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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.

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.

December 2014

Does Cognitive Therapy Have an Enduring Effect Superior to Keeping Patients on Medication?

Cuijpers, P., Hollon, S. D., van Straten, A., Bockting, C., Berking, M., & Andersson, G. (2013). Does cognitive behaviour therapy have an enduring effect that is superior to keeping patients on continuation pharmacotherapy? A meta-analysis. BMJ open, 3(4).

In another in a series of meta analyses by this primarily Dutch group, Cuijpers and colleagues tackle the question of whether the longer term effects of cognitive behavioral therapy (CBT; a short time-limited treatment for depression) outweighs the long term effects of continuation on anti depression medications. CBT is considered an efficacious treatment for depression (see my June 2014 Blog). CBT also has comparable effects as antidepressant medications, but CBT tends to have lower rates of treatment drop outs. What is not clear is whether short term CBT leads to lasting change that is comparable to long term use of medications for depression. One could argue for example, that short term CBT or other comparable psychological interventions teaches patients skills or changes psychological functioning such that future recurrences of depression are less likely. That is, psychological interventions may cause changes that eventually will prevent relapse. Pharmacotherapy on the other hand, may not result in psychological change or acquisition of new skills to forestall a relapse. In fact, patients with chronic depression tend to be kept on medications indefinitely, and patients who recently remit (i.e., no longer have symptoms of depression) are typically kept on pharmacotherapy for another 6 to 12 months to reduce the risk of recurrence. Information about the relative longer term effects of short term treatment with a psychological intervention like CBT versus longer term maintenance on pharmacotherapy can help practitioners and patients decide on the best course of action depending on patient preferences. Cuijpers and colleagues asked: is short term CBT without continuation of treatment as effective as short term treatment of pharmacotherapy with and without long term continuation? They conducted a meta analysis in which the effects of short term CBT were compared to pharmacotherapy in adults diagnosed with depression across follow up periods of 6 to 18 months. Nine studies representing 506 patients were included in the meta analysis. There was a non-significant trend showing that short term CBT outperformed continuation pharmacotherapy at one-year post treatment. On the other hand, CBT resulted in better long term outcomes compared to pharmacotherapy that was discontinued at post treatment. The odds of dropping out of treatment were significantly higher for those receiving pharmacotherapy compared to CBT. There were no differences in any of the findings for type of antidepressant medications.

Practice Implications

The findings reaffirm CBT as a first-line treatment of depressive disorders. It also suggests that equally effective other psychological treatments may also have similar enduring effects compared to pharmacotherapy. Patients and providers need to consider all of the evidence when weighing the pros and cons of psychotherapy or medications for the treatment of depression. Although pharmacotherapy might be more widely available to patients through primary care physicians, the research is suggesting that enduring effects and treatment compliance are higher among those who have access to psychological interventions.
Attitudes Toward Seeking Mental Health Care Have Become Increasingly Negative in the Past 40 Years

Mackenzie, C. S., Erickson, J., Deane, F. P., & Wright, M. (2014). Changes in attitudes toward seeking mental health services: A 40-year cross-temporal meta-analysis. Clinical Psychology Review, 34(2), 99-106.

Rates of treatment for mental disorders in developed countries have increased over time and this is largely due to the dramatic rise in the use of medications, such as antidepressants over the past 30 years. Concurrently the proportion of people receiving outpatient psychotherapy has declined. Despite the increase of pharmacological interventions, many mental health services in the US do not meet evidence based guidelines, and most people with mental disorders in the US and Canada are not receiving care. Barriers to accessing care include: lack of knowledge (not knowing where to get help); structural barriers (financial costs), and attitudes (stigma, belief that one should handle the problem oneself, and belief that treatment will not help). There is a great deal of evidence that negative attitudes about seeking and receiving help are the most consistent reasons related to low service utilization in Canada and the US. Efforts to reduce stigma, in part, have attempted to define mental illness as a medical or biological disorder likely with the intent of reducing blame of the individual for his or her problems. As Mackenzie and colleagues indicate, this coincided with an aggressive direct-to-consumer advertising of psychotropic medications for mental disorders. And so the perception that mental disorders are biological and that require biological treatments became entrenched in the population. However, as I summarized in the PPRNet October 2013 Blog endorsing neurobiological causes of mental illness is associated with seeing the disorder as persistent, unchangeable, and serious. This increases social distance, which is an aspect of stigma. In their meta analysis, Mackenzie and colleagues reviewed all published studies over the past 40 years that used the Attitudes Toward Seeking Professional Help Scale. They analysed 22 studies with a total sample size of 6,796. They used cross-temporal meta-analysis to correlate year of the study with total scores on the scale. The correlation was large and negative (r = -.53) indicating that participants’ help-seeking attitudes have become significantly more negative over time.

