For patients with a major depressive disorder, the investigational melatonergic antidepressant Valdoxan (agomelatine) has improved the quality of sleep without causing daytime somnolence, investigators reported here.

In a six-week double-blind, randomized trial comparing Valdoxan with the antidepressant Effexor (venlafaxine), Valdoxan acted faster in improving subjective sleep onset and quality, without causing daytime sleepiness, Stanford researchers reported here at a meeting of the European Congress of Neuropsychopharmacology

Valdoxan is a potent agonist of melatonin receptors and an antagonist at serotonin-2C (5-Ht ) receptors, said Christian Guilleminault, M.D., associate director of the Sleep Disorders Clinic and Research Center at Stanford.

The multicenter trial included 332 adults with a history of major depressive disorder. Of these, 165 were randomized to Valdoxan (25 mg daily at the outset) and 167 to Effexor (75 mg daily at the outset). Depending on improvement, physicians could increase the dose.

The final scores for the Hamilton Depression Rating Scale (HAM-D) were 9.9 in the Valdoxan arm and 11.0 in the Effexor group. The two medications had equivalent antidepressant effects, the researchers reported.

In an evaluation of the patients’ sleep onset and sleep quality, the researchers reported that the Valdoxan patients improved significantly compared with the Effexor patients on a series of measures. These included ease of getting to sleep, quality of sleep, daytime sleepiness, and “feeling good.”

Patients were evaluated by items in the Leeds Sleep Evaluation Questionnaire (LSEQ), which the patients responded to weekly for the first four weeks and then again at six weeks. These items included the GTS (ease of getting to sleep) and the QOS (quality of sleep).

As early as the end of the first week, patients treated with Valdoxan reported significantly better improvement for the “getting to sleep” (p = 0.007) and “quality of sleep” (p = 0.015), items on the LSEQ scale. This difference continued throughout the study (p = 0.001 for the GTS group; p = 0.021 for the QOS group).

Visual analogue scales (VAS) were used to see whether Valdoxan affected patients’ daytime function; the VAS dimensions were “daytime sleepiness” and “feeling good.” The average VAS scores for these items were also significantly better for the Valdoxan patients compared with the Effexor patients, Dr. Guilleminault said.

The study was funded by Servier, which developed Valdoxan, now in Phase III clinical trials.

Source: European Neuropsychopharmacology. 2005;(15): Supplement 3.