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Furukawa, T.A., Cipriani, A., Atkinson, L.A., Leucht, S., Ogawa, Y., … Salanti, G. (2016). Placebo response rates in antidepressant trials: A systematic review of published and unpublished double-blind randomised controlled studies. Lancet Psychiatry, 3, 1059-1066.

The placebo response in medication trials is an interesting and important phenomenon. Placebo response refers to improvement in clients that is due to therapeutically powerful factors like client’s expectations that an intervention will be effective and to the therapeutic relationship with the health care provider. In medication trials, placebo is seen as problematic because researchers typically want to demonstrate the effectiveness of the active medication (e.g., selective serotonin re-uptake inhibitors) independent of any other factors. For this reason, randomized clinical trials of medications are often double-blind and placebo controlled (i.e., clients and clinicians are unaware of who received the active medication and who received the inert placebo pill). It has widely been suspected that over the years the placebo response has been increasing in antidepressant trials possibly due to the types of patients included in trials (i.e., more recently, patients with more severe symptoms are included) and to other methodological issues (e.g., use of multi-centre trials, dosing schedule). An increasing placebo response is suspected of contributing to the growing number of failed anti-depressant trials (i.e., trials that show little or no effectiveness of the medication). Using advanced statistical methods, Furukawa and colleagues evaluated in a meta analysis if placebo response in medication trials was increasing over time. They defined a response as a 50% or greater reduction in observer-rated depression scale scores from baseline to 8 weeks. Their review included 252 placebo controlled trials of antidepressants from 1978 to 2015. Placebo response rates ranged widely from 0% to 70% (I² = 74.1%) with a mean placebo response of 35% to 40%. Year of publication was not significantly related to placebo response rate after controlling for methodological variables like length of the trial, multi-centre trials, and dose regimen. That is, once change in the methodology of conducting trials over time was accounted for, the placebo response appeared to remain largely the same from year to year.

Practice Implications

The placebo response is very real and complicates our understanding of how and why antidepressants might work for some patients. About 35% to 40% of patients who benefit from antidepressants may be benefitting largely because of the expectation of getting better. Greater treatment response to antidepressants for a large proportion of patients appears to be dependent on the therapeutic features of supportive contact with a caring health professional.

Fried, E.I. (2016). The 52 symptoms of major depression: Lack of content overlap among seven common depression scales. Journal of Affective Disorders.

Depression is a leading cause of disability in the world and an important reason why people seek psychotherapy. Depression is also the most commonly studied disorder in psychological treatment studies. Measuring depression with self-report or clinician rating scales seems straight forward, but it turns out that it is not. This is important for clinicians because we assume that scales assess depressive symptoms in a reliable way, and that this measurement gives a valid indicator of a patient’s level of depression and improvements in the depressive symptoms. In this review Fried examined the content of the seven of the most common measures of depression including: the Beck Depression Inventory (BDI), the Centre for Epidemiological Studies Depression Scale (CESD), and the Hamilton Rating Scale for Depression (HRDS). Many might assume depression to represent a single construct – meaning depression is sometimes thought to represent one unitary thing that is consistent across individuals. Because of that assumption, some might consider depression scales to be interchangeable. But according to Fried, these seven scales listed a total of 52 different symptoms. Using a statistical approach called a Jaccard Index, Fried found that the overlap in symptoms among the different depression scales was low (i.e., different scales seemed to be tapping into different symptoms). When he reviewed the content of each scale, this low overlap seemed clear. For example, the BDI (developed by the founder of CBT) emphasizes cognitive symptoms of depression, the CESD has a number of items that are only indirectly related to depressive symptoms (like interpersonal sensitivity), and the HRDS (often used in medication trials to evaluate side effects) emphasizes somatic symptoms like insomnia, fatigue, and sexual dysfunction. Perhaps this lack of overlap is not so surprising given that the concept of depression is likely multidimensional and not representative of a single uniform construct.

Practice Implications

So what does this mean for clinical practice? Many clinicians use a depression scale to assess their patients and monitor their outcomes. Which scale one uses seems to make a difference in terms of what is being measured and what outcomes are monitored. Using the BDI will emphasize the cognitive aspects of depression, whereas ratings with the HRDS may emphasize the somatic aspects of depression. Fried recommends that researchers use more than one scale, and if the findings differ across scales, then that provides more nuanced information about the effects and outcomes of depression and its treatment. Perhaps the same can be said for clinical practice – if clinicians use only one depression scale, then they should be aware of what aspects of depression or what kind of information about their patent’s depression that the scale is providing.

The Great Psychotherapy Debate: Starting in April, 2015 I review parts of The Great Psychotherapy Debate (Wampold & Imel, 2015) in the PPRNet Blog. This is the second edition of a landmark, and sometimes controversial, book that surveys the evidence for what makes psychotherapy work. You can view parts of the book in Google Books.

