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Dreissen, E., Dekker, J.J.M., Peen, J., Van, H.L., Maiana, G…. Cuijpers, P. (2020). The efficacy of adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression: A systematic review and meta-analysis of individual participant data. Clinical Psychology Review, 80.

Depression is the single largest contributor to disability worldwide. There are a number of established treatments for depression including antidepressant medications and psychotherapies. One of the psychological treatments that is evidence-based is short-term psychodynamic psychotherapy (STPP). There is evidence in the general psychotherapy research literature that combining psychotherapy with antidepressant medications is more efficacious than providing medications alone. However, no meta-analysis has looked specifically at adding STPP to antidepressant medication. In this meta-analysis Driessen and colleagues analysed data from 7 studies that compare STPP plus medications versus antidepressant medications alone, or that compare STPP plus medications versus supportive therapy plus medications. Although the number of studies was small, the unique aspect of this meta-analysis is that Driessen and colleagues were able to get all of the individual level data from each study, so they were able to analyse data from 482 participants. Typical meta analyses only look at study level data (effects reported from the study as a whole) and not individual level data (effects for each individual who participant in each study). So, the results from Driessen and colleagues’ study provides a more precise and specific analysis of the findings. Combined treatment of STPP and antidepressant medications was significantly more efficacious than antidepressants with and without supportive therapy at post-treatment, but the effects were small (d = 0.26, SE = 0.01, p = .01). At follow up, combined treatment of STPP and antidepressant medications was again more efficacious than antidepressant medications and supportive therapy, but the effects were moderately large (d = 0.50, SE = 0.10). Other findings also suggested that STPP’s specific interventions provided significant added benefit over and above the non-specific effects of supportive therapy. The findings were consistent whether or not analyses were done on studies with complete versus incomplete data, controlling for baseline depression scores, and use or not of a treatment manual. Overall, the quality of the studies was good, and the findings were stable across studies.

Practice Implications

People with depression and their clinicians might expect better outcomes in terms of depressive symptoms if they combine STPP and antidepressant medications, rather than receiving medications alone. The benefits might be related to the specific interventions of STPP, which suggests that therapists may need specific training and supervision in order to make the most of STPP’s effectiveness.

Cuijpers, P., Noma, H., Karyotaki, E.,  Vinkers, C.H., Cipriani, A., & Furukawa, T.A. (2020). A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry, 19, 92-107.

Mental disorders represent a significant health burden worldwide, with over 350 million people affected. Depression is the second leading cause of disease burden. There is ample evidence that psychotherapies and pharmacotherapies are effective in the treatment of depression. There is also evidence for the efficacy of different types of psychotherapy (CBT, IPT, PDT), and for different types of antidepressant medications. Some research suggests that combining psychotherapy and medications is better than either intervention alone, but the evidence is inconclusive. Existing meta analyses only compare two existing treatments directly to each other at a time: psychotherapy vs medications, psychotherapy vs combined treatments, medications vs combined treatments. In this meta-analysis, Cuijpers and colleagues use a method called “network meta-analysis” to study the relative impact of medications, psychotherapy, or their combination. Network meta-analysis is controversial because it relies on indirect comparisons to estimate effects. For example, let’s say one study compared medications (A) to psychotherapy (B), and another study compared medication (A) to combination treatment (C), then a network meta-analysis would estimate the effects of psychotherapy vs combination treatment by using the transitive principle (if A = B, and B = C, then A = C). This logic relies on everything being equivalent across studies. However, in treatment trials one cannot assume that the different studies comparing A, B, and C are equivalent in terms of quality and bias (in fact, we know they are not). In any case, Cuijpers and colleagues found that combined treatment was superior to ei­ther psychotherapy alone or pharmacotherapy alone in terms of standardized effect sizes (0.30, 95% CI: 0.14-0.45 and 0.33, 95% CI: 0.20-0.47). No significant difference was found between psychotherapy alone and pharmacotherapy alone (0.04, 95% CI: –0.09 to 0.16). Interestingly, acceptability (defined as lower patient drop-out rate and better patient adherence to the treatment) was significantly better for combined treatment compared with pharmacotherapy (RR=1.23, 95% CI:

1.05-1.45), as well as for psychotherapy compared with pharmacotherapy (RR=1.17, 95% CI: 1.02-1.32). In other words, pharmacotherapy alone was less acceptable to patients than another treatment approach that included psychotherapy.

Practice Implications

This network meta-analysis by a renowned researcher and in a prestigious journal adds to the controversy around the relative efficacy of psychotherapy vs medications vs their combination. What is clear is that patients find medication alone to be less acceptable as a treatment option, and previous research shows that patients are 4 times more likely to prefer psychotherapy over medications. Unfortunately, most people with depression receive medications without psychotherapy.

Merz, J., Schwarzer, G., & Gerger, H. (2019). Comparative efficacy and acceptability of pharmacological, psychotherapeutic, and combination treatments in adults with posttraumatic stress disorder: A network meta-analysis. JAMA Psychiatry, 76, 904-91.

Posttraumatic stress disorder (PTSD) is a highly debilitating disorder characterized by re-experiencing trauma, avoidance of situations related to the trauma, negative mood and cognitions, and hyperarousal. The lifetime prevalence of PTSD in the population is about 8%, and PTSD is associated with a great deal of medical problems, and social and economic burden. Difference between a variety of psychological treatment approaches for PTSD are small and not statistically significant. Some treatment guidelines tend to recommend both psychotherapy and pharmacotherapy to treat PTSD, but other guidelines indicate only psychotherapy as the first-line treatment. Merz and colleagues conducted a meta-analysis to examine comparative outcomes and acceptability of psychotherapy and pharmacotherapy and their combination in adults with PTSD. The authors focused on randomized controlled trials because these designs tend to produce the most reliable evidence. The authors identified 12 published studies with a total of 922 participants. Six of the studies included data on long term outcomes. The meta-analytic procedures that the authors used in this study included network meta-analyses (which some have argued may produce unreliable results) and direct comparison meta-analysis (which is more reliable, but resulted in fewer studies being included here). I report in this blog only results that were consistent between the network and direct comparison analyses. Pharmacological and psychotherapeutic treatments and their combinations were not significantly different in their effectiveness immediately post-treatment. However, at long-term follow-up psychotherapy was significantly more beneficial than pharmacotherapy (SMD, −0.63; 95% CI, −1.18 to −0.09). Combined psychotherapy plus pharmacotherapy was not significantly more effective that pharmacotherapy alone (SMD, −1.02; 95% CI, −2.77 to 0.72), and combined treatment was not more effective that psychotherapy alone (SMD, 0.06; 95% CI, −0.31 to 0.42). There were also no statistically significant differences between psychotherapy, pharmacotherapy, or their combination in the acceptability of treatments to participants as defined by differing rates of dropping out from the studies.

Practice Implications

This meta-analysis of a small number of studies suggests that psychotherapy produces better long-term outcomes than pharmacotherapy for PTSD. There is also a suggestion that combining psychotherapy and pharmacotherapy does not improve outcomes compared to either treatment alone. This research area seems to be new and not well developed, but so far, the results seem to favor psychotherapy for longer term outcomes. These findings are similar to those from a larger meta-analysis for depression. In that study, the authors suggested that the long-term benefit of psychotherapy was due to participants learning coping and interpersonal skills that were not gained from receiving pharmacological intervention alone.

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.

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.