No abstract

The objective of this international, 8-week, randomized, double-blind study was to show the superiority of the antidepressant efficacy of agomelatine, the first MT1/MT2 receptor agonist and 5-HT2C receptor antagonist antidepressant, versus fluoxetine in outpatients fulfilling Diagnostic and Statistical Manual of Mental Disorders-volume IV-TR criteria for major depressive disorder of severe intensity, defined by a baseline Hamilton Depression Rating Scale (HAM-D17) total score of at least 25 and CGI severity of illness score of at least 4. Patients received agomelatine 25-50 mg/day (n=252) or fluoxetine 20-40 mg/day (n=263) for 8 weeks. The main efficacy outcome measure was HAM-D17 total score (change from baseline to last post-baseline assessment). Secondary outcome measures were Clinical Global Impressions-improvement (CGI), severity (CGI-S), anxiety (HAM-A), and sleep (HAM-D sleep items) scores. The mean decrease in HAM-D17 total score over 8 weeks was significantly greater with agomelatine than fluoxetine with a between-group difference of 1.49 (95% confidence interval, 0.20-2.77; P=0.024). The percentage of responders at last post-baseline assessment was higher with agomelatine on both HAM-D17 (decrease in total score from baseline ≥50%; 71.7% agomelatine vs. 63.8% fluoxetine; P=0.060) and CGI-improvement (score 1 or 2; 77.7 vs. 68.8%; P=0.023). There was a significant between-group difference of 0.37 (95% confidence interval, 0.06-0.68) in HAM-D sleep subscore in favor of agomelatine (P=0.018). Similar improvements were observed on HAM-A with agomelatine and fluoxetine. Both treatments were safe and well tolerated. In conclusion, in this study, agomelatine showed superior antidepressant efficacy over fluoxetine in treating patients with a severe episode of major depressive disorder after 8 weeks of treatment with a good tolerability profile.

As a treatment of last resort, no controlled trial against a comparable treatment is possible. It appears reasonable to offer SST to patients with suicidal and deluded depression or with frequently swinging moods, not responding to other treatments.

Objectives-To document the circumstances and care of patients with schizophrenia who had recently been discharged from local psychiatric inpatient services, and to establish the extent to which misgivings about community care might be justified.Design Main outcome measures-Diagnosis elicited by present state examination, global social disability rating, use of services during the three months before interview.Results-89 of the 140 patients (64%) had been ill for five or more years, yet few were former long stay inpatients. 55% (50/91; 95% confidence interval 45% to 65%) of those interviewed had current psychotic mental states and 22% (27/124; 16% to 31%) were functioning socially at very poor or severely maladjusted levels. 86% (107/124) were unemployed. The majority of patients had seen a mental health or social service professional, yet only 16% (20/124) were in specialised accommodation (excluding hospitals) and only 23% (17/73) of those eligible had used day care. Small numbers of people had experienced homelessness (two) or imprisonment (four over six months).Conclusions-Many schizophrenic patients leaving local psychiatric inpatient care have active symptomatology and profound social disabilities. Community care was characterised by high rates of contact with service professionals but little supported accommodation or day activity. This group of clients may require dedicated provision, which would actively encourage them to use services protected from the demands ofthose with less severe illness. IntroductionPolicies of closing large mental hospitals and reproviding for patients in the community were adopted in Britain over three decades ago, yet few data have emerged on the workings of replacement services.' Recent studies of resettlement projects for long stay hospital patients have reported somie success,25 yet much evidence points to mentally ill people, especially people with schizophrenia,6 being homeless,78 in poverty, or imprisoned.9 Consequently, misgivings about the everyday effectiveness ofservices in caring for both long stay and shorter stay patients are continuing to grow both in Britain and the United States.'0 12We documented and quantified the circumstances and care of former inpatients with schizophrenia who had recently been discharged from local psychiatric services in order to establish the extent to which these

Agomelatine (S 20098) has a unique and new pharmacological profile. It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder (DSM-IV criteria). The methodology used was a conventional double-blind design comparing three different doses of agomelatine (1, 5 and 25 mg once a day) with placebo over an 8-week treatment period. Paroxetine was used as the study validator. Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were included. On the pivotal analysis, the mean final HAM-D total score (Full Analysis Set LOCF) demonstrated agomelatine 25 mg to be statistically more effective than placebo. This was confirmed by other analyses and criteria (responders, remission, subpopulation of severely depressed patients, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression-Severity of Illness). Agomelatine 25 mg alleviated the anxiety associated with depression, as measured on Hamilton Anxiety Scale. Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to validate the study methodology and population. Agomelatine, whatever the dose, showed good acceptability with a side-effects profile close to that of placebo. In conclusion, this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose.

Depression has a range of meaning-from a description of normal unhappiness, through persistent and pervasive ways of feeling and thinking, to psychosis. Textbook descriptions of depression seen in hospitals are often very different from presentations in primary care.In recent community surveys, 2% of the population suffered from pure depression (evenly distributed between mild, moderate, and severe), but another 8% suffered from a mixture of anxiety and depression. Even patients with symptoms not severe enough to qualify for a diagnosis of either anxiety or depression alone have impaired working and social lives and many unexplained physical symptoms, leading to greater use of medical services.Key practical questions relate to treatment. Is any required at all and, if so, what sort and for how long?

The limited evidence base suggests that valproate can be effective as a monotherapy for the treatment of both PTSD and mood symptoms. A double blind controlled study should be the next step to robustly study the efficacy of valproate on the treatment of PTSD.

Many cultures give rise to apparently genuine cases of ghost possession. Neuroleptics may relieve symptoms of exorcism-resistant possession.