Ignite Creation Date:
2024-05-06 @ 6:56 PM
Last Modification Date:
2024-10-26 @ 2:57 PM
Study NCT ID:
NCT05833087
Status:
RECRUITING
Last Update Posted:
2024-01-05
First Post:
2023-04-15
Brief Title:
Schema Therapy for Patients With Chronic Treatment Resistant Depression
Sponsor:
Region of Southern Denmark
Organization:
Region of Southern Denmark
Study Overview
Official Title:
A Randomized Controlled Trial of Schema Therapy for Patients With Chronic Treatment Resistant Depression
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DEPRE-ST
Brief Summary:
The goal of this clinical study is to test a particular form of psychotherapy called schema therapy for people with difficult-to-treat depression when depression is very lengthy or difficult to cure with antidepressive medication Researchers will compare the group of participants receiving schema therapy to a group receiving standard psychotherapeutic treatment to see if schema therapy is more effective on depression symptoms and other important issues for the participant
The main question the study aims to answer is
- Can schema therapy be a more effective treatment for difficult-to-treat depression than other forms of psychotherapy offered in psychiatry today
People who have difficult-to-treat depression are a special group of patients who are more strained in a wide range of areas of life than other people with depression They also more often have childhood trauma as well as simultaneous personality disorder or personality traits that brings challenges in everyday life Currently we can not offer a sufficiently effective psychiatric treatment for this group of people
Schema therapy was developed to help patients who do not have sufficient effect of the usual psychotherapeutic treatments It also addresses personality disorders or problematic traits and childhood trauma directly in the therapy
The project will include 129 participants in total of which half will receive schema therapy
Treatment is provided at four psychiatric centers at both the Southern and the Capital Region of Denmark
Participants receiving schema therapy will be given 30 sessions of weekly therapy as well as the opportunity for the rest of the standard care package in the Danish secondary mental health system that is treatment with psychopharmacological medicine and meetings with next-to-kin and other parts of the participants support system
Participants receiving the standard treatment will receive 6-16 sessions of individual or group therapy with a range of other psychotherapies that are not schema therapy as well as the other parts of the standard care package as listed above
If schema therapy proves to be more effective for treatment of difficult-to-treat depression than the treatment offered today it may give rise to more extended use of schema therapy in and outside psychiatry This means that the toolbox for the treatment of difficult-to-treat depression is expanded with a new specialized and effective psychotherapeutic tool
The main question the study aims to answer is
- Can schema therapy be a more effective treatment for difficult-to-treat depression than other forms of psychotherapy offered in psychiatry today
People who have difficult-to-treat depression are a special group of patients who are more strained in a wide range of areas of life than other people with depression They also more often have childhood trauma as well as simultaneous personality disorder or personality traits that brings challenges in everyday life Currently we can not offer a sufficiently effective psychiatric treatment for this group of people
Schema therapy was developed to help patients who do not have sufficient effect of the usual psychotherapeutic treatments It also addresses personality disorders or problematic traits and childhood trauma directly in the therapy
The project will include 129 participants in total of which half will receive schema therapy
Treatment is provided at four psychiatric centers at both the Southern and the Capital Region of Denmark
Participants receiving schema therapy will be given 30 sessions of weekly therapy as well as the opportunity for the rest of the standard care package in the Danish secondary mental health system that is treatment with psychopharmacological medicine and meetings with next-to-kin and other parts of the participants support system
Participants receiving the standard treatment will receive 6-16 sessions of individual or group therapy with a range of other psychotherapies that are not schema therapy as well as the other parts of the standard care package as listed above
If schema therapy proves to be more effective for treatment of difficult-to-treat depression than the treatment offered today it may give rise to more extended use of schema therapy in and outside psychiatry This means that the toolbox for the treatment of difficult-to-treat depression is expanded with a new specialized and effective psychotherapeutic tool
Detailed Description:
Aims of study
The central aim of this study is to investigate whether Schema Therapy ST of longer duration up to 30 sessions outperforms the current treatment as usual TAU for patients with chronic and treatment resistant depression CTRD on depression outcomes at 12 months after baseline measurements as well as at 6 and 24 months time points after baseline It is hypothesized that the treatment effect in ST is mediated by changes in the psychological phenomenons called modes namely Healthy Adult Mode and Vulnerable Child Mode and that treatment effect is moderated by childhood adversity
A second aim is to expand the understanding of what constitutes a successful therapy by investigating relevant secondary outcomes at the same time points When dealing with chronic andor treatment resistant illnesses other success criteria such as level of functioning personal recovery or a completely different patient-generated outcome might be more obtainable than improvements in illness symptoms alone
The final aim for the study is to investigate and define the population of patients with CTRD It will be attempted to refine the Maudsley Staging Model for CTRD by including failed psychotherapy trials As a part of this it will be investigated whether patients with Treatment Resistant Depression TRD and Chronic Depression CD respectively can be adequately understood as exhibiting similar characteristics in symptoms and response to treatments
Background for study
CTRD-patients seem to differ substantially from non-CTRD patients in numerous respects factors such as adverse events in childhood higher prevalence of comorbid personality disorders as well as inhibiting personality features interpersonal behavior and cognitive styles
