Abstract
Background
We collaboratively designed three large trials of fluoxetine for stroke recovery to facilitate an individual patient data meta-analysis (IPDM).
Methods
We performed fixed effects meta-analyses on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months) and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined.
Findings
We recruited 5907 people (mean age 69∙5 years (SD 12∙3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, UK, Sweden and Vietnam; and randomized them to fluoxetine 20mg daily or matching placebo for 6 months. 5833 (98∙75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0∙96, 95% CI 0∙87 to 1∙05, p=0∙37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2∙64% vs 1∙8%, p=0∙03), falls with injury (6∙26% vs 4∙51%, p=0∙03), fractures (3∙15% vs 1∙39%, p<0∙0001) and hyponatraemia (1∙22% vs 0∙61%, p=0∙01) but reduced new depression (10∙05% vs 13∙42%, p<0∙0001). At 12 months, there was no difference in adjusted mRS (n=5760; COR 0∙98, 95% CI 0∙89 to 1∙07). Sensitivity analyses gave the same results.
Interpretation
Fluoxetine 20mg daily for six months did not improve functional recovery. It increased seizures, falls with injury, bone fractures but reduced depression frequency at 6 months.
Trial Funding
Stroke Association, National Institute of Health Research, Australian Government National Health and Medical Research Council, Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Brain Foundation, Swedish Society of Medicine, King Gustav V and Queen Victoria's Foundation of Freemasons and STROKE-Riksförbundet
We collaboratively designed three large trials of fluoxetine for stroke recovery to facilitate an individual patient data meta-analysis (IPDM).
Methods
We performed fixed effects meta-analyses on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months) and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined.
Findings
We recruited 5907 people (mean age 69∙5 years (SD 12∙3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, UK, Sweden and Vietnam; and randomized them to fluoxetine 20mg daily or matching placebo for 6 months. 5833 (98∙75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0∙96, 95% CI 0∙87 to 1∙05, p=0∙37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2∙64% vs 1∙8%, p=0∙03), falls with injury (6∙26% vs 4∙51%, p=0∙03), fractures (3∙15% vs 1∙39%, p<0∙0001) and hyponatraemia (1∙22% vs 0∙61%, p=0∙01) but reduced new depression (10∙05% vs 13∙42%, p<0∙0001). At 12 months, there was no difference in adjusted mRS (n=5760; COR 0∙98, 95% CI 0∙89 to 1∙07). Sensitivity analyses gave the same results.
Interpretation
Fluoxetine 20mg daily for six months did not improve functional recovery. It increased seizures, falls with injury, bone fractures but reduced depression frequency at 6 months.
Trial Funding
Stroke Association, National Institute of Health Research, Australian Government National Health and Medical Research Council, Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Brain Foundation, Swedish Society of Medicine, King Gustav V and Queen Victoria's Foundation of Freemasons and STROKE-Riksförbundet
| Original language | English |
|---|---|
| Journal | International Journal of Stroke |
| Early online date | 18 Mar 2024 |
| DOIs | |
| Publication status | E-pub ahead of print - 18 Mar 2024 |