Change in dysfunctional attitudes or cognitions is one of the specific mechanisms by which cognitive therapy (CT) is thought to be effective in the treatment of depression. In this part of their book, Wampold and Imel discuss the evidence that addresses the specific change mechanisms for CT. The reason they focus on CT is that CT is by far the most researched psychotherapy approach, and there is a substantial number of CT studies that have addressed this issue of change mechanisms. In an early meta analysis, Oei and Free (1995) found a significant relationship between change in cognitions and CT. However, in the same meta analysis, the authors found that CT and non-cognitive therapies did not differ in terms of their effects on cognitions. That is, most treatments, whether CT or not, appeared to change cognitions. In another study, three different interventions (behavioral activation, CT, and CT plus behavioral activation) all resulted in change in cognitions and improved depression. In other words, cognitive interventions do not seem to be needed to alter cognitions and reduce depression. Wampold and Imel argue that nonspecific processes in CT (and other psychotherapies for that matter) are largely responsible for the effectiveness of psychotherapy. For example, there is evidence to suggest that a number of patients show substantial symptom improvement early in treatment before specific cognitive techniques are introduced. Some have argued that this early favourable response is largely due to the effects of client expectations, reassurance, and remoralization rather than the specific procedures of the therapy. Moreover, patients who experience this remoralization early-on may be better at successfully applying techniques taught in CT. A large review of this literature concluded that there was insufficient evidence to support the notion that challenging thoughts was responsible for the positive effects of CT.

Practice Implications

This line of research appears to indicate that the specific practice of challenging thoughts or dysfunctional attitudes is not primarily responsible for patient change in CT. It may be that for any psychological treatment that has a cogent rationale for the disorder and is administered by an acknowledged expert, client progress may be determined largely by contextual factors. These factors may include a therapeutic alliance, client expectations of benefit, and client remoralization, which may in turn allow clients to benefit from the specific interventions of psychological treatments.

The Great Psychotherapy Debate: Since in April, 2015 I review parts of The Great Psychotherapy Debate (Wampold & Imel, 2015) in the PPRNet Blog. This is the second edition of a landmark, and sometimes controversial, book that surveys the evidence for what makes psychotherapy work. You can view parts of the book in Google Books.

Wampold, B.E. & Imel, Z.E. (2015). The great psychotherapy debate: The evidence for what makes psychotherapy work (2^nd edition). New York: Routledge.

The narrative about the relative efficacy of psychotherapies for depression has shifted over the past several decades. In the early days (1970s – 1980s) there appeared to be accumulating evidence that cognitive behavioural therapy (CBT) was more efficacious than “other psychotherapies”. However, today one look at the Society for Clinical Psychology list of empirically supported treatments for depression indicates that a variety of interventions are efficacious. In this part of their book, Wampold & Imel examine this change. Early in their book, they defined psychotherapy as: (1) based psychological principles, (2) involving a trained therapist and a client who is seeking help for a mental disorder, (3) intended to be helpful for the client’s complaints, and (4) adapted to the client’s problem. Wampold and Imel argue that many of the treatments compared to CBT in the early days did not meet this definition of psychotherapy. That is, many of the early comparison treatments were not bona-fide therapies; so the comparisons were not expected to be therapeutic. Common comparisons to CBT were “usual care”, “supportive therapy”, and “self directed care” that for the most part did not meet the definition of psychotherapy. Further, the providers of usual care or supportive therapy had no allegiance to the treatment or expectation that the intervention was useful, which eroded the credibility of these interventions for the client. When bona-fide psychotherapies are compared to each other, the effect sizes tend to be small or negligible. For example, Braun and colleagues (2013) conducted a large meta analysis of 53 studies with nearly 4,000 patients.  When they looked specifically at studies of bona fide therapies, and pairs of treatments that were compared in at least 5 studies, there were no differences between the treatments. Similar findings are reported in large a network meta analysis by Barth and colleagues (2013) (198 studies with 15,118 patients) that was summarized in the July 2014 PPRNet Blog.

Practice Implications

Psychotherapies that are based on sound psychological principles, delivered by trained therapists for clients who seek help and that are intended to be helpful for the client’s complaint are likely to be equally effective for depressive disorders. A variety of psychotherapies including, CBT, emotionally-focused therapy, interpersonal psychotherapy, and short-term psychodynamic therapy have demonstrated empirical support for their efficacy in treating depression. Client expectations of receiving benefit and therapist allegiance to treatment enhance the effectiveness of treatments.

Lichtman, J.H., Froelicher, E.S., Blumenthal, J.A., Carney, R.A., Doering, L.V., et al. (2014). Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: Systematic review and recommendations: A scientific statement from the American Heart Association. Circulation, 129, 1350-1369.

