In depressed patients treated successfully with cognitive therapy, antidepressants and continued talk therapy were equally effective for preventing relapse in a randomized trial, researchers said.
Among 241 patients with major depression and slow or incomplete responses to initial cognitive therapy -- putting them at increased risk for relapse or recurrence -- rates of these events 8 months after assignment to follow-up treatment were 32.7% with placebo therapy, 18.0% with fluoxetine (Prozac), and 18.3% with continued cognitive therapy (log-rank P<0.05 versus placebo for both active treatments), according to Robin B. Jarrett, PhD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues.
Hazard ratios for relapse/recurrence with fluoxetine and continued cognitive therapy versus placebo after 8 months were 0.481 (95% CI 0.23-1.01) and 0.519 (95% CI 0.26-1.06), respectively, with no difference between the two active treatments (HR 1.079, 95% CI 0.50-2.34), the researchers reported online in JAMA Psychiatry.
"Cognitive therapy responders at higher risk of relapse/recurrence due to slow or incomplete remission can be safely and effectively treated with either continuation phase cognitive therapy or switching modalities to fluoxetine," Jarrett and colleagues wrote.
All follow-up treatments were discontinued at the end of 8 months, after which relapse/recurrence rates ticked upward, the researchers noted.
With clinical follow-up extending 2 years after the end of the continuation therapies, relapse/recurrence rates in the three study arms were 56.3% in the placebo group, 41.1% in the fluoxetine group, and 45.2% in the cognitive therapy group.
Although there was little difference between fluoxetine and continued cognitive therapy in any of the study's objective outcomes, Jarrett and colleagues called the cognitive therapy "the more acceptable strategy" because patients had already responded to it in the acute-treatment phase and patients could continue seeing the same clinician delivering it.
The trial was motivated by uncertainty over the best approach for preventing the return of severe depression symptoms after initial responses to cognitive therapies, the researchers explained. In routine practice, most patients receive "a few months of treatment with antidepressants," they noted, with little data on how well they work in comparison with continued cognitive therapy.
Some observational and retrospective studies have found that such continuation therapy is effective at preventing relapse or recurrence, but the hypothesis "needs more systematic evaluation," Jarrett and colleagues wrote.
The current study enrolled patients from March 30, 2000, to July 9, 2008. A total of 523 were given an initial 12-week course of cognitive therapy and were assessed repeatedly during this time with the 17-item Hamilton depression scale. Of these, 113 failed to complete the acute treatment, 15 skipped the first blinded evaluation, and 103 showed no improvement.
Another 50 were excluded from the randomized follow-up treatment because they showed marked improvement, defined as Hamilton scores of 6 or less at the final seven assessments, pointing to low risk of returning symptoms. That left 241 considered to be at relatively high risk for relapse or recurrence.
Relapse was defined as an increase in symptoms meeting DSM-IV criteria for major depression in participants who had shown partial relief during the acute treatment. Recurrence was diagnosed in patients who had met criteria for remission lasting at least 8 months and then had a return of symptoms meeting DSM-IV major depression criteria.
At the end of the total of 32 months of continuation therapy and untreated follow-up, about 60% of patients assigned to fluoxetine and 56% of those randomized to continued cognitive therapy remained free of relapse or recurrence versus 43% of those assigned to placebo (P not reported).
That the cognitive therapy was not more effective than fluoxetine during the randomized phase surprised Jarrett and colleagues, who said they expected more recurrences and relapses in the antidepressant arm.
George Keepers, MD, of Oregon Health and Science University in Portland, who was not involved in the study, told MedPage Today in an email that the study's major limitation was its restriction to patients at high risk of returning depression.
Nevertheless, he said, it "suggests that patients who have a partial or unstable response to cognitive therapy should not be terminated from therapy and that the administration of antidepressants to this patient group may be helpful in preventing relapse."
The study was funded by the National Institute of Mental Health. Eli Lilly supplied fluoxetine and matched placebo free of charge.
Study authors reported relationships with a number of pharmaceutical companies including Pfizer, Lilly, AstraZeneca, GlaxoSmithKline, Bristol Myers-Squibb, Sanofi, Alkermes, Allergan, Novartis, Cyberonics, Forest, Takeda, Teva, Transcept, Otsuka, Roche, and others.
- Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
JAMA PsychiatrySource Reference: Jarrett R, et al "Preventing depressive relapse and recurrence in higher-risk cognitive therapy responders a randomized trial of continuation phase cognitive therapy, fluoxetine, or matched pill placebo" JAMA Psychiatry 2013; DOI: 10.1001/jamapsychiatry.2013.1969.