Comparative effectiveness of continuation and maintenance treatments for persistent depressive disorder in adults.

BACKGROUND: Persistent depressive disorder (PDD) is defined as a depressive disorder with a minimum illness duration of two years, including four diagnostic subgroups (dysthymia, chronic major depression, recurrent major depression with incomplete remission between episodes, and double depression). Persistent forms of depression represent a substantial proportion of depressive disorders, with a lifetime prevalence ranging from 3% to 6% in the Western world. Growing evidence indicates that PDD responds well to several acute interventions, such as combined psychological and pharmacological treatments. Yet, given the high rates of relapse and recurrences of depression following response to acute treatment, long-term continuation and maintenance therapy are of great importance. To date, there has been no evidence synthesis available on continuation and maintenance treatments of PDDs. OBJECTIVES: To assess the effects of pharmacological and psychological (either alone or combined) continuation and maintenance treatments for persistent depressive disorder, in comparison with each other, placebo (drug/attention placebo/non-specific treatment control), and treatment as usual (TAU). Continuation treatments are defined as treatments given to currently remitted people (remission is defined as depressive symptoms dropping below case level) or to people who previously responded to an antidepressant treatment. Maintenance therapy is given during recovery (which is defined as remission lasting longer than six months). SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 28 September 2018. An earlier search of these databases was also conducted for RCTs via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 Dec 2015). In addition we searched grey literature resources as well as the international trial registers ClinicalTrials.gov and ICTRP to 28 September 2018. We screened reference lists of included studies and contacted the first author of all included studies. SELECTION CRITERIA: We included randomized (RCTs) and non-randomized controlled trials (NRCTs) in adults with formally diagnosed PDD, receiving pharmacological, psychological, or combined continuation and maintenance interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted and analyzed data. The primary efficacy outcome was relapse/recurrence rate of depression. The primary acceptance outcome was dropout due to any reason other than relapse/recurrence. We performed random-effects meta-analyses using risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included 10 studies (seven RCTs, three NRCTs) involving 840 participants in this review, from which five studies investigated continuation treatments and five studies investigated maintenance treatments. Overall, the included studies were at low-to-moderate risk of bias. For the three NRCTs, the most common source of risk of bias was selection of reported results. For the seven RCTs, the most common sources of risk of bias was non-blinding of outcome assessment and other bias (especially conflict of interest due to pharmaceutical sponsoring).Pharmacological continuation and maintenance therapiesThe most common comparison was antidepressant medication versus tablet placebo (five studies). Participants taking antidepressant medication were probably less likely to relapse or to experience a recurrent episode compared to participants in the placebo group at the end of the intervention (13.9% versus 33.8%, RR 0.41, 95% CI 0.21 to 0.79; participants = 383; studies = 4; I² = 54%, moderate quality evidence). Overall dropout rates may be similar between participants in the medication and placebo group (23.0% versus 25.5%, RR 0.90, 95% CI 0.39 to 2.11; RCTs = 4; participants = 386; I² = 64%, low quality evidence). However, sensitivity analyses showed that the primary outcome (rate of relapse/recurrence) showed no evidence of a difference between groups when only including studies with low risk of bias.None of the studies compared pharmacological or psychological treatments versus TAU.Psychological continuation and maintenance therapiesOne study compared psychological therapies versus attention placebo/non-specific control. One study compared psychotherapy with medication. The results of the studies including psychotherapy might indicate that continued or maintained psychotherapy could be a useful intervention compared to no treatment or antidepressant medication. However, the body of evidence for these comparisons was too small and uncertain to draw any high quality conclusions.Combined psychological and pharmacological continuation and maintenance therapiesThree studies compared combined psychological and pharmacological therapies with pharmacological therapies alone. One study compared combined psychological and pharmacological therapies with psychotherapeutic therapies alone. However, the body of evidence for these comparisons was too small and uncertain to draw any high quality conclusionsComparison of different antidepressant medications Two studies reported data on the direct comparison of two antidepressants. However, the body of evidence for this comparison was too small and uncertain to draw any high quality conclusions. AUTHORS' CONCLUSIONS: Currently, it is uncertain whether continued or maintained pharmacotherapy (or both) with the reviewed antidepressant agents is a robust treatment for preventing relapse and recurrence in people with PDD, due to moderate or high risk of bias as well as clinical heterogeneity in the analyzed studies.For all other comparisons, the body of evidence was too small to draw any final conclusions, although continued or maintained psychotherapy might be effective compared to no treatment. There is need for more high quality trials of psychological interventions. Further studies should address health-related quality of life and adverse events more precisely, as well as assessing follow-up data.

