- Email: [email protected]
Haemopoietic stem-cell transplantation for systemic sclerosis – Authors' reply
Correspondence
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Loo H, Hale A, D’haenen H. Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol 2002; 17: 239–47. Kennedy SH, Emsley R. Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharm 2006; 16: 93–100. Olie JP, Kasper S. Efficacy of agomelatine, a MT1/ MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int J Neuropsychopharmacol 2007; 10: 661–73. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008; 5: e45. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009; 373: 746–58. Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between antidepressant prescribing and suicide in Australia, 1991–2000: trend analysis. BMJ 2003; 326: 1008. Quera-Salva M-A, Hajak G, Philip P, et al. Comparison of agomelatine and escitalopram on nighttime sleep and daytime condition and efficacy in major depressive disorder patients. Int Clin Psychopharmacol 2011; 26: 252–62. Naismith SL, Lewis SJG, Rogers N. Sleep and cognition in neurodegenerative disease. Prog Brain Res 2011; 190: 21–52. Kennedy SH, Rizvi SJ. Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness. CNS Drugs 2010; 24: 479–99. McAllister-Williams RH, Baldwin DS, Haddad PM, Bazire S. The use of antidepressants in clinical practice: focus on agomelatine. Hum Psychopharmacol 2010; 25: 95–102. Laux G, Inn/MÜnchen WA, VIVALDIStudiengruppe. Antidepressive Therapie mit Agomelatin in der Facharztpraxis: Ergebnisse der VIVALDI-Studie. Psychopharmakotherapie 2011; 18: 18–26. Dodd S, Malhi GS, Tiller J, et al. A consensus statement for safety monitoring guidelines of treatments for major depressive disorder. Aust N Z J Psychiatry 2011; 45: 712–25.
Haemopoietic stem-cell transplantation for systemic sclerosis Richard Burt and colleagues (Aug 6, p 498)1 propose, on the basis of a single-centre trial of 19 patients, www.thelancet.com Vol 379 January 21, 2012
that autologous haemopoietic stemcell transplantation (HSCT) might be the new standard of care for diffuse systemic sclerosis. Although the study strongly supports the use of immunosuppression in systemic sclerosis, several limitations are to be noted. First, a cross-over design after only 6 months’ treatment with so few patients is exceedingly difficult to interpret definitively for either toxicity or efficacy. Second, the endpoints of Rodnan skin score and forced vital capacity have substantial serial test variability and other studies require more robust differences to prove effect in a potentially toxic therapy. Third, follow-up of only 24 months is too brief to determine durable response or effects on organ failure or death. There were no deaths in either treatment group, which is very unusual in severe systemic sclerosis and suggests either insufficient duration of follow-up or selection of patients with less severe disease. Moreover, meaningful improvements in severe systemic sclerosis have been reported beyond 24 months after HSCT.2 As Burt and colleagues note, the multicentre ASTIS and SCOT trials are currently maturing to reach sufficient follow-up and numbers of patients to address these concerns. The findings of these trials will be crucial for determination of standards of care in systemic sclerosis, since HSCT for autoimmune diseases requires compelling data with sufficient numbers of patients and detailed long-term outcomes to change practice.3 And practising physicians and decision makers might require greater evidence of clinical benefit to change practice habits than investigators think.4,5 We declare that we have no conflicts of interest.
*Keith M Sullivan, Frederick M Wigley, Christopher P Denton, Jacob M van Laar, Daniel E Furst [email protected] Division of Cellular Therapy, Duke University, Durham, NC 27710, USA (KMS); Scleroderma Center, Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA (FMW); Centre for
Rheumatology, Royal Free Hospital and University College London, London, UK (CPD); Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK (JMvL); and Division of Rheumatology, University of California, Los Angeles, CA, USA (DEF) 1
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Burt RK, Shah SJ, Dill K, et al. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per months for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet 2011; 378: 498–506. Nash RA, McSweeney PA, Crofford LJ, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe system sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007; 110: 1388–96. Couzin-Frankel J. Replacing an immune system gone haywire. Science 2010; 327: 772–74. Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA 2003; 290: 1624–32. Ubel PA, Silbergleit R. Behavioral equipoise: a way to resolve ethical stalemates in clinical research. Am J Bioethics 2011; 11: 1–8.
