Clinical trial NCT06916429: The Effectiveness of Psychological Interventions for Common Mental Disorders
Official title: The Effectiveness of Psychological Interventions for Common Mental Disorders (EPIC): A Randomized Waitlist-controlled Superiority Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Common Mental Disorders and/or Stress Related Symptoms
Keywords: psychotherapy
common mental disorders
depression
anxiety
randomized controlled trial
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: the Danish Psychological Association
name: The Danish Regions: Foundation for Medical Research
First posted: 2025-04-08
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The primary aim of "the Effectiveness of Psychological Interventions for Common mental disorders" (EPIC) randomized controlled trial is to investigate whether a significantly larger symptom improvement is observed after approximately four months of psychotherapeutic treatment in the Danish primary sector compared to in a waiting list control group. The secondary aim is to investigate whether specific client and therapy characteristics predicting the effect of the therapy can be identified, and whether the quality of the working alliance is related to the outcome of therapy. The final aim is to investigate potential patterns of symptom development in the waiting list control group and client characteristics predicting these trajectories. The main hypothesis of the EPIC trial is:

1) We will find a significantly higher symptom improvement on the primary outcome measure (PHQ-ADS) among clients who receive psychotherapy approximately four months after beginning therapy, compared to clients in the waiting list control group. In addition, we hypothesize to find significantly better outcomes in the psychotherapy group on all secondary outcome measures after approximately four months of therapy.

Researchers will compare:

* Psychotherapy starting within 14 days after the randomization date with
* Placement on a waiting list for psychotherapy with treatment starting approximately four and a half months after the randomization date

to investigate whether a larger symptom improvement is observed in the group receiving psychotherapy compared to the waiting list control group.

Participants will:

* Be referred by their general practitioner (GP) for publicly subsidized psychotherapy treatment in the primary care sector in Denmark, based on one of 11 referral reasons.
* Complete the baseline questionnaire containing background information, the primary and secondary outcome measures, and predictor questionnaires, and subsequently be randomized to either psychotherapy beginning within two weeks or a waiting list control group.
* Receive a brief symptom questionnaire (the PHQ-ADS) every other week after the randomization date via an SMS-based solution provided by REDCap.
* Complete the primary and secondary outcome measures approximately four and a half, eight and a half, and 16 and a half months after the randomization date.

Detailed description: Aims:

The primary aim of this randomized controlled trial is to investigate whether a significantly higher symptom improvement is observed after approximately four months of psychotherapeutic treatment in the Danish primary sector compared to a waiting list control group. A supplementary aim is to explore whether the treatment effect is maintained during follow-up assessed approximately eight and 16 months after the beginning of treatment. The secondary aim of the study is to investigate whether specific client and therapy characteristics predicting the effect of the therapy can be identified, and whether the quality of the therapeutic alliance measured after approximately five weeks of therapy is related to the outcome of therapy. The final aim of the study is to investigate potential patterns of symptom development in the waiting list control group and identify client characteristics that may predict these trajectories.

The hypotheses of the study are as follows:

* We will find a significantly higher symptom improvement on the primary outcome measure (PHQ-ADS) among clients who receive psychotherapy approximately four months after beginning therapy, compared to clients in the waiting list control group. In addition, we hypothesize to find significantly better outcomes in the psychotherapy group on all secondary outcome measures after approximately four months of therapy.
* The client's coping strategies, emotion regulation strategies, and level of personality pathology will be significantly related to symptom change and treatment dropout after approximately four months of therapy, and to symptom change in the waitlist group approximately four and a half months after randomization. Conversely, the therapeutic orientation of the psychologist will not be independently related to symptom change after approximately four months of therapy.
* The quality of the working alliance after approximately five weeks of therapy will be significantly related to symptom change on the PHQ-ADS after approximately four months of therapy.
* We will explore whether the symptom improvement observed after approximately four months persists eight and 16 months after the beginning of therapy.
* Finally, we will explore the symptom trajectories in the waiting list control group and possible client predictors of these trajectories.

Primary Analysis:

- The primary analysis of the general treatment effect in the practice sector will consist of a multilevel longitudinal regression model. This model will assess the difference in the rate of change between the intervention group and the control group in the PHQ-ADS scores over a period of approximately four months of therapy.

Secondary Analyses:

* As a secondary analysis of the treatment effect, a multilevel logistic regression model will compare the difference in reliable remission rates on the PHQ-9 and the GAD-7 between the intervention group and the control group after approximately four months of therapy. The reliable remission rates on the PHQ-9 and the GAD-7 are employed by the IAPT in the UK and the PMHC in Norway, enabling us to benchmark our results with other studies examining the impact of psychotherapy in primary sectors similar to Denmark.
* Another secondary analysis of the treatment effect will compare differences between the intervention group and the control group after approximately four months of therapy on the secondary continuous outcome measures, specifically the SPS, the CPS, the WHO-5, and the NEQ (see Measures).
* Finally, in a secondary analysis of the treatment effect at follow-up, multilevel regression models will compare the pre-post change in the treatment group approximately eight and 16 months after the beginning of therapy with the change found after four months, and multilevel logistic regression models will compare the reliable remission rates on the PHQ-9 and the GAD-7 found at eight and 16 months with the rate found after approximately four months.