[Remote treatment from a psychotherapeutic point of view]. / Fernbehandlung aus psychotherapeutischer Sicht.

There is a broad variety of digital applications available that may enhance psychotherapeutic treatment and potentially lead to enhanced care of mentally ill patients, yet these applications cannot replace psychotherapeutic treatment. Among them are videoconferencing technologies, which allow psychotherapists and their patients to communicate over long distances. Beside this, internet-based treatment programs and health-apps are available for prevention and treatment of mental disorders. The following article describes chances and risks related to the use of digital applications in the care of mentally ill patients.For digital applications to enhance psychotherapeutic care, they need to be applied as thoroughly as psychotherapeutic interventions delivered in direct contact. This means, that diagnostics and education about treatment and setting need to be delivered in direct contact between psychotherapist and patient. The article further describes current regulatory frameworks relevant to the use of digital applications in psychotherapeutic care.

Increasing the effectiveness of psychotherapy in routine care through blended therapy with transdiagnostic online modules (PsyTOM): study protocol for a randomized controlled trial.

BACKGROUND: In blended therapy, face-to-face psychotherapy and Internet-based interventions are combined. Blended therapy may be advantageous for patients and psychotherapists. However, most blended interventions focus on cognitive behavioral therapy or single disorders, making them less suitable for routine care settings. METHODS: In a randomized controlled trial, we will compare blended therapy and face-to-face therapy in routine care. We intend to randomize 1152 patients nested in 231 psychotherapists in a 1:1 ratio. Patients in the blended therapy group will receive access to a therapeutic online intervention (TONI). TONI contains 12 transdiagnostic online modules suited for psychodynamic, cognitive behavioral, and systemic therapy. Psychotherapists decide which modules to assign and how to integrate TONI components into the psychotherapeutic process to tailor treatment to their patients' specific needs. We will assess patients at baseline, 6 weeks, 12 weeks, and 6 months. Patients enrolled early in the trial will also complete assessments at 12 months. The primary outcomes are depression and anxiety at 6-month post-randomization, as measured by PHQ-8 and GAD-7. The secondary outcomes include satisfaction with life, level of functioning, personality traits and functioning, eating pathology, sexual problems, alcohol/drug use, satisfaction with treatment, negative effects, and mental health care utilization. In addition, we will collect several potential moderators and mediators, including therapeutic alliance, agency, and self-efficacy. Psychotherapists will also report on changes in symptom severity and therapeutic alliance. Qualitative interviews with psychotherapists and patients will shed light on the barriers and benefits of the blended intervention. Furthermore, we will assess significant others of enrolled patients in a sub-study. DISCUSSION: The integration of online modules which use a common therapeutic language and address therapeutic principles shared across therapeutic approaches into regular psychotherapy has the potential to improve the effectiveness of psychotherapy and transfer it into everyday life as well help save therapists' resources and close treatment gaps. A modular and transdiagnostic setup of the blended intervention also enables psychotherapists to tailor their treatment optimally to the needs of their patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00028536. Registered on 07.06.2022.