Authors’ reply We thank the SCOT principal investigators Keith Sullivan and Daniel Furst, and their colleagues, for comments on our study. First, crossover in ASSIST was allowed at 12 months, not 6 months.1 The optimum dose or duration of cyclophosphamide treatment that will improve lung function is unknown since no published studies document an improvement in lung function with cyclophosphamide. Second, Sullivan and colleagues’ criticism of defining disease progression on the basis of only Rodnan skin score (mRSS) and forced vital capacity (FVC) endpoints overlooks the fact that the endpoints mRSS, FVC, high-resolution CT imaging of involved lung, and 36-item Short Form Health Survey (SF-36) all changed equally in our study.1 Indeed, this endpoint critique would be applicable to previous studies in systemic sclerosis, including the Scleroderma Lung Research Study Group trial,2 which reported “modest benefit” of daily oral cyclophosphamide on the basis of a mean FVC that in reality deteriorated on cyclophosphamide treatment (but declined less rapidly when compared with placebo). Finally, Sullivan and colleagues’ concerns that the ASSIST
Science Photo Library
Brain & Mind Research Institute, University of Sydney, Camperdown, NSW 2050, Australia (IBH, NLR); and School of Management and Marketing, Institute for Health and Social Science Research, Central Queensland University, Mackay, QLD, Australia (NLR)
219
Correspondence
Science Photo Library
For a podcast on the ASSIST trial go to http://download.thelancet. com/flatcontentassets/audio/ lancet/2011/05august.mp3
follow-up of 24 months is too brief is also inconsistent with previous publications, since the Scleroderma Lung Research Study Group trial reported with 1-year follow-up.2 Sullivan and colleagues state that to have no deaths in either group is unusual. Different transplant regimens at different stages of disease will have different toxic effects, and different effects on death and outcomes.3,4 Like any immune-based therapy, the toxic effects and outcome of haemopoietic stem-cell transplantation is a consequence of the immune drug or drugs used, selection of patients, and centre effects (podcast). Our decision to allow crossover at 1 year was made in the interest of patients’ benefit and might also have prevented subsequent deaths in the control group. Sullivan and colleagues’ criticism that patient selection contributed to the favourable ASSIST outcome is correct but is not a fault, since a properly designed trial should exclude patients at high risk of death. Extensive precardiac assessment to exclude primary cardiac involvement and pulmonary arterial hypertension selected for patients early after diagnosis who are most likely to have low transplant-related mortality. Optimisation of patient selection, conditioning regimen (drugs), and centre experience is important before starting large phase 3 trials and before assuming that there will be similar outcomes from other trials. One need look no further than the pilot study using the SCOT trial regimen5 in which 12 of 34 patients died and two of the 22 who survived developed treatmentrelated myelodysplastic syndrome. We look forward to the availability of data from all studies including SCOT, ASTRIS, and ASSIST II to help clinicians in this difficult disease. We declare that we have no conflicts of interest.
*Richard K Burt, Mahai Gheorghiade, Sanjiv Shah, Eric Ruderman, James Schroeder [email protected] Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
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Burt RK, Shah SJ, Dill K, et al. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet 2011; 378: 498–506. Tashkin DP, Elashoff R, Clements PJ, et al, for the Sclerodermap; Lung Study Research Group. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006; 354: 2655–66. Burt RK, Abinun M, Farge-Bancel D, et al. Risks of immune system treatments. Science 2010; 328: 825–26. Burt RK, Loh Y, Pearce W, et al. Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA 2008; 299: 925–36. Nash RA, McSweeney PA, Crofford LJ, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007; 110: 1388–96.
