Background and Purpose-We performed a double-blind, placebo-controlled study to investigate the effectiveness of amitriptyline for the prophylactic treatment of patients with acute thalamic stroke in preventing central poststroke pain. Methods-Subject received, in a randomized sequence, either amitriptyline titrated from 10 to 75 mg in extended-release form or placebo over a therapy period of 365 days. We documented the time when pain developed; the intensity, type, site, and distribution of pain; and the presence/absence and type of allodynia. Results-Thirty-nine patients (23 women and 16 men; age range, 36 to 68 years) with central poststroke pain participated.The placebo group showed a pain rate of 21% within 1 year after the diagnosis of thalamic stroke compared with 17% in the group under prophylactic treatment with amitriptyline. Average (SE) time to pain was 318 (23) days for patients in the placebo group and 324 (24) days for patients in the amitriptyline group. Conclusions-With the achieved sample sizes of this study and a pain rate of approximately 21% in the placebo group, any near-perfect pain protection would have been detected. Near-perfect pain protection, in this context, refers to pain in Ͻ2.4% of the recruited patients treated with amitriptyline or in approximately 89% of placebo-treated patients. Larger studies are recommended to test the hypothesis that prophylactic amitriptyline reduces but does not completely prevent central poststroke pain. Key Words: amitriptyline Ⅲ antidepressive agents Ⅲ cerebrovascular accident Ⅲ pain Ⅲ thalamic diseases C entral poststroke pain (CPSP) was first described by Dejerine and Roussy 1 in 1906 as a spontaneous pain after a thalamic stroke. It has been known as "thalamic pain syndrome" for decades, and its management is still a challenge for treating physicians today. Since the discovery of the effects of carbamazepine and tricyclics, these substances have been used in the treatment of CPSP. In a carefully controlled trial performed in 15 patients with CPSP, the authors were unable to demonstrate a statistically significant effect of carbamazepine, whereas amitriptyline produced a statistically significant reduction of pain compared with placebo. 2 Thus far, no studies on CPSP have been published to answer the question of whether treatment at the beginning of stroke demonstrates a prophylactic effect in preventing central pain mechanism. The primary objective of this study was to evaluate, under controlled conditions, the efficacy of amitriptyline for preventing CPSP. We performed a placebocontrolled, double-blind study to determine whether amitriptyline at an increasing dose could significantly reduce CPSP in patients with thalamic stroke. Subjects and MethodsThe study was performed as a randomized, double-blind, placebocontrolled trial. Patients were randomized after they had provided informed consent to administration of amitriptyline or placebo within the first day after the onset of stroke was diagnosed. The study medication was slowly titrated from 10 t...