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Furukawa, T.A., Shinohara, K., Sahker, E., Karyotaki, E., Miguel, C., ….Cuijpers, P. (2021). Initial treatment choices to achieve sustained response in major depression: A systematic review and network meta-analysis. World Psychiatry, 20, 387-396.

Two common treatments for major depression are antidepressant medications and psychotherapy, both of which have been tested in randomized controlled trials. Antidepressants are among the most prescribed medications, and an increasing number of patients are on longer-term use of these medications. However, it is unclear as to whether choosing antidepressant medication or psychotherapy at the beginning or the acute phase of depression will lead to a sustained response in the longer term. In this network meta-analysis, Furukawa and colleagues examine the important question: “which therapies can get me well and keep me well?” The authors selected randomized controlled studies in which antidepressants or psychotherapy, or their combination were prescribed and compared to each other or to a control condition (treatment as usual or placebo pill). In these studies, adult participants with major depression remained in the treatment or control condition up to 12 months post-treatment. Psychotherapies included many known treatments like CBT, behavioral activation, psychodynamic therapy, and interpersonal psychotherapy. This network meta-analysis included 81 trials representing over 13,000 patient participants. Combined psychotherapy plus antidepressant medication resulted in a more sustained response to treatment (better outcomes) in the long run than control comparisons (OR: 2.52, 95% CI: 1.66, 3.85). Psychotherapy alone was more effective in the long run than pharmacotherapy alone (OR: 1.53, 95% CI: 1:00 – 2.35). The advantage of combined treatment over antidepressants alone was about 14% to 16%, whereas the advantage of psychotherapy over antidepressants was about 12%. There were no differences in longer term effectiveness among the different types of psychotherapy.

Practice Implications

This study shows that the effects of psychotherapy when initiated in the acute phase of major depression (at the outset of symptoms) are enduring over a longer time frame. Psychotherapies outperformed antidepressant medications, standard treatment, and pill placebo. The results also suggested that adding pharmacotherapy to psychotherapy did not interfere with the enduring effects of psychotherapy. The authors suggest that treatment guidelines for depression should be updated to emphasize psychotherapy as the preferred initial treatment option.

McPherson, S., Wicks, C. & Tercelli, I. (2020). Patient experiences of psychological therapy for depression: A qualitative metasynthesis. BMC Psychiatry, 20, 313. https://doi.org/10.1186/s12888-020-02682-1

Many times, researchers choose what to study in psychotherapy trials without really consulting patients who are receiving the care. For example, researchers are often primarily interested in how well psychotherapies reduce symptoms in patients with a particular disorder, or researchers might be interested in certain constructs that might affect patient outcomes (e.g., therapeutic alliance, therapist empathy). But are these the things that patients are really interested in when they seek psychological therapy? Although many treatment guidelines emphasize patient choice and experience, none of them take research of patient experiences into account to develop the guidelines. When presented with findings from randomized controlled trials of psychotherapy, patients reported that the research was of limited value in helping them make an informed choice about therapy. In this metasynthesis of qualitative studies, McPherson and colleagues aimed to bring together qualitative evidence concerning adult patients’ experiences of psychotherapy for depression. Qualitative research typically involves interviewing patients and systematically categorizing their responses into meaningful themes. The authors found 38 qualitative studies involving patient interviews of their experiences in receiving psychotherapy for depression. Several key themes emerged from the analysis. First, many people who receive remote therapy primarily from a computer program felt dissatisfied because of the lack of or limited contact with a real person therapist. Most patients did not feel connected to the computerized therapy and so their motivation waned quickly. Second, patients found psychological models and techniques to be less relevant than their need for help with their immediate family or social problems that likely triggered their depressive symptoms. This points to the primary importance of quality of life and of the social and cultural context for patients, despite that many psychological therapies tend to focus on symptoms almost exclusively. Third, this metasynthesis pointed to reports of negative effects of therapy, in which some therapeutic techniques like body scans induced flashbacks in some patients. Other patients had mixed or sometimes negative feelings about requirements for homework, which sometimes felt overwhelming, culturally out of step, or irrelevant.

Practice Implications

This metasynthesis of patient experiences in psychotherapy point to the importance of asking patients about their goals, expectations, and preferences in therapy. The findings highlight the importance of some common factors across therapies (e.g., therapist warmth and humanness, collaborative agreement on tasks and goals, and patient factors like culture and individual differences). Patients prefer human connection with therapists, and they tend to place less value on techniques of therapy. Patients also tend to value outcomes related to quality of life, social connection, and they want therapy consistent with their cultural values. Patients should be fully involved in a collaborative discussion about which therapy you offer them, how you provide the therapy, and what they want to achieve in therapy.

