Are there predictors of outcome in depressed elderly nursing home residents during treatment with mirtazapine orally disintegrating tablets?

BACKGROUND: Treatment studies of depression in residential care are limited. Reports of predictors of response are rare. In the largest nursing home prospective antidepressant trial reported, we examined predictors of response. METHODS: This was a 12-week open-label study of mirtazapine orally disintegrating tablets performed in 30 US nursing homes. Subjects were men and women aged >or=70, with a Mini Mental State Exam (MMSE) score >or=10, who had a depressive disorder that required antidepressant treatment. Mirtazapine was started at 15 mg at bedtime, and adjusted to 15-45 mg/day. A 16-item Hamilton Depression Rating Scale was used to assess depression at baseline, weeks 2, 4, 8, and 12 or early termination. RESULTS: One hundred and twenty-four patients received at least one dose of study drug and of these, 119 had at least one post-drug assessment. Mean age was 82.9 years and 72% were female. Response rates at 12 weeks were 47% on the HAMD and 54% on the CGI. Age, sex, MMSE score, medical burden, history of prior depression, and baseline HAMD severity were not significantly associated with HAMD response (>or=50% improvement) and in most cases correlations were trivial, <0.1. Advanced age, medical burden, and cognitive impairment did not predict adverse events. CONCLUSIONS: In this sample of depressed nursing home residents treated with mirtazapine orally disintegrating tablets, advanced age, medical illness, and cognitive impairment did not predict response. The findings suggest that these variables need not be viewed as obstacles to treatment.

Mirtazapine orally disintegrating tablets in depressed nursing home residents 85 years of age and older.

INTRODUCTION: Treatment studies of depression in the very oldest patients are infrequent. For these reasons, this study of mirtazapine orally disintegrating tablets was carried out in nursing home residents>or=85 years old with physician-diagnosed depression. The naturalistic conditions of the study allowed us to include patients with cognitive impairment, concomitant medications and comorbid illness. METHODS: This was a subgroup analysis of nursing home residents>or=85 years old who took part in a larger 12-week open-label trial. Patients were eligible if they had physician-diagnosed depression, and a Mini-Mental State Exam score>or=10. The physician or nurse coordinator obtained data from healthcare professionals in daily contact with the patient to complete the Clinical Global Impression (CGI) scale, a modified 16-item Hamilton Depression Scale (HAM-D), and the Cornell Scale for Depression in Dementia (CSDD). Treatment-emergent adverse events were recorded. RESULTS: Of the 50 patients enrolled at 23 sites, 72% completed the 12-week trial. The mean age of the participants was 89.3 years. The mean HAM-D score declined from 16.9 at baseline to 7.3 at endpoint (ITT, LOCF analysis) For the CSDD, the mean score declined from 15.1 to 7.1. The percentage of responders on the CGI-Improvement (CGI-I) scale increased at each assessment reaching 55% at endpoint. Only 10% of the patients discontinued treatment because of adverse events. There was a mean increase in weight of 1.32 lbs (0.6 kg) at day 84. CONCLUSION: Although lacking a placebo control, this naturalistic study suggests that mirtazapine orally disintegrating tablets were effective and well tolerated in this sample of depressed nursing home residents>or=85 years of age.

Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression.

BACKGROUND: The "long/short"polymorphism (5HTTLPR) in the promoter of the serotonin transporter gene (SLC6A4) has been proposed as a pharmacogenetic marker for antidepressant efficacy. Some but not all studies have found that the short form of 5HTTLPR (S allele) results in decreased efficacy of selective serotonin reuptake inhibitors. OBJECTIVE: To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride, 2 frequently prescribed antidepressants with differing pharmacologic profiles, in geriatric depression. DESIGN: Double-blind, randomized 8-week study. SETTING: Eighteen academic and private outpatient clinics. PATIENTS: We evaluated 246 cognitively intact patients 65 years or older with major depression. INTERVENTIONS: Antidepressant therapy with 15 to 45 mg/d of mirtazapine (n = 124) or 20 to 40 mg/d of paroxetine (n = 122). MAIN OUTCOME MEASURES: The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale, severity of adverse events and dosing compliance indexes, and discontinuations due to adverse events. Outcome measures were stratified according to 5HTTLPR genotypes. RESULTS: Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response. Among mirtazapine-treated patients, there was little indication that the 5HTTLPR genotype affected antidepressant efficacy. However, the 5HTTLPR polymorphism had a dramatic effect on adverse events. Among paroxetine-treated subjects, S allele carriers experienced more severe adverse events during the course of the study, achieved significantly lower final daily doses, and had more discontinuations at days 14, 21, 28, 42, and 49. Surprisingly, among mirtazapine-treated subjects, S allele carriers had fewer discontinuations due to adverse events, experienced less severe adverse events, and achieved higher final daily doses. CONCLUSIONS: These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors. However, the major effect was on the tolerability of these drugs rather than efficacy. Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action.

Gepirone extended-release treatment of anxious depression: evidence from a retrospective subgroup analysis in patients with major depressive disorder.

