Depression Outcomes Among Patients Treated With Fluoxetine for Stroke Recovery
Authors: Osvaldo P. Almeida, Graeme J. Hankey, Andrew Ford, Christopher Etherton-Beer, Leon Flicker, Maree Hackett, Gillian E. Mead, Martin S. Dennis, Laurent Billot, Stephen Jan, Thomas Lung, Veronica Murray, Erik Lundström, Craig S. Anderson, Robert Herbert, Gregory Carter, Geoffrey A. Donnan, Huy-Thang Nguyen, John Gommans, Qilong Yi, Qiang Li, Severine Bompoint, Sarah Barrett, Anne Claxton, Julia O’Dea, Michelle Tang, Clare Williams, Shenae Peterson, Christie Drummond, Uyen-Ha Hong, Linh-Thi My Le, Tram-Thi Bich Ngo, Yen-Bao Mai, Huyen-Thanh Han, Nhu-Quynh Truong, Huong-Thi Nguyen, Hai-Thanh Ngo, -Thi Binh Nguyen, Oanh-Thi Kieu Ha, Trang-Le Huyen Nguyen, Richard I. Lindley, Peter New, Andrew Lee, Thanh-Trung Tran, Loan-Tran Truc Mai Le, Thuy-Le Vu Kieu, Sang-Van Nguyen, Thuy-Anh Diem Nguyen, Tam-Nhat Dang, Hanh-Thi Truc Phan, Loan-Thi Ngoc Vo, Mai-Hue Nguyen, Hanh-Cao Dang, Hong-Thi Tran, Linh-Thi Cam Dam, Trinh-Thi Kim Ngo, Thai-Nguyen Thanh Pham, Binh-Nguyen Pham, Nha-Thi Thanh Dao, Huong-Thi Bich Nguyen, Linh-Thi Cam Le, Chi-Minh Do, Huy-Quoc Huynh, Giau-Thi Kim Tran, Oanh-Thi Le, Ly-Thi Khanh Tran, Chinh-Dinh Duong, Duong-Van Kieu, Na Le, Hoa-Ngoc Nguyen, Binh-Van Le, Long-Thanh Nguyen, Long-Van Nguyen, Tuan-Quoc Dinh, Tan-Van Vo, Tram-Ngoc Bui, Uyen-Thi To Hoang, Hien-Thi Bich Nguyen, Ha-Thi Thu Nguyen, Nga-Thuy Lam, Khanh-Kim Le, Phuong-Thanh Trinh, Hop-Quang Huynh, Thao-Thi Thu Nguyen, Huyen-Ngoc Lu, Tham-Hong Pham, Sam-Hoanh Nguyen, Ninh-Hong Le, Giang-Truong Nguyen, Bich-Thi Doan, Sung-Phuoc Pham, Duong-Huu Luong, Ha-Van Mai, Thuc-Van Tran, Phuong-Thi Do, Hoai-Thi Le, Chi-Van Nguyen, Phuong-Doan Nguyen, Ton-Duy Mai, Phuong-Viet Dao, Dung-Tien Nguyen, Dai-Quoc Khuong, Trung-Xuan Vuong, Lan-Tuong Vu, Ngoc-Duc Ngo, Hanh-Hong Dang, Phuong-Thai Truong, Ngan-Thi Le, Hoa-Van Hoang, Chung-Quang Do, Minh-Thao Nguyen, Anh-Hai Dam, Quynh-Nhu Le, Ngoc-Hoang Nguyen, Tuyen-Van Nguyen, Toan-Dinh Le, Ha-Thi Hai Dinh, Cuong –Van Pham, Khanh-Thi Ngoc Thach, Linh-Hai Nguyen, Loan-Thi Nguyen, Vien-Chi Le, Phuong-Hong Tran, Tai-Anh Nguyen, Tuan-Van Le, Luyen-Van Truong, Tue-Chau Bui, Ngoc-Xuan Huynh, Lap-Van Dinh, An-Gia Pham, Trang-Thi Huyen Le, Vy-Tuong Nguyen, Yen-Hai Nguyen, Thang-Ba Nguyen, Huy Thai, Quyen-Thi Ngoc Pham, Khoa-Duy Dao, Quoc-Nguyen Bao Pham, Thuong-Thi Huyen Dang, Huong-Huynh To Dinh, Trang-Mai Tong, Thuy-Thi Vu, Si-Tri Le, Tai-Ngoc Tran, Phuong-Hoai Tran, Ngoc-Thuy Nhu Dinh, Binh-Thanh Nguyen, Vinh-Phuong Do, Anh-Ngoc Nguyen, Binh-Thi Thanh Nguyen, David Blacker, Lindsey Bunce, Ai Ling Tan, Darshan Ghia, Gillian Edmonds, Nicole O’Loughlin, Megan Ewing, Kerri-Ann Whittaker, Lorralee Deane, Yash Gawarikar, Brett Jones, Maria Lopez, Koushik Nagesh, Emma Siracusa, Stephen Davis, Amy McDonald, Jess Tsoleridis, Rachael McCoy, David Jackson, Gab Silver, Timothy R. Bates, Amanda Boudville, Lynda Southwell, Dennis Cordato, Alan J. McDougall, Cecilia Cappelen-Smith, Zeljka Calic, Shabeel Askar, Qi Cheng, Raymond Kumar, Richard Geraghty, Maree Duroux, Megan Ratcliffe, Samantha Shone, Cassandra McLennan, Ramesh Sahathevan, Casey Hair, Stanley Levy, Beverley Macdonald, Benjamin Nham, Louise Rigney, Dev Nathani, Sumana Gopinath, Vishal Patel, Abul Mamun, Benjamin Trewin, Chun Phua, Ho Choong, Lauren Tarrant, Kerry Boyle, Luisa Hewitt, Monique Hourn, Amanda Masterson, Kim Oakley, Karen Ruddell, Colette Sanctuary, Kimberley Veitch, Camelia Burdusel, Lina Lee, Gary Cheuk, Jeremy Christley, Tabitha Hartwell, Craig Davenport, Kate Hickey, Rosanna Robertson, Michelle Carr, Sam Akbari, Hannah Coyle, Megan O’Neill, Cameron Redpath, Caroline Roberts, Marjan Tabesh, Toni Withiel, Kapila Abeysuriya, Andrew Granger, Angela Abraham, Chermaine Chua, Dung Do Nguyen, Vathani Surendran, Melissa Daines, David Shivlal, Mudassar Latif, Noreen Mughal, Patricia Morgan, Martin Krause, Miriam Priglinger, Ehsan E. Shandiz, Susan Day, Lay Kho, Michael Pollack, Judith Dunne, Helen Baines, Merridie Rees, Jenni White, Aicuratiya Withanage, Candice Delcourt, Cheryl Carcel, Alejandra Malavera, Amy Kunchok, Elizabeth Ray, Elizabeth