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Cuijpers, P., Sijbrandij, E.M., Koole, S.L., Andersson, G., Beekman, A.T. & Reynolds, C.F. (2014). Adding psychotherapy to antidepressant medication in depression and anxiety disorders: A meta-analysis. World Psychiatry, 13(1), 56-67.

Anxiety and depressive disorders occur at a high rate and are very burdensome to those who suffer. These disorders are also related to high levels of health care costs, loss of productivity, and lower quality of life. Both pharmacological and psychotherapeutic interventions are effective, yet in recent years there has been a trend for patients to receive psychotropic interventions alone rather than psychotherapy. Cuijpers and colleagues (2014) conducted a meta analysis comparing pharmacotherapy alone versus pharmacotherapy combined with psychotherapy. Studies in the meta analysis included a variety of disorders such as depressive disorders and anxiety disorders. (Meta analysis is an important tool to review and combine the effects of interventions across a large number of studies. Rather than simply counting studies with positive, neutral, or negative findings, meta analysis allows one to calculate an effect size, average the effect sizes across different studies, and look at predictors or moderators of the effects. Aggregated effect sizes in a meta analysis are much more reliable [i.e., dependable] than any single study result). Cuijpers and colleagues’ meta analysis included 52 studies with 3,623 patients. Most studies tested cognitive behavioral therapy, though a large minority also included interpersonal psychotherapy and psychodynamic therapy. Most studies used selective serotonin reuptake inhibitors (SSRI), though some included tricyclic antidepressants and others. There was a moderately large overall difference between pharmacotherapy versus combined pharmacotherapy plus psychotherapy for major depression, panic disorder, and obsessive compulsive disorder (OCD). That is, adding psychotherapy resulted in a clinically meaningful improvement above and beyond pharmacotherapy alone. There were no significant differences found for type of antidepressant medication or for type of psychotherapy. Eleven studies included a placebo control condition to which medication alone vs medication plus psychotherapy was compared. The effect of combining medication and psychotherapy was twice as large as the effect of medication alone when compared to a placebo control condition. Nineteen studies followed patients after treatment (from 3 to 24 months post treatment), and the superiority of combined treatment versus medication alone remained strong and significant well into follow up.

Practice Implications

There has been a trend over the past decade to provide medication as a first line of treatment for depression and anxiety disorders. However, the results of this meta analysis indicate that monotherapy with medication alone is not optimal treatment for most patients, and that psychotherapy results in additive clinically meaningful improvement for most patients. The additive effects of psychotherapy are especially pronounced for major depression, panic disorder, and OCD.

McHugh, K.R., Whitton, S.W., Peckham, A.D., Welge, J.A., & Otto, M.W. (2013). Patient preference for psychological vs pharmacological treatment of psychiatric disorders: A meta-analytic review. Journal of Clinical Psychiatry, 74, 595-602.

For the most part psychotherapy and pharmacological interventions have equivalent positive effects on depression in the short term, and psychotherapy has better outcomes in the long term (see my May, 2013 blog).  There is also evidence that the effects of medications for depression are overestimated (also in the May 2013 blog). Despite all of this evidence, psychotherapy use has remained the same or declined slightly over the past 10 years (currently at about 3.4% of the population), whereas medication use for depression has doubled to over 10% of the population. At the same time, guidelines for evidenced based practice emphasize incorporating patient preferences when there is an absence of evidence-based decision rules for treatment selection. Providing patients with their preferred treatment is associated with better treatment uptake and outcomes (see June, 2013 blog). McHugh and colleagues conducted a meta analysis to review the literature on patient preferences for psychological versus pharmacological interventions for mental health disorders among adults. They included studies with treatment and non-treatment seeking samples of patients with a variety of disorders. (A quick note about meta-analysis. Meta analysis is a way of statistically combining the effect sizes from a number of studies into a common metric so that an average effect size can be calculated. Meta analysis is now the standard by which studies are reviewed. Meta analysis results are much more reliable than any single study and so represent the best way to inform clinical practice from research findings). McHugh and colleagues identified 34 studies representing over 90,000 participants. Most studies were of depressive disorders and anxiety disorders. When given a preference, 75% of participants preferred psychotherapy over medication to treat their mental health problem. In treatment seeking samples, the percentage was lower at 69%, but still significantly in favour of psychotherapy. Younger people and women were more likely to prefer psychotherapy, though the findings still showed a preference for psychotherapy among older people and men. The availability of combining psychotherapy and medication did not affect the results, so that even when given the option of both psychotherapy and medication people still preferred psychotherapy alone.