There are about 15.4 million US adults with coronary heart disease. About 20% of those hospitalized for an acute coronary syndrome (ACS; that includes myocardial infarction or unstable angina) meet diagnostic criteria for major depression. An even larger percentage of those with heart disease show sub-clinical levels of depressive symptoms. As I reported in the June 2014 PPRNet Blog about 4% of the population suffer from depression, and so the rates of depression are substantially higher among those with ACS. There is a large body of research showing a reliable association between depression and increased morbidity and mortality after ACS. The goal of this scientific statement by the American Heart Association is to review current evidence for the role of depression as a risk factor among patients with ACS. The authors were particularly interested in studies looking at: (1) all cause mortality, (2) cardiac mortality, and (3) composite outcomes including mortality and nonfatal events. Fifty three studies, representing tens of thousands of patients were included in the review. Twenty one of 32 published studies indicated that depression is a risk factor for all-cause mortality after ACS. Fewer studies looked at the relationship between depression and cardiac mortality, but 8 of 12 studies suggested that depression is a risk factor for cardiac mortality after ACS. Finally evidence from 17 of 22 studies suggested that depression was a risk factor for combined outcomes of cardiac mortality, all cause mortality, and nonfatal cardiac events. The authors also reported on meta analyses looking at the association between depression and mortality following myocardial infarction. Depression increased the risk in individuals of mortality from 1.6 to 2.3 times. The authors concluded that the American Heart Association should elevate depression to the status of a risk factor for adverse medical events in patients with ACS.

Practice Implications

This scientific statement by the American Heart Association published in a technical journal read by cardiologists is important because it acknowledges a mental health problem as a risk factor for mortality from a common medical disease. The evidence is quite strong that depression increases the risk of death in those with heart disease, especially acute coronary syndrome (ACS). Some of the mechanisms for the risk may include genetic/physiological factors like inflammation, platelet aggregation, and the serotonin system that are associated with both depression and ACS. In addition, depression can result in less physical activity and poorer self care which could exacerbate a number of health problems that increase the risk for cardiac disease. Depression is also associated with increases in high risk health behaviors like smoking, sedentary lifestyle, and non-adherence to medical treatment. Assessing for and treating depression among patients who have a history of or are at risk of heart disease is important. If such a patient is depressed or has elevated depressive symptoms, then the depression should be treated in order to reduce the risk of death due to medical problems. In the July 2014 PPRNet Blog, I reported on a network meta analysis showing the positive effects of 7 psychotherapies for depression.

Hollon, S.D. & Beck, A.T. (2013). Cognitive and cognitive-behavioral therapies. In M.E. Lambert (Ed.), Bergin and Garfield’s Handbook of Psychotherapy and Behavior Change, 6th Edition (pp. 393-442). New York: Wiley.

Cognitive (CT) and cognitive behavioural therapies (CBT) are among the most empirically supported and widely practiced psychological interventions. CT emphasizes the role of meaning in their models of depression and CT interventions emphasise testing the accuracy of beliefs. More behavioural approaches like CBT see change in terms of classical or operant conditioning of behaviours, in which cognitive strategies are incorporated to facilitate behavioural change. In this section of their chapter, Hollon and Beck review research on CT for depression. Depression is the single most prevalent mental disorder and is a leading cause of disability in the world (see this month’s blog entry on the global burden of depression). Most patients have multiple episodes of depression (i.e., recurrent) and about 25% have episodes that last for 2 years or more (i.e., chronic). CT posits that depressed individuals have negative automatic thoughts that are organized into depressogenic automatic beliefs (or underlying assumptions) that put them at risk for relapse. Automatic beliefs can be organized in latent (or unconscious) schemas often laid down in childhood and activated by later stress that influence the way information is organized. In CT patients are taught to evaluate their beliefs (also called empirical disconfirmation), conduct “experiments” to test their accuracy and to modify core beliefs and reduce maladaptive interpersonal behaviours. Most reviews show that CT for depression is superior to no treatment (with large effects) and at least as effective as alternative psychological or pharmacological interventions. Most patients show a good response to CT with about one third showing complete remission. Although some practice guidelines have concluded that medications are preferred to CBT (or any psychotherapy) for severe depression, more recent meta analyses show that CT is as efficacious as medications and is likely better in the long term. CT also has an enduring effect that protects clients against symptoms returning. Medications, on the other hand suppress depressive symptoms only as long as the patient continues to take the treatment, but medications do not reduce underlying risk. As a result, relapse rates for medication treatment of depression are much higher than for CT. These findings suggest that patients who receive CT learn something that reduces risk for recurrence, which is the single biggest advantage that CT has over medications. Further, CT is free from problematic side effects that may occur with medications.

Practice Implications

CT and CBT are the most tested psychological treatments for depression and the evidence indicates that many patients benefit. CT and CBT are as effective as medications for reducing acute distress related to depression, and even for those with more severe depression when implemented by experienced therapists. CT has an enduring effect not found in medications, may also help prevent future episodes of depression, and may prevent relapse after medications are discontinued.