Pepper, Emily Duckett, Sally Ormond, Andrew Moey, Timothy Kleinig, Vanessa Maxwell, Chantal Baldwin, Wilson Vallat, Deborah Field, Romesh Markus, Kirsty Page, Danielle Wheelwright, Sam Bolitho, Steven Faux, Fix Sangvatanakul, Alexis Brown, Susan Walker, Jennifer Massey, Hillary Hayes, Pesi Katrak, Annie Winker, Alessandro Zagami, Alanah Bailey, Sarah Mccormack, Andrew Murray, Mark Rollason, Christopher Taylor, Fintan O’Rourke, Ye Min Kuang, Heike Burnet, Yvonne Liu, Aileen Wu, Diana Ramirez, Tissa Wijeratne, Sherisse Celestino, Essie Low, Cynthia Chen, Jennifer Bergqvist, Andrew Evans, Queenie Leung, Martin Jude, Rachael McQueen, Katherine Mohr, Latitia Kernaghan, Paul Stockle, Boon L. Tan, Sara Laubscher, Diana Schmid, Melissa Spooner, Bhavesh Lallu, Bronwen Pepperell, John Chalissery, Karim Mahawish, Susan DeCaigney, Paula Broughton, Karen Knight, Veronica Duque, Harry McNaughton, Jeremy Lanford, Vivian Fu, Lai-Kin Wong
Journal: JAMA Neurology (2021)

<h3>Importance</h3> One in 3 adults experiences clinically significant symptoms of depression during the first year after a stroke, but evidence to support the use of antidepressants in this population remains scant. <h3>Objective</h3> To investigate whether daily treatment with 20 mg of fluoxetine hydrochloride reduces the proportion of people affected by clinically significant symptoms of depression after stroke. <h3>Design, Setting, and Participants</h3> In this secondary analysis of the Assessment of Fluoxetine in Stroke Recovery parallel-group, randomized (1:1 assignment), double-blind, placebo-controlled clinical trial, 1221 participants in Australia, New Zealand, and Vietnam were recruited between January 11, 2013, and June 30, 2019, and were followed up for 6 months. Adults aged 18 years or older were recruited 2 to 15 days after experiencing a stroke associated with modified Rankin Scale score of 1 or higher. <h3>Interventions</h3> Fluoxetine hydrochloride, 20 mg, or matched placebo daily for 26 weeks. <h3>Main Outcomes and Measures</h3> A 9-item Patient Health Questionnaire (PHQ-9) score of 9 or lower was a prespecified secondary outcome of the trial. Assessments were completed at baseline and at 4, 12, and 26 weeks. Other outcomes of interest included participant-reported clinician diagnosis of depression, prescription of a nontrial antidepressant, or nonpharmacologic treatment of depression. Analysis was on an intention-to-treat basis. <h3>Results</h3> A total of 607 participants (378 men [62.3%]; mean [SD] age, 64.3 [12.2] years) were randomly assigned treatment with placebo, and 614 participants (397 men [64.7%]; mean [SD] age, 63.4 [12.4] years) were randomly assigned treatment with 20 mg of fluoxetine hydrochloride daily. The groups were balanced for demographic and clinical measures. At baseline, 112 patients (18.5%) in the placebo group and 116 patients (18.9%) in the fluoxetine group had PHQ-9 scores of 9 or higher. During follow-up, 126 of 596 participants (21.1%) treated with placebo and 121 of 598 participants (20.2%) treated with fluoxetine had PHQ-9 scores of 9 or higher (<i>P</i> = .70). A similar proportion of participants with PHQ-9 scores less than 9 at baseline who were treated with fluoxetine hydrochloride and placebo developed PHQ-9 scores of 9 or higher during the trial (placebo, 72 of 488 [14.8%]; and fluoxetine, 63 of 485 [13.0%];<i>P</i> = .43). A slightly higher number of participants in the placebo group than in the fluoxetine group had a participant-reported clinician diagnosis of depression (42 of 602 [7.0%] vs 26 of 601 [4.3%];<i>P</i> = .05). By week 26, 14 participants (2.3%) in the placebo group and 12 participants (1.9%) in the fluoxetine group had died (<i>P</i> = .67). <h3>Conclusions and Relevance</h3> Routine daily treatment with 20 mg of fluoxetine did not decrease the proportion of people affected by clinically significant symptoms of depression after a stroke, nor did it affect the proportion of people prescribed an antidepressant or receiving nonpharmacologic treatments compared with placebo. <h3>Trial Registration</h3> http://anzctr.org.auIdentifier:ACTRN12611000774921