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The Psychotherapy Practice Research Network (PPRNet) blog began in 2013 in response to psychotherapy clinicians, researchers, and educators who expressed interest in receiving regular information about current practice-oriented psychotherapy research. It offers a monthly summary of two or three published psychotherapy research articles. Each summary is authored by Dr. Tasca and highlights practice implications of selected articles. Past blogs are available in the archives. This content is only available in English.

December 2016

Effects of Combining Psychotherapy and Pharmacotherapy on Quality of Life in Depression

Kamenov, K., Twomey, C., Cabello, M., Prina, A.M., & Ayuso-Mateos, J.L. (2016). The efficacy of psychotherapy, pharmacotherapy, and their combination on functioning and quality of life in depression: A meta-analysis. Psychological Medicine, doi: 10.1017/S0033291716002774.

Both psychotherapy and pharmacotherapy are efficacious for reducing symptoms of depression. Some studies suggest that functioning (i.e., the ability to engage in work, school, and social activities) and quality of life (i.e., satisfaction with these activities and perception of one’s health) are just as important to depressed patients as is reducing their symptoms. In fact, many patients place greater priority on improving functioning compared to reducing symptoms. In this meta analysis, Kamenov and colleagues assess the relative efficacy of psychotherapy vs pharmacotherapy in improving functioning and quality of life. They also evaluate if combining psychotherapy and pharmacotherapy is efficacious relative to either treatment alone. The meta analysis included k = 153 studies of over 29,000 participants. Psychotherapies often included CBT and interpersonal psychotherapy. Compared to control groups (k = 37 to 52) both psychotherapy (g = 0.35, 95% CI = 0.24, 0.46) and medications (g = 0.27, 95% CI = 0.21, 0.32) significantly improved functioning. Also, compared to controls both psychotherapy (g = 0.35, 95% CI = 0.26, 0.44) and medications (g = 0.31, 95% CI = 0.24, 0.38) significantly improved quality of life in depressed participants. In studies that directly compared psychotherapy and medications, there were no significant differences when it came to improving functioning, but there was a small significant advantage to psychotherapy over medication for improving quality of life (g = 0.21, 95% CI = 0.01, 0.43). Combined psychotherapy and medications (k = 19) was more effective to improve functioning compared to pharmacotherapy alone (g = 0.34, 95% CI = 0.18, 0.50) and compared to psychotherapy alone (g = 0.32, 95% CI = 0.14, 0.49). Combined treatment was also more efficacious for improved quality of life compared to medications alone (g = 0.36, 95% CI = 0.11, 0.62) and to psychotherapy alone (g = 0.39, 95% CI = 0.19, 0.58).

Practice Implications

Combined treatment of medications and psychotherapy is more effective than either treatment alone for improving functioning and quality of life. However, most patients prefer psychotherapy to medications, and some studies indicate that many patients choose not to get treated at all rather than receive medications. Further, quality of life can be substantially compromised by medication side effects. Clinicians should take these factors into account when considering monotherapy with antidepressant medications or combined treatment of pharmacotherapy and psychotherapy for depression.
Placebo Response Rates in Antidepressant Trials

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.

September 2016

No Added Value to Adding Antidepressants to Psychotherapy

Karyotaki, E., Smit, Y., Henningsen, H., Huibers, M.J.H., Robays, J., de Beurs, D., & Cuijpers, P. (2016). Combining pharmacotherapy and psychotherapy or monotherapy for major depression? A meta-analysis on the long-term effects. Journal of Affective Disorders, 194, 144-152.

Depression is a highly prevalent disorder and is expected to become the second largest cause of disability by 2020. Part of the reason for this high level of burden is that depression tends to be a recurrent disorder with high rates of mortality and morbidity. The post-treatment effects of psychotherapy and pharmacotherapy for treating mild to moderate depression are comparable, and combining the two interventions appears to result in better outcomes. Treatment guidelines recommend pharmacotherapy for at least six months to prevent relapse of depressive symptoms. But to what extent does combined antidepressants with psychotherapy result in a different response than pharmacotherapy or psychotherapy alone in the longer term? The meta analysis by Karotaki and colleagues was conducted to address this question. They defined psychotherapy to include any psychological intervention between a therapist and patient that was verbal in nature, and that included in-person, internet-based, telephone, or bibliotherapy components. Types of psychotherapy included CBT, interpersonal, dynamic, and problem solving therapy. Only studies with outcomes at six months or longer (up to 48 months) after the start of treatment were included. The meta analysis included 23 studies with a total of 2164 patients with major depression who receive combined therapy in at least one arm of the study. Antidepressants included SSRIs, SNRIs, and tricyclic medications. In the acute phase treatment (i.e., in studies of treatment during the occurrence of depressive symptoms), combining antidepressants with psychotherapy was more effective than antidepressants alone. But combined treatment was not more effect than psychotherapy alone at six months or longer after the start of treatment. In maintenance treatment (i.e., in studies to prevent relapse of depression) psychotherapy with antidepressants was more effective that pharmacotherapy alone. Type of psychotherapy or medication did not affect any of the results.

