135/9781506326139.n404 · Cited by 1,538
A Reference Bayesian Test for Nested Hypotheses and its Relationship to the Schwarz Criterion
Kass, R. E., & Wasserman, L. (1995) · Journal of the American Statistical Association · doi:10.1080/01621459.1995.10476592 · Cited by 1,254
Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer's Disease
Schneider, L. S., Tariot, P. N., Dagerman, K. S., Davis, S. M., Hsiao, J. K., Ismail, M. S., Lebowitz, B. D., Lyketsos, C. G., Ryan, J. M., Stroup, T. S., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061240 · Cited by 1,206
Bupropion-SR, Sertraline, or Venlafaxine-XR after Failure of SSRIs for Depression
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Stewart, J. W., Nierenberg, A. A., Thase, M. E., Ritz, L., Biggs, M. M., Warden, D., Luther, J. F., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052963 · Cited by 1,033
Medication Augmentation after the Failure of SSRIs for Depression
Trivedi, M. H., Fava, M., Wisniewski, S. R., Thase, M. E., Quitkin, F., Warden, D., Ritz, L., Nierenberg, A. A., Lebowitz, B. D., Biggs, M. M., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052964 · Cited by 1,002
Bruce, M. L., Ten Have, T. R., Reynolds III, C. F., Katz, I. I., Schulberg, H. C., Mulsant, B. H., Brown, G. K., McAvay, G. J., Pearson, J. L., & Alexopoulos, G. S. (2004) · JAMA · doi:10.1001/jama.291.9.1081 · Cited by 963
Self-citationRisk factors for suicide in later life
Conwell, Y., Duberstein, P. R., & Caine, E. D. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01347-1 · Cited by 701
Reynolds III, C. F., Frank, E., Perel, J. M., Imber, S. D., Cornes, C., Miller, M. D., Mazumdar, S., Houck, P. R., Dew, M. A., Stack, J. A., et al. (1999) · JAMA · doi:10.1001/jama.281.1.39 · Cited by 659
Self-citationBallard, C., Hanney, M. L., Theodoulou, M., Douglas, S., McShane, R., Kossakowski, K., Gill, R., Juszczak, E., Yu, L.-M., & Jacoby, R. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70295-3 · Cited by 567
Nelson, J. C., & Papakostas, G. I. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09030312 · Cited by 552
Testing for baseline balance in clinical trials
Senn, S. (1994) · Statistics in Medicine · doi:10.1002/sim.4780131703 · Cited by 503
Maintenance Treatment of Major Depression in Old Age
Reynolds, C. F., Dew, M. A., Pollock, B. G., Mulsant, B. H., Frank, E., Miller, M. D., Houck, P. R., Mazumdar, S., Butters, M. A., Stack, J. A., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052619 · Cited by 476
Self-citationTaylor, W. D. (2014) · New England Journal of Medicine · doi:10.1056/nejmcp1402180 · Cited by 423
QTc Prolongation, Torsades de Pointes, and Psychotropic Medications
Beach, S. R., Celano, C. M., Noseworthy, P. A., Januzzi, J. L., & Huffman, J. C. (2013) · Psychosomatics · doi:10.1016/j.psym.2012.11.001 · Cited by 353
The Mental Health and Substance Use Workforce for Older Adults: In Whose Hands?