Jennissen, S., Huber, J., Ehrenthal, J.C., Schauenburg, H., & Dinger, U. (2018). Association between insight and outcome of psychotherapy: Systematic review and meta-analysis. The American Journal of Psychiatry. Published Online: https://doi.org/10.1176/appi.ajp.2018.17080847

For many authors, one of the purported mechanisms of change in psychotherapy is insight. In fact, the utility of insight for clients with mental health problems was first proposed over 120 years ago by Freud and Breuer. Briefly, insight refers to higher levels of self-understanding that might result in fewer negative automatic reactions to stress and other challenges, more positive emotions, and greater flexibility in cognitive and interpersonal functioning. Although insight is a key factor in some psychodynamic models, it also plays a role in other forms of psychotherapy. Experiential psychotherapy emphasises gaining a new perspective through experiencing, and for CBT insight relates to becoming more aware of automatic thoughts. Jennissen and colleagues defined insight as patients understanding: the relationship between past and present experiences, their typical relationship patterns, and the associations between interpersonal challenges, emotional experiences, and psychological symptoms. In this study, Jennissen and colleagues conducted a systematic review and meta analysis of the insight-outcome relationship, that is the relationship between client self-understanding and symptom reduction. They reviewed studies of adults seeking psychological treatment including individual or group therapy. The predictor variable was an empirical measure of insight assessed during treatment but prior to when final outcomes were evaluated. The outcome was some reliable and empirical measure related to symptom improvement, pre- to post- treatment. The review turned up 22 studies that included over 1100 patients mostly with anxiety or depressive disorders who attended a median of 20 sessions of therapy. The overall effect size of the association between insight and outcome was r = 0.31 (95% CI=0.22–0.40, p < 0.05), which represents a medium effect. Moderator analyses found no effect of type of therapy or diagnosis on this mean effect size, though the power of these analyses was low.

Practice Implications

The magnitude of the association between insight and outcome is similar to the effects of other therapeutic factors such as the therapeutic alliance. When gaining insight, patients may achieve a greater self-understanding, which allows them to reduce distorted perceptions of themselves, and better integrate unpleasant experiences into their conscious life. Symptoms may be improved by self-understanding because of the greater sense of control and master that it provides, and by the new solutions and adaptive ways of living that become available to clients.

Author email: Simone.Jennissen@med.uni-heidelberg.de

Razza, L. B., Moffa, A. H., Moreno, M. L., Carvalho, A. F., Padberg, F., Fregni, F., & Brunoni, A. R. (2018). A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 81, 105-113.

Transcranial magnetic stimulation (TMS) is a new treatment for depression thought to modulate brain activity through electromagnetic pulses delivered by a coil placed over the patient’s scalp. A meta analysis shows that TMS may be effective in treating depressive disorders when compared to a placebo control, although only 18.6% of those receiving TMS were no longer depressed at the end of treatment. The placebo control condition usually involves a sham version of TMS in which the coil is placed over the scalp but no magnetic stimulation is applied. In antidepressant trials, the placebo response is quite high such that approximately 40% of patients respond to the placebo condition (in antidepressant trials, the placebo condition includes an identical pill that is inert). In this meta analysis, Razza and colleagues assess the placebo response in TMS. They included only double blind randomized controlled trials (i.e., trials in which both the patient and physician were not aware if the treatment was real or a sham). The authors estimated the placebo response based on pre- to post-sham TMS scores of common measures of depression. The meta analysis included 61 studies of over 1300 patients. The main result showed that sham response was large (g = 0.80; 95%CI = 0.65–0.95). Trials including patients with only one episode of depression or who were not treatment resistant (g =0.67, 95%CI = 0.06–1.28, p= 0.03) had higher placebo responses than those trials in which patients previously had two or more failed antidepressant treatments (g = 0.5, 95%CI = 0.03–0.99, p = 0.048).

Practice Implications

The results of this meta analysis demonstrates a high placebo response in trials testing TMS. This is similar to the high level of placebo response commonly seen in patients in antidepressant medication trials. It appears that psychological factors like attention, instillation of hope, patient expectations of receiving benefit, and perhaps working alliance may account for an important portion of why pharmacological and other medical interventions appear to work for those with depressive disorders. This is particularly true for patients who are receiving treatment for the first time or for whom previous medical treatment was successful.

