ABSTRACT
INTRODUCTION: A significant number of mania patients fail to respond to current pharmacotherapy, thereby there is need for novel augmentation strategies. The results of some early studies showed the effectiveness of cholinomimetics in the treatment of mania. One open case series suggested the efficacy of donepezil in the treatment of bipolar disorder. Our aim was to explore whether an oral cholinesterase inhibitor, donepezil, administered during a 4-week treatment period, would benefit patients with acute mania. METHODS: We conducted a 4-week double-blind, placebo-controlled trial of donepezil as an adjunctive treatment to lithium in patients with acute mania. Eligible subjects were randomly assigned to receive donepezil or placebo in addition to lithium. Donepezil was started at 5 mg/day, and increased to 10 mg/day in the first week. Patients were rated with the Young Mania Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS) at baseline, day 1, week 1, week 2, and week 4. RESULTS: Out of the 30 patients who were enrolled, 15 were on donepezil and 15 were on placebo. All patients completed the 4-week trial. On the first day, there was a difference of 1.97 units on the psychomotor symptoms scale of the YMRS in the donepezil group as compared to the placebo group (t = 2.39, P = 0.02). There was a difference of 0.57 units (t = 2.09, P = 0.04) in the speech item and a difference of 0.29 units in the sexual interest item (t = 2.11, P = 0.04) in the donepezil group as compared to the placebo group. The total YMRS difference on the first day approached the conventional significance level (1.97 units, t = 1.84, P = 0.07). Over the course of 4 weeks, we failed to find that donepezil produced any significant difference in the YMRS (6.71 units difference, t = -1.44, P = 0.16) or the BPRS scale (1.29 units difference, t = -0.33, P = 0.75) as compared to placebo. Ten subjects (66.67%) in both groups met the criteria for clinical response (Fisher's exact P = 1.00). Five subjects (33.33%) in the donepezil group met the criteria for clinical remission while nine subjects (60.00%) in the placebo group met the remission criteria (Fisher's exact P = 0.27). CONCLUSION: Use of the oral anticholinergic donepezil had some benefit in the augmentation of lithium treatment on the first day, but did not provide any significant benefits in the long-term.
ABSTRACT
In order to study the clinical effect of bilateral capsulotomy in patients with refractory obsessive compulsive disorder (OCD), 35 patients with refractory obsessive compulsive disorder for whom anti-OCD medications and psychological/behavior therapy had failed, underwent MRI-guided stereotactic bilateral anterior capsulotomy. Pre- and post-operative Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) scores were determined by psychiatrists. All patients underwent fluorodeoxyglucose positron emission tomography evaluation before and 6 months after the operation. Twenty patients became OCD symptom-free (57%), 10 experienced significant improvement (29%) and five experienced no significant improvement (14%). There were significant decreases in Y-BOCS, HAMD and HAMA scores. Our results show that MRI-guided stereotactic bilateral capsulotomy is a precise, safe and effective therapy for refractory obsessive compulsive disorder. This promising technique may also improve anxiety and depression in addition to OCD. OCD patients who have not responded to medication, psychotherapy or behavioral therapy might benefit from MRI-guided stereotactic bilateral capsulotomy.
