Modafinil Augmentation of Selective Serotonin Reuptake Inhibitor Therapy in MDD Partial Responders with Persistent Fatigue and Sleepiness

Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, and Department of Psychiatry, University of Pittsburgh Medical Center, PA, USA.
Annals of Clinical Psychiatry (Impact Factor: 2.36). 07/2007; 19(3):153-9. DOI: 10.1080/10401230701464858
Source: PubMed


Partial response, no response, or residual symptoms following antidepressant therapy is common in clinical psychiatry. This study evaluated modafinil in patients with major depressive disorder (MDD) who were partial responders to adequate selective serotonin reuptake inhibitor (SSRI) therapy and excessive sleepiness and fatigue.
This retrospective analysis pooled the data of patients (18-65 yrs) who participated in two randomized, double-blind, placebo-controlled studies of modafinil (6-week, flexible-dose study of 100-400 mg/day or 8-week, fixed-dose study of 200 mg/day) plus SSRI therapy. Patients (n=348) met criteria for several residual symptoms (Epworth Sleepiness Scale [ESS] score>or=10; 17-item Hamilton Depression Scale [HAM-D] score between 4 and 25; and Fatigue Severity Scale [FSS] score>or=4).
Compared to placebo, modafinil augmentation rapidly (within 1 week) and significantly improved overall clinical condition (Clinical Global Impression-Improvement), wakefulness (ESS), depressive symptoms (17-item HAM-D), and fatigue (FSS) (p<.01 for all). At final visit, patients receiving modafinil augmentation experienced statistically significant improvements in overall clinical condition, wakefulness, and depressive symptoms. Modafinil was well tolerated in combination with SSRI.
Results of this pooled analysis provide further evidence suggesting that modafinil is an effective and well-tolerated augmentation therapy for partial responders to SSRI therapy, particularly when patients continue to experience fatigue and excessive sleepiness.

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    • "org/10.1016/j.ejphar.2014.10.063i et al., 2006); the dopamine D 2 /D 3 agonist pramipexole is a potentially efficacious treatment strategy in patients that do not respond to standard antidepressant therapies (Cusin et al., 2013); and the wake promoting agent modafinil has also shown some effectiveness in treatment-resistant depression patients that report fatigue and sleepiness (Fava et al., 2007). The wake promoting effects of modafinil are thought to work via binding to the dopamine and norepinephrine transporters, thereby affecting dopaminergic and adrenergic signaling (Wisor, 2013). "
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    ABSTRACT: Major depression is a prevalent and debilitating disorder and a substantial proportion of patients fail to reach remission following standard antidepressant pharmacological treatment. Limited efficacy with currently available antidepressant drugs highlights the need to develop more effective medications for treatment resistant patients and emphasizes the importance of developing better preclinical models that focus on treatment resistant populations. This review discusses methods to adapt and refine rodent behavioral models that are predictive of antidepressant efficacy to identify populations that show reduced responsiveness or are resistant to traditional antidepressants. Methods include separating antidepressant responders from non-responders, administering treatments that render animals resistant to traditional pharmacological treatments, and identifying genetic models that show antidepressant resistance. This review also examines pharmacological and non-pharmacological treatments regimes that have been effective in refractory patients and how some of these approaches have been used to validate animal models of treatment-resistant depression. The goals in developing rodent models of treatment- resistant depression are to understand the neurobiological mechanisms involved in antidepressant resistance and to develop valid models to test novel therapies that would be effective in patients that do not respond to traditional monoaminergic antidepressants. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmacology 11/2014; 753. DOI:10.1016/j.ejphar.2014.10.063 · 2.53 Impact Factor
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    • "In addition, modafinil is described as being helpful with residual symptoms such as fatigue and sedation (84, 85). However, the CANMAT guideline has described two meta-analyses of placebo-controlled RCTs that have reported that, despite many advantages, overall negative results (17, 84, 85). "
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    ABSTRACT: This paper aims to introduce, summarize, and emphasize the importance of the 'Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition'. The guideline broadly covers most aspects of the pharmacological treatment of patients in Korea diagnosed with moderate to severe major depression according to the DSM-IV TR. The guideline establishment process involved determining and answering a number of key questions, searching and selecting publications, evaluating recommendations, preparing guideline drafts, undergoing external expert reviews, and obtaining approval. A guideline adaptation process was conducted for the revised edition. The guideline strongly recommends pharmacological treatment considered appropriate to the current clinical situation in Korea, and should be considered helpful when selecting the appropriate pharmacological treatment of patients diagnosed with major depressive disorder. Therefore, the wide distribution of this guideline is recommended.
    Journal of Korean Medical Science 04/2014; 29(4):468-484. DOI:10.3346/jkms.2014.29.4.468 · 1.27 Impact Factor
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    • "Many of the agents used in the management of depression were originally designed for other purposes, but also found to produce an antidepressant effect. For example, modafinil is a novel psychostimulant that has demonstrated efficacy as an adjunct to SSRI antidepressant therapy (Fava et al, 2007). Due to its relative lack of drug interactions, modafinil may be a good alternative for elderly patients who are often receiving multiple medications. "
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