McFarquhar, T., Luyten, P., & Fonagy, P. (2018). Changes in interpersonal problems in the psychotherapeutic treatment of depression as measured by the Inventory of Interpersonal Problems: A systematic review and meta-analysis. Journal of Affective Disorders, 226, 108-123.

Interpersonal problems are commonly reported by depressed people. Interpersonal problems are seen by many as both a cause of depressive symptoms and as a result of depression. Depression may be the result of lacking basic human needs like social supports, stable relationships, and intimacy. One of the most important ways of assessing interpersonal problems is with the Inventory of Interpersonal Problems (IIP). The IIP is based on a circumplex model of two independent dimensions: affiliation (friendliness vs hostility) and status (dominance vs submissiveness). Greater problems in any of these domains or any combination of these domains may lead to interpersonal distress that result in or are the result of depression. Many psychotherapies target interpersonal problems in their treatment of depression: Interpersonal Psychotherapy (IPT), Short Term Dynamic Psychotherapy (STDP), and Emotion Focused Therapy (EFT). In this meta-analysis, McFarquhar and colleagues evaluated whether psychotherapy for depression is related to changes in interpersonal distress and whether specific types of interpersonal problems at baseline are related to treatment outcomes for depression at post-treatment. The authors looked at both randomized and non-randomized trials of psychotherapy for adults with depression. They found 10 studies that met inclusion criteria, six of which were randomized controlled trials. Psychotherapy for depression resulted large positive changes in interpersonal problems (overall pre- to post-treatment ES g=0.74, 95% CI=0.56–0.93). Unfortunately, there were too few studies (k = 3) that met meta-analytic criteria to do an analysis of pre-treatment interpersonal distress as a predictor of depression outcomes. However, of 8 studies that looked at this question, six showed that higher interpersonal distress was associated with poorer outcomes for depression at post-treatment.

Practice Implications

Given that interpersonal problems both cause and are caused by depressive symptoms, targeting relationship difficulties (lack of social support, conflict in relationships, low intimacy, relationship avoidance) in psychotherapy should be a priority. This meta-analysis showed that interpersonal distress improves after psychotherapy for depression, and there was some evidence that higher interpersonal problems at the outset may reduce the effects of the therapy for depressive symptoms.

Driessen, E., Hollon, S.D., Bockting, C.L.H., Cuijpers, P., Turner, E.H. (2015). Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US National Institutes of Health-funded trials. PLoS ONE 10(9): e0137864. doi:10.1371/journal.pone.0137864.

In 2008 Turner published a well-known study in which he found that almost 50% of antidepressant trials registered with the Food and Drug Administration in the US were never published or were positively “spun” (i.e., essentially negative findings were interpreted to be positive). Almost all of the unpublished trials showed unfavorable results for the antidepressants’ effects. By contrast, the published studies were almost always were positive. This is evidence of publication bias caused by selective publication of some data and suppression of other data. As you can imagine, this has important implications for treatment of depression as the published record appeared to over-inflate effects of antidepressants by 25% (the mean effect size decreased from g = .41 [CI_95% 0.36~0.45] to 0.31 [0.27~0.35] when unpublished studies were included). Has the same type of publication bias occurred in the published record of psychotherapy’s efficacy? In this study by Driessen and colleagues, the authors reviewed all psychotherapy studies for depression funded by the National Institutes of Mental Health in the US between 1972 and 2008. They wanted to determine which ones were published, which were never published, and what the impact of nonpublication was on the mean effect size. Of the 55 grants that were funded, 13 (26.3%) were never published, and the authors were able to obtain data from 11 of those unpublished studies. The overall mean effect size (psychological treatment versus a control condition) of unpublished studies was g = 0.20 (CI_95% -0.11~0.51) indicating a small non-significant effect. The overall mean effect size for published studies was g = 0.52 (CI_95% 0.37~0.68) indicating a medium significant effect. Adding the unpublished studies to published studies resulted in a 25% decrease in effect size estimate to g = 0.39 (0.08~0.70), indicating a small but significant effect of psychotherapy.

Practice Implications

This study indicated that psychotherapy is effective but that the effects are likely smaller than indicated in the published record. As in the case of antidepressant medication research, a minority of researchers may not publish findings that are not in line with their preconceived expectations or wished-for results. Regardless, there is certainly room for psychotherapy to improve. After decades of focusing largely on the efficacy of specific psychotherapies like CBT, psychodynamic therapies, and interpersonal therapy, perhaps it is time to shift to studying how and why therapies work, and which patients benefit from specific interventions. There are promising avenues such as research on: repairing therapeutic alliance tensions, enhancing therapist expertise, progress monitoring and feedback, client factors, and managing countertransference.