Depression Outcomes Similar With Antidepressants, CBT

Pam Harrison

December 10, 2015

There is no difference in response or remission rates produced by second-generation antidepressants and those achieved by cognitive-behavioral therapies (CBT) in the treatment of major depressive disorder (MDD), a systematic review and meta-analysis indicates.

"In general, psychiatrists and primary care providers have tended to see medication as superior to CBT because the dose of a medication prescribed is consistent, whereas CBT delivered by one therapist may be quite different from CBT delivered by a different therapist," study coauthor Bradley Gaynes, MD, MPH, Department of Psychiatry, University of North Carolina at Chapel Hill, told Medscape Medical News.

"But since evidence shows that CBT can be as effective as medication, clinicians should consider psychotherapy to be a valid and effective treatment option for MDD and discuss the advantages and disadvantages to both treatments."

The study was published online December 8 in the BMJ.

With lead author Halle R. Amick, MSPH, University of North Carolina at Chapel Hill, investigators identified 11 randomized, controlled trials in which a second-generation antidepressant medication was compared with CBT. Ten trials compared the use of antidepressant therapy with CBT alone, and three trials compared antidepressant monotherapy with antidepressant therapy given with CBT. Together, the 11 trials provided information on 1511 patients with MDD.

The second-generation antidepressant medications evaluated in the trials included fluoxetine (multiple brands), fluvoxamine (Luvox, Ani Pharmaceuticals, Inc), paroxetine (multiple brands), sertraline (Zoloft, Pfizer Inc), venlafaxine (multiple brands), citalopram (multiple brands), and escitalopram (Lexapro, Forest Laboratories, Inc).

With regard to remission rates, investigators included data from three trials (with four comparisons) involving 432 patients, measured between 12 and 16 weeks. Analysis indicated that patients treated with an antidepressant had numerically lower remission rates, at 40.7%, but rates were not significantly different from those of patients who received CBT, at 47.9%.

"For response, we included results from 660 patients studied in five trials (six comparisons)," Amick and colleagues wrote.

Comparing response rates between 8 and 16 weeks, "treatment effects were similar for second generation antidepressants and cognitive behavioral therapies at 44.2% vs 45.5%," they add.

Two trials involving three comparisons and 249 patients reported change in scores on the 17-item Hamilton Rating Scale for Depression at 8 weeks or longer. Again, no statistically significant difference was detected between treatment response to medication and responses to CBT.

Relapse Rates

Three trials reported relapse rates during follow-up when patients were off treatment. In one trial, 10.6% of patients who had received antidepressant therapy relapsed within 6 months of being off treatment, compared with 2.1% and 6.1% of patients treated with rational emotive therapy and CBT, respectively.

In another trial, relapse rates within the first year of follow-up were 39% among patients who had received CBT; 53% for patients who had been treated with an antidepressant and who continued to receive treatment during follow-up; and 59% for those who were initially treated with an antidepressant but who were switched to placebo during follow-up.

The third trial reported recurrence rates during the second year of follow-up. For patients who had been treated with CBT, 24% experienced recurrence, compared with 52% for patients who had received antidepressant therapy (P = .06).

Owing largely to small numbers of patients in each group in this third trial, the difference between relapse rates was not statistically significant, Amick and colleagues note.

With regard to adverse events, "reporting was generally poor, particularly for serious adverse events and specific adverse events," the authors observe. As a result, the investigators analyzed discontinuation rates as proxies for adverse events.

More patients treated with a second-generation antidepressant than those receiving CBT withdrew from studies because of adverse events.

Again, however, the difference between the two treatment approaches was not statistically significant, nor were rates of dropouts due to lack of efficacy significantly different.

Of the three trials that compared antidepressant monotherapy and the combination of antidepressant therapy plus CBT, the authors found no statistically significant difference between the comparator arms in either remission or response rates.

"There is an existing body of evidence that shows CBT to be effective in treating MDD, so we were not completely surprised to find no significant difference between the two approaches," Amick told Medscape Medical News.

"However," she added, "given that side effects are often reported with antidepressant medications and are not generally expected with psychotherapy, we were somewhat surprised to find no difference between second-generation antidepressants and CBT in withdrawal rates due to adverse events."

