Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-09T07:34:24.024Z Has data issue: false hasContentIssue false
  • English
  • Français

Modafinil Augmentation of SSRI Therapy in Patients with Major Depressive Disorder and Excessive Sleepiness and Fatigue: A 12-Week, Open-label, Extension Study

Published online by Cambridge University Press:  07 November 2014

Michael E. Thase ,
Maurizio Fava ,
Charles DeBattista ,
Sanjay Arora  and
Rod J. Hughes
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction:

Many patients with major depressive disorder (MDD) treated with selective serotonin reuptake inhibitors have residual symptoms (eg, persistent fatigue, excessive sleepiness) despite an overall antidepressant response. Placebo-controlled studies indicate that modafinil, a wake-promoting agent, may relieve residual symptoms.

Methods:

This 12-week, open-label, dose titration, extension study followed an 8-week placebo-controlled study of modafinil augmentation in patients with MDD. The dose was 100–400 mg/day. The median stable dose was 300 mg/day. Assessments were the Epworth Sleepiness Scale, Brief Fatigue Inventory, Clinical Global Impression of Improvement scale, 17-item Hamilton Rating Scale for Depression, and Montgomery-Åsberg Depression Rating Scale.

Results:

Of the 245 patients treated, 194 completed the study; 70% reported Clinical Global Impression of Improvement scale responses of “much improved” or “very much improved” between open-label baseline and final visit (previous randomized modafinil group: 74%; placebo group: 66%). When data were analyzed for four subsets of patients (former modafinil responders, placebo responders, modafinil nonresponders, and placebo nonresponders), improvements in scores on all outcome measures were at least twice as great among former modafinil and placebo nonresponders compared with responders. Most common adverse events were headache (18%), nausea (9%), and dizziness (7%); all were generally mild to moderate in severity.

Conclusion:

Twelve weeks of modafinil augmentation relieved excessive sleepiness, reduced fatigue, and improved patients' overall clinical condition, including mood.