Eden, J., Maslow, K., Le, M., & Blazer, D. G. (2013) · Cited by 351
Raskin, J., Wiltse, C. G., Siegal, A., Sheikh, J., Xu, J., Dinkel, J. J., Rotz, B. T., & Mohs, R. C. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.6.900 · Cited by 329
Singer, B. H. (2005) · Encyclopedia of Statistical Sciences · doi:10.1002/0471667196.ess1502.pub3 · Cited by 251
Crossley, N. A., & Bauer, M. (2007) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v68n0617 · Cited by 246
Mamo, D. C., Graff, A., Mizrahi, R., Shammi, C., Romeyer, F., & Kapur, S. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.06091479 · Cited by 241
Nelson, J. C., Delucchi, K., & Schneider, L. S. (2008) · The American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000308883.64832.ed · Cited by 230
Treatment of Depression Improves Physical Functioning in Older Adults
Callahan, C. M., Kroenke, K., Counsell, S. R., Hendrie, H. C., Perkins, A. J., Katon, W. J., Noël, P. H., Harpole, L. H., Hunkeler, E. M., Unützer, J., et al. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53151.x · Cited by 204
A Systematic Review of Treatments for Refractory Depression in Older People
Cooper, C., Katona, C., Lyketsos, K., Blazer, D., Brodaty, H., Rabins, P., de Mendonça Lima, C. A., & Livingston, G. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10081165 · Cited by 176
Gallo, J. J., Morales, K. H., Bogner, H. R., Raue, P. J., Zee, J., Bruce, M. L., & Reynolds, C. F. (2013) · BMJ · doi:10.1136/bmj.f2570 · Cited by 172
Self-citationAntidepressants' Black-Box Warning — 10 Years Later
Friedman, R. A. (2014) · New England Journal of Medicine · doi:10.1056/nejmp1408480 · Cited by 171
Schatzberg, A. F., & Roose, S. P. (2006) · American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000194645.70869.3b · Cited by 143
Mechanism of Action of Aripiprazole Predicts Clinical Efficacy and a Favourable Side-Effect Profile
Hirose, T., Uwahodo, Y., Yamada, S., Miwa, T., Kikuchi, T., Kitagawa, H., Burris, K. D., Altar, C. A., & Nabeshima, T. (2004) · Journal of Psychopharmacology · doi:10.1177/026988110401800308 · Cited by 128
Myths and realities of the menopause.
Matthews, K. A. (1992) · Psychosomatic Medicine · doi:10.1097/00006842-199201000-00001 · Cited by 120
Allard, P. O., Gram, L. F., Timdahl, K., Behnke, K., Hanson, M., & Søgaard, J. (2004) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1190 · Cited by 106
Leontjevas, R., Gerritsen, D. L., Smalbrugge, M., Teerenstra, S., Vernooij-Dassen, M. J. F. J., & Koopmans, R. T. C. M. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60590-5 · Cited by 89
Treating Older Adults With Schizophrenia: Challenges and Opportunities
Jeste, D. V., & Maglione, J. E. (2013) · Schizophrenia Bulletin · doi:10.1093/schbul/sbt043 · Cited by 87
Kamel, E., McNeill, G., & Van Wijk, M. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801204 · Cited by 77
Reynolds, C. F., Frank, E., Perel, J. M., Mazumdar, S., Dew, M. A., Begley, A. E., Houck, P. R., Hall, M. H., Mulsant, B. H., Shear, M. K., et al. (1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.11.1418 · Cited by 64
Self-citationPilot Study of Augmentation With Aripiprazole for Incomplete Response in Late-Life Depression
Sheffrin, M., Driscoll, H. C., Lenze, E. J., Mulsant, B. H., Pollock, B. G., Miller, M. D., Butters, M. A., Dew, M. A., & Reynolds, C. F. (2009) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.07m03805 · Cited by 61
Self-citationAn open trial of aripiprazole augmentation for SSRI non‐remitters with late‐life depression
Rutherford, B. R., Sneed, J. R., Miyazaki, M., Eisenstadt, R., Devanand, D., Sackeïm, H. A., & Roose, S. P. (2007) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1775 · Cited by 60
Older Adults With Severe, Treatment-Resistant Depression
Unützer, J., & Park, M. (2012) · JAMA · doi:10.1001/2012.jama.10690 · Cited by 56
Haupt, D. W., Fahnestock, P. A., Flavin, K. S., Schweiger, J. A., Stevens, A., HESSLER, M. J., Maeda, J. A., Yingling, M. D., & Newcomer, J. W. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301392 · Cited by 51
Self-citationSteffens, D. C., Nelson, J. C., Eudicone, J. M., Andersson, C., Yang, H., Tran, Q.-V., Forbes, R. A., Carlson, B. X., & Berman, R. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2564 · Cited by 50
Reynolds, C. F., Dew, M. A., Martire, L. M., Miller, M. D., Cyranowski, J. M., Lenze, E. J., Whyte, E. M., Mulsant, B. H., Pollock, B. G., Karp, J. F., et al. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2443 · Cited by 49
Self-citationReliability and applicability of movement disorder rating scales in the elderly
Sweet, R. A., DeSensi, E. G., & Zubenko, G. S. (1993) · Journal of Neuropsychiatry · doi:10.1176/jnp.5.1.56 · Cited by 48
Kok, R., Nolen, W. A., & Heeren, T. J. (2007) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1823 · Cited by 44
Addressing cardiometabolic risk during treatment with antipsychotic medications
Amiel, J. M., Mangurian, C. V., Ganguli, R., & Newcomer, J. W. (2008) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e328314b74b · Cited by 43
Self-citationConway, C. R., Chibnall, J. T., Cumming, P. D., Mintun, M. A., Gebara, M. A., Perantie, D. C., Price, J. L., Cornell, M. E., McConathy, J., Gangwani, S., et al. (2014) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2014.01.003 · Cited by 25
Maust, D. T., Oslin, D. W., & Thase, M. E. (2013) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2013.01.030 · Cited by 25
Weber, E., STACK, J. A., Pollock, B. G., Mulsant, B. H., Begley, A. E., Mazumdar, S., & Reynolds, C. F. (2000) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200008000-00011 · Cited by 22
Self-citationGoing Beyond Antidepressant Monotherapy for Incomplete Response in Nonpsychotic Late-Life Depression
Maust, D. T., Oslin, D. W., & Thase, M. E. (2012) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31826576cf · Cited by 22
Kinon, B. J., Kollack‐Walker, S., Jeste, D. V., Gupta, S., Chen, L., Case, M., Chen, J., & Stauffer, V. L. (2014) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988714541867 · Cited by 17
Eden, J., Maslow, K., Le, M., & Blazer, D. G. (2012) · Cited by 7
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Metadata
- Authors
- Lenze, E. J., Mulsant, B. H., Blumberger, D. M., Karp, J. F., Newcomer, J. W., Anderson, S. J., Dew, M. A., Butters, M. A., Stack, J. A., Begley, A. E., & Reynolds, C. F.
- Affiliations
- Washington University in St. Louis (US)
- Centre for Addiction and Mental Health (CA)
- University of Pittsburgh (US)
- Florida Atlantic University (US)
- Corresponding author
- Lenze, Eric J
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 386
- Issue
- 10011
- Pages
- 2404-2412
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC4690746
- OpenAlex
- W1780931260
- Cited by
- 283
- References
- 60
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 25 · 2023: 28 · 2022: 26 · 2021: 25 · 2020: 50 · 2019: 26 · 2018: 21 · 2017: 21 · 2016: 23 · 2015: 6
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Update notices
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P30 MH90333, R01 MH083660)
- National Heart, Lung, and Blood Institute
- Roche
- Centre for Addiction and Mental Health
- Brain and Behavior Research Foundation
- National Center for Complementary and Integrative Health
- American Foundation for Suicide Prevention
- Centre for Addiction and Mental Health Foundation
- National Center on Minority Health and Health Disparities
- National Institutes of Health
- H. Lundbeck A/S
- National Palliative Care Research Center
- Fondation Brain Canada
- John A. Hartford Foundation
- Commonwealth of Pennsylvania
- National Institute on Aging
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- treatment-resistant depression, geriatric depression, elderly patients, antidepressant augmentation, venlafaxine, akathisia, antipsychotic adverse effects, remission, tolerability, number needed to treat, number needed to harm, adverse drug reactions, anticholinergic effects
- MeSH terms
- Aripiprazole, Aged, Antidepressive Agents, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Parkinson Disease, Secondary, Recurrence, Treatment Outcome, Akathisia, Drug-Induced, Depressive Disorder, Treatment-Resistant
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