Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era

Abstract

Importance of the field Treatment-resistant depression (TRD) is common and debilitating. Initial treatment is often insufficient to achieve full remission in a given depressive episode, resulting in more frequent episodes, worsened severity, and major disability. Areas covered in this review This review surveys literature on the diagnosis and pharmacological management of TRD in light of recent developments. Evidence regarding commonly used treatment options is critically examined and key recommendations are offered. The review ends by considering drugs acting on the melatonin, acetylcholine, and glutamate systems that hold promise as future options for TRD. What the reader will gain Recent trends and research findings have impacted how the evidence supporting different approaches to TRD should be evaluated. For example, many earlier TRD studies employed tricyclics (TCAs) as the primary antidepressant, but TCAs have now been superseded by selective serotonin reuptake inhibitors (SSRIs) in routine clinical practice. This deficiency has been addressed by the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, the largest effectiveness study of TRD ever conducted. However, design characteristics of the STAR*D study preclude simple comparisons with earlier studies. Take home message A shortcoming of most treatment recommendations for TRD is their reliance on older studies that do not reflect the current preeminence of SSRIs in clinical practice. This has distorted the prioritization of pharmacological strategies for TRD. Efforts to correct this distortion with effectiveness research, designed to better reflect current practice trends, require critical consideration of the strengths and limitations of this approach.

Venlafaxine pharmacokinetics focused on drug metabolism and potential biomarkers

“…Actually, patients treated with antidepressant drugs including VEN have exhibited large inter-individual variability in drug outcomes (efficacy vs. adverse effects), a fact explained by genetic and nongenetic factors [8,15,[34][35][36][37][38][39]. Thus, bearing in mind that the development of novel antidepressant agents has failed, efforts should be concentrated in establishing more effective and safer regimens taking into account patients' individual characteristics [35,38,[40][41][42].…”

The Role of Atypical Antipsychotics in Inadequate‐response and Treatment‐resistant Depression

“…Typical neuroleptics (TNs) and atypical antipsychotics, which are henceforth termed 'second-generation antipsychotics' (SGAs) in this chapter, have been used as an augmentation therapy for depression for a long time, starting with clozapine and haloperidol or low-potency neuroleptic agents (Bauer et al, 2007;Chen et al, 2011;Fava, 2001;Konstantinidis et al, 2007;Philip et al, 2010;Shelton & Papakostas, 2008). However, the recognition of extra-pyramidal side effects and the subsequent risk of tardive dyskinesia discouraged the continued use of TNs (Corell et al, 2004;Goodwin et al, 2009;Nelson, 1987).…”

A systematic review of light therapy on mood scores in major depressive disorder: light specification, dose, timing and delivery

“…The interaction of the antidepressant effect of medication limits the understanding of the efficacy of light therapy. In addition, non-responders to therapies are common [50]. Therefore, it is necessary to identify patients groups who are homogenous, for example, those who are antidepressant medication-resistant prior to the commencement of light therapy, or patients either currently in or not currently in a depression episode.…”