Type
Original Research
Information
CNS Spectrums , Volume 11 , Issue 2 , February 2006 , pp. 93 - 102
Copyright
Copyright © Cambridge University Press 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Maurice-Tison, S, Verdoux, H, Gay, B, Perez, P, Salamon, R, Bourgeois, ML. How to improve recognition and diagnosis of depressive syndromes using international diagnostic criteria. Br J Gen Pract. 1998;48:1245–1246.Google ScholarPubMed
2.Tylee, A, Gastpar, M, Lepine, JP, Mendlewicz, . DEPRES II (Depression Research in European Society II): a patient survey of the symptoms, disability and current management of depression in the community. DEPRES Steering Committee. Int Clin Psychopharmacol. 1999;14:139–151.Google Scholar
3.Nierenberg, AA, Keefe, BR, Leslie, VC, et al.Residual symptoms in depressed patients who respond acutely to fluoxetine. J Clin Psychiatry. 1999;60:221–225.Google Scholar
4.Fava, GA, Fabbri, S, Sonino, N. Residual symptoms in depression: an emerging therapeutic target. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:1019–1027.Google Scholar
5.Fava, M. Symptoms of fatigue and cognitive/executive dysfunction in major depressive disorder before and after antidepressant treatment. J Clin Psychiatry. 2003;64(suppl 14):30–34.Google Scholar
6.Judd, LL, Akiskal, HS, Maser, JD, et al.Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as a predictor of rapid relapse. J Affect Disord 1998;50:97–108.Google Scholar
7.Beasley, CM Jr, Koke, SC, Nilsson, ME, Gonzales, JS. Adverse events and treatment discontinuations in clinical trials of fluoxetine in major depressive disorder: an updated meta-analysis. Clin Ther. 2000;22:1319–1330.Google Scholar
8.Zajecka, JM. Clinical issues in long-term treatment with antidepressants. J Clin Psychiatry. 2000;61 (suppl 2):20–25.Google Scholar
9.Thase, ME. Therapeutic alternatives for difficult-to-treat depression: a narrative review of the state of the evidence. CNS Spectr. 2004;9:808–821.Google Scholar
10.Sharpley, AL, Cowen, PJ. Effect of pharmacologic treatments on the sleep of depressed patients. Biol Psychiatry. 1995;37:85–98.Google Scholar
11.Bauer, M, Forsthoff, A, Baethge, C, et al.Lithium augmentation therapy in refractory depression–update 2002. Eur Arch Psychiatry Clin Neurosci. 2003;253:132–139.Google Scholar
12.Collaborative Working Group on Clinical Trial Evaluations. Atypical antipsychotics for treatment of depression in schizophrenia and affective disorders. J Clin Psychiatry. 1998;59(suppl 12):41–45.Google Scholar
13.Joffe, RT, Schuller, DR. An open study of buspirone augmentation of serotonin reuptake inhibitors in refractory depression. J Clin Psychiatry. 1993;54:269–271.Google Scholar
14.Dimitriou, EC, Dimitriou, CE. Buspirone augmentation of antidepressant therapy. J Clin Psychopharmacol. 1998;18:465–469.Google Scholar
15.Marangell, LB. Augmentation of standard depression therapy. Clin Ther. 2000;22(suppl A):A25–A38.CrossRefGoogle ScholarPubMed
16.Baumgartner, A. Thyroxine and the treatment of affective disorders: an overview of the results of basic and clinical research. Int J Neuropsychoparmacol. 2000;3:149–165.Google Scholar
17.Bauer, M, Whybrow, PC. Thyroid hormone, neural tissue and mood modulation. World J Biol Psychiatry. 2001;2:59–69.CrossRefGoogle ScholarPubMed
18.Prange, AJ Jr.Novel uses of thyroid hormones in patients with affective disorders. Thyroid. 1996;6:537–543.Google Scholar
19.Markovitz, PJ, Wagner, S. An open-label trial of modafinil augmentation in patients with partial response to antidepressant therapy. J Clin Psychopharmacol. 2003;23:207–209.Google Scholar
20.Menza, MA, Kaufman, KR, Castellanos, A. Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry. 2000;61:378–381.Google Scholar
21.Schwartz, TL, Azhar, N, Cole, JK, et al.An open-label study of adjunctive modafinil in patients with sedation related to serotonergic antidepressant therapy. J Clin Psychiatry. 2004;65:1223–1227.CrossRefGoogle ScholarPubMed
22.DeBattista, C, Lembke, A, Solvason, HB, Ghebremichael, R, Poirier, J. A prospective trial of modafinil as an adjunctive treatment of major depression. J Clin Psychopharmacol. 2004;24:87–90.Google Scholar
23.DeBattista, C, Doghramji, K, Menza, MA, et al.Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry. 2003;64:1057–1064.CrossRefGoogle ScholarPubMed
24.Fava, M, Thase, ME, DeBattista, C. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry. 2005;66:85–93.Google Scholar
25.Hamilton, M. Hamilton Depression Scale. In: Guy, W, ed. ECDEU Assessment Manual for Psychopharmacology Revised Edition. Rockville, Md: National Institute of Mental Health, U.S. Department of Health, Education, and Welfare: 1976:179–192.Google Scholar
26.Johns, MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep. 1991;14:540–545.Google Scholar
27.Krupp, LB, LaRocca, NG, Muir-Nash, J, Steinberg, AD. The Fatigue Severity Scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46:1121–11234.Google Scholar
28.Guy, W. ECDEU Assessment Manual for Psychopharmacology, Revised. Rockville, Md. U.S. Department of Health, Education and Welfare; 1976.Google Scholar
29.Mendoza, TR, Wang, XS, Cleeland, CS, et al.The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer. 1999;85:1186–1196.Google Scholar
30.Montgomery, SA, Åsberg, M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–389.Google Scholar
31.Iosifescu, DV, Nierenberg, AA, Mischoulon, D, et al.An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder. J Clin Psychiatry. 2005;66:1038–1042.Google Scholar
32.Papakostas, GI, Petersen, TJ, Nierenberg, AA, et al.Ziprasidone augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder. J Clin Psychiatry. 2004;65:217–221.CrossRefGoogle ScholarPubMed
33.Boutrel, B, Koob, GF. What keeps us awake: the neuropharmacology of stimulants and wakefulness-promoting medications. Sleep. 2004;27:1181–1194.Google Scholar
34.Engber, TM, Dennis, SA, Jones, BE, Miller, MS, Contreras, PC. Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: comparison with amphetamine. Neuroscience. 1998;87:905–911.Google Scholar
35.Saletu, B, Frey, R, Krupka, M, et al.Differential effects of a new central adrenergic agonist—modafinil—and D-amphetamine on sleep and early morning behaviour in young healthy volunteers. Int J Clin Pharmacol Res. 1989;9:183–195.Google ScholarPubMed
36.Deroche-Gamonet, V, Darnaudery, M, Bruino-Slot, L, Piat, F, Le Moal, M, Piazza, PV. Study of the addictive potential of modafinil in naive and cocaine-experienced rats. Psychopharmacology (Berl). 2002;161:387–395.Google ScholarPubMed
37.Myrick, H, Malcolm, R, Taylor, B, LaRowe, S. Modafinil: preclinical, clinical, and post-marketing surveillance—a review of abuse liability issues. Ann Clin Psychiatry. 2004;16:101–109.CrossRefGoogle ScholarPubMed