Recent developments in the psychobiology and pharmacotherapy of depression: optimising existing treatments and novel approaches for the future

Abstract

Effective antidepressants include monoamine oxidase inhibitors and tricyclic antidepressants, selective serotonin re-uptake inhibitors and novel agents, including serotonin and noradrenaline re-uptake inhibitors. Although effective, current treatments most often produce partial symptomatic improvement (response) rather than symptom resolution and optimal functioning (remission). While current pharmacotherapies target monoaminergic systems, different symptoms of major depressive disorder (MDD) may have distinct neurobiological underpinnings and other neurobiological systems are likely involved in the pathogenesis of MDD. In this article a review of current pharmacotherapeutic options for MDD, current understanding of the neurobiology and pathogenesis of MDD and a review of new and promising directions in pharmacological research will be provided. It is generally accepted that no single neurotransmitter or system is responsible for the dysregulation found in MDD. While agents that affect monoaminergic systems will likely continue to be first-line treatments for MDD for the foreseeable future, a number of new and novel agents, including corticotropin-releasing factor antagonists, substance P antagonists and antiglucocorticoids show considerable promise for refining treatment options. In order to better understand the neurobiology and treatment response of MDD, it is probable that more sophisticated theory-driven typologies of MDD will have to be developed.

Antidepressant-Like Effect of D2/3 Receptor-, but not D4 Receptor-Activation in the Rat Forced Swim Test

“…However, given the implication of the D 2 receptor in reward and addiction, one would have to clearly separate antidepressant activity from the risk for potential abuse (Caine et al, 1997;Haddad, 1999;Ellinwood et al, 2002;Rouge-Pont et al, 2002;Farvolden et al, 2003). Furthermore, activation of dopamine function and/or supersensitivity of dopaminergic neurotransmission may play an important role in the induction of mania episodes in patients with bipolar disorders (D'Aquila et al, 2003), another obstacle for the use of D 2 receptor agonists for the treatment of depression (Massat et al, 2002;Yatham, 2002;Serretti et al, 2004).…”

Co-Expression Network Analysis Revealed That the ATP5G1 Gene Is Associated With Major Depressive Disorder

“…Major depressive disorder (MDD), a common mental disorder with a lifetime prevalence of around 15% in the general population (Tsai, 2006), is predicted to become the second leading cause of disability-adjusted life years in 2020 (Murray and Lopez, 1997). Many different studies have proposed hypotheses regarding the pathogenesis of depression, such as the dysfunctional monoamine theory of depression (Farvolden et al, 2003), the hypothesis of disturbed neuroplasticity (Christoffel et al, 2011), and the inflammatory, oxidative, and nitrosative stress (O&NS) theory of depression (Leonard and Maes, 2012). However, there is no definitive evidence to support any of these theories.…”

Depression and Pain: Independent and Additive Relationships to Anger Expression

“…In a recent study of postcombat mental health problems and functional impairment of U.S. Army and National Guard soldiers, Thomas et al" found that, at 3 months after deployment, 43.1% of active duty soldiers endorsed getting angry with someone and kicking or smashing something at least once, 37.5% endorsed threatening someone with physical violence, and 17.7% reported getting into a fight with someone and hitting the person. Similar prevalence rates were observed in National Guard personnel.…”