Valdoxan now available for depression

26 June 2009, 09:30am

Servier has launched Valdoxan (agomelatine) for the treatment of major depressive episodes in adults.

PHARMACOLOGY

Valdoxan (agomelatine) offers a novel approach to the treatment of depression with a pharmacological profile entirely distinct from SNRIs and SSRIs.

Agomelatine is a synthetic analogue of the hormone melatonin and is a melatonergic agonist (MT₁ and MT₂ receptors) and 5HT_2C antagonist.¹

Agomelatine resynchronises circadian rhythms in animal models of circadian rhythm disruption. Agomelatine increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin.¹

Agomelatine does not effect the uptake of serotonin, noradrenaline or dopamine. The inhibition of 5HT_2C, increases noradrenaline and dopamine release in the frontal cortex. Agomelatine has no effect on monoamine uptake and no affinity for α, β adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine receptors.¹

CLINICAL STUDIES

Data from two studies investigating the affect of agomelatine (25–50mg daily) in patients with depression (score of 22 or more on the Hamilton Depression Rating Scale) over six weeks showed agomelatine treatment was significantly more effective than placebo.^2,3

In a pooled analysis of data from three studies examining the effect of agomelatine in severe depression, agomelatine treatment (25–50mg daily) was significantly more effective than placebo in patients with a severity of 25 or more on the Hamilton Depression Rating Scale (HAMD). There was an increase in magnitude of the agomelatine-placebo difference with increasing severity of the baseline HAMD score.⁴

Separate double blind studies compared the efficacy of agomelatine 25–50mg daily to venlafaxine 75–150mg daily and to sertraline 50–100mg daily for short-term and long-term symptom alleviation assessed using a Clinical Global Impression rating scale. Agomelatine showed significant clinical superiority at week one, week six and after six months compared with venlafaxine and after week six compared with sertraline.⁵

Agomelatine demonstrated a significantly favourable difference on rest/activity circadian rhythms compared to sertraline.⁶ In addition a significant decrease in sleep latency and an increase in sleep efficiency was observed in the agomelatine group.⁶

Another study assessed the long-term efficacy of agomelatine in the prevention of depressive relapses following an initial response to agomelatine 25mg or 50mg daily. Over a 10-month period the incidence of relapse in patients treated with agomelatine was significantly lower than the placebo treatment group.⁷

In a study comparing the effect of agomelatine 50mg daily and venlafaxine 150mg daily on sexual function, agomelatine resulted in significantly less deterioration in total sexual function using the Sex Effects Scale compared with venlafaxine. Comparison to placebo was not evaluated in this study.⁸

In a study that assessed the effect of agomelatine 25–50mg daily and venlafaxine 75–150mg daily on sleep disorders, quality of sleep, sleep awakening and time to sleep scores were significantly in favour of agomelatine compared to venlafaxine. There was no significant difference between the groups in whether the patients felt more or less drowsy.⁹

During treatment, Valdoxan (agomelatine) does not cause weight gain, has a low risk of sexual dysfunction, low incidence of gastrointestinal disturbance and an overall incidence rate of adverse effects similar to placebo. Agomelatine is not associated with discontinuation symptoms following abrupt cessation of treatment.The incidence of elevated liver enzyme transaminases was higher in the agomelatine treatment groups compared to the placebo groups.¹⁰

View Valdoxan drug record

REFERENCES:

Valdoxan Summary of Product Characteristics. February 2009.
Kennedy, S.H. and Emsley, R. Placebo controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol 2006, 16: 93–100.
Olie, J.P. and Kasper, S. Efficacy of agomelatine, a MT₁/MT₂ receptor agonist with 5HT_2C antagonistic properties in major depressive disorder. Int J Neuropsychopharmacol 2007, 10: 661–673.
Montgomery S, Kasper S. Severe depression and antidepressants: focus on a pooled analysis of placebo-controlled studies on agomelatine. Int Clin Psychopharmacol 2007: 22; 283–91.
Kasper S, Lemoine P. Comparative efficacy of the antidepressants agomelatine, venlafaxine and sertraline. Eur Neuropsychopharmacol: 18 Suppl 4; S331–2.
Kasper S. Effect of agomelatine on rest-activity in patients with major depressive disorder compares to sertraline. Int J Neuropsychopharmacol 2008: 11 Suppl 1; 193.
Goodwin G, Rouillon F et al. Long-term treatment with agomelatine: prevention of relapse in patients with major depressive disorder over 10 months. Eur Neuropsychopharmacol: 18 Suppl 4; S338–9.
Kennedy S, Rizvi S et al. A double-blind comparison of sexual functioning, antidepressant efficacy, and tolerability between agomelatine and venlafaxine XR. J Clin Psychopharmacol 2008: 28;329–33.
Lemoine P, Guilleminault C et al. Improvement in subjective sleep in major depressive disorder with a novel antidepressant, agomelatine: randomized, double-blind comparison with venlafaxine. J Clin Psychiatry 2007: 68;1723–32.
CHMP Assessment report for Valdoxan. Committee for Medicinal Products for Human Use. Accessed via www.emea.europa.eu/humandocs/PDFs/EPAR/valdoxan/H-915-en6.pdf on 18.06.09