Abstract:
Affective disorders such as depression and anxiety are a major cause of disability and place a
burden on society from both economic and social perspectives. In spite of over 50 years of effort
in drug discovery and development, a substantial increase in the efficacy of antidepressant
therapies has not been achieved, although improvements in safety and tolerability have been
observed in newer drug therapies. Despite the advances in the anti-depressant therapy with
various serotonergic and noradrenergic agents, a substantial unmet medical need in the treatment
of depressive illness remains. These needs range from efficacy in treatment resistant patients, to
improved onset, to reductions in side effects such as emesis or sexual dysfunction. To address
these needs, there are numerous combination therapies and novel targets that have been identified
that may demonstrate improvements in one or more areas. At one end of the spectrum is
combination therapies that maintain the benefits associated with standard anti-depressant drugs
and at the other end more novel targets, such as neurotrophins (BDNF, IGF), based on recent
findings that antidepressants induce neurogenesis could fit to the need of antidepressant therapy.
This review summarizes the pathological detail of depression, current anti-depressant therapy
and development of non-monoamine-based antidepressants, and provides a progress report on
some of the most promising current strategies