Desvenlafaxine succinate

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Pristiq (Wyeth)
50 mg and 100 mg extended release tablets
Approved indication: depression
Australian Medicines Handbook section 18.1.4

Venlafaxine is a serotonin reuptake inhibitor which, at higher doses, also inhibits reuptake of noradrenaline. It is metabolised in the liver to desvenlafaxine which also has antidepressant actions. The decision to market the active metabolite might be related to the expiry of the patent on the controlled release formulation of venlafaxine.

Desvenlafaxine is well absorbed and only needs to be taken once a day. Although it is mainly metabolised by conjugation, desvenlafaxine is partly metabolised by cytochrome P450 3A4. Inhibitors of this enzyme, such as ketoconazole, may increase plasma concentrations of desvenlafaxine. The half-life of desvenlafaxine is 11 hours, but this may be increased by hepatic impairment. As almost half the dose is excreted unchanged in the urine, less frequent dosing is recommended for people with renal impairment.

Desvenlafaxine was compared to placebo in 234 patients with major depressive disorder. The mean score on the Hamilton Rating Scale for Depression was 23.7. The 120 patients randomised to use desvenlafaxine took 100 mg for two weeks then increased to 200 mg. After eight weeks the mean depression score had fallen to 14.1 with desvenlafaxine and 15.1 with placebo. This difference was not significant.¹

A larger randomised trial evaluated the efficacy of daily desvenlafaxine in 114 patients who took 100 mg, 116 who took 200 mg, 113 who took 400 mg and in 118 who took a placebo. At the start of the study the mean score on the Hamilton Rating Scale for Depression was approximately 23. After eight weeks the mean reduction in the score was 10.6 with 100 mg, 9.6 with 200 mg, 10.7 with 400 mg and 7.7 with placebo. Only the reductions in the 100 mg and 400 mg groups were significantly better than the placebo response.²

Another eight-week study compared desvenlafaxine 200 mg and 400 mg to placebo. The scores on the Hamilton Rating Scale were reduced by 12.6 with 200 mg, 12.1 with 400 mg and by 9.3 with placebo.³

In the clinical trials the most common adverse effects of desvenlafaxine were nausea, dry mouth, somnolence, anorexia, constipation and nervousness.^1,2 Other adverse effects include vomiting, dizziness, blurred vision, sexual dysfunction, hypertension, increased cholesterol and triglycerides and altered liver function. Approximately 12% of patients who took desvenlafaxine withdrew from trials because of adverse events. Ideally, the dose should be tapered off as stopping the drug abruptly can cause discontinuation reactions.

Venlafaxine is metabolised to desvenlafaxine by cytochrome P450 2D6. Giving the metabolite as a drug bypasses this step so there could be less potential for drug interactions, but there is little evidence that desvenlafaxine has any advantage over venlafaxine. The precautions for prescribing the two drugs are similar. Overseas, the manufacturer applied to have desvenlafaxine approved for the treatment of menopausal hot flushes, but the US Food and Drug Administration has asked for more data and in Europe the application has been withdrawn.

The recommended dose in depression is 50 mg daily, but until recently there was little published information about this dose. Two trials have compared desvenlafaxine 50 mg and 100 mg to placebo. After eight weeks, both doses had reduced the scores on the Hamilton Rating Scale, but only the 50 mg dose was significantly better than placebo in both trials.^4,5 It appears that higher doses may have more adverse effects, but no additional benefit. For patients who are being satisfactorily managed with venlafaxine there seems little reason to change to desvenlafaxine.

manufacturer provided additional useful information

The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Notes on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).