Practice Implications

Attitudes toward seeking mental health services have become increasingly negative over the past four decades, which is consistent with worsening public stigma about mental health. This has coincided with an increase in the use of psychotropic medications and a decline in psychotherapy during the same period, despite evidence that psychotherapy is as effective as medications and preferred by patients. As Mackenzie and colleagues suggest, it is possible that attitudes toward mental health care have become increasingly negative due to efforts to convince the public that mental disorders have a neurobiolobic etiology and require biological treatments. When appropriate, clinicians should not promote biological explanations at the expense of psychosocial explanations for mental disorders. Psychological explanations and treatments may result in patients experiencing a greater sense of optimism about change, and greater personal control over the treatments they receive.

June 2014

Cognitive Therapy 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.

April 2014

Medication Versus Psychotherapy for Depressive and Anxiety Disorders

Cuijpers P, Sijbrandij M, Koole SL, Andersson G, Beekman AT, Reynolds III CF (2013). The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: A meta-analysis of direct comparisons. World Psychiatry, 12, 137-148.

Both psychotherapy and antidepressant medications are efficacious treatments for depression and anxiety disorders. However, there remains some debate about whether they are equally effective for all disorders, and whether psychotherapy and antidepressants are equally efficacious for each disorder. As I indicated in the March 2014 blog, antidepressant medications alone have become the first line of treatment for many who have depressive and anxiety disorders. However, a recent meta analysis concluded that monotherapy with medication alone was not optimal treatment for most patients, and that adding psychotherapy results in clinically meaningful improvement for most patients. Cuijpers and colleagues (2013) reported on an overall meta analysis of the studies in which psychotherapy and medication were directly compared to each other in adults with depressive disorders, panic disorder, generalized anxiety disorder (GAD), social anxiety disorder (SAD), or post-traumatic stress disorder (PTSD). They combined the effects of 67 studies including 5,993 patients. Forty studies included depressive disorders and 27 included anxiety disorders. Most therapies (49 of 78) were characterized as cognitive behavioral therapy (CBT), and the others included interpersonal psychotherapy, psychodynamic therapy, and non-directive counselling. Most patients were seen in individual treatment for 12 to 18 sessions. The most commonly prescribed medications were selective serotonin reuptake inhibitors (SSRI). The overall mean effect size for the difference between psychotherapy and medications was almost zero, indicating no significant difference. Regarding specific disorders and treatments, pharmacotherapy was more effective for dysthymia, but the effect size was small. By contrast, psychotherapy was more effective for OCD, and the effect size was moderately large. SSRI had similar effects to psychotherapy, but non-directive counselling was less effective than pharmacotherapy, though the effect was small.

Practice Implications

This meta analysis by Cuijpers and colleagues found that the differences between psychotherapy and antidepressant medications were non-existent for major depression, panic disorder, and SAD. Although antidepressants were more effective for dysthymia, the difference was small and disappeared when study quality was controlled, and so this finding is not reliable. Psychotherapy was clearly more effective for OCD even after adjusting for study quality and other factors. This is the first meta analysis to show the relative superiority of psychotherapy for OCD, and suggests psychotherapy as a first line treatment. The meta analysis only looked at post treatment results and not at longer term effects. There is evidence from other research showing that antidepressants do not have strong effects after patients stop taking them, whereas psychotherapy’s effects tend to be sustained in the longer term.

This month...

Type of Research

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May 2015

Practice Implications

February 2015

Practice Implications

December 2014

Practice Implications

Practice Implications

June 2014

Practice Implications

April 2014

Practice Implications

Psychotherapy Practice Research Network (PPRNet)