In this 8-week double-blind multicenter trial, we evaluated the efficacy and safety of 2 fixed doses of agomelatine in patients with moderate to severe major depressive disorder. Primary efficacy variable was the change in 17-item Hamilton Depression Rating Scale (HAM-D17) total score from baseline to week 8/end of treatment. Secondary efficacy assessment compared the improvements in clinical response and remission (HAM-D17), Clinical Global Impression--Improvement Score, Clinical Global Impression--Severity Score, Hospital Anxiety and Depression (HAD), sleep (Leeds Sleep Evaluation Questionnaire), disability (Sheehan Disability Scale), and overall Quality of Life in Depression Scale between the agomelatine and placebo groups. Eligible patients (n = 511; baseline mean HAM-D17 score = 27.0) were randomized (1:1:1) to once-daily agomelatine, 25 mg; agomelatine, 50 mg; or placebo. Agomelatine 50 mg provided a statistically significant improvement in HAM-D17 score from first baseline visit through week 8 compared with placebo (week 8 treatment difference, 2.5; P = 0.004), whereas agomelatine 25 mg did not show (P = 0.505) a significant improvement. Treatment differences for all secondary efficacy variables were also statistically significant for agomelatine 50 mg versus placebo: Clinical Global Impression--Improvement (P = 0.012); Clinical Global Impression--Severity difference (P = 0.003); improvement in HAD total score, 2.2 (P = 0.014); patients' ability to get sleep (P < 0.001); quality of sleep (P = 0.002). Both doses of agomelatine were well tolerated relative to placebo. However, clinically notable transient aminotransferase elevations were observed in 4.5% of the patients in the agomelatine 50 mg group. The results showed significant antidepressant efficacy of agomelatine 50 mg/d, including a positive effect on sleep compared with placebo in outpatients with moderate to severe major depressive disorder.

This is the first controlled study examining weight gain in bipolar illness and the first demonstration that premorbid weight is in the normal range for bipolar subjects. Subsequent weight gain is probably related to illness and treatment variables.

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clinicaltrials.gov Identifier: NCT00411242.

Adult Primary Ciliary Dyskinesia (PCD) has not been well characterised. Patients have varied radiological severity of disease and lung function impairment and limited data is available regarding prognosis. In this retrospective study we describe and characterise a large adult PCD cohort, and identify determinates of disease progression using longitudinal lung function data.We retrospectively analysed 151 adult patients at a single tertiary centre. Overall mortality was 4.6% over a 7-year median follow-up period. Lung function decline was estimated at 0.49%FEV1predicted/year. Older age at diagnosis showed moderate negative correlation with FEV1%predicted at diagnosis (r = -0.30; p = 0.01) and increased Pseudomonas aeruginosa colonisation (p < 0.01) but not longitudinal FEV1%predicted (β = 0.001; (95% CI:-0.35,0.35)). Within multivariate mixed models of FEV1 adjusting for ciliary ultrastructure, HRCT scoring of severity of bronchial wall dilatation (p < 0.01) and extent of bronchiectasis (p = 0.03) showed evidence of modifying the decline in FEV1 with age. Lung function decline additionally differed by ciliary ultrastructure (p = 0.04) with patients with microtubular defects having the greatest decline.Our study reveals a large proportion of adult PCD patients are diagnosed late with lower FEV1 and increased P. aeruginosa colonisation at diagnosis. Increased disease burden on HRCT and microtubular defects on ciliary ultrastructure predicts progressive lung function decline. This study highlights the need for early diagnosis alongside prospective multi-centre disease-specific trials to confirm triggers for lung function decline and identify potential novel therapeutic strategies.