Dr Gaynes also pointed out that nonpharmacologic options can be more appealing than medication for some patients, especially if patients are fearful of side effects or of getting "hooked" on medication.

"Primary care providers who offer effective alternatives to antidepressant drugs allow their patients to participate fully in the shared decision-making process," Dr Gaynes said. "This in turn can help ensure that treatments of MDD are selected and managed correctly."

"Intriguing" Signal

In an accompanying editorial, Mark Sinyor, MD, Mark Fefergrad, MD, and Ari Zaretsky, MD, all with the Sunnybrook Health Sciences Centre, Toronto, Canada, pointed out that findings reported by Amick and colleagues are "generally consistent" with findings from previous meta-analyses, although this study uniquely confined the analysis to second-generation antidepressants.

"More intriguing is the signal from some trials that CBT could be associated with a lower risk of relapse than antidepressants once treatment stops," the editorialists write.

"This finding, although statistically uncertain, aligns with the orientation of CBT towards training patients to be their own therapists."

The editorialists also suggest that given the high rates of relapse in MDD, the fact that CBT appears to prevent relapse more effectively than antidepressant medication is a "meaningful finding" that contributes to growing evidence showing that CBT is effective at preventing recurrence of depression.

"Ultimately, the results of this analysis should be simultaneously reassuring and disappointing for patients and their doctors," the editorialists write.

The results are reassuring, they note, because if patients prefer or can choose only one strategy, "choosing that option is unlikely to affect a patient's chances of improvement, remission or tolerance of treatment."

On the other hand, results from the meta-analysis might be considered disappointing, because there was so little reliable evidence upon which to evaluate the effectiveness of either treatment strategy, they write.

Given that the World Health Organization has projected that depression will be the leading cause of disease burden worldwide in 2030, more meaningful steps need to be taken toward primary prevention, the editorialists suggest.

"These steps should include efforts to correct social antecedents of major depressive disorder such as poverty and lack of education, along with improved mental health curriculums in schools," they add. "Ultimately such efforts could decrease the financial, personal and interpersonal burden of this important illness."

Corroborates Existing Evidence

Irving Kirsch, PhD, associate director, Program in Placebo Studies and the Therapeutic Encounter, Harvard Medical School, Boston, Massachusetts, agreed that the current results corroborate existing evidence that CBT is superior to antidepressant medications for the prevention of relapse.

"This is consistent with other data going all the way back to a large National Institute of Mental Health Collaborative Trial, where they found equal relapse rates following CBT, interpersonal psychotherapy, and placebo and higher relapse rates for a tricyclic antidepressant," he told Medscape Medical News.

Dr Kirsch added that it is not just psychotherapy that produces lower relapse rates but just about anything other than medication. For example, a trial of the use of exercise for patients with depression was conducted in which one group of patients was treated only with a selective serotonin reuptake inhibitor (SSRI) antidepressant drug, one group was treated with exercise alone, and a third group was treated with both exercise and SSRI therapy.

"Where you got the high relapse rates were in both the SSRI monotherapy group and the SSRI plus exercise group, and you got a very low relapse rate with the exercise alone group," Dr Kirsch said. "If you had asked me a few years ago whether I thought CBT teaches patients to be their own therapist, as the editorialists suggested, I would have said, yes, exactly.

"But right now, from other data that I have seen, I see it as not so much an advantage of CBT as a disadvantage of the antidepressants, because I believe that antidepressants may be inducing increased vulnerability to relapse compared to other treatments not limited to CBT."

The project was funded bu the Agency for Healthcare Research and Quality through a contract with the RTI-UNC Evidence-based Practice Center. Dr Sinyor has received grant support from the American Foundation for Suicide Prevention; the Physicians' Services Incorporated Foundation, the Dr Brenda Smith Bipolar Fund, and the University of Toronto's Psychiatry Excellence Fund. Dr Fefergrad receives residuals from two CBT books published by WW Norton and Company; Dr Zaretsky receives residuals from one CBT book published by the same company. Dr Kirsch has disclosed no relevant financial relationships.

BMJ. Published online December 8, 2015. Full text, Editorial

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