Stay the course—is it justified? Sube Banerjee and colleagues (July 30, p 403)1 report on sertraline (a Selective Serotonin Reuptake Inhibitor [SSRI]) or mirtazapine (a noradrenergic and specific serotonergic antidepressant) for treatment of depression in people with dementia (HTT-SADD trial). They show that (1) neither compound is superior to placebo in resolving symptoms of depression, and (2) there is a higher rate of adverse events associated with treatment than with placebo. Their findings seem to be consistent with those of other sertraline trials.2 Banerjee and colleagues3 conclude that the present practice of using these antidepressants as firstline therapy should be reassessed. Most trials to date, including HTTSADD, have examined sertraline, and only a few have addressed other antidepressants including citalopram or venlafaxine. Clinical trials are underway, but to date the efficacy of other SSRI or serotonin noradrenergic reuptake inhibitors in the treatment of depression in people with dementia remains largely unknown. Although Banerjee and colleagues’ article provides important information for consideration in clinical decision
making in the treatment of concurrent depression and dementia, we believe that it is premature to suggest that the use of all antidepressant treatments is ineffective. Group findings are not readily applicable to the care of individuals in clinical settings: there is probably substantial variation in individuals’ clinical response and tolerance even within the same class of drug. Even if predictors of these were known, different antidepressants or a combination of low doses of antidepressants might need to be attempted before the optimum treatment is identified. Until these issues are explored further, it seems reasonable to continue current clinical practice. AAS is funded by the Canadian Institutes of Health Research (CIHR) (Frederick Banting and Charles Best Canada Graduate Scholarships—Doctoral Awards). PEL has received funding from the Cullen Family and St Paul’s Hospital Foundation; he has received honoraria for speaking and participating in advisory boards for Janssen-Ortho, Novartis, and Pfizer, and is a co-investigator on the Alzheimer’s Drug Therapy Initiative (ADTI) funded by the BC Ministry of Health Services and on the clinical trials at the University of British Columbia Clinic for Alzheimer Disease and Related Disorders receiving funding from Baxter, Bristol-Myers Squibb, Elan, Janssen-AI, Pfizer, Hoffman-La Roche, and Genentech. GYRS is supported by a Clinical Genetics Investigatorship award from the CIHR; he has received research support from Baxter, Bristol-Myers Squibb, Elan, Janssen-AI, Pfizer, Hoffman-La Roche, and Genentech as an Alzheimer clinical trial centre for C5R at UBC. CJ acknowledges receiving funding from CIHR and the BC Ministry of Health Services through the ADTI. PEL, GYRH, and CJ are supported by the Ralph Fisher and Alzheimer’s Society of British Columbia Professorship in Alzheimer’s Research.
Amir A Sepehry, *Philip E Lee, Ging Yuek Robin Hsiung, Claudia Jacova [email protected] University of British Columbia, Vancouver, BC V6Z 1Y6, Canada 1
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Banerjee S, Hellier J, Dewey M, et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet 2011; 378: 403–11. Rosenberg PB, Drye LT, Martin BK, et al. Sertraline for the treatment of depression in Alzheimer disease. Am J Geriatr Psychiatry 2010; 18: 136–45. Hogan DB, Bailey P, Carswell A, et al. Management of mild to moderate Alzheimer’s disease and dementia. Alzheimers Dement 2007; 3: 355–84.
www.thelancet.com Vol 379 January 21, 2012
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Loo H, Hale A, D’haenen H. Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol 2002; 17: 239–47. Kennedy SH, Emsley R. Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharm 2006; 16: 93–100. Olie JP, Kasper S. Efficacy of agomelatine, a MT1/ MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int J Neuropsychopharmacol 2007; 10: 661–73. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008; 5: e45. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009; 373: 746–58. Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between antidepressant prescribing and suicide in Australia, 1991–2000: trend analysis. BMJ 2003; 326: 1008. Quera-Salva M-A, Hajak G, Philip P, et al. Comparison of agomelatine and escitalopram on nighttime sleep and daytime condition and efficacy in major depressive disorder patients. Int Clin Psychopharmacol 2011; 26: 252–62. Naismith SL, Lewis SJG, Rogers N. Sleep and cognition in neurodegenerative disease. Prog Brain Res 2011; 190: 21–52. Kennedy SH, Rizvi SJ. Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness. CNS Drugs 2010; 24: 479–99. McAllister-Williams RH, Baldwin DS, Haddad PM, Bazire S. The use of antidepressants in clinical practice: focus on agomelatine. Hum Psychopharmacol 2010; 25: 95–102. Laux G, Inn/MÜnchen WA, VIVALDIStudiengruppe. Antidepressive Therapie mit Agomelatin in der Facharztpraxis: Ergebnisse der VIVALDI-Studie. Psychopharmakotherapie 2011; 18: 18–26. Dodd S, Malhi GS, Tiller J, et al. A consensus statement for safety monitoring guidelines of treatments for major depressive disorder. Aust N Z J Psychiatry 2011; 45: 712–25.
