Antidepressant Pharmacotherapy – Do the Benefits Outweigh the Risks?

Major depressive disorder (MDD) is a debilitating and often recurrent psychiatric illness that impacts the lives of millions. Approximately 20 percent of individuals will experience at least one depressive episode during their lives, and the high rates of chronic morbidity (depressive episodes typically last for several months) and mortality (owing to suicide) attributed to this disorder constitute one of the largest global economic disease burdens (Kessler et al., 2005). Despite the considerable burden of depression, our understanding of its pathophysiology and the therapeutic mechanisms of action of antidepressant drugs remains incomplete. In fact, much of what we currently understand about the neuropathology of depression is derived from the observed effects of known antidepressants on the brain. This situation is confounded by the fact that currently available antidepressant drugs are of limited clinical efficacy – the antidepressant response typically takes several weeks to develop, and a substantial proportion of patients do not experience a significant improvement in depressive symptoms, or full clinical remission. Furthermore, because antidepressant efficacy varies significantly as a function of symptom severity, the benefit of antidepressant therapy may be limited or nonexistent in patients with mild to moderate depressive symptoms, which represent the majority of clinical cases (Fournier et al., 2010). When the inadequate efficacy profiles of antidepressant drugs are weighed against our limited understanding of depression, the therapeutic action of antidepressants, and the potential negative side effects of these drugs arising from nonspecific actions, a difficult question arises: do the benefits of antidepressant pharmacotherapy outweigh the risks? In this chapter, we explore the development of the current theories of depression etiology, the hindrances of current antidepressant therapeutics, and how the poor understanding of the mechanism of antidepressant action contributes to a haphazard interpretation of the benefits and consequences arising from their non-specific interactions. Through the use of a simple single-synapse experimental approach, we have gained insights into the impact of non-specific antidepressant actions on neuronal function, and our findings will be discussed in this context. Finally, we will explore prospective developments in the field of depression pharmacotherapy that may hold the potential to revolutionize the way we understand and treat depression.