根據六月份Journal of Clinical Psychiatry的研究報告，那些對血清素再吸收抑制劑﹝SSRI﹞治療無法有效反應或忍受的病患，將可改以mirtazapine (Remeron)做為有效的治療方法，但改以buspirone (Buspar)做為增強治療則無法提供相當的助益。Lauren Marangell，雖並未參與這兩項研究，確告訴WebMD：「雖然mirtazapine的研究與之前及臨床上實證的結果相同，但能夠獲得更多的數據資料總是好的。它呈現出百分之四十八的反應率，與其他同樣是從SSRI轉換至其他治療的結果幾乎相同。因此，我們可以得到這樣的結論，mirtazapine不完全是比較好的治療方法，但確實是個不錯的另個選擇。」
Dual-Action Antidepressant Works as SSRI Alternative
Mirtazapine Strategy Effective, but Buspirone Falls Short
By Aman Shah, MD
WebMD Medical News
Reviewed by Michael W. Smith, MD
July 23, 2001 -- For depressed patients who don't respond to or can't tolerate an SSRI, switching to mirtazapine (Remeron) is an effective strategy, but augmentation with buspirone (Buspar) is unlikely to offer much benefit, according to studies in the June issue of the Journal of Clinical Psychiatry.
Lauren Marangell, MD, tells WebMD that the mirtazapine study is consistent with what has been reported before and is being done in clinical practice, but that it's always best to have more data. "It shows a 48% response rate, which is fairly consistent with other studies of switching from one SSRI to another. So the conclusion is not that mirtazapine is necessarily, better but [that it] is one option," says Marangell, who was not involved in either study.
Researchers enrolled 103 patients with a major depressive disorder who had either not responded to or not tolerated treatment with fluoxetine (Prozac), paroxetine (Paxil), or sertraline (Zoloft). Patients were randomized to an immediate switch to mirtazapine, a newer antidepressant with action on both the serotonergic and noradrenergic systems, or a switch to mirtazapine after a 4-day washout period.
Almost half the patients showed a 50% or more reduction in their depression rating scales after 8 weeks of therapy. There was no difference between the immediate-switch patients and patients who switched following the washout period. The researchers report that the drug was well tolerated, with sedation and weight gain being the most common side effects. Patients also reported fewer problems with sexual function after switching to mirtazapine.
"We showed it was safe, and it worked," says co-author David Dunner, MD, director of the Center for Anxiety and Depression and professor of psychiatry and behavioral sciences at the University of Washington Medical Center in Seattle. "It's another important option for patients."
"It helps prove that switching does work, and that there are other options, so they shouldn't lose hope," says Marangell, associate professor of psychiatry and behavioral sciences and director of the Mood Disorders Center at Baylor College of Medicine in Houston.
"But the important caveat is don't switch drugs too early," Marangell says. "You don't want to switch after a week or two, because that doesn't give the first drug enough chance to work. How long to do the first drug isn't clear, but generally from 4 to 8 weeks. And if you get a partial response, try it even longer. But if you get no response, then switch to a different type of drug -- [a non-SSRI] like mirtazapine."
"Sometimes you get people who get partially better -- maybe 50-60% better," says Marangell. "They can get out of bed and go to work, but they can't really concentrate very well. And they're not as interested in things. For those patients, the options are the same -- switching to a different agent or adding something else. For some people, adding something else is a good option when they don't want to lose that 60% response to the first drug. That's where the augmentation strategies can be really helpful."
The second study, a randomized, double-blinded study of 102 patients with major depressive disorder who had failed treatment with an SSRI was conducted by Finnish researchers led by Bjorn G. Appelberg, MD, of the department of psychiatry at the University of Helsinki. One week after augmenting treatment with buspirone in patients already taking fluoxetine or citalopram (Celexa), patients experienced a significantly greater reduction in depressive symptoms compared with those taking placebo.
However, at the end of the 6-week study, patients taking placebo were doing just as well as those on combination therapy -- both groups had reduction in depression. But those with the most severe depression did have significantly greater reductions in depression scores than those in the placebo group.
"Not an impressive finding," says Dunner, regarding the buspirone study. "It looks like it's a safe [drug] combination, but I don't know that it's an effective combination -- they only found a difference in the first week, then it disappeared."
The reason for the short-term improvement could lie in the sedating effects of buspirone, Dunner says. "So if patients are anxious and sleepless, you may see changes in depressive symptoms -- that's why they saw an effect in the first week. But the lack of sustained effect is troubling."