Differential effects of milnacipran and fluvoxamine,
especially in patients with severe depressions and agitated depressions:A case control study
ミルナシプランとフルボキサミンの比較
特に重症うつ病と焦燥感の強いうつ病においての比較研究　

Toshihiko Fukuchi M.D.

*Fukuchi Clinic

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In Japan, due to the delay of the introduction of SSRIs, a unique situation has emerged, in which SSRIs and a SNRI (milnacipran) have started to be marketed almost simultaneously. This has given us a special momentum to compare clinical efficacy and profile of effectiveness of SSRI and SNRI directly.

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1: Is there any discrepancy of effectiveness between milnacipran and fluvoxamine as a function of severity of depression?

2: Is there any different profile of the efficacy as a function of individual clinical symptoms of depression?

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Subjects

All of the study subjects in the milnacipran group were outpatients (n=112) who fulfilled the DSM IV criteria for major depression (American Psychiatric Association, 1994) and had been treated with milnacipran by me from April 1999 to February 2001.

As controls, I chose 112 patients out of 241 who fulfilled the above-mentioned inclusion and exclusion criteria, except for being given fluvoxamine instead of milnacipran and who had been treated with fluvoxamine by me from April 1999 to February 2001. These were matched in age, sex, and depression severity, and were chosen randomly using a computer.

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Methods

The main parameters for efficacy was the change in total and individual scores on a 17-item HDRS test between baseline and end-point, and the patients were examined and assessed every 1 or 2 weeks during the observation period.

The observations continued until the HDRS score remained at a plateau for more than 3 successive weeks after initial improvement or decreased to less than 7 points.
Those patients whose total HDRS score decreased by 50% from the baseline were considered as 'responders', while 'remission' was defined as a state in which the total HDRS score was less than 7 points.
Further, we defined patients with a baseline HDRS score of more than 19 points as severe.

Adverse events were obtained by open questioning, and recorded at the initial interview (baseline) and each subsequent visit.

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Results

Drop-outs.
There were no statistically significant differences between the two groups.

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Efficacy of treatment

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Adverse Events.
Incidences of adverse effects commonly noted during treatment with TCAs, such as constipation, dry mouth, vertigo, and somnolence, were remarkably low in both groups.

・ There were no statistically significant differences or trend of difference between the two groups overall, a statistically significant difference in favor of milnacipran over fluvoxamine was found in moderately or severely depressed patients with an HDRS score greater than 19 points.

・ Analysis of HDRS factors, significant differences between the treatment groups in favor of milnacipran were found for the three 'insomnia' factors as well as the 'agitation' factor.

・ The tolerability profile of milnacipran was not significantly different from that of fluvoxamine in the present study. With both drugs, the incidences of conventional adverse events such as anticholinergic and antihistamine effects were remarkably low.

・ On the other hand, there was a characteristic trend for each drug, urological manifestations occurred at a higher rate in the milnacipran recipients in the current series, whereas upper digestive tract symptoms such as epigastric distress were predominate in the SSRI-treated patients.

SNRIs are preferred to SSRIs for moderately or severely depressed outpatients with HDRS scores greater than 19 points, and especially for those with marked agitation and insomnia.