Progress in Neuro-Psychopharmacology and Biological Psychiatry
Case reportEfficacy of milnacipran on the depressive state in patients with Alzheimer's disease
Introduction
In Alzheimer's disease (AD) patients, depression is not a rare condition. The prevalence of major depression has been reported to be within the range of 20–25% (Migliorelli et al., 1994, Olin et al., 2002) of AD patients. Depression in AD patients is associated with earlier placement out of the community into a nursing home (Steele et al., 1990), and is also associated with greater impairments in the quality of life (Gonzales-Salvdor et al., 2000) as well as with increased caregiver depression and burden (Gonzales-Salvdor et al., 1999). Although some tricyclic anti-depressants (TCAs) have been found to improve depression in AD, the anti-cholinergic effects of these medicines are critical to cognitive function in AD patients (Teri et al., 1991). Recently, serotonin selective reuptake inhibitors (SSRIs) have been recommended for depression in AD patients due to their minimal anti-cholinergic effects, although their efficacy has remained controversial and further studies are needed.
Milnacipran (1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane hydrochloride) is a novel anti-depressant agent that is a selective serotonin and noradrenaline reuptake inhibitor (SNRI) (Puech et al., 1997, Briley, 1998), and is reported to be devoid of any postsynaptic activity (Moret et al., 1985). Although milnacipran has been reported to be effective and safe for elderly depressive patients (Tignol et al., 1988), thus far there has been no study focusing on its effects on depression in AD patients. We describe here the efficacy and safety of milnacipran on depression with AD through its open trial for 11 patients. To our knowledge, this is the first paper reporting SNRI treatment of depression in AD patients.
Section snippets
Patients
A consecutive series of 11 patients were enrolled in this study, and all 11 participants were recruited from the outpatient clinic of Ishizaki Hospital, and provided written informed consent for study participation. The study was carried out in accordance with the ethics and principles embodied in the Declaration of Helsinki of 1975. Clinical diagnosis of AD was made utilizing DSM-IV (American Psychiatric Association, 1994) and NINCDS/ADRDA (McKhann et al., 1984) criteria. In addition, all 11
Results
Eight patients took milnacipran for more than 12 weeks (72.7%); and 3 patients discontinued the treatment within 12 weeks. The reasons for discontinuation were emergence of hypomanic state for one patient (Case 5) and dropout for two patients (Cases 9 and 10). Case 10, however, resumed the treatment of milnacipran due to recurrence of depression thereafter.
Table 1 shows the background characteristics of the 11 patients analyzed. Their mean age was 75.2 ± 9.4 (range 56–84) years. Of the 11
Discussion
In our study, all the 11 patients demonstrated a remarkable improvement in depression with milnacipran treatment. Within 12 weeks, 8 of 11 patients reached remission (remission rate, more than 70%). Previous studies on depressive state in AD patients treated with anti-depressants demonstrated that the remission rates using clomipramine and fluoxetine, respectively, are 82% (Petracca et al., 1996) and 47% (Petracca et al., 2001), and that the rate of 30% reduction in HAM-D scores using
Acknowledgment
This study was supported by a Research Grant for Longevity Sciences (14C-4) from the Ministry of Health, Labor and Welfare of Japan.
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