Fava M, Rosenbaum J F, Kolsky A R, Alpert J E, Nierenberg A A, Spillmann M, Moore C, Renshaw P, Bottiglieri T, Moroz G, Magni G
Depression Clinical and Research Program, Massachusetts General Hospital, Boston 02114, USA.
J Clin Psychopharmacol. 1999 Aug;19(4):329-35. doi: 10.1097/00004714-199908000-00008.
Tolcapone is a catechol-O-methyltransferase (COMT) inhibitor that has shown efficacy in the treatment of Parkinson's disease. The authors undertook the first study on the efficacy of this COMT inhibitor in the treatment of major depressive disorder (MDD). The authors also wanted to assess the effects of tolcapone on the choline and myoinositol resonances in the left caudate and dorsolateral frontal lobe through proton magnetic resonance spectroscopy and on whole blood levels of S-adenosyl-L-methionine (SAMe). The study enrolled 21 adults (10 men and 11 women; mean age, 42.6 +/- 9.6 years) with MDD, which was diagnosed using the Structured Clinical Interview for DSM-IV, and an initial score of > or = 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17). Patients were then treated openly for 8 weeks with tolcapone 400 mg twice daily. Treatment efficacy was assessed with the HAM-D-17, the Clinical Global Impressions Severity (CGI-S) scale, and the Beck Depression Inventory (BDI). Among all subjects (N = 21), there were significant (p < .0001) decreases at endpoint in HAM-D-17 scores (from 19.4 +/- 2.9 to 10.7 +/- 5.5), CGI-S scores (from 3.9 +/- 0.6 to 2.4 +/- 1.1), and BDI scores (from 21.6 +/- 8.1 to 12.3 +/- 8.6). Eight patients (38%) dropped out before completing the 8-week open study because of diarrhea, elevated liver function tests, increased anxiety, and noncompliance. No significant effects were noted on choline and myoinositol resonance or on SAMe levels in whole blood before and after 2 weeks of tolcapone treatment. The preliminary results suggest that tolcapone may be a promising agent in the treatment of MDD. Furthermore, double-blind, placebo-controlled studies are necessary to confirm this impression.
托卡朋是一种儿茶酚-O-甲基转移酶（COMT）抑制剂，已显示出对帕金森病的治疗效果。作者开展了关于这种COMT抑制剂治疗重度抑郁症（MDD）疗效的首个研究。作者还想通过质子磁共振波谱评估托卡朋对左侧尾状核和背外侧额叶中胆碱和肌醇共振的影响，以及对全血S-腺苷-L-甲硫氨酸（SAMe）水平的影响。该研究纳入了21名患有MDD的成年人（10名男性和11名女性；平均年龄42.6±9.6岁），MDD通过《精神疾病诊断与统计手册》第四版（DSM-IV）的结构化临床访谈进行诊断，且在17项汉密尔顿抑郁评定量表（HAM-D-17）上的初始评分≥16分。患者随后接受为期8周的开放治疗，每天两次服用400毫克托卡朋。使用HAM-D-17、临床总体印象严重程度（CGI-S）量表和贝克抑郁量表（BDI）评估治疗效果。在所有受试者（N = 21）中，终点时HAM-D-17评分（从19.4±2.9降至10.7±5.5）、CGI-S评分（从3.9±0.6降至2.4±1.1）和BDI评分（从21.6±8.1降至12.3±8.6）均有显著下降（p <.）。8名患者（38%）在完成8周开放研究前因腹泻、肝功能检查结果升高、焦虑增加和不依从性而退出。托卡朋治疗2周前后，未观察到对胆碱和肌醇共振或全血SAMe水平有显著影响。初步结果表明，托卡朋可能是治疗MDD的一种有前景的药物。此外，需要进行双盲、安慰剂对照研究来证实这一印象。
