Treatment Approaches to Major Depressive Disorder Relapse
Schmidt M.E.a · Fava M.b · Zhang S.a · Gonzales J.a · Raute N.J.a · Judge R.a
Part 1: Dose Increase
aLilly Research Laboratories, Indianapolis, Ind., and bDepression Clinical and Research Program, Massachusetts General Hospital, Boston, Mass., USA
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Objective: Although continuing antidepressant treatment after patients have responded to medication has been shown to greatly reduce the risk of relapse, this risk is not eliminated. A number of theories have been proposed to account for this apparent loss of efficacy. A common initial approach to managing relapse is to increase the dose of antidepressant. We prospectively evaluated the likelihood of response to increasing the fluoxetine doses in patients relapsing during a long-term efficacy study of two fluoxetine dosing regimens. Method: Patients meeting the DSM-IV criteria for major depressive disorder with modified HAMD17 scores ≧18 and CGI-severity scores ≧4 were treated for 13 weeks with open-label 20 mg/day fluoxetine in a multicenter US study. Responders (n = 501) were randomized to 20 mg fluoxetine daily, placebo, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. If the patients relapsed during the continuation phase, they were offered a 25-week optional rescue treatment phase during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/day reinitiated, (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. The results of the rescue phase for the latter two groups who relapsed while on continuation treatment with fluoxetine are reported. Response was defined as a 50% reduction in the modified HAMD17 score since time of relapse and a CGI-severity score ≤2. Additional efficacy analyses included HAMD and CGI-severity changes from baseline to endpoint. Safety measures included assessment of treatment-emergent adverse events, vital signs, and laboratory measures. Results: Overall, patients relapsing during the continuation treatment responded to an increased dose (57% of the 40-mg-daily group and 72% of the enteric-coated 90-mg-twice-weekly group). Mean modified HAMD17 scores decreased from a mean of approximately 20 to below 8 and were maintained for up to 6 months in the responders. Thirty-five percent of patients either did not respond or initially responded but again relapsed after augmentation of medication. Conclusions: The patients relapsing after initially responding to fluoxetine can benefit from an increase in fluoxetine dose. These results also generally support increasing dose as a first-line treatment strategy for a patient who has relapsed while taking a previously effective dose of an antidepressant. Increasing enteric-coated fluoxetine 90 mg once weekly to twice weekly appeared to be as well-tolerated and effective in restoring response as increasing a daily fluoxetine dose from 20 to 40 mg.
© 2002 S. Karger AG, Basel
Agency for Health Care Policy and Research: Treatment of major depression; in Agency for Health Care Policy and Research (ed): Clinical Practice Guideline No 5 – Depression in Primary Care, vol 2. Rockville, Agency for Health Care Policy and Research, 1993.
- World Health Organization Mental Health Collaborating Centres: Pharmacotherapy of depressive disorders: A consensus statement. J Affect Disord 1989;17:197–198.
- American Psychiatric Association: Practice guidelines for major depressive disorder in adults. Am J Psychiatry 1993;150:1–26.
- Frank E, Kupfer DJ, Perel JM, Cornes C, Jarrett DB, Mallinger AG, Thase ME, McEachran AB, Grochocinski VJ: Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1990;47:1093–1099.
Rush AJ: Strategies and tactics in the management of maintenance treatment for depressed patients. J Clin Psychiatry 1999;60(suppl 14):21–26.
- Byrne S, Rothschild AJ: Loss of antidepressant efficacy during maintenance therapy: Possible mechanisms and treatments. J Clin Psychiatry 1998;59:279–288.
- Fava M, Rappe SM, Pava JA, Nierenberg AA, Alpert JE, Rosenbaum JF: Relapse in patients on long-term fluoxetine treatment: Response to increased fluoxetine dose. J Clin Psychiatry 1995;56:52–55.
- Schmidt ME, Fava M, Robinson J, Judge R: The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder. J Clin Psychiatry 2000;61:851–857.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 1994.
- Fredman SJ, Fava M, Kienke AS, White CN, Nierenberg AA, Rosenbaum JF: Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: A survey of current ‘next-step’ practices. J Clin Psychiatry 2000;61:403–408.
- Nierenberg AA, Alpert JE: Depressive breakthrough. Psychiatr Clin North Am 2000;23:731–742.
- Jarrett RB, Kraft D, Schaffer M, Witt-Browder A, Risser R, Atkins DH, Doyle J: Reducing relapse in depressed outpatients with atypical features: A pilot study. Psychother Psychosom 2000;69:232–239.
Fava M: Management of nonresponse and intolerance: Switching strategies. J Clin Psychiatry 2000;61(suppl 2):10–12.
Fava M: New approaches to the treatment of refractory depression. J Clin Psychiatry 2000;61(suppl 1):26–32.
- Cohen BM, Baldessarini RJ: Tolerance to therapeutic effects of antidepressants. Am J Psychiatry 1985;142:489–490.
- Mann JJ: Loss of antidepressant effect with long-term monoamine oxidase inhibitor treatment without loss of monoamine oxidase inhibition. J Clin Psychopharmacol 1983;3:363–366.
Stewart JW, Quitkin FM, McGrath PJ, Amsterdam J, Fava M, Fawcett J, Reimherr F, Rosenbaum J, Beasley C, Roback P: Use of pattern analysis to predict differential relapse of remitted patients with major depression during 1 year of treatment with fluoxetine or placebo. Arch Psychiatry 1998;55:334–343.
- Mischoulon D, McColl-Vuolo R, Howarth S, Lagomasino IT, Alpert JE, Nierenberg AA, Fava M: Management of major depression in the primary care setting. Psychother Psychosom 2001;70:103–107.
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