Antidepressant – vortioxetine

The majority of modern depression and anxiety treatments modulate the serotonin, or 5-HT, signalling pathways. However, response can be variable so there is still room in the market for alternatives

Vortioxetine

The majority of modern depression and anxiety treatments modulate the serotonin, or 5-HT, signalling pathways, on account of their role in regulating mood, emotions and sleep, and the typically low levels of serotonin in affected patients. Various points within these pathways have been targeted, including preventing the chemical’s reuptake, stopping its degradation, and direct action at the serotonin receptors, and many drugs have more than one mode of action. However, not all patients respond, and that response can be variable, so there is still room in the market for alternatives.

One such novel antidepressant, vortioxetine, is being developed by Lundbeck, and has been licensed to Takeda in the US and Japan.1 It has a different mechanism of action from existing drugs – it is an agonist at the 5-HT1A receptors, an antagonist at the 5-HT3 and 5-HT7 receptors, and inhibits the sodium-dependent 5-HT transporter.

In a six-week randomised, double blind, placebo-controlled efficacy and tolerability trial, a total of 600 adults with major depressive disorder were given 5mg daily doses of vortioxetine or placebo, followed by a two-week medication-free discontinuation period.2 However, there were no significant differences in effect on depression between the treated patients and those given placebo.

More effect was seen in a long-term open label trial extension. In this study, 535 patients with major depressive disorder were given 2.5, 5 or 10mg doses.3 The main adverse events that were reported included headache, nausea and nasopharyngitis. By the end of the study, the proportion of responders had risen from 63% to 94%.

Its effects have also been compared with duloxetine. In this study, 611 patients with major depressive disorder were given 2.5 or 5mg of vortioxetine, 60mg duloxetine or placebo once a day.4 Although, again, some improvements were seen with vortioxetine, the reductions in depression symptoms were not statistically significant.

However, a fourth trial gave better results. Here, 301 patients with generalised anxiety disorder were given 5mg doses of vortioxetine or placebo for eight weeks.5

A significantly higher rate of remission was seen in those patients given the drug, with the most common treatment-related adverse events being headache, nausea, dizziness and dry mouth. Despite the mixed results, the drug has been submitted for approval in both the US and Europe.

References

1. B. Bang-Andersen et al. J. Med. Chem. 2011, 54, 3206

2. R. Jain et al. Int. J. Neuropsychopharmacol. 2013, 16, 313

3. D.S. Baldwin et al. Curr. Med. Res. Opin. 2012, 28, 1717

4. A.R. Mahableshwarkar et al. Curr. Med. Res. Opin. 2013, epub ahead of print

5. L. Bidzan et al. Eur. Neuropsychopharmacol, 2012, 22, 847

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