Anhedonia is a core symptom of major depression and a key prognostic factor that is often poorly explored in clinical trials of major depressive disorder (MDD). Beyond symptomatic remission, psychosocial functioning also reveals difficulty in achieving remission in patients with MDD. The main objective of this study was to explore the interrelationships between social functioning and anhedonia on a longitudinal basis.

In total, 1570 outpatients treated for MDD with agomelatine were included. Severity of depression and levels of anhedonia and of psychosocial functioning were assessed at inclusion and at 10–14 weeks, with specific standardized scales (MADRS, QFS, SHAPS, CGI). Multivariate regression and mediation analyses were performed.

Using multivariate regression, we showed that improvement of anhedonia was the strongest predictor of improvement in psychosocial functioning (odds ratio = 7.3 [4.3–12.1] P < 0.0001). In addition, mediation tests confirmed that the association between improvement of depressive symptoms and improvement of social functioning was significantly underpinned by the improvement of anhedonia over time. Finally, we explored the determinants of the dissociation of the response, i.e., the persistence of psychosocial dysfunctioning despite a symptomatic response to antidepressant treatment, which remains a widespread situation in clinical practice. We showed that this dissociation was strongly predicted by persistence of anhedonia.

Our results suggest that anhedonia is one of the strongest predictors of psychosocial functioning, along with symptomatic remission, and should be carefully assessed by health professionals, in order to optimize pharmacological as well as non-pharmacological management of depression.

Agomelatine is a newer antidepressant but, to date, no studies have been carried out investigating its effects on C-reactive protein (CRP) levels in major depressive disorder (MDD) before and after treatment. The present study aimed (i) to investigate the effects of agomelatine treatment on CRP levels in a sample of patients with MDD and (ii) to investigate if CRP variations were correlated with clinical improvement in such patients.

30 adult outpatients (12 males, 18 females) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of MDD were recruited in “real-world,” everyday clinical practice and treated with a flexible dose of agomelatine for 12 weeks. The Hamilton Rating Scale for Depression (HAM-D) and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to evaluate depressive symptoms and anhedonia, respectively. Moreover, serum CRP was measured at baseline and after 12 weeks of treatment.

Agomelatine was effective in the treatment of MDD, with a significant reduction in HAM-D and SHAPS scores from baseline to endpoint. CRP levels were reduced in the whole sample, with remitters showing a significant difference in CRP levels after 12 weeks of agomelatine. A multivariate stepwise linear regression analysis showed that higher CRP level variation was associated with higher baseline HAM-D scores, controlling for age, gender, smoking, BMI, and agomelatine dose.

Agomelatine’s antidepressant properties were associated with a reduction in circulating CRP levels in MDD patients who achieved remission after 12 weeks of treatment. Moreover, more prominent CRP level variation was associated with more severe depressive symptoms at baseline.

A case of agomelatine-induced hepatotoxicity is described in a 47-year female patient who has received the drug, 25 mg/day, for 4 months, for the treatment of depression.

The patient was admitted to the Department of Gastroenterology because of fatigue and nausea, with concomitant elevation of alanine aminotransferase (ALT), 550 U/L, and asparagine aminotransferase (AST), 300 U/L.

Liver biopsy showed diffuse lymphocyte infiltration in the dilated portal spaces without lesion of hepatic lobules. Several weeks after stopping agomelatine, the liver enzymes returned to normal. Subsequently, small gallstones in common bile duct were detected and removed by the endoscopic sphincterotomy.

It is hypothesized that choledocholithiasis could theoretically increase a risk of developing agomelatine-induced hepatotoxicity in this patient. Any pre-existing liver disease should be a contraindication for treatment with agomelatine.

The present trial informs clinicians about switching conditions with the antidepressant agomelatine after the failure of a treatment with either paroxetine or venlafaxine.

The total number of discontinuation-emergent symptoms, according to the Discontinuation-Emergent Signs and Symptoms checklist, was compared in double-blind conditions after 3 switching options: immediate substitution or initiation of agomelatine (25 mg/day p.o.) with either a short- or long-tapering of the previous drug. Secondary objectives included tolerability and safety assessments and the early clinical benefit after the switch.

For all switching options, a withdrawal syndrome was observed 1 week after cessation of the selective serotonin reuptake inhibitor (SSRI)/serotonin–norepinephrine reuptake inhibitor (SNRI) treatment. Psychic symptoms were the most frequently reported, and somatic symptoms were comparatively few. Early discontinuation symptoms after cessation of SSRI/SNRI treatment did not prejudice the antidepressant benefits of agomelatine over 8 weeks.

Both abrupt and start–taper switching with agomelatine are options in everyday practice for those patients who have not responded to either paroxetine or venlafaxine. However, regardless of the switching strategy, the present double-blind study shows that early discontinuation symptoms that arise upon cessation of SSRI/SNRI can alter the patients’ perception of the clinical benefit of the new antidepressant. Both practitioners and patients must be warned about these early discontinuation symptoms to prevent the symptoms from being confounded with a lack of therapeutic benefit of the new treatment.

Adverse effects of antidepressant drug treatmenton sexual function are well documented but the effects of antidepressants on sperm production have not been researched extensively.

A narrative of an interventional case report of sperm parameters in a 30-year-old Caucasian man with a diagnosis of mixed depressive and anxiety disorder, who underwent citalopram treatment, followed by agomelatine treatment. Clinical observations prompted a review of the pre-clinical and clinical literature on the effects of antidepressant administration or treatment on sperm production and parameters. Findings from the review are discussed to suggest potential underlying mechanisms.

Abnormal sperm parameters were associated with treatment with the SSRI citalopram. There was an improvement in sperm concentration, motility, progressive motility and sperm morphology following its withdrawal. There was no similar association during subsequent treatment with agomelatine. The clinical observations reflect findings from animal studies, which indicate that antidepressants can have untoward effects on spermatogenesis.

SSRI treatment can be associated with impaired semen quality. Potential underlying mechanisms include changes in sperm DNA integrity, activation of IDO and shifting tryptophan metabolism. Further studies of the effects of antidepressants on spermatogenesis might benefit from including investigation of changes in IDO activity during antidepressant administration.

A pooled-analysis on the long-term outcome in four head-to-head studies: agomelatine versus fluoxetine, sertraline, and (twice) escitalopram.

A meta-analytic approach was used. Hamilton Depression Rating Scale (HAM-D) scores, response and remission rates, Clinical Global Impression of Improvement (CGI-I) scores, response and remission rates, and completion rates/discontinuation rates due to adverse events were analyzed.

At the last post-baseline assessment on the 24-week treatment period, the final HAM-D-17 score was significantly lower in patients treated with agomelatine than in patients treated with selective serotonin reuptake inhibitors (SSRIs), as well in the total group of patients with severe depression (P = 0.014 and 0.040, respectively). HAM-D response rates at the end of 24 weeks were significantly higher in patients treated with agomelatine than in patients treated with SSRIs, as well in the total group of patients with severe depression (P = 0.031 and 0.048, respectively). HAM-D remission rates at the end of 24 weeks were numerically but not significantly higher in patients treated with agomelatine than in patients treated with SSRIs. Final CGI-I scores were significantly lower for agomelatine. CGI-I response as well as remission rates were numerically higher in patients treated with agomelatine, without statistical significance. The percentage of patients with at least one emergent adverse event leading to treatment discontinuation was 9.4% in patients treated with SSRIs and 6.6% in patients treated with agomelatine (P = 0.065).

The present pooled analysis shows that, from a clinical point of view, agomelatine is at least as efficacious as the investigated SSRIs with a trend to fewer discontinuations due to adverse events.