Allegiance Bias and Treatment Quality as Moderators of the Effectiveness of Humanistic Psychotherapy: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: In many countries, humanistic psychotherapy (HPT) is viewed as a broad psychotherapeutic approach and is accepted in health care systems. To qualify for reimbursement by health insurance in Germany, psychotherapy approaches have to be evaluated positively by the German Scientific Board of Psychotherapy (GSBP). The GSBP examined HPT and its subapproaches based on an application by a number of professional organizations affiliated with HPT (Work Group Humanistic Psychotherapy, WGHPT). The GSBP came to the decision that none of the HPT subapproaches provided sufficient evidence to be evaluated as evidence based. Potential reasons for the discrepancy between international recognition of HPT and GSBP's decision will be explored: researchers' allegiance may have led to a risk of bias disadvantaging HPT. Furthermore, the evaluation criteria of the GSBP did not systematically consider whether HPT was conceptualized bona fide and implemented with sufficient treatment integrity in the studies. OBJECTIVE: This systematic review will re-examine the studies included in the review of the GSBP. Within 2 comparisons (HPT vs control and HPT vs other psychotherapeutic interventions), we will examine moderating effects of treatment quality (bona fide and treatment integrity) and allegiance on the effectiveness of HPT. METHODS: This review is based on the prior systematic review by the GSBP. The GSBP examined randomized controlled trials (RCTs) and studies with non-RCTs of HPT interventions for individuals with mental disorders. All studies suggested by the WGHPT were included; moreover, the GSBP conducted searches in standard electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, and PSYNDEX) and handsearches in relevant systematic reviews and contacted experts. A total of 2 independent GSBP reviewers performed study screening using a structured form. On the basis of the prior work of the GSBP, all studies that were positively screened by the GSBP will be included in this review. Data will be extracted independently by 4 authors. Standardized mean difference will be calculated, and possible publication bias will be tested using funnel plots and Egger test. A priori defined subgroup or meta-regression analyses will be performed for treatment quality, allegiance, type of nonactive control, study quality, type of subapproach, and target population (children and adolescents or adults). RESULTS: The GSBP identified 115 eligible studies that will be reanalyzed in this systematic review. CONCLUSIONS: Results about moderator effects of treatment quality and allegiance will provide important information about their impact on the evaluation of HPT and other psychotherapy approaches and can be used for further evaluation methods. TRIAL REGISTRATION: PROSPERO CRD42019128983; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=128983. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/15140.

Placebo and nocebo reactions in randomized trials of pharmacological treatments for persistent depressive disorder. A meta-regression analysis.

BACKGROUND: We aimed to investigate placebo and nocebo reactions in randomized controlled trials (RCT) of pharmacological treatments for persistent depressive disorder (PDD). METHODS: We conducted a systematic electronic search and included RCTs investigating antidepressants for the treatment of PDD. Outcomes were the number of patients experiencing response and remission in placebo arms (=placebo reaction). Additional outcomes were the incidence of patients experiencing adverse events and related discontinuations in placebo arms (=nocebo reaction). A priori defined effect modifiers were analyzed using a series of meta-regression analyses. RESULTS: Twenty-three trials were included in the analyses. We found a pooled placebo response rate of 31% and a placebo remission rate of 22%. The pooled adverse event rate and related discontinuations were 57% and 4%, respectively. All placebo arm outcomes were positively associated with the corresponding medication arm outcomes. Placebo response rate was associated with a greater proportion of patients with early onset depression, a smaller chance to receive placebo and a larger sample size. The adverse event rate in placebo arms was associated with a greater proportion of patients with early onset depression, a smaller proportion of females and a more recent publication. CONCLUSIONS: Pooled placebo and nocebo reaction rates in PDD were comparable to those in episodic depression. The identified effect modifiers should be considered to assess unbiased effects in RCTs, to influence placebo and nocebo reactions in practice. LIMITATIONS: Limitations result from the methodology applied, the fact that we conducted only univariate analyses, and the number and quality of included trials.

Effectiveness of metacognitive interventions for mental disorders in adults: a systematic review protocol (METACOG).

INTRODUCTION: Whereas the efficacy of cognitive-behavioural therapy has been demonstrated for a variety of mental disorders, there is still need for improvement, especially regarding less prevalent or more severe disorders. Recently, metacognitive interventions have been developed and are now available for a variety of diagnoses. Still, a systematic review investigating the effectiveness of different metacognitive interventions for various mental disorders is missing. METHODS AND ANALYSIS: Randomised controlled trials (RCTs), cross-over and cluster RCTs and non-randomised controlled trials on metacognitive interventions (ie, metacognitive therapy, metacognitive training, others) in adults with any mental disorder will be included. As comparators, another psychological or pharmacological treatment, a combined psychological and pharmacological treatment, treatment as usual or no active treatment are eligible. Outcomes refer to efficacy and acceptability of metacognitive interventions. ETHICS AND DISSEMINATION: In light of the popularity of metacognitive interventions, the systematic review will provide researchers, clinicians and patients with substantial information on the intervention's effectiveness across different mental disorders. Results will be published in peer-reviewed journals and disseminated through a patient workshop.