No abstract

BACKGROUNDPrevious studies have suggested that fluoxetine could improve neurological recovery after stroke. The EFFECTS trial was designed to test the hypothesis that administration of fluoxetine for 6 months after acute stroke would improve functional outcome. METHODSEFFECTS was an investigator-led, parallel group, randomised, placebo-controlled trial that enrolled non-depressed stroke patients aged 18 years or older between two and 15 days after stroke onset in 35 hospitals in Sweden. The patients had a clinical diagnosis of ischemic or intracerebral haemorrhage with persisting focal neurological deficits at inclusion. A webbased randomisation system which incorporated a minimisation algorithm was used to allocate participants to fluoxetine 20 mg once daily or matching placebo capsules for 6 months with a ratio of 1:1. Patients, care providers, investigators, and outcomes assessors were masked to the allocation. The primary outcome was functional status, measured with the modified Rankin Scale (mRS) at 6 months. Patients were analysed according to their treatment allocation. EFFECTS is registered with ClinicalTrials.gov, number NCT02683213. FINDINGS Recruitment started 20 Oct 2014 and ended 28 June 2019, when the planned 1500 patients were included (750 to fluoxetine and 750 to placebo). mRS data were available for 737/750 (98%) in the fluoxetine group and 742/750 (99%) in the placebo group. The primary outcome -distribution across mRS categories-was neutral (common odds ratio adjusted for minimisation variables 0•94 [95% CI 0•78 to 1•13], p=0•42). Fluoxetine reduced depression

Depression has a substantial impact on HRQL. Our results indicate that treatments for depression are associated with significant improvement in EQ-5D index score over a course of 6 months. Self-reported patient valuations are important outcomes for cost-utility analysis of new treatments for depression and the present study provides important evidence for future economic evaluations.

The neurotransmitter metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured by mass fragmentography in 83 patients with melancholia (diagnosed by the Newcastle Inventory and the Research Diagnostic Criteria), and 66 healthy volunteer controls. After adjustment by analysis of covariance for differences between the subject groups in body height, age and sex distribution, significantly (P less than 0.001) lower concentrations of 5-HIAA and HVA were found in the melancholia patients than in the controls. HMPG did not differ between the groups. The differences could not be accounted for by differences in timing or examination techniques, and not by previously administered drugs (all patients were drug-free at the examination, but a minority had taken small amounts of psychotropic drugs prior to the wash-out period). The differences persisted after excluding the suicidal patients. There were no clear-cut differences between unipolar and bipolar patients. It is suggested that the reduced concentrations of 5-HIAA and HVA in the melancholic patients may be due to altered serotonin and/or dopamine functions in the central nervous system, which may be connected with an increased vulnerability to certain types of affective illness.