Research paper
Early effect on general interest, and short-term antidepressant efficacy and safety of agomelatine (25–50 mg/day) and escitalopram (10–20 mg/day) in outpatients with Major Depressive Disorder. A 12-week randomised double-blind comparative study

https://doi.org/10.1016/j.jad.2016.03.048Get rights and content

Highlights

  • Agomelatine is associated with an improved general interest of outpatients.

  • This antidepressant relieves depressive symptoms and functional impairment.

  • The good tolerability of this treatment is confirmed over 12 weeks.

Abstract

Background

A double-blind, randomized, study was conducted in 29 centers in Romania to evaluate the effect of agomelatine 25–50 mg/day (n=144 patients) on general interest, overall clinical efficacy, and functionality in comparison with escitalopram 10–20 mg/day (n=143 patients) in out-patients diagnosed with moderate to severe Major Depressive Disorder (MDD).

Methods

The primary endpoint of the study was the score difference between agomelatine and escitalopram were assessed on the item 13 of the Quick Inventory of Depressive Symptomatology (16-Item) Self-Report (QIDS-SR16) over the first week period. Secondary measures include the primary criterion on the 12-week period, the within-group evolution over 12 weeks of the 17-item Hamilton Depression Scale (HAM-D17) total score, CGI severity of illness (CGI-S) and CGI-I scores, and functionality by using the self-rated Sheehan Disability Scale (SDS).

Results

After one week, the mean General Interest score showed no statistically significant difference between treatments. Over 12 weeks, patients felt more and more interested in other people and activities than before having taken medication. Both agomelatine and escitalopram improved depressive symptoms and symptom-related functional impairment of patients. Both agomelatine and escitalopram were well-tolerated by patients.

Limitations

The strength of our results would benefit from additional data from trials using a similar design and other active comparators.

Conclusion

There was no difference in week 1 changes of interest between agomelatine and escitalopram. The relatively good tolerability of agomelatine and escitalopram is confirmed.

Introduction

Agomelatine is an antidepressive agent with agonistic MT1/MT2 and an antagonistic 5-HT2C receptor activity (Guardiola-Lemaitre et al., 2014). Its antidepressant efficacy has been repeatedly demonstrated at doses of 25–50 mg for the treatment of the full range of depressive symptoms in patients with moderate to severe Major Depressive Disorder (MDD) (de Bodinat et al., 2010). Agomelatine is an effective antidepressant with similar efficacy to other currently available compounds (Taylor et al., 2014). Head-to-head clinical trials have consistently established the antidepressant efficacy and favourable tolerability profile of agomelatine against compounds of SSRI and SNRI classes (Corruble et al., 2013, Hale et al., 2010, Kasper et al., 2010, Lemoine et al., 2007). Of notice, compared to venlafaxine (Lemoine et al., 2007) or sertraline (Kasper et al., 2010), agomelatine is endowed with earlier clinical benefits in terms of perceived improvement and daytime functioning, clear thinking and awakening condition.

According to the DSM 5, a diminished or loss of interest is key for the diagnosis of depressive episode. Patients with MDD exhibit a loss of interest for everyday life and lack of pleasure for usually pleasurable activities. Loss of interest is an important issue for patients with depression as positive affects are strongly involved in the recovery of interpersonal, social, and occupational functioning, as well as to adherence of treatment. The loss of interest has been shown to predict poor outcome of antidepressant treatment in adults with moderate to severe depression (Uher et al., 2012). To our best knowledge, there is no published data of randomized controlled trials that specifically describe the effects of a currently prescribed antidepressant on diminished –or loss of- interest in patients, especially in the early phase of treatment.

The objectives of the present study were to investigate the early effect (after one week) of agomelatine on general interest in out-patients with moderate to severe MDD, by using a Visual Analogue Scale (VAS) reflecting item 13 (General interest) of the Quick Inventory of Depressive Symptomatology (16-Item) Self-Report (QIDS-SR16) (Rush et al., 2003). Secondarily, the efficacy and the tolerability of a 12-week treatment period with agomelatine have been estimated. Escitalopram was used as the active comparator and was given in line with the current prescribing guidelines (Garnock-Jones et al., 2010).

Section snippets

Study design

A double-blind, randomised study was conducted in 29 centers in Romania from June 2011 to April 2013. The study was run in accordance with the principles of Good Clinical Practice E6 of the International Conference of Harmonisation (CPMP/ICH/135/95) and the Declaration of Helsinki, Finland. The study was approved by the relevant local ethics committees and included patients suffering from moderate to severe Major Depressive Disorder (MDD) and having given their written informed consent.

A

Patients

Of the 417 initially selected patients, 287 (68.8%) were randomly allocated to receive agomelatine (144 patients) or escitalopram (143 patients) for 12 weeks (Fig. 1). There was no significant difference in demographic characteristics between both treatment groups (Table 1). The average age of the randomised patients was 46.7±9.6 years and 82.2% of them were female. The mean duration of the current episode was similar in both treatment groups (3.2±2.5 versus 3.0±2.2 months in the agomelatine

Discussion

This double-blind, multicentric randomised study is the first to compare the early effect of two antidepressants on the evolution of the general interest of MDD outpatients. It demonstrates a similar effect of agomelatine and escitalopram on this dimension as early as the first week of treatment. From week 2 to the end of the 12-week study period, both treatments progressively improve the General Interest score of patients. Such improvement is critical as it parallels patients’ preference for

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