Prophylactic Effects of Agomelatine for Poststroke Depression

A Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Agomelatine in the Prevention of Poststroke Depression

The incidence of depression in stroke patients with frontal lobe involvement was reported to be as high as 42%. Agomelatin, a type 1/2 melatonin receptor agonist and serotonin 2C receptor antagonist, is effective in treatment of depression, but whether it can prevent poststroke depression (PSD) remains unknown. The PRAISED trial is a multicenter, randomized, double-blind trial and is designed to evaluate the efficacy and safety of agomelatine in the prevention of PSD in stroke patients with frontal lobe involvement. The primary outcome is the rate of post-stroke depression for 180 days.

This PRAISED trial is a multicenter, randomized, double-blind trial to evaluate the efficacy and safety of agomelatine in the prevention of PSD in patients with acute ischemic stroke. The sample size is 420. The participants will be randomized to receive a 6-month treatment of agomelatine 25mg/d or placebo 25mg/d. The primary end point is the proportion of PSD within 180 days. PSD is defined as the Hamilton Depression Rating Scale-17 (HAMD-17) ≥7 or diagnosis of depression by the Diagnostic and Statistical Manual of mental disorders-V (DSM-V). The second end point are rate of recurrence of ischemic stroke within 90 days, modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), vascular death, transient ischemic attack (TIA)/stroke or myocardial infarction during the 6-months, cognitive function(Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)), Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Stroke Specific Quality Of Life (SS-QOL) scale, adherence to medication, adverse events. The study consists of five visits including the day of randomization, day 14±3 days, day 28±3 days, day 90±7 days, day 180±7 days.

Inclusion Criteria:

1. aged 18~75 years;
2. within 7 days after stroke onset;
3. CT or MRI showed lesions involving the frontal lobe;
4. mRS≤2 before onset for recurrent ischemic stroke;
5. HAMD-17<8 before enrollment;
6. NIHSS<16;
7. be consious and able to complete the relevant assessment scales.

Exclusion Criteria:

1. hemorrhagic stroke;
2. with major depressive disorder, or have taken antidepressants within 30 days before stroke onset, or HAMD-17 ≥8;
3. with other mental illnesses;
4. history of drug abuse or alcohol dependence in the past 1 year
5. with life-threatening illnesses or disorders which may affect the completion of the relevant assessment scale (e.g., hearing, language, visual impairment, etc.)
6. with cognitive impairment who cannot complete the relevant assessment scale
7. with serious neurodegeneration diseases (such as Parkinson's disease, Alzheimer's disease, etc.)
8. infection or carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV)
9. serum ALT level ≥ 2 times of the upper limit of the reference interval or TBIL level > 1.5 times of the upper limit of the reference interval
10. renal dysfunction (creatinine clearance < 90 ml/min/1.73 m2)
11. allergic to or contra-indicated to agomelatine
12. lactose intolerance
13. pregnant or breast-feeding women
14. withdraw from other clinical trials within 4 weeks or participating in other clinical trials
15. unsuitable for inclusion considered by the investigators