OBJECTIVE: To evaluate the efficacy and tolerability of gepirone extended-release (ER) tablets in patients with major depressive disorder (MDD) and high ratings of anxiety (anxious depression). METHOD: This subgroup analysis was derived from an 8-week, double-blind, placebo-controlled study of gepirone ER in patients with MDD. Male and female patients 18 to 69 years of age who met DSM-IV criteria for MDD and had high ratings of anxiety (Hamilton Rating Scale for Depression [HAM-D-17] total score > or = 20 and HAM-D-17 factor I [anxiety/somatization] score > 6) were included in this subgroup analysis. Eligible patients with anxious depression were randomly assigned to receive either placebo or gepirone ER, 20 mg to 80 mg daily. Patient assessments were performed at weeks 1, 2, 3, 4, 6, and 8. Treatment efficacy was evaluated by mean HAM-D-17 total scores and mean changes from baseline in (1) HAM-D-17 total scores, (2) HAM-D-17 factor I (anxiety/somatization) scores, and (3) HAM-D-17 item 12 (anxiety, psychic) scores. All statistical tests were 2-sided and considered statistically significant if the p value was <.05. Between-group comparisons were analyzed using least-squares analysis of variance on the change from baseline at each visit with the last observation carried forward (LOCF). The Cochran-Mantel-Haenszel test adjusting for center was also performed on the percentage of patients in each treatment group at each visit (LOCF) who met the response criterion on the HAM-D-17 (> or = 50% decrease from baseline) or remission criterion (HAM-D-17 total score < or = 7). RESULTS: Gepirone ER-treated patients (N = 58) experienced a statistically significant (p <.05) reduction in mean HAM-D-17 total score at week 3, 6, and 8 compared with placebo-treated patients (N = 75). A statistically significant effect (p <.05) in favor of gepirone ER was observed in mean change from baseline in HAM-D-17 total scores and for HAM-D factor I (anxiety/somatization) scores from week 2 onward. A statistically significant (p < or =.01) effect in favor of gepirone ER was observed in HAM-D-17 item 12 (anxiety, psychic) scores throughout the 8-week trial. There were significantly more patients in the gepirone ER group compared with the placebo group who were HAM-D-17 responders (p <.05) at endpoint and who met the criteria for HAM-D-17 remission at week 3 (p <.05) and weeks 6 and 8 (p <.01). Overall, gepirone ER was well tolerated, with rates of weight gain and sexual dysfunction comparable to placebo. Adverse events were generally mild to moderate. The most commonly reported adverse events were dizziness and nausea. CONCLUSIONS: Gepirone ER is an effective and well-tolerated treatment for patients with anxious depression.

Open-label study of mirtazapine orally disintegrating tablets in depressed patients in the nursing home.

OBJECTIVE: To evaluate the efficacy and tolerability of mirtazapine orally disintegrating tablets in depressed, elderly nursing home residents, under naturalistic study conditions. METHODS: In this open-label 12-week study, mirtazapine orally disintegrating tablets (15-45 mg/day) were administered to patients > or =70 years old with physician-diagnosed depression and a Mini-Mental State Examination (MMSE) score > or =10. Patients with medical comorbidities, cognitive impairment and/or concomitant medications were enrolled if they met study inclusion criteria and had illnesses and/or medication dosages that were considered stable. Assessments were performed at baseline by physicians and at days 14, 28, 56, and 84 (or early termination) by physicians or nurse coordinators using the Clinical Global Impression (CGI) scale, the 16-item Hamilton Rating Scale for depression (Ham-D-16 (the standard 17-item scale minus item 14)), and the Cornell Scale for Depression in Dementia (CSDD). Tolerability was evaluated based on treatment-emergent adverse events. RESULTS: A total of 119 patients in the intent-to-treat (ITT) group were treated with mirtazapine orally disintegrating tablets (mean daily dose: 19.4 mg) and evaluated for efficacy. At endpoint, 54% of patients in the ITT group showed CGI-I response (defined as a CGI-I score of 1 or 2 ('very much' or 'much' improved) and 47% were Ham-D-16 responders (defined as decrease from baseline of at least 50% in Ham-D-16 total score). CSDD mean scores and Ham-D-16 mean total scores demonstrated a progressive decrease from baseline to trial completion. The decrease in Ham-D scores from baseline to day 84 was statistically significant (p < 0.0001). Mean changes from baseline to day 84 were -6.6 +/- 6.9 (CSDD score) and -7.9 +/- 7.4 (Ham-D-16 total score). Ham-D Factor I, Factor VI and item 1 scores also decreased. Fourteen of 124 patients in the all-subjects-treated (AST) group (11.3%) discontinued prematurely due to adverse events. The most frequently occurring adverse events were urinary tract infection (19%), accidental injury (18%), fall (18%), somnolence (12%), and upper respiratory infection (12%). Mean body weight increased by 0.7 +/- 2.25 kg (1.54 +/- 5 lb) from baseline to day 28, and by 1.3 +/- 3.36 kg (2.86 +/- 7.4 lb) from baseline to day 84. CONCLUSIONS: The results suggest that mirtazapine orally disintegrating tablets provide antidepressant efficacy and are a relatively well-tolerated treatment for depression in this patient population of elderly nursing home residents with medical and cognitive comorbidities.