Practice Implications

The meta analysis suggests that in the treatment of patients who currently have depressive symptoms (acute phase) psychotherapy alone is as effective in the long run as combining psychotherapy with antidepressants. However combination treatment is more effective that antidepressants alone, presumably because of the added value of psychotherapy. To prevent relapse (maintenance phase), combined treatment of pharmacotherapy and psychotherapy was more effective than antidepressants alone. Psychotherapy may be a viable alternative to combined treatment with medications for treatment of current active depressive symptoms. Psychotherapy often results in patients improving their interpersonal skills and coping mechanisms which they can then use to sustain their improvements in the longer term.
Interpersonal Psychotherapy for Mental Health Problems

Cuijpers, P., Donker, T., Weissman, M.M., Ravitz, P., & Cristea, I.A. (2016). Interpersonal psychotherapy for mental health problems: A comprehensive meta-analysis. American Journal of Psychiatry, 173, 680-687.

Interpersonal psychotherapy is a structured therapy that was originally developed for the treatment of depression. The therapy focuses on stressful life events like grief, interpersonal disputes, life transitions, social isolation or deficits that may cause symptoms. Interpersonal psychotherapy also helps people to connect with social supports and improve their relationships. The treatment emphasizes developing a therapeutic alliance, psychoeducation, and choosing an interpersonal focus. Recently, several trials have been conducted to assess the efficacy of interpersonal psychotherapy for other mental health problems like addictions, eating and anxiety disorders. In this comprehensive meta analysis, Cuijpers and colleagues looked at all randomized controlled trials of interpersonal psychotherapy for any mental disorder. The review included 90 studies representing over 11,000 patients. Most of the studies targeted depression, but some studies used interpersonal psychotherapy to treat other disorders. The effect size of the difference between interpersonal psychotherapy and control conditions was moderately large (g = 0.60), indicating that interpersonal psychotherapy was efficacious. Interpersonal psychotherapy was as effective as other psychotherapies (g = 0.06), and as effective as antidepressant medications (g = -0.13). Combined interpersonal psychotherapy and medications was more effective than interpersonal psychotherapy alone, but the effect size of the difference was small (g = 0.24). The combination of monthly maintenance interpersonal therapy plus daily pharmacotherapy was significantly more effective in preventing relapse of depression compared to pharmacotherapy alone or interpersonal psychotherapy alone (odds ratios between 0.34 and 0.36 with confidence intervals not crossing 0). The effects of interpersonal psychotherapy for eating disorders was mixed largely because of the small number of studies and lower quality of studies. For anxiety disorders, interpersonal psychotherapy was as effective as other treatments (g = -0.16) and more effective than control conditions (g = 0.82).

Practice Implications

Interpersonal psychotherapy showed moderate to large effects in the treatment of depression and anxiety disorders, and it was as effective as other interventions. Interpersonal psychotherapy may be effective for eating disorders as well, though the evidence is less clear. Patients and providers need to have more treatment options since no one treatment is effective for all patients. The relationship emphasis of interpersonal psychotherapy provides an important alternative to medications or cognitive behavioral therapy for some patients.

December 2015

CBT or Antidepressant Medications as the First-Line Treatment for Severe Depression

Weitz, E.S., Hollon, S.D., Twisk, J., van Straten, A., Huibers, M.J.H., David, D., …. Cuijpers, P. (2015). Baseline depression severity as moderator of depression outcomes between cognitive behavioral therapy vs pharmacotherapy: An individual patient data meta-analysis. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2015.1516.

