JOURNAL OF PALLIATIVE MEDICINE Volume 18, Number 4, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2014.0412
Aripiprazole for the Treatment of Depression in Palliative Care Laura E. Meyer-Junco, PharmD, BCPS
Dear Editor: Depression often coincides with terminal illness and may reduce the quality of life in patients with limited life expectancies. Ideally then, the goal in palliative care is to treat this psychological symptom as quickly as possible to salvage the patient’s remaining days. However, traditional antidepressants may take several weeks to reach therapeutic effect, which is time our patients do not have. In searching for solutions to this challenge, psychostimulants with their rapid onset of action within 24 to 48 hours have become attractive agents for depression in palliative care except for those patients with significant cardiovascular disease, cognitive disturbances, or insomnia.1 Thus, the search for other quick-acting agents to address this issue of pharmaceutical latency should continue, especially when considering patients with treatment-resistant depression who may need intervention the most. Borrowing from our psychiatry colleagues, one atypical agent may be particularly well suited for palliative care—aripiprazole. Aripiprazole received FDA approval for adjunctive treatment of major depressive disorder in 2008. In the randomized, double-blinded, placebo-controlled studies leading up to its approval and after, the addition of aripiprazole to traditional antidepressant therapy resulted in rapid improvements in depression scores.2 In a pooled analysis of two large randomized 14-week trials, patients previously receiving selective serotonin reuptake inhibitors (SSRIs) or serotoninnorepinephrine reuptake inhibitors (SNRIs) demonstrated a significant response with adjunctive aripiprazole as early as the first week of therapy. From the second week onward, remission rates were also significantly greater with aripiprazole augmentation.3 In palliative care, where time is limited and multiple etiologies often exist for physical symptoms such as nausea and pain, a multimodal approach to treatment is taken. In the same vein, a multimodal approach to psychological symptoms such as depression may also be warranted. In the pooled analysis described above, the authors postulated that depression remission with combination therapy was likely the result of a synergistic mechanism. In addition to serotonin modulation provided by the SSRI or SNRI, aripiprazole functioned as a partial agonist at the dopamine receptors D2 and D3 thereby also modulating dopamine transmission. Although not adequately studied, depression response with aripiprazole monotherapy might be achievable given its activity as a partial agonist at both serotonin and dopamine receptors. At least one
case report exists to support aripiprazole monotherapy in depression, but more formal investigations are needed.4 At doses of 2–20 mg/day (starting dose 5 mg/day), aripiprazole was well tolerated in the pooled analysis described previously.3 Discontinuation rates due to adverse effects were low (3.5%), with the most common adverse reactions being akathisia, restlessness, insomnia, fatigue, blurred vision, and constipation.3 In a pooled analysis of older patients (age 50–67), dizziness was more common than in younger subjects, but akathisia was actually less common. Cardiovascular adverse events and tardive dyskinesia were not reported in this six-week trial.5 With its quick therapeutic effect, multimodal mechanism of action, and relatively well-tolerated side effect profile, aripiprazole might just be the solution to managing the palliative care patient with treatment-resistant depression and only weeks to live. References
1. Garcia C, Lynn R, Breitbart W: Psychotropic medications in palliative care. Primary Psychiatry 2009;16:25–32. 2. Seo RJ, MacPherson H, Young AH: Atypical antipsychotics and other therapeutic options for treatment of resistant major depressive disorder. Pharmaceuticals 2010;3:3522– 3542. 3. Thase ME, Trivedi MH, Nelson JC, et al.: Examining the efficacy of adjunctive aripiprazole in major depressive disorder: A pooled analysis of 2 studies. Prim Care Companion J Clin Psychiatry 2008;10:440–447. 4. Yokoyama Y, Kitamura H, Someya T: Aripiprazole monotherapy in a patient with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:1124– 1125. 5. Steffens DC, Nelson JC, Eudicone JM, et al.: Efficacy and safety of adjunctive aripiprazole in major depressive disorder in older patients: A pooled subpopulation analysis. Int J Geriatr Psychiatry 201;26:564–572.
UIC College of Pharmacy at Rockford, Rockford, Illinois.
