Management of Major Depression in the Primary Care Setting

Mischoulon, David; McColl-Vuolo, Rachel; Howarth, Shauna; Lagomasino, Isabel T.; Alpert, Jonathan E.; Nierenberg, Andrew A.; Fava, Maurizio

doi:10.1159/000056233

Cited by 23 publications

(14 citation statements)

References 46 publications

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“…These results challenge the view that the efficacy of an agent prematurely discontinued is diminished when such an agent is restarted, a phenomenon referred to as discontinuation-induced refractoriness [21]. They also generally support reinitiation of the same antidepressant as a ‘first-line’ treatment strategy for a patient who has relapsed after stopping a previously effective antidepressant.…”

Section: Discussionmentioning

confidence: 93%

Treatment Approaches to Major Depressive Disorder Relapse

Fava

Schmidt

Zhang

et al. 2002

Psychother Psychosom

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Background: Anecdotal reports concerning mood disorder patients suggest restarting drug treatment in patients who prematurely discontinue it may be associated with a diminished chance of response upon rechallenge. We evaluated the likelihood of response to reinitiation of fluoxetine treatment in patients relapsing after switching to placebo during a long-term efficacy study of two different dosing regimens of fluoxetine. Method: Patients who met the DSM-IV major depressive disorder criteria with modified HAMD17 scores ≧18 and CGI-Severity scores ≧4 were treated with open-label 20 mg/day fluoxetine for 13 weeks in a multicenter US study. Responders (n = 501) were randomized to placebo, 20 mg fluoxetine daily, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. Patients relapsing during the continuation phase were offered 25 weeks of double-blind rescue treatment 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. Only the results of the rescue phase for the group who relapsed while on continuation treatment with placebo are reported here. Analyses included percentage of responders (50% reduction of modified HAMD17 and CGI-Severity ≤2) and assessments of change from baseline to endpoint (HAMD, CGI-Severity). Safety measures included assessment of vital signs, laboratory measures, and treatment-emergent adverse events. Results: Of 122 patients assigned to placebo, 57 (47%) relapsed during continuation treatment. Fifty-five (96%) of these elected to enter double-blind rescue treatment. Overall, patients who relapsed upon switching to placebo responded well to reinitiation of fluoxetine (62%). The mean modified HAMD17 score decreased from 20 to less than 9 and was maintained for up to 6 months. Thirty-eight percent of patients either did not respond or initially responded but again relapsed after reinitiation of medication. Conclusion: This study suggests that patients who, after an initial response to fluoxetine, relapse upon switching to placebo have a relatively high probability of responding to the reinitiation of fluoxetine treatment. These results challenge the view that the efficacy of an agent prematurely discontinued is diminished when such an agent is restarted. They also generally support reinitiation of the same antidepressant as a ‘first-line’ treatment strategy in patients who relapsed after stopping a previously effective antidepressant.

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Section: Discussionmentioning

confidence: 93%

Treatment Approaches to Major Depressive Disorder Relapse

Fava

Schmidt

Zhang

et al. 2002

Psychother Psychosom

Self Cite

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“…While this is common practice among psychiatrists, who typically follow their patients relatively closely during long-term treatment, frequent follow-up visits and dose adjustments may not be as common in primary care, where more than 10% of the patients suffer from significant depressive symptoms and are often undertreated [18]. …”

Section: Discussionmentioning

confidence: 99%

Treatment Approaches to Major Depressive Disorder Relapse

Schmidt

Fava

Zhang

et al. 2002

Psychother Psychosom

Self Cite

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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.

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“…What emerges from these studies is the failure of the mental health specialist to improve the outcome of major depression in the primary care setting [16]. The introduction of more tolerable and easy-to-use antidepressant drugs, compared with the traditional tricyclics (which required dosages that nonpsychiatric physicians were reluctant to use), has blurred the difference among physicians in prescribing antidepressant drugs.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%