Major depressive disorder is a debilitating disease that presents with symptoms such as depression, impairment of cognitive function, insomnia, loss of interest and appetite. A journal published in 2016, highlighted that disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD. Management primarily comprises psychotherapy and pharmacological treatment. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence.
This extremely complex disease is thought to be caused by both genetic and environmental factors. A study showed that children exposed to physical, sexual or emotional abuse have a high risk of developing MDD. However, it is poorly understood because there has been no established mechanism sufficient enough to explain all the aspects of the disease.
Research shows that this condition has been associated with alterations in regional brain volumes, particularly the hippocampus, and with functional changes in brain circuits, such as the cognitive control network and the affective-salience network. Furthermore, disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD.
Pharmacotherapy for MDD has been available since the introduction of tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs) in the 1950s. The first SSRIs were introduced in the 1980s and, due to their improved safety and tolerability profiles relative to TCAs and MAOIs they became the most widely prescribed medications for treating depression and related disorders (Bauer et al., 2008). The 2011 APA guideline recommends SSRIs as the first-line medications for late-onset depression as it has less prominent adverse-effect profile thus promoting better compliance. However, citalopram has recently been reported to cause dose-dependent QT prolongation therefore it is not recommended in patients with congenital long QT syndrome.
Psychotherapy and pharmacological treatment are the mainstay in the management of MDD. This is because reports show that in all patient populations, combination of pharmacological treatment and psychotherapy provides the fastest and most sustained response. Recent studies show, the use of this combination therapy results in significant improvement of depressive symptoms; increased quality of life; and better treatment compliance for treatments longer than 3 months. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence. Cognitive-behavioral therapy is a structured, and didactic form of therapy which focuses on helping individuals identify and modify maladaptive thinking and behavior patterns (16 to 20 sessions). Mindfulness-based cognitive therapy (MBCT) was designed to reduce relapse among individuals who have been successfully treated for an episode of recurrent major depressive disorder.
In a presentation at the 2017 US Psych Congress, held September 16-19, Michael E. Thase, MD, professor of psychiatry at the Perelman School of Medicine of the University of Pennsylvania, provided updates on antidepressant management. Dr Thase explored pharmacologic treatments of depression, including first-line antidepressants not mentioned in the most recent American Psychiatric Association (APA) guidelines from 2010.
Drugs used in the treatment of MDD include Aripiprazole, Brexpiprazole, Olanzapine, Quetiapine, and Risperidole and recently introduced drugs include Vilazodone and Vortioxetine.
Dr Thase noted the high potency and the well tolerability of Vilazodone, which is a recently introduced antidepressants and that Vortioxetine has “enhancing effects on complex cognition, not necessarily memory or concentration but perhaps multi-step sequencing,”.
As adjunctive therapy, second-generation antidepressants (SGAs) have been recommended in patients who are seriously ill or incapacitated. The 2008 American College of Physicians (ACP) guideline suggested that patient preferences on pharmacotherapy should be taken into consideration when administering second-generation antidepressants to treat depressive disorders.
Combination of antidepressants had been regarded as bad therapy but it is now commonly practiced in the management of treatment-resistant depression. The 2011 version of the American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients with Major Depressive Disorder guideline emphasized the need for a careful assessment of the symptoms, rating scale measurements by a clinician or the patient and a concrete analysis of therapeutic benefits and side effects of the chosen treatment and to customize a proper treatment plan for each patient based on it.
Aripiprazole, brexpiprazole, olanzapine, quetiapine, and risperidole appear effective as adjunctive antidepressants, while olanzapine, quetiapine, and lurasidone are effective as monotherapy for bipolar depression. Additionally, quetiapine has established efficacy as monotherapy for major depressive disorder.