Practice Implications:

In all subsamples, participants were 3 times more likely to prefer psychotherapy to medication for their mental disorder. Patient preference for treatment is a core component of evidence based mental health practice that improves outcome and reduces drop outs. Without evidence for superiority for one treatment over another, patients should be given their preference, and on average patients overwhelmingly prefer psychotherapy. To optimize outcomes in clinical settings, providers should consider patient preferences, including their preference for psychotherapy over medication.

Author email: kmchugh@mclean.harvard.edu

Handbook of Psychotherapy and Behavior Change: Starting in March 2013 I will review one chapter a month from the Handbook of Psychotherapy and Behavior Change in addition to reviewing psychotherapy research articles. Book chapters have more restrictive copy right rules than journal articles, so I will not provide author email addresses for these chapters. If you are interested, the Handbook table of content can be viewed on Amazon.

Forand, N.R., DeRubeis, R.J., & Amsterdam, J.D. (2013). Combining medication and psychotherapy in the treatment of major mental disorders. In M.J. Lambert (Ed.) Bergin and Garfield’s handbook of psychotherapy and behaviour change (6^th ed.), pp. 735-774. Hoboken, N.J.: Wiley.

This comprehensive chapter covers evidence for combining medication and psychotherapy for several disorders. This month I report on the section of the chapter on schizophrenia. Practice guidelines recommend antipsychotic medications as the first line treatment for Schizophrenia. However, up to 30% of individuals show an initial poor response and an additional 30% of patients continue to experience symptoms. Medication side effects can be debilitating, resulting in poor adherence and therefore reduced effectiveness. Further, Schizophrenia spectrum disorders are heterogenous in presentation and course, and so a “one size fits all” approach will not be effective for some or many. Psychotherapies can enhance the effectiveness of medications at different phases of treatment to hasten recovery or reduce medication-resistant symptoms. CBT for schizophrenia was developed to treat persistent medication-resistant positive psychotic symptoms (i.e., positive symptoms refer to delusions, hallucinations, disorganized speech and behaviour; whereas negative symptoms refer to restrictions in: emotions, thoughts, speech, and initiating goal directed behaviors). CBT focuses on reappraising the power and source of hallucinations, evaluating delusions, and addressing motivational deficits. CBT appears to be effective for chronic symptoms of schizophrenia with small to moderate effects, and these effects appear to be enduring. There is currently less and mixed evidence for CBT to speed recovery from first episode psychosis and to improve relapse rates. There is also evidence suggesting the effects of family psychoeducation to reduce relapse and to improve caregiver outcomes. However, family psychoeducation requires the participation of a caregiver, which may be a challenge that limits its utility. There is promising research on multidisciplinary rehabilitation programs that include case management, behaviour management, social skills training, social cognitive training, and cognitive remediation. There is also controversial research on providing psychological interventions alone or in a staged approach (i.e, in which earlier and less severe stages are treated with more benign interventions, and later stages are treated more aggressively with medication). However there are as yet no well-controlled clinical data to support this approach.

Practice Implications

Adjunctive psychosocial treatments appear to improve symptomatic and functional outcomes in individuals with schizophrenia spectrum disorders. CBT is best suited for treating chronic positive psychotic symptoms, but its effect on relapse prevention is equivocal. Individuals who are at risk for relapse might benefit from family psychoeducation, if the caregiver can be engaged. Multidisciplinary rehabilitation programs are a promising avenue of treatment.

Handbook of Psychotherapy and Behavior Change: Starting in March 2013 I will review one chapter a month the Handbook of Psychotherapy and Behavior Change in addition to reviewing psychotherapy research articles. Book chapters have more restrictive copy right rules than journal articles, so I will not provide author email addresses for these chapters. If you are interested, the Handbook table of content can be viewed on Amazon.

