Journal name: Neuropsychiatric Disease and Treatment Article Designation: Review Year: 2015 Volume: 11 Neuropsychiatric Disease and Treatment Dovepress Running head verso: Saltiel and Silvershein Running head recto: Individualized pharmacotherapy for major depressive disorder open access to scientific and medical research DOI: http://dx.doi.org/10.2147/NDT.S73261 Open Access Full Text Article REVIEW Major depressive disorder: mechanism-based prescribing for personalized medicine Philip F Saltiel1 Abstract: Individual patients with depression present with unique symptom clusters – before, Daniel I Silvershein2 during, and even after treatment. The prevalence of persistent, unresolved symptoms and their contribution to patient functioning and disease progression emphasize the importance of finding 1Department of Psychiatry, New York University School of Medicine/ the right treatment choice at the onset and the utility of switching medications based on subopti- Langone Medical Center New mal responses. Our primary goal as clinicians is to improve patient function and quality of life. York University Behavioral Health Programs, New York University Pearl In fact, feelings of well-being and the return to premorbid levels of functioning are frequently Barlow Center for Memory Evaluation rated by patients as being more important than symptom relief. However, functional improve- and Treatment, New York, NY, USA; ments often lag behind resolution of mood, attributed in large part to persistent and functionally 2Department of Medicine, New York University School of Medicine/ impairing symptoms – namely, fatigue, sleep/wake disturbance, and cognitive dysfunction. Thus, Langone Medical Center, New York, patient outcomes can be optimized by deconstructing each patient’s depressive profile to its NY, USA component symptoms and specifically targeting those domains that differentially limit patient For personal use only. function. This article will provide an evidence-based framework within which clinicians may tailor pharmacotherapy to patient symptomatology for improved treatment outcomes. Keywords: MDD, tailored pharmacotherapy, patient-specific profile, individualized pharmacotherapy Defining depression Depression is the most common psychiatric disorder and the leading cause of dis- ability worldwide.1,2 In the US, about 7%–9% of the adult population experiences a major depressive episode (MDE) each year and an estimated 8 million (3.4%) meet criteria for major depressive disorder (MDD).3–5 The cognitive, emotional, and physi- cal symptoms of depression translate to considerable impairments in psychosocial functioning across physical, social, and educational/occupational domains.6,7 Indirect Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 137.108.70.14 on 15-Jan-2020 workplace costs alone, characterized by low productivity (presenteeism) and days missed (absenteeism), account for over 60% of the total economic burden of depres- sion and twice as much as that attributed to direct medical costs.8 The likelihood of long-term treatment success is improved with early and accurate diagnosis, continual multidimensional assessment, and rational pharmacotherapy tailored to the patient’s symptomatology, coexisting disorders, and treatment needs.9 Yet achieving these outcomes is confounded by the personal and multidimensional nature of the disease itself. There are no validated biological tests that can be used to diagnose depression. Further, without objective outcomes measures, clinicians must gauge treatment response and make clinical decisions over time based on subjective impressions of patient-reported symptoms.9–11 Correspondence: Daniel I Silvershein Validated assessment tools (eg, Montgomery–Åsberg Depression Rating Scale, Concorde Medical Group, PLLC, 235 Hamilton Rating Scale for Depression [HAM-D ]) based on core criteria (Table 1)12 East 38th Street, New York, NY, USA 24 Email [email protected] can facilitate the categorical diagnosis of depression and help track the presence and submit your manuscript | www.dovepress.com Neuropsychiatric Disease and Treatment 2015:11 875–888 875 Dovepress © 2015 Saltiel and Silvershein. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further http://dx.doi.org/10.2147/NDT.S73261 permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Powered by TCPDF (www.tcpdf.org) 1 / 1 Saltiel and Silvershein Dovepress Table 1 DSM-5 criteria for MDE • At least five of the following symptoms that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning • At least one of the symptoms is 1) depressed mood or 2) loss of interest or pleasure • Symptoms must be present almost every day for at least 2 weeks 1. Depressed mood most of the day 2. Diminished interest or pleasure in all or most activities 3. Significant unintentional weight loss or gain 4. Insomnia or sleeping too much 5. Agitation or psychomotor retardation noticed by others 6. Fatigue or loss of energy 7. Feelings of worthlessness or excessive guilt 8. Diminished ability to think or concentrate, or indecisiveness 9. Recurrent thoughts of death • Diagnosis of recurrent MDD requires 2 MDEs separated by at least 2 months in which criteria are not met for an MDE Abbreviations: DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; MDD, major depressive disorder; MDE, major depressive episode. severity of symptoms at each visit.11,13,14 However, clini- often show greater depressive illness burden as symptoms cians may find it more practical to ask about symptoms persist.24–27 The Sequenced Treatment Alternatives to Relieve directly through the course of the patient interview. Direct Depression (STAR*D) study of nearly 4,000 ‘real-world’ questioning combined with a clinical impression formed by outpatients reported a cumulative remission rate of 67% after the patient’s speech, affect, and appearance can help define four treatment steps; however, about 70% relapsed within how individual symptoms adversely affect patient-specific 1 year.25 Figure 1 depicts a schematic representation of the functioning and quality of life (QoL). If the symptom profile progressive nature of depression, and illustrates the need of an MDE is not properly assessed before and during a for achieving and sustaining full symptom recovery early in For personal use only. well-orchestrated antidepressant trial, ongoing symptoms disease pathogenesis.22 may not be easily distinguished from treatment-related Symptoms that persist during remission are associ- side effects or from those due to comorbid psychiatric or ated with relapse, recurrence, and ultimately, treatment medical conditions.15–18 About half of patients who report resistance.15,27,28 During a 3-year prospective study of normal functioning consider themselves to be in remission 267 depressed patients, Conradi et al assessed the weekly from depression despite persistent depressive symptoms.19 presence of individual symptoms during each phase of Therefore, understanding the relationship between the depression (Figure 2).29 Study participants who relapsed symptoms of depression and how they adversely affect within 8 weeks reported a greater overall symptom sever- patient functioning is essential for optimized clinical deci- ity during the remission period than those who remained in sion making. remission for greater than 8 weeks (ie, in recovery). Gradual accumulation of subthreshold symptoms over time appeared Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 137.108.70.14 on 15-Jan-2020 Defining recovery to trigger the relapse, suggesting that the initial MDE had The gold standard for treatment is the full resolution of symp- not resolved and remained subsyndromal only temporarily. toms and associated improvements in function and QoL.9,11,14 In fact, patients with unresolved depressive symptoms are While response to treatment implies a clinically meaningful three times as likely to relapse as patients with asymptom- degree of symptom reduction (typically defined as 50% atic recovery.28 reduction in pretreatment symptom severity), remission and The prevalence of unresolved symptoms and their con- recovery require that the symptoms of depression be absent or tribution to disease progression emphasize the importance of close to it (Figure 1).20–22 Many clinical studies define remis- finding the right treatment choice at the onset and switching sion as low scores on rating scales, which is not equivalent medications if necessary based on suboptimal responses. to an asymptomatic state.23,24 Further, as depressed mood Moreover, feelings of well-being and the return to premorbid and loss of interest generally overshadow other symptoms of levels of functioning are frequently rated by patients as more depression, when mood improves, patients may misguidedly important than symptom relief, yet functional improvements be considered in remission. In fact, most patients considered often lag behind resolution of mood.6,30