Longitudinal Clusters of Long-Term Trajectories in Patients with Early-Onset Chronic Depression: 2 Years of Naturalistic Follow-Up after Extensive Psychological Treatment.

INTRODUCTION: In clinical trials, mostly group-level treatment effects of repeated cross-sectional measures are analyzed. However, substantial heterogeneity regarding individual symptom profiles and the variability of treatment effects are often neglected, especially over the long-term course. To provide effective personalized treatments, investigations of these characteristics are urgently needed. METHODS: Depression severity ratings over 104 weeks of follow-up after year-long treatment with the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or Supportive Psychotherapy (SP) were analyzed. Longitudinal cluster analysis and multinomial logistic regression analysis were conducted to investigate intraindividual trajectories from one of the largest psychotherapy trials in early-onset chronic depression. RESULTS: Two-year post-study-treatment trajectories of N = 188 patients with early-onset chronic depression were grouped into four prototypical clusters. Overall, 16.0% of patients remitted (cluster 1) and most of them did not receive any treatment during the 2-year follow-up. However, 84.0% of patients continued to experience subthreshold (37.2% cluster 2) or major depressive symptoms (46.8% clusters 3-4) and spent on average more than half of the follow-up in pharmacological and psychological treatment. Hierarchical regression analysis indicated that previous study treatment with CBASP or SP did not significantly predict cluster allocation, while baseline variables accounted for a large proportion of explained variance (R2 N = 0.64). CONCLUSION: While some patients experienced stable remission over 2 years of follow-up, the majority of patients experienced subthreshold or major depressive symptoms regardless of former study treatment with CBASP or SP. This calls for a long-term perspective implementing staging and innovative treatment approaches such as the sequential model or modular psychotherapy.

Symptom Change during Waitlist for Medicated and Nonmedicated Patients with Chronic Depression.

INTRODUCTION: Patients seeking psychotherapy often spend time on waitlist (WL), the effect of which is largely unknown. WL patients may forego alternative non-psychotherapeutic assistance and thus do more poorly than had they not been placed on a WL. The course of symptoms might also be influenced by use of antidepressant medication (ADM), an issue that remains unexplored in the literature. OBJECTIVE: In a naturalistic setting, WL symptom change before inpatient psychotherapy (mean weeks of waiting = 22.6) was assessed in a sample (N = 313) of chronically depressed patients. METHODS: Using the Beck Depression Inventory-II, patients' symptoms were tracked at assessment, when admitted to treatment (i.e., after WL), at posttreatment and 1-year follow-up. Multilevel growth curve analysis was used to examine waitlist change for the whole sample as well as for ADM users and nonmedicated patients. RESULTS: Symptoms were reduced significantly from assessment to admittance (Cohen's d = 0.47). Symptoms reduced less for ADM users (d = 0.39) than for nonmedicated patients (d = 0.65). CONCLUSION: The findings indicate that chronically depressed patients experience a decrease in symptoms during WL, quite likely due to treatment expectations. We discuss whether less symptom improvement for ADM users could be attributed to iatrogenic comorbidity and a higher degree of demoralization in this group.

The multi-level outcome study of psychoanalysis for chronically depressed patients with early trauma (MODE): rationale and design of an international multicenter randomized controlled trial.

BACKGROUND: Whether and how psychotherapies change brain structure and function is unknown. Its study is of great importance for contemporary psychotherapy, as it may lead to discovery of neurobiological mechanisms that predict and mediate lasting changes in psychotherapy, particularly in severely mentally ill patients, such as those with chronic depression. Previous studies have shown that psychoanalytic psychotherapies produce robust and enduring improvements in not only symptom severity but also personality organization in patients who have chronic depression and early life trauma, especially if therapy is delivered at a high weekly frequency. METHODS/DESIGN: Patients with chronic major depression and a history of early life trauma will be recruited, assessed, and treated across 3 international sites: Germany, Switzerland, and the United States. They will be randomized to one of two treatment arms: either (1) once weekly psychoanalytic psychotherapies, or (2) 3-4 times weekly psychoanalytic psychotherapies. They will have full clinical characterization as well as undergo MRI scanning at study baseline prior to randomization and again one year later. A group of matched healthy controls will undergo similar assessments and MRI scanning at the same time points to help discern whether study treatments induce brain changes toward or away from normal values. Primary study outcomes will include anatomical MRI, functional MRI, and Diffusion Tensor Imaging measures. Study hypotheses will be tested using the treatment-by-time interaction assessed in multiple general linear models with repeated measures analyses in an intent-to-treat analysis. DISCUSSION: MODE may allow the identification of brain-based biomarkers that may be more sensitive than traditional behavioral and clinical measures in discriminating, predicting, and mediating treatment response. These findings could help to personalize care for patients who have chronic depression patients and early life trauma, and they will provide new therapeutic targets for both psychological and biological treatments for major depressive illness.

