aprepitant and Depressive-Disorder--Major

A single-item sleep quality scale (SQS) was developed as a simple and practical sleep quality assessment and psychometrically evaluated.. SQS measurement characteristics were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and morning questionnaire-insomnia (MQI) according to prespecified analysis plans in separate clinical studies of patients with insomnia and depression. Patients with insomnia (n = 70) received 4 weeks' usual care with an FDA-approved hypnotic agent; patients with depression (n = 651) received 8 weeks' active or experimental therapy.. Concurrent criterion validity (correlation with measures of a similar construct) was demonstrated by strong (inverse) correlations between the SQS and MQI (week 1 Pearson correlation -.76) and PSQI (week 8 Goodman-Kruskal correlation -.92) sleep quality items in populations with insomnia and depression, respectively. In patients with depression, stronger correlations between the SQS and PSQI core sleep quality components versus other items supported convergent/divergent construct validity (similarity/dissimilarity to related/unrelated measures). Known-groups validity was evidenced by decreasing mean SQS scores across those who sleep normally, those borderline to having sleep problems, and those with problems sleeping. Test-retest reliability (intraclass correlation coefficient) was .62 during a 4-week period of sleep stability in patients with insomnia and .74 in stable patients with depression (1 week). Effect sizes (standardized response means) for change from baseline were 1.32 (week 1) and .67 (week 8) in populations with insomnia and depression, respectively. Mean SQS changes from baseline to week 8 convergently decreased across groups of patients with depression categorized by level of PSQI sleep quality improvement.. The SQS possesses favorable measurement characteristics relative to lengthier or more frequently administered sleep questionnaires in patients with insomnia and depression.. Registry: ClincalTrials.gov, Title: Treatment of Patients With Major Depressive Disorder With MK0869, Identifier: NCT00034983, URL: https://clinicaltrials.gov/ct2/show/NCT00034983.

Topics: Adult; Aged; Aprepitant; Comorbidity; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Paroxetine; Psychometrics; Reproducibility of Results; Sleep Initiation and Maintenance Disorders; Surveys and Questionnaires

Aprepitant is a neurokinin 1 receptor antagonist approved for prevention of chemotherapy-induced and post-operative nausea and vomiting. Early studies demonstrated promising antidepressant activity as monotherapy, although this was unsupported by subsequent phase 3 trials. This phase 2 study evaluated whether aprepitant potentiated the antidepressant effects of paroxetine.. Outpatients with major depressive disorder were randomized to aprepitant 200 mg + paroxetine 20 mg, paroxetine + placebo, or aprepitant + placebo for 6 weeks. The primary endpoint was change in HAMD-17 total score. Secondary/exploratory endpoints included changes in HAMA, CGI-S, CGI-I, and HAMD Item-1 scores at week 6.. A total of 79, 78, and 79 patients received aprepitant + paroxetine, paroxetine + placebo, and aprepitant + placebo, respectively. At week 6, mean changes in HAMD-17 were -11.0 (95% confidence interval [CI]: -12.7, -9.4), -11.7 (95% CI: -13.3, -10.0), and -9.5 (95% CI: -10.9, -8.1), respectively. Pairwise comparisons of HAMD-17 change with combination therapy versus paroxetine alone demonstrated no significant difference (p = 0.567). Changes in CGI-S, CGI-I, and HAMD Item-1 scores were also comparable, although there was a greater reduction in anxiety (HAMA) with paroxetine alone than aprepitant + paroxetine (p = 0.045). Adverse events were generally more common with the combination than either monotherapy.. Concomitant use of aprepitant + paroxetine for 6 weeks did not provide greater antidepressant benefit compared with paroxetine + placebo in patients with major depression.

Topics: Adult; Antidepressive Agents; Aprepitant; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Morpholines; Neurokinin-1 Receptor Antagonists; Paroxetine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

An early clinical trial suggested that the substance P (neurokinin(1) receptor) antagonist, aprepitant, might provide a unique mechanism of antidepressant activity. Phase III trials were conducted to confirm these findings.. Five 8-week, randomized, double-blind, parallel-groups, placebo-controlled, multicenter trials in outpatients with Major Depressive Disorder were performed. Aprepitant 160 mg and placebo were included in all trials. Aprepitant 80 mg and paroxetine 20 mg (active comparator) were included in three trials. Approximately 150 patients were enrolled per treatment group in each trial. The primary end point was the mean change-from-baseline of the first 17 items of the Hamilton Rating Scale for Depression (HAM-D(17)) score at 8 weeks. A positron emission tomography (PET) study was also performed in normal subjects to determine the relationship between neurokinin(1) receptor occupancy and aprepitant plasma concentrations in dosing regimens relevant to the trials.. No statistically significant differences from placebo on the HAM-D(17) were observed at week 8 for either dose of aprepitant in any of the trials, whereas paroxetine 20 mg was significantly (p

Topics: Adult; Antidepressive Agents; Aprepitant; Brain; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Personality Inventory; Positron-Emission Tomography; Reproducibility of Results; Substance P; Treatment Outcome

Substance P (neurokinin-1 [NK1]) receptor antagonists appear to be effective antidepressant and anxiolytic agents, as indicated in 3 double-blind clinical trials. In laboratory animals, they promptly attenuate the responsiveness of serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine (NE) neurons to agonists of their cell-body autoreceptors, as is the case for some antidepressant drugs that are currently in clinical use. Long-term, but not subacute, antagonism of NK1 receptors in rats increases 5-HT transmission in the hippocampus, a property common to all antidepressant treatments tested thus far. This enhancement seems to be mediated by a time-dependent increase in the firing rate of 5-HT neurons. Mice with the NK1 receptor deleted from their genetic code also have an increased firing rate of 5-HT neurons. Taken together, these observations strongly suggest that NK1 antagonists could become a new class of antidepressant and anxiolytic agents.

Topics: Adrenergic alpha-Agonists; Animals; Antiemetics; Anxiety; Aprepitant; Autoreceptors; Depressive Disorder, Major; Electrophysiology; Hippocampus; Locus Coeruleus; Mice; Mice, Mutant Strains; Morpholines; Neurokinin-1 Receptor Antagonists; Norepinephrine; Phenylephrine; Photomicrography; Raphe Nuclei; Receptors, Neurokinin-1; Serotonin; Substance P