1. Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial
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Graeme J. Hankey, Maree L. Hackett, Osvaldo P. Almeida, Leon Flicker, Gillian E. Mead, Martin S. Dennis, Christopher Etherton-Beer, Andrew H. Ford, 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, and Lai-Kin Wong
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Placebo-controlled study ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Modified Rankin Scale ,Fluoxetine ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,education ,Stroke ,Aged ,education.field_of_study ,business.industry ,B790 ,Recovery of Function ,Odds ratio ,Middle Aged ,medicine.disease ,Clinical trial ,Treatment Outcome ,Female ,Neurology (clinical) ,Stroke recovery ,business ,Selective Serotonin Reuptake Inhibitors ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Background: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population.Methods: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921.Findings: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [Interpretation: Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke.Funding: National Health and Medical Research Council of Australia.
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- 2020