Haemopoietic stem-cell transplantation for systemic sclerosis Richard Burt and colleagues (Aug 6, p 498)1 propose, on the basis of a single-centre trial of 19 patients, www.thelancet.com Vol 379 January 21, 2012
that autologous haemopoietic stemcell transplantation (HSCT) might be the new standard of care for diffuse systemic sclerosis. Although the study strongly supports the use of immunosuppression in systemic sclerosis, several limitations are to be noted. First, a cross-over design after only 6 months’ treatment with so few patients is exceedingly difficult to interpret definitively for either toxicity or efficacy. Second, the endpoints of Rodnan skin score and forced vital capacity have substantial serial test variability and other studies require more robust differences to prove effect in a potentially toxic therapy. Third, follow-up of only 24 months is too brief to determine durable response or effects on organ failure or death. There were no deaths in either treatment group, which is very unusual in severe systemic sclerosis and suggests either insufficient duration of follow-up or selection of patients with less severe disease. Moreover, meaningful improvements in severe systemic sclerosis have been reported beyond 24 months after HSCT.2 As Burt and colleagues note, the multicentre ASTIS and SCOT trials are currently maturing to reach sufficient follow-up and numbers of patients to address these concerns. The findings of these trials will be crucial for determination of standards of care in systemic sclerosis, since HSCT for autoimmune diseases requires compelling data with sufficient numbers of patients and detailed long-term outcomes to change practice.3 And practising physicians and decision makers might require greater evidence of clinical benefit to change practice habits than investigators think.4,5 We declare that we have no conflicts of interest.
*Keith M Sullivan, Frederick M Wigley, Christopher P Denton, Jacob M van Laar, Daniel E Furst [email protected] Division of Cellular Therapy, Duke University, Durham, NC 27710, USA (KMS); Scleroderma Center, Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA (FMW); Centre for
Rheumatology, Royal Free Hospital and University College London, London, UK (CPD); Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK (JMvL); and Division of Rheumatology, University of California, Los Angeles, CA, USA (DEF) 1
2
3 4
5
Burt RK, Shah SJ, Dill K, et al. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per months for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet 2011; 378: 498–506. Nash RA, McSweeney PA, Crofford LJ, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe system sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007; 110: 1388–96. Couzin-Frankel J. Replacing an immune system gone haywire. Science 2010; 327: 772–74. Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA 2003; 290: 1624–32. Ubel PA, Silbergleit R. Behavioral equipoise: a way to resolve ethical stalemates in clinical research. Am J Bioethics 2011; 11: 1–8.
Authors’ reply We thank the SCOT principal investigators Keith Sullivan and Daniel Furst, and their colleagues, for comments on our study. First, crossover in ASSIST was allowed at 12 months, not 6 months.1 The optimum dose or duration of cyclophosphamide treatment that will improve lung function is unknown since no published studies document an improvement in lung function with cyclophosphamide. Second, Sullivan and colleagues’ criticism of defining disease progression on the basis of only Rodnan skin score (mRSS) and forced vital capacity (FVC) endpoints overlooks the fact that the endpoints mRSS, FVC, high-resolution CT imaging of involved lung, and 36-item Short Form Health Survey (SF-36) all changed equally in our study.1 Indeed, this endpoint critique would be applicable to previous studies in systemic sclerosis, including the Scleroderma Lung Research Study Group trial,2 which reported “modest benefit” of daily oral cyclophosphamide on the basis of a mean FVC that in reality deteriorated on cyclophosphamide treatment (but declined less rapidly when compared with placebo). Finally, Sullivan and colleagues’ concerns that the ASSIST
Science Photo Library
Brain & Mind Research Institute, University of Sydney, Camperdown, NSW 2050, Australia (IBH, NLR); and School of Management and Marketing, Institute for Health and Social Science Research, Central Queensland University, Mackay, QLD, Australia (NLR)
219
Correspondence
Science Photo Library
For a podcast on the ASSIST trial go to http://download.thelancet. com/flatcontentassets/audio/ lancet/2011/05august.mp3
follow-up of 24 months is too brief is also inconsistent with previous publications, since the Scleroderma Lung Research Study Group trial reported with 1-year follow-up.2 Sullivan and colleagues state that to have no deaths in either group is unusual. Different transplant regimens at different stages of disease will have different toxic effects, and different effects on death and outcomes.3,4 Like any immune-based therapy, the toxic effects and outcome of haemopoietic stem-cell transplantation is a consequence of the immune drug or drugs used, selection of patients, and centre effects (podcast). Our decision to allow crossover at 1 year was made in the interest of patients’ benefit and might also have prevented subsequent deaths in the control group. Sullivan and colleagues’ criticism that patient selection contributed to the favourable ASSIST outcome is correct but is not a fault, since a properly designed trial should exclude patients at high risk of death. Extensive precardiac assessment to exclude primary cardiac involvement and pulmonary arterial hypertension selected for patients early after diagnosis who are most likely to have low transplant-related mortality. Optimisation of patient selection, conditioning regimen (drugs), and centre experience is important before starting large phase 3 trials and before assuming that there will be similar outcomes from other trials. One need look no further than the pilot study using the SCOT trial regimen5 in which 12 of 34 patients died and two of the 22 who survived developed treatmentrelated myelodysplastic syndrome. We look forward to the availability of data from all studies including SCOT, ASTRIS, and ASSIST II to help clinicians in this difficult disease. We declare that we have no conflicts of interest.