Forand, N.R., DeRubeis, R.J., & Amsterdam, J.D. (2013). Combining medication and psychotherapy in the treatment of major mental disorders. In M.J. Lambert (Ed.) Bergin and Garfield’s handbook of psychotherapy and behaviour change (6^th ed.), pp. 735-774. Hoboken, N.J.: Wiley.

This comprehensive chapter covers evidence for combining medication and psychotherapy for several disorders. This month I report on the section of the chapter on depression. Psychotherapy and antidepressant medications appear to have similar efficacy in short-term treatment trials, though psychotherapy has better outcomes than medication in the longer term. Psychotherapeutic treatments including Brief Dynamic Therapy (BDT), Interpersonal Psychotherapy (IPT), and Cognitive Behavioral Therapy (CBT) confer enduring benefit by preventing relapse and recurrence when compared to discontinuing medication. Antidepressant medication is modestly effective during initial short-term treatments with remission rates less than 50% and long term recurrence range from 40% to 85%. Combining medication with psychotherapy provides a small to moderate short term advantage over monotherapy of medication or psychotherapy. Combining medication and psychotherapy is more useful for when considering chronicity rather than severity of depression. The results are consistent for BDT, IPT, and for CBT.  In the longer term, efficacy of combined treatments is not better than either monotherapy. Taken together, the evidence for combined therapy for depression is modestly positive with little evidence that treatments interfere with each other (by contrast, see the March 2013 blog for findings of interference in combined therapy for anxiety disorders). Nevertheless, prolonged continuation of medication monotherapy is an added expense that is often ineffective. In fact, prolonged antidepressant medication maintenance can worsen the course of depressive illness for some, and efficacy tends to fade after 3 to 6 months of maintenance. Finally, there is emerging evidence of progressive tolerance (tachyphylaxis) or even worsening of symptoms during medication maintenance. Studies suggest that psychotherapy added to maintenance medication was associated with decreased relapse rates when compared to medication alone in the longer term.

Practice implications

Combined treatments (antidepressant medication plus psychotherapy) for major depression provide modest incremental improvements in response over monotherapy. Results of combination treatments are better, though still modest, for those with chronic depression. The evidence does not support the use of combined treatments for mild to moderate depression, unless the individual does not responds to initial monotherapy. Practitioners could consider monotherapy (i.e., psychotherapy or medication) first, followed by switching therapy or augmenting therapy for non-responders. If a patient is started on short term monotherapy of medication, practitioners may consider switching to psychotherapy for better long term relapse prevention.

Niemeyer, H., Musch, J., & Pietrowsky, R. (2013). Publication bias in meta-analyses of the efficacy of psychotherapeutic interventions for depression. Journal of Consulting and Clinical Psychology, 81, 58-74.

Meta-analyses are important ways of summarizing effects of medical and psychological interventions by aggregating effect sizes across a large number of studies. (Don’t stop reading, I promise this won’t get too statistical). The aggregated effect size from a meta analysis is more reliable than the findings of any individual study. That is why practice guidelines almost exclusively rely on meta analyses when making practice recommendations (see for example the Resources tab on this web site). However meta analyses are only as good as the data (i.e., studies) that go into them (hence, the old adage: “garbage in, garbage out”). For example, if the studies included in a meta analysis are a biased representation of all studies, then the meta analysis results will be unreliable leading to misleading practice guidelines. One problem that leads to unreliable meta analyses is called publication bias. Publication bias often refers to the tendency of peer reviewed journals not to publish studies with non-significant results (e.g., a study showing a treatment is no better than a control condition). Publication bias may also refer to active suppression of data by researchers or industry. Suppression of research results may occur because an intervention’s effects were not supported by the data, or the intervention was harmful to some study participants. In medical research, publication bias can have dire public health consequences (see this TED Talk). There is lots of evidence that publication bias has lead to a significant over-estimation of the effects of antidepressant medications (see Turner et al (2008) New England Journal of Medicine). Does publication bias exist in psychotherapy research, and if so does this mean that psychotherapy is not as effective as we think? A recent study by Niemeyer and colleagues (2013) addressed this question with the most up to date research and statistical techniques. They collected 31 data sets each of which included 6 or more studies of psychotherapeutic interventions (including published and unpublished studies) for depression. The majority of interventions tested were cognitive behavioral therapy, but interpersonal psychotherapy, and brief psychodynamic therapy were also included. The authors applied sophisticated statistical techniques to assess if publication bias existed. (Briefly, there are ways of assessing if the distribution of effect sizes across data sets fall in a predictable pattern called a “funnel plot” – specific significant deviations from this pattern indicate positive or negative publication bias). Niemeyer and colleagues found minimal evidence of publication bias in published research of psychotherapy for depression. This minimal bias had almost no impact on the size of the effect of psychotherapy for depression.

