Reboxetine is the first commercially available norepinephrine reuptake inhibitor developed specifically as a first line therapy for major depressive disorder. In vitro and in vivo pharmacological studies indicated that reboxetine methanesulphonate has high affinity and selectivity for the human norepinephrine transporter over the serotonin and dopamine transporters. Pharmacological specificity is further demonstrated by the absence of affinity for 45 transmitter receptors and CNS targets. Pharmacokinetic studies demonstrated that reboxetine is suitable for twice daily administration (8-10 mg/day) and that it exhibits minimal drug-drug interactions. The starting dose of reboxetine should be reduced in the elderly, in patients with renal or hepatic impairment, or in patients receiving potent CYP3A inhibitors. A total of 20 phase II/III clinical studies comprising placebo-controlled, active comparator-controlled and open-label uncontrolled studies in both short-term and long-term treatment of major depression have been conducted. In the treatment of major depression, reboxetine was superior to placebo in 5 of 12 short- or long-term placebo-controlled studies and was comparable in efficacy to active comparators in 3 out of 3 active-controlled studies. Unlike conventional tricyclic antidepressants (TCAs), reboxetine had only minimal sedative and cardiovascular liabilities, probably due to increased pharmacological specificity of reboxetine as compared with TCAs. Unlike serotonin reuptake inhibitors, this selective and specific norepinephrine reuptake inhibitor demonstrated a distinct side-effect profile with diminishing sexual dysfunction and GI side effects. The availability of this agent has afforded patients suffering from major depressive disorder a new class of agents to combat the debilitating consequence of this psychiatric disease. The demonstrated pharmacological specificity of this compound has provided the psychopharmacology community with a tool to elucidate the role of norepinephrine in brain functions. Testing this agent in different animal models has enabled the exploration of the role of modulation of norepinephrine tone in the therapy of CNS disorders beyond depression.

Sexual side-effects due to antidepressant treatment are an important consideration when selecting a treatment regimen and can influence patient compliance. Sexual function during treatment with the selective noradrenaline reuptake inhibitor reboxetine, the selective serotonin reuptake inhibitor (SSRI) fluoxetine and placebo has been assessed in a multicentre, randomized, 8-week, double-blind study of 450 patients diagnosed with major depressive disorder. Sexual function was measured by the Rush Sexual Inventory completed by male and female patients and administered at baseline, week 4 and week 8. The results indicate that reboxetine was similar to placebo and superior to fluoxetine in its effect on overall sexual function. There was a greater degree of sexual satisfaction in the reboxetine group compared to fluoxetine (P=0.02). The percentage of female patients able to achieve orgasm increased during the study period for women who received reboxetine and placebo, but decreased for those who received fluoxetine. These results suggest that reboxetine may be of particular benefit for patients at risk for sexual dysfunction with SSRIs.

Sexual side-effects due to antidepressant treatment are an important consideration when selecting a treatment regimen and can influence patient compliance. Sexual function during treatment with the selective noradrenaline reuptake inhibitor reboxetine, the selective serotonin reuptake inhibitor (SSRI) fluoxetine and placebo has been assessed in a multicentre, randomized, 8-week, double-blind study of 450 patients diagnosed with major depressive disorder. Sexual function was measured by the Rush Sexual Inventory completed by male and female patients and administered at baseline, week 4 and week 8. The results indicate that reboxetine was similar to placebo and superior to fluoxetine in its effect on overall sexual function. There was a greater degree of sexual satisfaction in the reboxetine group compared to fluoxetine (P=0.02). The percentage of female patients able to achieve orgasm increased during the study period for women who received reboxetine and placebo, but decreased for those who received fluoxetine. These results suggest that reboxetine may be of particular benefit for patients at risk for sexual dysfunction with SSRIs.