Blog

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.

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.

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.