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Debate: What’s the Evidence for the Evidence-Based Treatments of Depression?

Debate: What’s the Evidence for the Evidence-Based Treatments of Depression?

POINT

The Specific Efficacies of CBT and IPT Have Not Been Established

In the past few years, large meta-analyses of antidepressant drug treatments for major depression have failed to show distinct advantages over placebo. The authors of one such report provocatively concluded that the new antidepressant drugs are either placebos or act as placebos and therefore are not clinically meaningful. Some authors have argued that such findings advance the utility of the evidence-based nondrug treatments—cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT).1

But what holds for the goose often holds for the gander. We have undertaken reviews of both CBT and IPT as treatments for major depression.2,3 When compared with plausible control psychotherapies, they also showed minimal differentiation. Just as some authors claim that the evidence shows that antidepressant drugs are no more than placebos, the same suggestions have been put forth about CBT and IPT. For instance, the psychologist Gary Greenberg4(p316) advanced the view that CBT is more an ideology and a “method of indoctrination into the pieties of American optimism.”

The key issue then is why do the so-called evidence-based or empirically supported treatments (ESTs) for depression (ie, antidepressant drugs, CBT, IPT) produce this perplexing result when all 3 are invariably positioned in treatment guidelines as the mainstay of treatment for managing depression?

We offer 2 principal reasons here. First, we outline the methodological limitations of psychotherapy efficacy research and the role that this has played in falsely positioning CBT and IPT as first-line or superior treatments for depres-sion. As part of this, we consider what is meant by the placebo effect. Second, we discuss the negative impact of universally applying treatments across nonspecific disorders, such as major depression.

Methodological issues

The supportive evidence base for CBT and IPT as superior treatments for major depression is less substantive than generally considered because of 3 critical methodological flaws in efficacy research.5 First, differential effects generally disappear when analyses are limited to therapies that are intended to be therapeutic (bona fide therapies). For example, when meta-analyses specifically removed non–bona fide therapies, CBT did not differ from other psychotherapies for acute-phase treatments of major depression.6 A more recent meta-analysis quantified comparable effects when contrasting IPT (eg, coping-oriented couples therapy, supportive psychotherapy) with other psychotherapies, including CBT for depression—a finding that is consistent with our review of IPT studies.3,7

Studies or meta-analyses that have shown the superiority of CBT and IPT have generally used benign, ineffective control strategies (eg, wait-list assignment) in randomized controlled trials (RCTs), leading to false positioning of CBT and IPT as superior treatments. Treatment-as-usual comparators also tend to favor the active psychotherapy, because therapist enthusiasm, patient expectancy, and other common factors are less likely to be activated in the treatment-as-usual condition.8

For example, the meta-analysis undertaken by Cuijpers and colleagues7 reported a moderate to large effect of IPT in the acute treatment of depression compared with other treatment methods. Control groups in RCTs of the effectiveness of psychotherapy consisted of treatment as usual; wait-list; and inert nontherapies, which risked false boosting of IPT effect sizes. Requesting a therapist to be inert (in so-called clinical management) or to provide a psychotherapy with only nonspecific therapeutic ingredients is difficult for any therapist to implement.

We are not asserting that all treatments are equal, but rather that flawed procedures and paradigms may obscure quantification of true treatment efficacy. Nonetheless, the evidence to date does not support the reified status of CBT and IPT as universal treatments for treating clinical depression.

Evaluating psychotherapies (especially CBT and IPT) is made even more difficult by a second key methodological issue—the role of nonspecific therapeutic factors. Evidence of psychotherapy’s benefits that emerge from its specific ingredients (ie, techniques and therapeutic approaches integral to the therapy’s theoretical model) is lacking; meta-analyses have quantified that only an 8% variance in psychotherapeutic outcome was accounted for by such a specific therapeutic component.9 Furthermore, dismantling designs have shown that key components of CBT were not responsible for therapeutic benefit, and others have observed that most improvement occurs before the formal introduction of cognitive restructuring techniques.10,11

Most of the improvement during psychotherapy is therefore likely to be a consequence of nonspecific effects common to all therapies—namely, an emotionally charged confiding therapeutic relationship, a healing setting, a clear rationale, and a treatment procedure believed by both patient and therapist to be restorative.12 If the impact of the specific psychotherapeutic ingredient is low—with estimates of up to only 15%—this makes it extremely difficult to quantify its specific impact when compared with any other plausible psychotherapy that provides those nonspecific ingredients.13 This issue also helps explain why meta-analyses that support CBT and IPT show significant differences only when the control therapy lacks the key nonspecific therapeutic ingredients. Proper evaluation of the effectiveness of CBT and IPT therefore needs to recognize this major methodological limitation.

This general finding is worthy of some clarification. The use of the term “placebo-controlled trials” has a clear connotation—that the nonactive-treatment group receives a placebo or, by definition, an inert treatment. But should we equate the beneficial nonspecific effects of a therapeutic intervention—whether as a component of psychotherapy or of good clinical care when a therapist principally prescribes an antidepressant drug—as necessarily inert? All psychotherapists effectively prescribe themselves and, while we have long recognized the phenomenon of nonspecific and placebo effects, we doubt whether their impact is sufficiently appreciated.

Kirsch14 reviewed studies of sham surgeries for patients with Parkinson disease, knee surgery, and angina pectoris and rejected the view that placebo treatments are, by definition, inert. As a component of psychotherapy, they provide the integral, curative, nonspecific that may actually activate spontaneous remission and may provide ongoing benefits. We should not be dismissive of these types of effects and should realize that the term “placebo effect” does not capture the reality that optimal, nonspecific, therapeutic ingredients are powerful and not, in fact, inert. We also need to recognize the distinct contribution of placebo effect in RCTs, which makes clarification of the specific effects of each therapy more difficult, especially for the psychotherapies. This issue should be embraced in study designs rather than ignored or summarily dismissed.

The third methodological issue relevant to psychotherapy efficacy research concerns underestimation of the role of therapeutic allegiance. Allegiance is not only strongly associated with outcome (with effect sizes of up to 0.65), but it may also equalize treatment differences.15 Meta-analyses have attributed almost one-third of the variance in effect sizes to therapeutic allegiance, and therapeutic allegiance also accounts for 69% of the variance in outcome.16,17 On the basis of these results, others have quantified that 92.5% of the time therapeutic allegiance alone may predict the treatment that will be most successful.18 Studies that position CBT and IPT as first-line treatments for depression rarely consider this factor.

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