Secondary Predictor Analyses:

* In addition, we will conduct multilevel longitudinal regression models using the predictor variables (i.e., the client's sociodemographic and clinical characteristics, coping strategies, emotion regulation strategies, and level of personality pathology) as fixed effect predictors. The dependent variable will be the rate of change in the PHQ-ADS, measured in both arms of the trial after approximately four months of therapy. Moreover, we will conduct multilevel logistic regression analyses and repeat the predictor analyses in both arms of the study, using the treatment dropout rate as a binary dependent variable.
* Moreover, a multilevel regression model on the association between the client-rated working alliance after approximately five weeks of therapy and the rate of change in the PHQ-ADS after approximately four months of therapy is conducted. In this analysis, the change score on the PHQ-ADS from treatment start to the fifth therapy week will be included as a covariate.

Exploratory Analyses:

- Finally, we will conduct growth mixture modeling to investigate whether clusters of clients with distinctively different symptom trajectories, i.e., distinct patterns of change in the PHQ-ADS during the waiting list period, can be identified in the waiting list sample. Moreover, we will explore the clients' sociodemographic and clinical characteristics, as well as their coping strategies, emotion regulation strategies, and levels of personality pathology, as potential predictors of the identified growth classes using multilevel multinomial logistic regression.

All analyses are conducted as intention-to-treat with multiple imputations of missing data.

Study Design:

The study is designed as a pragmatic randomized controlled trial with a block randomization of clients referred by their general practitioner (GP) for psychotherapy treatment in the primary care sector in Denmark. The clients are randomized in a 1:1 allocation ratio to one of the following options:

* Psychotherapy starting within 14 days of the randomization date
* Placement on a waiting list for psychotherapy, with treatment starting four and a half months after the randomization date.

Participants:

Participants will typically be referred by their GP based on one of 11 referral reasons, which include:

* Victims of traffic and other accidents
* Relatives of seriously mentally ill persons
* Persons suffering from a seriously debilitating illness
* Relatives of persons suffering from a seriously debilitating illness
* Relatives of recently deceased persons
* Persons who have attempted suicide
* Women having undergone an induced abortion after the 12th week of pregnancy
* Persons who, before the age of 18, have been victims of incest or other sexual assaults
* Persons aged 18 or above with mild to moderate depression
* Persons aged 18 or above with mild to moderate anxiety disorder, including mild to moderate OCD.

Procedure:

* Psychologists practicing in the Danish primary sector who have a waiting time of at least four months for psychotherapy treatment will be recruited for the study.
* The participating psychologists will inform all new clients referred by a GP about the possibility of participating in the trial.
* Clients who provide written consent will automatically receive the first set of questionnaires.
* Clients who complete the baseline questionnaires are subsequently randomized to either psychotherapy beginning within two weeks or a waiting list.
* Clients in either arm of the trial will receive the PHQ-ADS (see Outcome Measures) every other week via an SMS-based solution provided by REDCap.
* All questionnaires mentioned under the section on "primary and secondary outcome measures" in the section on Outcome Measures are sent out approximately four and a half, eight and a half, and 16 and a half months after the date of the randomization.

Ethics:

* The study has been approved by the Institutional Review Board at the Department of Psychology, University of Copenhagen.
* All data will be stored on drives approved by the Danish Data Protection Authority as appropriately secure, and all rules from the General Data Protection Regulation will be respected.

Dissemination of Results:

* The results of the study will be disseminated in at least two scientific articles published in international peer-reviewed journals.
* In addition, a report will be prepared for the Danish Regions and the Danish Psychological Association, presenting the conclusions of the study and its possible implications for practice.

Eligibility criteria: Inclusion Criteria:

Clients:

* All clients who meet the criteria for one of the eleven referral reasons for psychotherapeutic treatment in the Danish primary sector.
* Clients who read and speak proficient Danish to fill in the questionnaires.
* Clients who agree to be randomized through their informed consent.

Psychologists:

* All practicing psychologists employed by the Danish primary sector.
* Psychologists who can commit to the deadlines for beginning treatment.
* Psychologists with at waiting time of approximately four months or longer.

Exclusion Criteria:

- Clients considered unfit for participation or urgently needing psychological or medical help, as determined by the therapist.

Primary outcomes:
measure: Patient Health Questionnaire Anxiety-Depression Scale (PHQ-ADS)
timeFrame: Measured at: Baseline, bi-weekly, four and a half months after randomization date, eight and a half months after randomization date, 12 months after randomization date
Secondary outcomes:
measure: Sheehan Disability Scale (SDS)
timeFrame: Measured at: Baseline, four and a half months after randomization date, eight and a half months after randomization date, 12 months after randomization date
measure: The WHO-5 well-being index (WHO-5)
timeFrame: Measured at: Baseline, four and a half months after randomization date, eight and a half months after randomization date, 12 months after randomization date
measure: Cohen's Perceived Stress Scale (PSS)
timeFrame: Measured at: Baseline, four and a half months after randomization date, eight and a half months after randomization date, 12 months after randomization date
measure: The Client Satisfaction Questionnaire (CSQ)
timeFrame: Measured at: Baseline, four and a half months after randomization date.
measure: The Negative Effects Questionnaire (NEQ)
timeFrame: Measured at: Baseline and four and a half months after randomization date.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: University of Copenhagen
state: Central Region
Study officials:
affiliation: University of Copenhagen
name: Stig Poulsen, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Aalborg University
name: Ole Karkov Østergård, Associate Professor
role: STUDY_CHAIR
affiliation: University of Copenhagen
name: Carsten Hjorthøj, Associate Professor
role: STUDY_CHAIR
affiliation: University of Copenhagen
name: Celia Faye Jacobsen, PhD
role: STUDY_CHAIR
References: