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Lurasidone: A New Option for Older Adults with Bipolar Disorder?
Accepted Manuscript Title: Lurasidone: a New Option for Older Adults with Bipolar Disorder? Author: Soham Rej PII: DOI: Reference:
S1064-7481(17)30450-5 http://dx.doi.org/doi: 10.1016/j.jagp.2017.09.003 AMGP 917
To appear in:
The American Journal of Geriatric Psychiatry
Received date: Accepted date:
3-9-2017 5-9-2017
Please cite this article as: Soham Rej, Lurasidone: a New Option for Older Adults with Bipolar Disorder?, The American Journal of Geriatric Psychiatry (2017), http://dx.doi.org/doi: 10.1016/j.jagp.2017.09.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Word Count (<1000): 617 Abstract Word Count: N/A #References (≤7): 7 #Tables: 0 #Figures: 0 Lurasidone: A New Option for Older Adults with Bipolar Disorder? Invited Perspective Article on Forester et al.’s - "Safety and Effectiveness of Long-term Treatment with Lurasidone in Older Adults with Bipolar Depression: Post-hoc Analysis of a 6 Month, Open-label Study” Soham Rej, M.D., M.Sc.1 1
Geri-PARTy Research Group, Dept. of Psychiatry, Jewish General Hospital/Lady Davis Institute, McGill University, Montreal, QC, Canada Corresponding Author: Soham Rej M.D., MSc, Dept. of Psychiatry, Jewish General Hospital/Lady Davis Institute, McGill University, 4333 Cote-Ste-Catherine, Montreal, QC, Canada, H3T 1E4, 514-340-8222 x27506, email: [email protected] Conflicts of Interest and Source of Funding/Acknowledgements: The author declare no conflict of interest. No specific funding was received for this paper. Soham Rej has received salary support from the Fonds de Recherche du Quebec-Santé (FRQS) and the Canadian Institute of Health research (CIHR). Previous Presentation: None of the content of this manuscript had been previously presented. Keywords (>3): Lurasidone, Bipolar Disorder, Older Adults
Page 1 of 6
Invited Perspective Article: “Lurasidone: A New Option for Older Adults with Bipolar Disorder?” By 2030, more than 50% of bipolar disorder patients will be aged ≥60 years old1. There is very little clinical trial data focusing on older age bipolar disorder (OABD), with the largest open-label study prior to 2015 having 57 patients (treated with lamotrigine) and the grand majority of studies having less than 20 patients2. To compound this issue, depression remains one of the more difficult-to-treat aspects of bipolar disorder. There is a lack of data regarding depression in OABD, particularly for the longer-term maintenance phase of treatment2.
Forester et al.’s paper in this issue of the American Journal of Geriatric Psychiatry contributes much-needed longer-term treatment data for depression in OABD3. The authors found that the novel atypical antipsychotic, lurasidone, was both efficacious and well-tolerated in the medium-/longer-term treatment of OABD depression. Their post-hoc analysis examined 141 patients aged 55-75 treated with lurasidone either as monotherapy or adjunctive pharmacotherapy over 6-month open-label follow-up following an initial 6-week randomized controlled trial (RCT). There were consistent improvements in a number of depression and functional outcomes, such as the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression-Bipolar Scale (CGI-BP). Along these lines, approximately 85% of patients had some response in depressive symptoms at 6-month follow-up. These results echo findings from the adult literature4 and the anecdotal clinical experience of myself and colleagues using lurasidone in OABD patients.
Page 2 of 6
An interesting aspect of this study was the relatively large sample size, which allowed an estimation of lurasidone dosing in geriatric bipolar disorder patients. Most patients used 6080mg/day of lurasidone, which appeared to be efficacious, well-tolerated, and was only slightly lower than modal doses used in adult bipolar depression4. This runs slightly against the clinical lore that doses equal to or above 60mg (especially >80mg), but can actually worsen depressed mood4. The data from this analysis will give clinicians some guidance about ideal lurasidone dosing in OABD patients.
As well, minimal changes were observed in a number of important adverse effect outcomes, such as weight, cholesterol, triglycerides and Hemoglobin A1c. This is important, since many antipsychotics, and even valproate and lithium can be associated with weight gain and metabolic syndrome.
There may be some points of caution, however, when applying Forester et al.’s findings into clinical practice. For example, recent data has associated antipsychotic use with acute kidney injury5, which I and colleagues have observed anecdotally with our patients on lurasidone and other antipsychotics. Also although rates of akathisia and tremor were also relatively low in their sample, it is unclear how these rates would be in even older geriatric patients with bipolar disorder. As Forester et al. state, 80% of patients in their post-hoc analysis were aged 55-65, with many patients with physical comorbidities excluded. There still remains a great need for data in older and more vulnerable old geriatric patients with bipolar disorder – e.g. patients aged ≥65
Page 3 of 6
and especially ≥75, including those with worse physical and cognitive comorbidity. Such data will be needed to verify claims of effectiveness and tolerability in “real-world” OABD patients.
Limitations aside, this paper expands on recent exciting OABD pharmacotherapy trial data from the past year. Sajatovic et al. performed a post-hoc analysis of the original 6-week lurasidone trial, finding it to be effective for acute depression in OABD patients aged 55-756. Young and his GERI-BD colleagues completed the first-ever randomized controlled-trial of OABD patients, finding that lithium and valproate were effective in late-life mania7. Given the difficulties of conducting randomized clinical trials in OABD7, the approach of increasingly recruiting older geriatric patients into adult bipolar disorder trials and performing post-hoc (or even planned) analyses is an exciting one. Hopefully the coming years will yield similarly exciting novel treatment data for older adults with bipolar disorder!
Page 4 of 6
References 1.
Jeste DV, Alexopoulos GS, Bartels SJ, et al. Consensus statement on the upcoming crisis in geriatric mental health: Research agenda for the next 2 decades. Arch Gen Psychiatry. 1999;56(9):848-853.
2.
Sajatovic M, Strejilevich SA, Gildengers AG, et al. A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force. Bipolar disorders. 2015;17(7):689-704.
3.
Forester BP, Sajatovic M, Tsai J, Pikalov A, Cucchiaro J, Loebel A. Safety and Effectiveness of Long-term Treatment with Lurasidone in Older Adults with Bipolar Depression: Post-hoc Analysis of a 6 Month, Open-label Study. Am J Geriatr Psychiatry. In Press.
4.
Loebel A, Cucchiaro J, Silva R, et al. Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebocontrolled study. The American journal of psychiatry. 2014;171(2):169-177.
5.
Hwang YJ, Dixon SN, Reiss JP, et al. Atypical antipsychotic drugs and the risk for acute kidney injury and other adverse outcomes in older adults: a population-based cohort study. Annals of internal medicine. 2014;161(4):242-248.
6.
Sajatovic M, Forester BP, Tsai J, et al. Efficacy of Lurasidone in Adults Aged 55 Years and Older With Bipolar Depression: Post Hoc Analysis of 2 Double-Blind, PlaceboControlled Studies. The Journal of clinical psychiatry. 2016;77(10):e1324-e1331.
Page 5 of 6
7.
Young RC, Mulsant BH, Sajatovic M, et al. GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder. The American journal of psychiatry. 2017.
Page 6 of 6
S1064-7481(17)30450-5 http://dx.doi.org/doi: 10.1016/j.jagp.2017.09.003 AMGP 917
To appear in:
The American Journal of Geriatric Psychiatry
Received date: Accepted date:
3-9-2017 5-9-2017
Please cite this article as: Soham Rej, Lurasidone: a New Option for Older Adults with Bipolar Disorder?, The American Journal of Geriatric Psychiatry (2017), http://dx.doi.org/doi: 10.1016/j.jagp.2017.09.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Word Count (<1000): 617 Abstract Word Count: N/A #References (≤7): 7 #Tables: 0 #Figures: 0 Lurasidone: A New Option for Older Adults with Bipolar Disorder? Invited Perspective Article on Forester et al.’s - "Safety and Effectiveness of Long-term Treatment with Lurasidone in Older Adults with Bipolar Depression: Post-hoc Analysis of a 6 Month, Open-label Study” Soham Rej, M.D., M.Sc.1 1
Geri-PARTy Research Group, Dept. of Psychiatry, Jewish General Hospital/Lady Davis Institute, McGill University, Montreal, QC, Canada Corresponding Author: Soham Rej M.D., MSc, Dept. of Psychiatry, Jewish General Hospital/Lady Davis Institute, McGill University, 4333 Cote-Ste-Catherine, Montreal, QC, Canada, H3T 1E4, 514-340-8222 x27506, email: [email protected] Conflicts of Interest and Source of Funding/Acknowledgements: The author declare no conflict of interest. No specific funding was received for this paper. Soham Rej has received salary support from the Fonds de Recherche du Quebec-Santé (FRQS) and the Canadian Institute of Health research (CIHR). Previous Presentation: None of the content of this manuscript had been previously presented. Keywords (>3): Lurasidone, Bipolar Disorder, Older Adults
Page 1 of 6
Invited Perspective Article: “Lurasidone: A New Option for Older Adults with Bipolar Disorder?” By 2030, more than 50% of bipolar disorder patients will be aged ≥60 years old1. There is very little clinical trial data focusing on older age bipolar disorder (OABD), with the largest open-label study prior to 2015 having 57 patients (treated with lamotrigine) and the grand majority of studies having less than 20 patients2. To compound this issue, depression remains one of the more difficult-to-treat aspects of bipolar disorder. There is a lack of data regarding depression in OABD, particularly for the longer-term maintenance phase of treatment2.
