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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.

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.

May 2015

Effects of Antidepressants in Treating Anxiety Disorders Are Overestimated

Roest, A.M., de Jonge, P., Williames, G.D., de Vries, Y.A., Shoevers, R.A., & Turner, E.H. (2015). Reporting bias in clinical trials investigating second-generation antidepressants in the treatment of anxiety disorders: A report of 2 meta-analyses. JAMA Psychiatry, doi:10.1001/jamapsychiatry.2015.15.

Previous research has shown that the effects of antidepressant medications for treating depression may be over estimated by as much as 35%. This occurs because of publication bias, which refers to the tendency among researchers and editors to prefer to publish positive findings, and also occurs due to the occasional practice of the pharmaceutical industry to suppress negative findings. In these meta analyses, Roest and colleagues assess publication bias in the research of antidepressant medications to treat anxiety disorders (i.e., generalized anxiety disorder [GAD], panic disorder [PD), social anxiety disorder [SAD], post traumatic stress disorder [PTSD], and obsessive compulsive disorder [OCD]). Anxiety disorders are very common in the population, with an estimated year-prevalence of 12%. Second generation antidepressants (i.e., selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) are the primary pharmacologic treatment for anxiety disorders. Roest and colleagues were also interested in outcome reporting bias, which refers to mis-reporting non-positive findings as if they were positive findings, and spin which refers to interpreting non-positive results as beneficial findings. Positive findings refer to the pharmacological agent significantly outperforming a placebo, and non-positive findings refer to pharmacological agents not significantly outperforming a placebo. Pharmaceutical companies in the US must register any trial with the Food and Drug Administration (FDA) prior to starting the trial if the company wishes to apply for US marketing approval. And so, all medication trials and their findings, whether positive or non-positive must be listed in the FDA register. Despite being listed with the FDA, not all trials and findings get published in peer reviewed journals. This causes a problem for reviews and meta analyses that tend only to focus on published trials, and prescribing physicians tend only to read published trials and reviews. In their meta analyses Roest and colleagues compared findings from all FDA registered medication trials to those that were published in peer reviewed journal. Fifty seven trials were registered with the FDA but only 48 were published. Regarding publication bias, the proportion of studies with positive findings indicating efficacy of antidepressant medications in FDA trials was 72%, whereas the proportion of studies with positive findings in trials published in a journal was 96%. Overall, trials were 5 times more likely to be published if they were positive than if they were non-positive. Regarding outcome reporting bias, 3 of 16 trials that were non-positive in the FDA review were reported as positive in journal publications. Regarding spin, an additional 3 of the 16 non-positive trials interpreted non-positive results as if they were positive. Effect sizes in the FDA data was g = .33 indicating a small average effect size of the medications for anxiety disorders, but the effect size in published journals was g = .38 indicating a small to moderate effect. This represents a 15% over estimation of the effects of the antidepressant medications for anxiety disorders in the published literature.

Practice Implications

The effects of antidepressant medications for anxiety disorders appear to be over estimated by 15% in the published literature. This inflation is not as large as the 35% over estimation in the published literature of the effects of antidepressant medications for depression. By contrast, as I reported in a previous PPRNet Blog, publication bias in psychotherapy trials is small and has little impact on the overall estimate of psychotherapy’s efficacy. Effect sizes for psychological interventions for anxiety disorders are moderate to large, g = .73. Combining medications and psychotherapy only modestly improves efficacy of treatments, and medications may interfere with the efficacy of psychological interventions.

February 2015

Placebo Response is Increasing in Trials of Antipsychotic Medications

Rutherford, B.R., Pott, E., Tandler, J.M., Wall, M.M., Roose, S.P., & Lieberman, J.A. (2014). Placebo response in antipsychotic clinical trials: A meta-analysis. JAMA Psychiatry, doi:10.1001/jamapsychiatry.2014.1319.

The placebo response refers to improvements in symptoms among participants in medication trials that cannot be specifically attributed to the active ingredient of the intervention. For this reason, it is common to have a placebo control condition in trials of medications. In these trials, some participants are randomly assigned to the medication condition, and some are randomly assigned to a placebo control condition. Typically, the placebo is a pill that looks exactly like the medication but that has no active ingredient. Both patients and providers are blind or unaware of whether the patient is receiving the active medication or the placebo. The placebo response is usually attributed to a number of sources: (1) the patient’s expectation of receiving benefit, (2) the patient’s contact with a caring provider and the healing effect of factors like therapeutic alliance and provider empathy, (3) statistical and measurement error, and (4) random changes in patient symptoms that are unrelated to the medication or the placebo. The first two sources are psychological factors that are often specifically active and purposefully enhanced in psychotherapies. That is, some psychotherapists actively work to develop an alliance with the patient and to align therapeutic interventions with patient expectations and preferences. (For a broader discussion, see my review of Common Factors in this month’s PPRNet blog.) The placebo response can sometimes be quite powerful such that antidepressant medications, and antipsychotic medications for example, only tend to be modestly superior to placebo. People with schizophrenia have cognitive difficulties that may reduce their expectations of receiving benefits from treatment. These patients also have significant interpersonal difficulties so that their alliance with health care providers may be significantly hampered. For these reasons, it may be possible that the placebo response may play a smaller role in the medical treatment of patients with schizophrenia. Rutherford and colleagues conducted a meta analysis of 105 studies of over 24,000 participants from 1960 to the present. Their goal was to examine if the average drug-placebo difference decreased significantly over time (i.e. across years of publication). They found that the placebo response significantly increased from 1960 to the present. That is, the average placebo patient tended to get worse in the 1960s, but by the 2000s the average placebo participant tended to get better. The effect of this trend was large (r = .52). By contrast, treatment change associated with antipsychotic medications decreased over time, and the effect of this trend was moderate (r = -.26). The authors suggested possible explanations for this trend. The average participant in drug trials in the 1960s was more severely ill than the average patient enrolled in drug trials in the 2000s. It is possible that the placebo response is more powerful in less severely ill individuals. Also, the authors suggested that a number of study design factors (e.g., multi site vs single site trials, financial incentives to recruit more patients may result in less severely ill and younger samples) may also contribute to this trend.

Practice Implications

One of the practical implications of these findings is that drug companies may be less inclined to fund research and development of new medications for mental illnesses if the research is increasingly showing only modest benefits over control conditions. On the other hand, health care workers who provide: support and empathy, a positive therapeutic alliance, positive expectations about benefits of treatment, attention to patient preferences, and a coherent narrative to understand their patient’s illness may help to enhance the effects of interventions including antipsychotic medications. This may be especially true for younger and less severely ill individuals with schizophrenia.

This month...

Type of Research

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September 2016

Practice Implications

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December 2015

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November 2015

Practice Implications

May 2015

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February 2015

Practice Implications

Psychotherapy Practice Research Network (PPRNet)