Writing Sample -- New Business Proposal
Reboxetine, a selective norepinephrine (also noradrenaline) reuptake inhibitor (NARI) is an effective and well-tolerated antidepressant. Depression is a serious disease that affects patients differently. Medical research has shown that there are various subsets of patients with depression who respond favorably to different antidepressant agents. While over $60 billion dollars is spent each year on antidepressant medication, ongoing research has shown that depression can be differentiated based on severity and etiology. Therefore, it makes sense that the treatment of depression should be individualized.
A large part of differential diagnosis in patients who present with depressive symptoms is understanding the role of various neurotransmitters in depression and the distinction between depression that is associated with norepinephrine (noradrenaline) deficiency and depression that is associated with serotonin deficiency. Whereas, selective serotonin reuptake inhibitors (SSRIs) are used to treat patients who are perceived to have a deficient amount of the neurotransmitter serotonin circulating in their brain at any given time; patients who lack sufficient quantities of the neurotransmitter noradrenaline would benefit from treatment with NARIs.
However, until recently, the role of noradrenaline has not been properly understood, or at least underappreciated. Noradrenaline deficiency is highly correlated with lack of energy, lack of interest, and loss of motivation. Each class of agents has a similar mechanism of action in that they are each selective inhibitors of the reuptake of targeted neurotransmitters. In addition, both NARIs and SSRIs allow the brain to benefit from the positive effects of greater availability of the targeted neurotransmitter, while avoiding the severe side-effect profile associated with nonselective antidepressants, such as the older tricyclic antidepressants (TCAs).
In many respects, reboxetine may represent a better treatment option for patients with depression than agents from the SSRI class. Notwithstanding the differences between serotonin, which is associated with mood regulation, and noradrenaline, which is associated with drive and motivation, reboxetine is a very useful therapeutic agent for treating various populations because of its efficacy and general tolerability. When compared to fluoxetine, a widely prescribed SSRI, reboxetine was shown to have a less severe side-effect profile, better effectiveness in the acute phase of depression, better efficacy as an agent for long-term management, and a more profound effect on social functioning. The overall role of reboxetine, and its potential as a first-line treatment option for patients with depression, can be broadly summarized based on its evaluation within the context of 3 important areas, including: efficacy, general tolerability, and clinical trial data.
Efficacy
There are numerous clinical trials measuring the efficacy of reboxetine relative to placebo and comparator agents (including fluoxetine) in which reboxetine is shown to be highly efficacious and, in many cases, the agent of choice depending on predefined end points. These assessments are based on qualitative and quantitative data, including individual patient response to treatment with reboxetine and widely used depression rating scales, such as the Hamilton Depression Rating scale (HAM-D), the Montgomery-Asberg Depression Rating scale, and the Clinical Global Depression Rating scale (CGI). Researchers in clinical trials found that severely depressed patients treated with reboxetine were half as likely to commit suicide as those treated with fluoxetine. In addition to the scales that measure the reduction of depressive symptoms, the recently validated Social Adaptation Self-Evaluation scale (SASS) has been used to measure the effects of reboxetine on improving social function in depressed patients. These results are significantly better than the results of any other agent in positively influencing this particular end point. The combination of the positive quantifiable effect of reboxetine on the relief of depressive symptoms and improved social function is highly correlated with an increased QOL (quality of life) in depressed patients.
General Tolerability
Assessment of the general tolerability of NARIs versus SSRIs is based on several criteria, including the incidence of adverse events, the side-effect profile, the severity of side effects, frequency of discontinuation, and tolerability in special populations. In general, reboxetine has a less severe side-effect profile than fluoxetine with respect to the following: with reboxetine there is less dry mouth, less sweating, fewer problems with abnormal heart rhythms, less blurred vision, and a lower incidence of hypotension and lightheadedness. While fluoxetine has an attractive side-effect profile relative to TCAs, SSRIs are associated with bradycardia, slowing at the sinus node, and insomnia. Moreover, in clinical trials, in general patients experienced high tolerability and a low rate of discontinuation when treated with reboxetine. Reboxetine?s low side-effect profile is attributable to its lack of affinity for serotonin and dopamine uptake as well as its lack of affinity for muscarinic, histaminergic, or adrenergic receptors. Moreover, unlike fluoxetine, reboxetine has a low incidence of drug/drug interactions. In particular, it does not interfere with the isoenzymes of the cytochrome P450 system, which are responsible for the metabolism of certain drugs, including lorazepam and MAOIs. (Fluoxetine is contraindicated for use in conjuction with MAOIs, and in many cases, with drugs that are metabolized through the P450 system.) This has tremendous implications for treatment of the elderly and patients who require multiple treatment regimens. With respect to quality of life, patients treated with reboxetine experienced less agitation, nervousness, anxiety, and gastrointestinal events than patients treated with flouoxetine.
Clinical Trial Data
There are numerous clinical trial data on reboxetine that include results from many clinical trials in which thousands of patients were enrolled. Currently, clinical research is ongoing to continue to evaluate the role of reboxetine as a first-line agent for the treatment of depression. Clinical trial data from various trials has compared reboxetine with placebo and with other antidepressants, including TCAs and SSRIs. Other trials have been designed for the purpose of evaluating the specific pharmacokinetic properties of reboxetine as well as this agent?s general efficacy, tolerability, side-effect profile, and effect in special populations. In summary, trial data to date has concluded that reboxetine can serve as a very powerful agent in the treatment of depression.