Amisulpride和fluoxetine合併使用對重鬱症治療效果及安全性之研究

Efficacy and safety of amisulpride and fluoxetine combination therapy in major depressive disorder

羅瑋琪(Wei-Chi Lo)

指導教授 ： 蔡義弘

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2010年)

https://doi.org/10.6832/KMU.2010.00137

摘要

目的: 憂鬱症是一種很常見的疾病，因此這種情感性疾患消耗大量的治療成本，在台灣占每年的藥物費用總額的2.18%。曾有文獻建議抗精神病藥物可以加速改善憂鬱症，然而很少研究提及併用血清速回收抑制劑和抗精神病藥。
方法: 這是一個雙盲安慰劑隨機分配並固定劑量的研究。本研究所得樣本為18歲以上合乎DSM-Ⅳ標準，ICD-9-CM 296.2x 重鬱症單純發作，其基準點 HAMD-D score≧14及HAMD-D 第三項score＜3之病患，病患接受九個星期的fluoxetine 20毫克加上amisulpride50毫克或安慰劑。這項研究包含五次訪視: 收案第一天、一周後、兩周後、五周後、九周後。以漢氏憂鬱症量表、家庭關懷度量表、簡氏症狀量表、臨床整體印象及生活滿意度量表作療效的評估，安全性的部分有生命徵象的測量及Simpson- Angus量表, 和Barnes 靜坐不能量表. 以paired t test比較各組本身的量表平均值，以了解在九個星期中各組治療是否有顯著改善，並以student’s t test比較兩組之間的各個量表分數差，從每次兩組的變化量差異分析，看兩組在重鬱症療效是否有顯著差異。最後使用重複量數(Repeated measures ANOVA)來進行分析，並以SAS中的mixed model來處理遺漏值的問題。
結果: 將34人隨機分為fluoxetine-amisulpride組及fluoxetine組，fluoxetine-amisulpride組共有16位， fluoxetine組有18位。結果顯示，兩組在基本資料部份除了婚姻狀態和過往身體疾病史有差異之外，其餘並無太大不同。將兩組分開來看，比較同一組內量表每次平均值的變化(與第一次的基準點相比較) ，以確定治療前後是否有改善，可以發現在漢氏憂鬱症量表和CGI評分中，合併用藥組在兩周內有較快改善憂鬱症狀，然而兩周之後的訪視就沒有比單用抗憂鬱劑組好。而第五和九周的評估測量，在家庭關懷度量表上，fluoxetine組(p < 0.01)比fluoxetine-amisulpride組改善(p < 0.05)更顯著，生活滿意度量表也可以看出fluoxetine組較穩定的改善。為了進一步分析比較兩組之間的療效差異，檢驗兩組每次訪視的量表評估數值與其第一次的差值，結果發現所有的差值相比之下都未達顯著統計差異。於是再進行遺漏值的分析，結論發現只有生活滿意度量表上有明顯差異(p< 0.05) ，而且是fluoxetine組表現較好。在安全性上兩組未有危險事件發生，也沒有明顯錐體外症候群產生。
結論: 由此結果可以看出，併用兩種藥物或單純使用抗鬱劑在研究期間對治療重鬱症患者皆有改善，但若以快速達到治療效果而言，併用藥物組在前兩周表現較佳，兩周後則沒有比較好。雖然兩組在量表淨差值比較未達顯著意義，在第五周之後的訪視上fluoxetine組還是進步多點，所以是否需要長期兩種藥物合併治療以及藥物之間的交互作用都是專家們可再重新思考的議題。

關鍵字

重鬱症 ； 百憂解 ； 首利安

並列摘要

Purpose of the study:
Depression is a common disease. Therefore, this affective disorder incurs high treatment costs. In Taiwan, it accounts for 2.18 % of total annual pharmacotherapy expenditures. It had been suggested that antipsychotic drugs be faster response in patients with dysthymia or major depression. However, little is known about the combination of a SSRIs and antipsychotic drugs.
Methods:
This double-blind, placebo-control, fixed dose, randomized study was conducted in a general hospital. Patients over 18 y/o fulfilled DSM-IV criteria for major depression, ICD-9-CM 296.2x, having a baseline HAM-D score≧14 and a HAM-D item 3 score＜3 were recruited into the treatment groups. The group of patients received nine weeks of treatment with a combination of fluoxetine 20mg with placebo or amisulpride 50mg. The study consisted of 5 visits: V1, Day 1; V2, 1 week later ; V3, 2 weeks later ; V4, 5 weeks later ; V5, 9 weeks later. The reduction in HAM-D, BSRS-50, Family Apgar, SF-36 and Clinical Global Impression( CGI) score relative to baseline was periodically estimated as an efficacy after treatment. Safety measurements included vital signs, Simpson- Angus scale , and Barnes Akathisia rating scale . The improvement of mean scores within each group during 5 visits was measured by paired t test . The comparison of these characteristics were analyzed by using 2 sample t-test for continuous variables between 2 groups. Missing data were analyzed by repeated measures ANOVA and mixed model of SAS.
Summary of results:
This study included 34 subjects . 16 patients were randomly assigned to fluoxetine-amisulpride group and 18 patients in fluoxetine group. Both of the two treatment groups were comparable at baseline as concerning demographics except marital status and medical history. Comparing the change of clinical status within each group, the fluoxetine-amisulpride group had better outcome in HAM-D and CGI in first 2 weeks, but above condition reversed during the last 2 visits. The fluoxetine group (p< 0.01) improved more significantly than the fluoxetine-amisulpride group (p<0.05) in APGAR and SF-36. Regarding the comparison of the net change of total score of each scale between groups, none of the mean net change was of statistical significance.
After dealing with the missing data, The results showed that, only the SF-36 mean score of the fluoxetine group was significantly higher than the score of fluoxetine-amisulpride group, and with statistical significance (p< 0.05). The safety of amisulpride group was comparable to that of placebo group, and extrapyramidal symptoms were infrequent.
Conclusions:
From these results, we can see significant improvement in major depressive disorder treatment no matter using amisulpride and antidepressant combination therapy or antidepressant only,but the fluoxetine-amisulpride group has better performance in HAM-D and CGI than combination therapy in first 2 weeks. No statistically significant difference between the two treatment groups was observed in most of those net changes of scores. So the necessity of long-term combination therapy and drug interaction should be re-considered by clinical experts.

並列關鍵字

major depressive disorder ； fluoxetine ； amisulpride

參考文獻

英文參考文獻

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), 4th edition. Washington, DC, American Psychiatric Association, 2000.

Amore M, Jori C; AMISERT Investigators. Faster response on amisulpride versus sertraline 50-100 mg in patients with dysthymia or double depression: a randomized, double-blind, parallel group study. Int Clin Psychopharmacol. 16(6): 317- 24, 2001 Nov.

American psychiatric association practice guideline for major depressive disorder in adults. Am J Psychiatry. 150:1-26, 1993.

American psychiatric association practice guidelines for the treatment of psychiatric disorders compendium 2006. Americanatric Psychiatric Association, 2006.