The American Psychiatric Association guidelines for the treatment of depression indicates that although psychotherapy is adequate for mild to moderate depression, anti-depressant medications are indicated for the treatment of severe depression in major depressive disorder. These recommendations are mainly based on the findings of the National Institute of Mental Health Treatment of Depression Collaborative Research Program that was published in the mid 1990s. Several authors since then have disputed this claim, but no meta-analyses have been done on the studies of head-to-head patient-level comparisons of psychotherapy vs antidepressant medications for the purpose of evaluating their relative efficacy for severity of depression. In this meta analysis, Weitz and colleagues look at medications vs psychotherapy for depression and then evaluate if initial severity of depressive symptoms helped to explain any differences. The authors looked at all studies that compared cognitive behavioral therapy (CBT) against antidepressant medications for depression. They focused on CBT because it was the most often studied of the psychotherapies in this context. A systematic review turned up 24 studies, and they were able to get original patient-level data from the authors of 16 of the 24 studies. This represented over 1,700 participants with major depression. These 16 studies were no different from the 8 studies that did not provide original data. Between 17% and 54% of the 1,700 depressed participants met criteria for severe depression at pre-treatment. There were no significant differences between antidepressant medications and CBT on clinically relevant outcomes in terms of “response” (i.e., improvement) or “remission” (i.e., symptom-free). In total, 63% of patients in the antidepressant medication condition and 58% of patients in the CBT condition responded to treatment, and 51% of patients in the antidepressant medication condition and 47% of patients in the CBT condition met criteria for remission. Most importantly, the effects of CBT and antidepressant medications on response to treatment or remission did not differ based on initial severity of depressive symptoms.

Practice Implications

Patients with severe depression were no more likely to require medication to get better than patients with less severe depression. This meta analysis that included the majority of studies that exist on the topic found no evidence to support the guidelines that severe depression should be treated with antidepressant medications over psychotherapy. The authors conclude that CBT may also be a first-line treatment for severe depression.

November 2015

The Logic of Placebos in Medicine and Psychotherapy

The Great Psychotherapy Debate: Since 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.

A couple of decades ago Martin Seligman famously said: “Whenever you hear someone demanding a double-blind study of psychotherapy, hold on to your wallet.” In this chapter, Wampold and Imel continue their examination of the Medical Model versus the Contextual Model for psychotherapy by discussing the viability of double-blind placebo control designs in psychotherapy. This topic sounds a little esoteric, but it’s not – this issue reaches into the very core of the definition of psychotherapy. A placebo-controlled trial in medicine often involves comparing a medication that contains an active biochemical ingredient versus a “sugar pill” that is exactly like the medication but without the active biochemical ingredient. Key to the placebo controlled design is that the health care provider, the patient, nor the researcher/evaluator knows which patient received which pill (i.e., the classic “double-blind” design). However, double-blinding is impossible in psychotherapy – the therapist must know what they are providing, which means that they know which treatment is expected to be effective, and which treatment is favoured by the researchers. Further, the researchers know which patients are getting which intervention of study condition. This affects a critical aspect of psychotherapy, that is, the therapist’s ability to provide a good rationale for the disorder and for the efficacious actions of the therapy. Additionally, patients are often aware that they are getting a pseudo-treatment in the placebo, and so their expectation of outcomes is also lowered (actually, this is often true in medical trials as well as most medications have side effects, and the absence of a side effect signals to the patient and the researcher that the patient is receiving the placebo). Wampold and Imel argue that common factors like emotional arousal, an acceptable explanation of the disorder, an understanding and empathic therapist, a structure to the treatment, and therapist and client expectations and hope are integral to the effectiveness of psychological therapies. They further argue that these are the very factors that medical trials try to control with a double-blind placebo controlled trial. Nonetheless placebo-like controls have been tried in psychotherapy to test the active or specific ingredients of a therapy – that is, to isolate the effects of active ingredients from the relationship context of the therapy. Placebo-like controls in psychotherapy have been called: minimal treatment, supportive counselling, non-directive counselling, etc. However, as mentioned, these placebo control conditions often contain elements that are integral to the effectiveness of psychotherapy, like: emotional arousal, an empathic therapist, and client expectations. And so not surprisingly, after reviewing meta-analyses of placebo-like conditions in psychotherapy research, Wampold and Imel conclude that when the studies are well constructed, these placebo-like conditions perform nearly as well as evidence-based treatments.

Practice Implications

What is the take home message for the clinician of this seemingly esoteric topic about research design? Although the placebo-controlled double-blind randomized design is the gold standard in medical research, this design is not possible or even logical for psychotherapy. The relationship, therapist factors, expectations, and contextual factors that one tries to control in a placebo-controlled trial are some of the very ingredients that are active in psychotherapy. The technical and specific ingredients of psychotherapies (e.g., transference interpretations, cognitive restructuring, two-chair techniques, etc.) are also part of the mix; but in the end, one cannot separate contextual relationship factors from techniques when it comes to providing psychotherapy.

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December 2016

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September 2016

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December 2015

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November 2015

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Psychotherapy Practice Research Network (PPRNet)