Antidepressant — duloxetine
As many as one in 20 people are thought to be affected by depression at any one time, and one in five at some point during their lives. Pharmaceutical treatment of depression depends on altering the brain chemistry of sufferers, particularly the three neurotransmitters serotonin, noradrenaline and dopamine. Modern antidepressant drugs act on one or more of these chemicals, and choosing the right drug for the right patient is often a case of trial and error, with the differences in activity profiles of otherwise similar compounds giving varying effects in different patients.
A new antidepressant being developed by Lilly, duloxetine, is a mixed reuptake inhibitor of both the hormones serotonin and noradrenaline. Both enantiomers are active, but the S isomer has a favourable pharmacological profile.1 In a multi-site double blind placebo controlled Phase II trial in 173 patients with major depression, subjects were given duloxetine, fluoxetine or placebo for 8 weeks.2 The patient group given duloxetine showed a statistically significant improvement in depressive symptoms. Estimated probabilities of response and remission were 64% and 56% respectively for duloxetine, 52% and 30% for fluoxetine, and 48% and 32% for placebo. Only mild side-effects were seen in patients given duloxetine, with insomnia and asthaenia the only statistically significant problems reported.
In a trial in 27 healthy young males with no history of psychiatric problems, subjects were given 20mg/day or 60mg/day of duloxetine, 100mg/day of the potent serotonin and noradrenaline reuptake inhibitor clomipramine, or placebo.3 Both doses of duloxetine induced significant effects on serotonin reuptake as blood levels of serotonin dropped. However, its effect on noradrenaline was much less clear as, in contrast to clomipramine, it did not impede the increase in blood pressure that follows an intravenous infusion of tyramine.
However, it is possible that this represents the threshold regimen for noradrenaline reuptake inhibition in human subjects. Despite this, duloxetine represents a promising potential new treatment for depression. The drug is also being investigated for treating urinary incontinence.