Practice Implications

This is a very important result indicating that despite a minor tendency toward a selective publication of positive results, the efficacy of all reviewed psychotherapy interventions for depression remained substantial, even after correcting for the publication bias. Niemeyer and colleagues’ findings demonstrate that publication bias alone cannot explain the considerable efficacy of psychotherapy for depression. Psychotherapeutic interventions can still be considered efficacious and recommended for the treatment of depression.

Author email address: helen.niemeyer@hhu.de

Handbook of Psychotherapy and Behavior Change: The Handbook of Psychotherapy and Behavior Change is perhaps the most important compendium of psychotherapy research covering a large number of research areas related to psychotherapy. Starting in March 2013, I will review one chapter a month in addition to reviewing psychotherapy research articles. Book chapters have more restrictive copy right rules than journal articles, so I will not provide author email addresses for these chapters. If you are interested, the Handbook table of content can be viewed on Amazon.

Forand, N.R., DeRubeis, R.J., & Amsterdam, J.D. (2013). Combining medication and psychotherapy in the treatment of major mental disorders. In M.J. Lambert (Ed.) Bergin and Garfield’s handbook of psychotherapy and behaviour change (6^th ed.), pp. 735-774. Hoboken, N.J.: Wiley.

This comprehensive chapter covers evidence for combining medication and psychotherapy for several disorders. This month I report on the section of the chapter on anxiety disorders. Monotherapy of medication or psychotherapy are each effective in treating anxiety disorders, though relapse rates can be high. Simultaneously combining medications and psychotherapy is a common practice that is endorsed by several treatment guidelines. Some may also believe that medication and psychotherapy have additive effects or that those who do not respond to one treatment might respond simultaneously to the other. For panic disorder, short term outcomes slightly favour combined therapy of medications (e.g., antidepressants like SSRIs) and psychotherapy (i.e., that often include exposure). However, long term outcome data indicate that combined treatment was no different than cognitive behavioural therapy (CBT) alone. There is also evidence that medications may interfere with exposure-based treatment of panic disorder so that relapse is greater with combination therapy. It is possible for example that medications may suppress fear-related cognitions thus preventing encoding of corrective information, and/or medication may inhibit extinction learning by suppressing cortisol secretion (in the short term) that facilitates consolidation of memories. The evidence for combining medication and psychotherapy for social anxiety disorder, post traumatic stress disorder, generalized anxiety disorder (GAD), and obsessive compulsive disorder are more mixed but still not clearly supportive of long term superiority of simultaneously combining medications and psychotherapy. Other combination approaches appear to show more promise. For example, there is better evidence for starting with a monotherapy initially and adding an alternative therapy for non-responders. Starting with medications first may allow allows cortisol to normalize over time perhaps reducing medication-induced inhibition of extinction learning. Then treatments such as exposure based CBT or brief dynamic therapy for GAD may be additionally helpful to those who do not respond to medication alone. The existing trials tend not to show evidence of incremental benefit of adding medication after initiating psychotherapy. CBT may be effective in helping individuals taper medications while maintaining treatment gains.

Practice implications

Simultaneously combining medication and psychotherapy for anxiety disorders may be common practice. There is an overall lack of evidence that combining treatments improves outcomes, especially in the longer term. Evidence points to medications interfering with the effectiveness of psychotherapy when they are initiated simultaneously. Compared to monotherapy, combined treatments are more complex, time-consuming, expensive, and expose the patient to increased side effect risk. Combination treatments may be best reserved for those who are refractory to initial monotherapy.