Valdoxan is a novel antidepressant indicated in the treatment of major depressive episodes in adults. The recommended dose of Valdoxan is 1 tablet of 25 mg once daily, taken orally at bedtime. After 2 weeks of treatment, if there is no improvement of symptoms, the dose of Valdoxan may be increased to 50 mg once daily, ie, two 25-mg tablets, taken together at bedtime. Transaminase tests should be performed in all patients: at initiation of treatment and then periodically. At treatment cessation, Valdoxan has been shown to be free of discontinuation symptoms. Overall, Valdoxan has been demonstrated to combine significant antidepressant efficacy resulting from the restoration of circadian rythms, and favorable tolerability profile. Contra-indications to the use of Valdoxan include hepatic impairment and concomitant use with potent CYP1A2 inhibitors.

Recommended dose of Valdoxan: one 25-mg tablet once daily taken orally at bedtime

Valdoxan has been demonstrated to be effective and safe through a large, comprehensive, international development programme including almost 6,000 adult patients with depression. These patients were adults, male and female, with different levels of severity and different symptomatic profiles and medical and family histories, and presenting with a first or recurrent depressive episode.

The recommended dose of Valdoxan is one 25-mg tablet once daily taken orally at bedtime.

After 2 weeks of treatment, if there is no improvement of symptoms, the dose may be increased to 50 mg once daily, ie, two 25-mg tablets, taken together at bedtime.Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free of symptoms.

Biological tests

In clinical studies, elevations of serum transaminases (>3 times the upper limit of the normal range) have been observed in patients treated with Valdoxan at particularly a 50-mg dose. When Valdoxan was discontinued in these patients, the serum transaminases usually returned to normal levels.

Liver function tests should be performed in all patients: at initiation of treatment and then periodically after around 6 weeks (end of acute phase), after around 12 and 24 weeks (end of maintenance phase), and thereafter when clinically indicated.

Any patient who develops increased serum transaminases should have his/her liver function tests repeated within 48 hours. Therapy should be discontinued if the increase in serum transaminases exceeds 3X upper limit of normal, and liver function tests should be performed regularly until serum transaminases return to normal.

If any patient develops symptoms suggesting hepatic dysfunction, liver function tests should be performed. The decision whether to continue the patient on therapy with Valdoxan should be guided by clinical judgement pending laboratory evaluations. If jaundice is observed, therapy should be discontinued.
Caution should be exercised when Valdoxan is administered to patients who consume substantial quantities of alcohol or who are treated with medicinal products associated with risk of hepatic injury.

Absence of discontinuation symptoms with Valdoxan

Valdoxan is free of discontinuation symptoms after abrupt cessation of treatment. In a study designed to assess discontinuation symptoms by the Discontinuation Emergent Signs and Symptoms (DESS) check list in patients with remitted depression, Valdoxan did not induce discontinuation syndrome after abrupt treatment cessation.

Montgomery SA, Kennedy SH, Burrows GD, Lejoyeux M, Hindmarch I. Int Clin Psychopharmacol. 2004;19:271-280.

Favorable tolerability profile of Valdoxan

Adverse reactions were usually mild or moderate, and occurred within the first 2 weeks of treatment. The most common adverse reactions were nausea and dizziness. These adverse reactions were usually transient, and did not generally lead to cessation of therapy.

In a specific sexual dysfunction comparative study with remitted depressed patients, that there was a numerical trend towards less emergent sexual dysfunction than venlafaxine for Sex Effects Scale (SEXFX) drive arousal or orgasm scores on Valdoxan. The pooled analysis of studies using the Arizona Sexual Experience Scale (ASEX) confirmed that Valdoxan was not associated with sexual dysfunction. In healthy volunteers, Valdoxan preserved sexual function in comparison with paroxetine.

Valdoxan had a neutral effect on body weight, heart rate, and blood pressure in clinical studies.

Contraindications

- Hypersensitivity to the active substance or to any of the excipients.
- Hepatic impairment (ie, cirrhosis or active liver disease).
- Concomitant use of potent CYP1A2 inhibitors (eg, fluvoxamine, ciprofloxacin).