316
Address correspondence to: Laura E. Meyer-Junco, PharmD, BCPS UIC College of Pharmacy at Rockford 1601 Parkview Avenue Rockford, IL 61107 E-mail: [email protected]
Copyright of Journal of Palliative Medicine is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Aripiprazole for the Treatment of Depression in Palliative Care Laura E. Meyer-Junco, PharmD, BCPS
Dear Editor: Depression often coincides with terminal illness and may reduce the quality of life in patients with limited life expectancies. Ideally then, the goal in palliative care is to treat this psychological symptom as quickly as possible to salvage the patient’s remaining days. However, traditional antidepressants may take several weeks to reach therapeutic effect, which is time our patients do not have. In searching for solutions to this challenge, psychostimulants with their rapid onset of action within 24 to 48 hours have become attractive agents for depression in palliative care except for those patients with significant cardiovascular disease, cognitive disturbances, or insomnia.1 Thus, the search for other quick-acting agents to address this issue of pharmaceutical latency should continue, especially when considering patients with treatment-resistant depression who may need intervention the most. Borrowing from our psychiatry colleagues, one atypical agent may be particularly well suited for palliative care—aripiprazole. Aripiprazole received FDA approval for adjunctive treatment of major depressive disorder in 2008. In the randomized, double-blinded, placebo-controlled studies leading up to its approval and after, the addition of aripiprazole to traditional antidepressant therapy resulted in rapid improvements in depression scores.2 In a pooled analysis of two large randomized 14-week trials, patients previously receiving selective serotonin reuptake inhibitors (SSRIs) or serotoninnorepinephrine reuptake inhibitors (SNRIs) demonstrated a significant response with adjunctive aripiprazole as early as the first week of therapy. From the second week onward, remission rates were also significantly greater with aripiprazole augmentation.3 In palliative care, where time is limited and multiple etiologies often exist for physical symptoms such as nausea and pain, a multimodal approach to treatment is taken. In the same vein, a multimodal approach to psychological symptoms such as depression may also be warranted. In the pooled analysis described above, the authors postulated that depression remission with combination therapy was likely the result of a synergistic mechanism. In addition to serotonin modulation provided by the SSRI or SNRI, aripiprazole functioned as a partial agonist at the dopamine receptors D2 and D3 thereby also modulating dopamine transmission. Although not adequately studied, depression response with aripiprazole monotherapy might be achievable given its activity as a partial agonist at both serotonin and dopamine receptors. At least one
case report exists to support aripiprazole monotherapy in depression, but more formal investigations are needed.4 At doses of 2–20 mg/day (starting dose 5 mg/day), aripiprazole was well tolerated in the pooled analysis described previously.3 Discontinuation rates due to adverse effects were low (3.5%), with the most common adverse reactions being akathisia, restlessness, insomnia, fatigue, blurred vision, and constipation.3 In a pooled analysis of older patients (age 50–67), dizziness was more common than in younger subjects, but akathisia was actually less common. Cardiovascular adverse events and tardive dyskinesia were not reported in this six-week trial.5 With its quick therapeutic effect, multimodal mechanism of action, and relatively well-tolerated side effect profile, aripiprazole might just be the solution to managing the palliative care patient with treatment-resistant depression and only weeks to live. References
1. Garcia C, Lynn R, Breitbart W: Psychotropic medications in palliative care. Primary Psychiatry 2009;16:25–32. 2. Seo RJ, MacPherson H, Young AH: Atypical antipsychotics and other therapeutic options for treatment of resistant major depressive disorder. Pharmaceuticals 2010;3:3522– 3542. 3. Thase ME, Trivedi MH, Nelson JC, et al.: Examining the efficacy of adjunctive aripiprazole in major depressive disorder: A pooled analysis of 2 studies. Prim Care Companion J Clin Psychiatry 2008;10:440–447. 4. Yokoyama Y, Kitamura H, Someya T: Aripiprazole monotherapy in a patient with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:1124– 1125. 5. Steffens DC, Nelson JC, Eudicone JM, et al.: Efficacy and safety of adjunctive aripiprazole in major depressive disorder in older patients: A pooled subpopulation analysis. Int J Geriatr Psychiatry 201;26:564–572.
UIC College of Pharmacy at Rockford, Rockford, Illinois.
316
Address correspondence to: Laura E. Meyer-Junco, PharmD, BCPS UIC College of Pharmacy at Rockford 1601 Parkview Avenue Rockford, IL 61107 E-mail: [email protected]
Copyright of Journal of Palliative Medicine is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
