Drug review – Valdoxan® (agomelatine)
Janet Marianne Jackson PhD
JUST Medical Media Limited, Auckland, New Zealand
Agomelatine is the first of a new class of antidepressants indicated for the treatment of major depressive episodes in adults. The pharmacology of agomelatine is different to all other antidepressants currently available. Agomelatine is a potent agonist of the melatonin receptors MT1 and MT2 in the suprachiasmic nucleus (SCN), where the biological clock that controls circadian rhythm is located. Agomelatine is also a selective antagonist of the 5HT2C (5-hydroxytryptamine) receptor, in the frontal lobe of the brain and the SCN. It has no affinity for any other receptors, including other classes of 5HT receptor that are associated with adverse events with other antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs). Agomelatine has been shown to resynchronise disrupted circadian rhythms in patients with major depressive disorder (MDD) and this may manifest clinically as improvements in mood, anxiety and sleep–wake cycles. Large placebo-controlled clinical trials have demonstrated the antidepressant efficacy of agomelatine in patients with MDD by reducing symptom severity scores in the short-term acute phase and in long-term studies of up to 10 months. Response, remission and relapse rates have also been favourable compared with placebo and with other antidepressants, including the SSRI sertraline and the serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine. Treatment adherence has also been shown to be good when compared with some other antidepressants, which may be related to the early onset of action with lack of delay in efficacy, as well as the lack of side-effects, such as sexual dysfunction or weight gain. Agomelatine has been shown to not compromise daytime alertness and to improve the sleep–wake cycle with greater efficacy than with other antidepressants. Unlike some other antidepressants, agomelatine does not cause discontinuation symptoms. The safety and tolerability profile of agomelatine is similar to placebo. When compared with other antidepressants, the efficacy of agomelatine in relieving symptoms of MDD early and in the longer term, without causing significant side-effects or discontinuation symptoms, and its effects on improving disturbed sleep–wake cycles associated with MDD, indicate that agomelatine is a potentially useful treatment for major depressive episodes in adults.