Correlates of chronic depression in the general population: results from the CoLaus|PsyCoLaus study.

PURPOSE: Previous population-based studies have partially provided inconsistent results regarding the co-variates of chronic depression, which were likely to be attributable to methodological limitations. The present paper that compared people with chronic major depressive disorder (MDD), non-chronic MDD and no mood disorder in the community focused on specific atypical and melancholic depression symptoms and subtypes of MDD, family history (FH) of mood disorders, measured physical cardio-vascular risk factors (CVRF), personality traits, coping style and adverse life-events. METHODS: Data stemmed from a population-based cohort including 3618 participants (female 53%, n=1918; mean age 50.9 years, s.d. 8.8 years). Among them 563 had a lifetime history of chronic MDD, 1060 of non-chronic MDD and 1995 of no mood disorder. Diagnostic and FH information were elicited through semi-structured interviews, CVRF were assessed through physical investigations. RESULTS: The major findings were that chronic MDD was associated with increase in appetite/weight and suicidal ideation/attempts during the most severe episode, higher exposure to life-events in adulthood, higher levels of neuroticism, lower levels of extraversion and lower levels of informal help-seeking behavior but less frequent FH of MDD compared to non-chronic MDD. CONCLUSION: Chronic MDD is associated with a series of potential modifiable risk factors which are accessible via psychotherapeutic approaches that may improve the course of chronic MDD.

Recovery from chronic depression and structural change: 5-year outcomes after psychoanalytic and cognitive-behavioural long-term treatments (LAC depression study).

OBJECTIVE: Psychotherapy of chronic depression has remained a challenge due to limited prognosis and high rates of recurrence. We present 5-year outcome data from a multicentre trial comparing psychoanalytic (PAT) and cognitive-behavioural (CBT) long-term treatments with randomized and preferred allocations analysing symptom (N = 227) and structural change (N = 134) trajectories. METHOD: Self- and blinded expert ratings of depression symptoms were performed at yearly intervals using the Beck Depression Inventory-II (BDI-II) and Quick Inventory of Depressive Symptoms (QIDS-C). Blinded expert ratings of Operationalized Psychodynamic Diagnosis (OPD) and the Heidelberg Restructuring Scale (HRS) at baseline, 1, 3, and 5 years assessed structural change in a subsample. RESULTS: Lasting and comparable symptom changes were achieved by PAT and CBT. However, compared to CBT, PAT was more successful in restructuring, a major goal of long-term psychodynamic treatments with high frequency and duration. LIMITATIONS: Due to practical reasons, the time criterion for chronic depression of an acute phase had to be defined for over 1 year in the present study, which does not correspond to the DSM-5 criterion of 2 years. Therapy duration and session frequency were not incorporated into the statistical models. CONCLUSION: Long-term psychotherapy helps patients with a yearlong history of depression and often multiple unsuccessful treatment attempts to achieve lasting symptom changes. Future follow-up will clarify whether restructuring promotes further sustainable improvements.

The Effectiveness of an Intensive Inpatient Psychotherapy Program for Chronic Depression: A naturalistic comparison with wait list.