*Richard K Burt, Mahai Gheorghiade, Sanjiv Shah, Eric Ruderman, James Schroeder [email protected] Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
220
1
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3
4
5
Burt RK, Shah SJ, Dill K, et al. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet 2011; 378: 498–506. Tashkin DP, Elashoff R, Clements PJ, et al, for the Sclerodermap; Lung Study Research Group. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006; 354: 2655–66. Burt RK, Abinun M, Farge-Bancel D, et al. Risks of immune system treatments. Science 2010; 328: 825–26. Burt RK, Loh Y, Pearce W, et al. Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA 2008; 299: 925–36. Nash RA, McSweeney PA, Crofford LJ, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007; 110: 1388–96.
Stay the course—is it justified? Sube Banerjee and colleagues (July 30, p 403)1 report on sertraline (a Selective Serotonin Reuptake Inhibitor [SSRI]) or mirtazapine (a noradrenergic and specific serotonergic antidepressant) for treatment of depression in people with dementia (HTT-SADD trial). They show that (1) neither compound is superior to placebo in resolving symptoms of depression, and (2) there is a higher rate of adverse events associated with treatment than with placebo. Their findings seem to be consistent with those of other sertraline trials.2 Banerjee and colleagues3 conclude that the present practice of using these antidepressants as firstline therapy should be reassessed. Most trials to date, including HTTSADD, have examined sertraline, and only a few have addressed other antidepressants including citalopram or venlafaxine. Clinical trials are underway, but to date the efficacy of other SSRI or serotonin noradrenergic reuptake inhibitors in the treatment of depression in people with dementia remains largely unknown. Although Banerjee and colleagues’ article provides important information for consideration in clinical decision
making in the treatment of concurrent depression and dementia, we believe that it is premature to suggest that the use of all antidepressant treatments is ineffective. Group findings are not readily applicable to the care of individuals in clinical settings: there is probably substantial variation in individuals’ clinical response and tolerance even within the same class of drug. Even if predictors of these were known, different antidepressants or a combination of low doses of antidepressants might need to be attempted before the optimum treatment is identified. Until these issues are explored further, it seems reasonable to continue current clinical practice. AAS is funded by the Canadian Institutes of Health Research (CIHR) (Frederick Banting and Charles Best Canada Graduate Scholarships—Doctoral Awards). PEL has received funding from the Cullen Family and St Paul’s Hospital Foundation; he has received honoraria for speaking and participating in advisory boards for Janssen-Ortho, Novartis, and Pfizer, and is a co-investigator on the Alzheimer’s Drug Therapy Initiative (ADTI) funded by the BC Ministry of Health Services and on the clinical trials at the University of British Columbia Clinic for Alzheimer Disease and Related Disorders receiving funding from Baxter, Bristol-Myers Squibb, Elan, Janssen-AI, Pfizer, Hoffman-La Roche, and Genentech. GYRS is supported by a Clinical Genetics Investigatorship award from the CIHR; he has received research support from Baxter, Bristol-Myers Squibb, Elan, Janssen-AI, Pfizer, Hoffman-La Roche, and Genentech as an Alzheimer clinical trial centre for C5R at UBC. CJ acknowledges receiving funding from CIHR and the BC Ministry of Health Services through the ADTI. PEL, GYRH, and CJ are supported by the Ralph Fisher and Alzheimer’s Society of British Columbia Professorship in Alzheimer’s Research.
Amir A Sepehry, *Philip E Lee, Ging Yuek Robin Hsiung, Claudia Jacova [email protected] University of British Columbia, Vancouver, BC V6Z 1Y6, Canada 1
2
3
Banerjee S, Hellier J, Dewey M, et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet 2011; 378: 403–11. Rosenberg PB, Drye LT, Martin BK, et al. Sertraline for the treatment of depression in Alzheimer disease. Am J Geriatr Psychiatry 2010; 18: 136–45. Hogan DB, Bailey P, Carswell A, et al. Management of mild to moderate Alzheimer’s disease and dementia. Alzheimers Dement 2007; 3: 355–84.
www.thelancet.com Vol 379 January 21, 2012