重覆透顱磁刺激對於憂鬱症病人之內外科無法解釋疼痛之效應

Analgesic Effect of Repetitive Transcranial Magnetic Stimulation on Medically Unexplained Pain in Patients with Medication-resistant Depression

目的：內外科無法解釋的疼痛 (medically unexplained symptoms of pain, MUS-pain) 在憂鬱症患者身 上是常見的，且會影響憂鬱症的治療成效。過去研究顯示：左背外側前額葉的重覆透顱磁刺激 (repetitive transcranial magnetic stimulation, rTMS) 能治療抗憂鬱劑治療頑固型憂鬱症，且rTMS 也對慢性疼痛 有療效。然而，rTMS 對於 MUS-pain 是否有效仍不清楚。方法：我們設計一個隨機合併有假性刺激控 制組 (sham-controlled) 的實驗，來研究是否左前額葉 rTMS（10Hz, 1,600 發／次，共 10 次）對於憂鬱 症之MUS-pain (n = 24) 能有改善。此外，在另一個用同樣 rTMS 參數來研究 10 次 rTMS 治療對於憂鬱 症狀是否改善的研究中，我們用 rTMS 治療二星期並且再追蹤16 位憂鬱症合併 MUS-pain 及 10 位無 疼痛之憂鬱症患者另外三個月，以了解疼痛症狀與憂鬱症狀之間的關連性。結果：在此研究中，我們 共招募了40 位帶有內外科無法解釋的疼痛的病人，以10 位沒有無法解釋的疼痛的病人。我們發現兩 星期10Hz rTMS 於左前額葉的治療，相較於假性刺激組，能顯著的改善 MUS-pain (p < 0.05)，而且其 止痛的療效與抗憂鬱的療效是獨立、不相關連的。此外，我們也發現了若憂鬱症個案之疼痛症狀對於 rTMS 沒有反應，則其憂鬱症狀在追蹤下有顯著較高的復發率。結論：本研究發現左前額葉高頻 rTMS 治療對於憂鬱症患者所表現出之內外科無法解釋的疼痛有著顯著止痛療效。我們的研究也暗示憂鬱症 患者的疼痛症狀需被正視，因為疼痛症狀對於其憂鬱症狀的長期穩定有著負面的影響。

Objectives: Medically unexplained symptoms of pain (MUS-pain) are common in patients with depression and can worsen clinical outcomes. High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been proven effective for managing treatment-resistant depression and chronic pain, and might relieve chronic MUS-pain. But whether left prefrontal rTMS has analgesic effects on MUS-pain remains unclear. Methods: A randomized sham-controlled rTMS study (10-Hz, 1600 pulses/session, 10 sessions) was conducted for 2 weeks to determine whether rTMS is effective in treating medication-resistant depressed patients with MUS-pain (n = 24). Furthermore, in another left prefrontal 10-Hz rTMS study originally targeting at antidepressant effects, we applied a 10-session rTMS therapy in patients with depression and MUS-pain (n = 16) and those with depression alone (n = 10) and followed them for another three months, in order to investigate the interaction between painful and depressive symptoms. Results: In this study, we totally recruited 40 patients with MUS-pain and 10 patients without MUS-pain. We found that a two-week navigated 10-Hz rTMS over the left DLPFC was signifi cantly more effective in treating MUS-pain than sham rTMS (p < 0.05), and the analgesic effects of the treatment was independent of its antidepressant effects. We also found a higher rate of relapse for depression in patients whose MUS-pain responded poorly to rTMS. Conclusion: Our report has identifi ed an rTMS analgesic effect for MUS-pain in depressed patients. Our data strongly indicate that MUS-pain should be aggressively identifi ed in patients with major depressive disorder because of its detrimental effect on treatment outcome.