BACKGROUND: Patients with chronic depression (CD) typically have an early symptom onset, more psychiatric comorbidities, more treatment attempts, and more frequent and longer inpatient hospitalizations than patients with major depressive disorders. The main purpose of this study was to investigate the effectiveness of an intensive inpatient psychotherapy program for patients with chronic depression (CD). The primary research question was whether two intensive psychodynamic inpatient treatments, affect phobia therapy (APT) and VITA, were superior to an outpatient wait list condition, receiving treatment as usual (TAU), at completion of treatment. To investigate if a potential difference between the intensive treatment and the wait list control group was dependent on a specific psychotherapeutic model, the study contrasted two therapies with similar intensity, but different theoretical rationales. METHODS: Two hundred eighty patients with CD were included in a naturalistic study. Patients were assessed at four time points; assessment, start of therapy, end of therapy and 1-year follow-up. Three comparisons were performed with patients matched across groups; Intensive inpatient treatment program (APT + VITA) vs wait list during treatment, APT vs VITA during treatment and APT vs VITA during follow-up. The outcome measure was the BDI-II. RESULTS: Intensive inpatient treatment program vs. wait list showed a significant difference in favor of the intensive treatment. No significant differences were found between APT and VITA during therapy or follow-up; but both groups had large effect sizes during treatment, which were maintained during follow-up. CONCLUSIONS: The intensive inpatient psychotherapy program showed superior effect on chronic depression over an outpatient wait list condition receiving treatment as usual (TAU), but no significant differences were found between the two intensive inpatient psychodynamic treatments. The results provide support for the effectiveness of an intensive inpatient psychotherapy program in treatment of chronic and severe disorders, such as CD, which could be of benefit for policymakers and the health care sector as they are allocating recourses efficiently. TRIAL REGISTRATION: This study has been retrospectively registered on ClinicalTrials.gov (NCT05221567) on February 3rd, 2022.

[Stopping antidepressants: withdrawal symptoms and rebound effects : Review and practical recommendations]. / Absetzen von Antidepressiva ­ Absetzsymptome und Rebound-Effekte : Übersicht und praktische Empfehlungen.

Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (AkdÄ) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range.

Acceptability of a technology-supported and solution-focused intervention (DIALOG+) for chronic depression: views of service users and clinicians.

BACKGROUND: Treating chronic depression represents a significant burden for the NHS, yet there is a lack of evidence-based interventions and research specifically focused on this condition. DIALOG+, a technology-assisted and resource-oriented intervention found effective for people with psychosis, may improve care for this service user group. The aim of this study was to explore the acceptability and relevance of DIALOG+ for the treatment of chronic depression in community-based settings. METHODS: A convenience sample of 16 mental health professionals and 29 service users with chronic depression tested the DIALOG+ intervention in routine community care appointments for 3 months across 3 different mental health NHS Trusts in England. Of these, 15 clinicians and 19 service users were individually interviewed about their experiences. Interview transcripts were analysed using thematic analysis by an analytic team which included a service user researcher. RESULTS: Analysis of the combined dataset identified five overarching themes: DIALOG+ Structure; Therapeutic Communication; Reflecting and Monitoring; Empowerment and Powerlessness; and The Impact of Technology. Overall, service users and clinicians were interested in the continued use of DIALOG+ as part of routine care. CONCLUSIONS: DIALOG+ was viewed as acceptable by both service users with chronic depression and their clinicians who work in community care settings, albeit with some caveats. Clinician training required significant improvements to address the issues that were referenced, most notably around support with using technology.

Comparing outcomes in chronic depression following inpatient psychotherapy for patients continuing versus discontinuing antidepressant medication.

Research indicates that combination of psychotherapy and antidepressant medication (ADM) provides cumulative effects and thus outperforms monotherapy in treating chronic depression. In this quasi-experimental study, we explored symptom change for patients with chronic depression treated with ADM when presenting for a 12-week psychotherapeutic inpatient treatment programme. We compared outcomes through treatment and follow-up of patients who continued medication with those who discontinued. We also tested possible moderator effects of initial depression severity on change between the groups. Based on prior research, we hypothesized that combination treatment would yield better results (i.e., more reduction in depression). Patients (N = 112) were referred from general practitioners or local secondary health care. Outcome was measured by Beck Depression Inventory-II (BDI-II), and comparisons were carried out using multilevel modelling. Although 35 patients discontinued ADM during treatment, 77 continued. Both continuers and discontinuers had a significant treatment effect that was maintained at 1-year follow-up. There was no difference in outcome between continuers and discontinuers of ADM. Patients with severe depression had significantly more symptom improvement than patients with moderate depression, but depression severity did not affect outcomes across continuers and discontinuers of ADM differently. The results could indicate that patients had developed resistance and/or tolerance to the prophylactic effects of medication and that ADM did not contribute to the reduction of depressive symptoms. The findings may also indicate that psychotherapy alone in some instances can be a viable alternative to continued combined treatment. Clinicians should carefully assess benefits of patients' ongoing use of antidepressant medication when entering psychotherapy.

Refractory depression - mechanisms and efficacy of radically open dialectical behaviour therapy (RefraMED): findings of a randomised trial on benefits and harms.

BACKGROUND: Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression. AIMS: To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627). METHOD: RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated. RESULTS: After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94-9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI -2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI -2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group. CONCLUSIONS: The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.