Forester et al.’s paper in this issue of the American Journal of Geriatric Psychiatry contributes much-needed longer-term treatment data for depression in OABD3. The authors found that the novel atypical antipsychotic, lurasidone, was both efficacious and well-tolerated in the medium-/longer-term treatment of OABD depression. Their post-hoc analysis examined 141 patients aged 55-75 treated with lurasidone either as monotherapy or adjunctive pharmacotherapy over 6-month open-label follow-up following an initial 6-week randomized controlled trial (RCT). There were consistent improvements in a number of depression and functional outcomes, such as the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression-Bipolar Scale (CGI-BP). Along these lines, approximately 85% of patients had some response in depressive symptoms at 6-month follow-up. These results echo findings from the adult literature4 and the anecdotal clinical experience of myself and colleagues using lurasidone in OABD patients.
Page 2 of 6
An interesting aspect of this study was the relatively large sample size, which allowed an estimation of lurasidone dosing in geriatric bipolar disorder patients. Most patients used 6080mg/day of lurasidone, which appeared to be efficacious, well-tolerated, and was only slightly lower than modal doses used in adult bipolar depression4. This runs slightly against the clinical lore that doses equal to or above 60mg (especially >80mg), but can actually worsen depressed mood4. The data from this analysis will give clinicians some guidance about ideal lurasidone dosing in OABD patients.
As well, minimal changes were observed in a number of important adverse effect outcomes, such as weight, cholesterol, triglycerides and Hemoglobin A1c. This is important, since many antipsychotics, and even valproate and lithium can be associated with weight gain and metabolic syndrome.
There may be some points of caution, however, when applying Forester et al.’s findings into clinical practice. For example, recent data has associated antipsychotic use with acute kidney injury5, which I and colleagues have observed anecdotally with our patients on lurasidone and other antipsychotics. Also although rates of akathisia and tremor were also relatively low in their sample, it is unclear how these rates would be in even older geriatric patients with bipolar disorder. As Forester et al. state, 80% of patients in their post-hoc analysis were aged 55-65, with many patients with physical comorbidities excluded. There still remains a great need for data in older and more vulnerable old geriatric patients with bipolar disorder – e.g. patients aged ≥65
Page 3 of 6
and especially ≥75, including those with worse physical and cognitive comorbidity. Such data will be needed to verify claims of effectiveness and tolerability in “real-world” OABD patients.
Limitations aside, this paper expands on recent exciting OABD pharmacotherapy trial data from the past year. Sajatovic et al. performed a post-hoc analysis of the original 6-week lurasidone trial, finding it to be effective for acute depression in OABD patients aged 55-756. Young and his GERI-BD colleagues completed the first-ever randomized controlled-trial of OABD patients, finding that lithium and valproate were effective in late-life mania7. Given the difficulties of conducting randomized clinical trials in OABD7, the approach of increasingly recruiting older geriatric patients into adult bipolar disorder trials and performing post-hoc (or even planned) analyses is an exciting one. Hopefully the coming years will yield similarly exciting novel treatment data for older adults with bipolar disorder!
Page 4 of 6
References 1.
Jeste DV, Alexopoulos GS, Bartels SJ, et al. Consensus statement on the upcoming crisis in geriatric mental health: Research agenda for the next 2 decades. Arch Gen Psychiatry. 1999;56(9):848-853.
2.
Sajatovic M, Strejilevich SA, Gildengers AG, et al. A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force. Bipolar disorders. 2015;17(7):689-704.
3.
Forester BP, Sajatovic M, Tsai J, Pikalov A, Cucchiaro J, Loebel A. Safety and Effectiveness of Long-term Treatment with Lurasidone in Older Adults with Bipolar Depression: Post-hoc Analysis of a 6 Month, Open-label Study. Am J Geriatr Psychiatry. In Press.
4.
Loebel A, Cucchiaro J, Silva R, et al. Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebocontrolled study. The American journal of psychiatry. 2014;171(2):169-177.
5.
Hwang YJ, Dixon SN, Reiss JP, et al. Atypical antipsychotic drugs and the risk for acute kidney injury and other adverse outcomes in older adults: a population-based cohort study. Annals of internal medicine. 2014;161(4):242-248.
6.
Sajatovic M, Forester BP, Tsai J, et al. Efficacy of Lurasidone in Adults Aged 55 Years and Older With Bipolar Depression: Post Hoc Analysis of 2 Double-Blind, PlaceboControlled Studies. The Journal of clinical psychiatry. 2016;77(10):e1324-e1331.
Page 5 of 6
7.
Young RC, Mulsant BH, Sajatovic M, et al. GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder. The American journal of psychiatry. 2017.
Page 6 of 6