With this knowledge ST may be a particularly promising treatment for CTRD as it targets both childhood adversity and particular inhibiting personality features Going to the root of problems ST can potentially have a more enduring effect on the presenting symptoms Also CTRD responds differently to psychotherapy than non-CTRD with smaller effects and with fewer sudden gains compared to non-chronic depression Longer duration of treatment also seems to be necessary a meta-analysis estimated a minimum of 18 sessions necessary to produce convincing results It is thus likely that a longer duration of ST therapy as opposed to the shorter TAU will still be cost-effective due to greater andor longer-lasting effects
Clinical practice varies widely in Denmark and internationally and the extent to which these patients are correctly diagnosed classified registered and referred to specialized prolonged CTRD treatment is unknown and probably not reflecting the true prevalence of CTRD-patients To some extent staging models encompass the differential features of CTRD but even the most elaborate and validated the Maudsley Staging Model MSM does not include treatment with psychotherapy as a variable The addition of former failed psychotherapy trials could possibly improve the predictive value on factors such as dropout short- and long-term effect of psychotherapy and effect of differential types of psychotherapy long duration ST vs TAU This could provide essential information for treatment selection as well as short- and even long-term prognosis
Study design
This is a multi-center two-arm parallel group assessor-blinded randomized controlled superiority study Participants will be allocated 1 1 to either 30 sessions of ST or to treatment as usual TAU for treating CTRD Both treatment conditions will include administration of medical treatment as appropriate following the usual treatment regimes in Danish secondary mental health services Data will be collected via interview and self-report at baseline prior to randomization and again at 6 12 and 24 months after baseline measurements
The treatment will take place at four psychiatric out-patient clinics in the Southern Odense and Capital CopenhagenNørrebro Frederiksberg Ballerup regions of Denmark
Schema therapists
The ST-therapists will be recruited on the basis of willingness to and availability for training 21 therapists will be trained in order to ensure enough available therapists in the case of therapist drop-out from the study As the risk for dropout of therapists has proven to be high privately practicing psychologists with schema therapy and prior psychiatric experience will be employed to provide treatment as needed on the sites
All therapists should have degrees within psychology medicine physiotherapy nursing or social work as well as prior psychotherapeutic experience After training in ST the therapists competency and adherence to the treatment protocol will be evaluated and therapists performing under the required level of competency will not be providing treatment in the study This is done by submission of one video recorded therapy session by each therapist with a current patient at the treatment site This patient is not part of the study intervention group and no further data is collected on the patient While the patient in the video will receive some sort of schema therapeutic intervention this is thought to be within the scope of the treatment that the patient would have otherwise received in treatment at the site The patient will be asked at the previous therapy session whether they would be willing to be video recorded at the next session for the purpose of the study A separate information sheet will be distributed for this purpose right before the initiation of recording
Throughout the study therapists will receive 15 hours of monthly supervision in groups of up to 10 therapists A selection of the therapy sessions for each therapist will be video-recorded and evaluated for adherence by research assistants A after the conclusion of intake assessments and B
Concomitant treatment
Psychopharmacological treatment and changes in medicine prescriptions are permitted by the psychiatrists working at the treatment sites since this is a part of the regular depression treatment in the Danish secondary psychiatric sector Medication use will be monitored via the electronic journal system Concomitant psychopharmacological or psychotherapeutic treatment outside of the treatment sites is discouraged but participants will still be included in the intent-to-treat-analyses Concomitant treatment will be registered as part of study data
Sample size
Sample size planning is based on previous studies that used the short form of the Hamilton Rating Scale for Depression HAM-D6 as their primary or secondary outcome In previous studies the standard deviation of HAM-D6 scores at end-of-treatment was around 35 within the intervention arms A difference of 2 units on the HAM-D6 ie d057 is considered clinically relevant this is the difference we would not like to miss in the comparison of the group averages at the 12 month measurement point On the HAM-D6 scale range 022 2 units correspond to an improvement on two of the six items depressed mood guilt feelings work and interest psychomotor retardation psychic anxiety general somatic symptoms At the conventional significance level of α005 two-tailed a total of N100 participants need to be randomized to detect the relevant group difference with 80 power
The number of randomized participants should be increased to account for clustering and dropout The therapy is administered individually not in groups therefore cluster effects are expected to be low intra-cluster correlation 001 but not zero because several participants are treated by the same therapist Dropout is assumed to be substantial in this patient population and should be compensated in the sample size calculation even if the main analysis uses imputation of missing data
With a cluster size of around 5 participants per therapist and accounting for a dropout of approximately 20 the total sample size should be increased to a total of 129 participants randomized 11 in each intervention arm
Recruitment participant information and consent
When referred to psychiatric treatment in the Mental Health Services Capital and Southern Regions of Denmark all new patients routinely go through a treatment intake interview At this interview the sites clinicians will also evaluate the possible participants eligibility for the study
Interested individuals are then contacted by the research team who will give further verbal and written information about the study by telephone and e-mail If the participant is still interested and eligible a minimum of 24 hours is given before the baseline interview to consider whether they would like to participate or not The baseline assessment interview takes place in a quiet setting either with physical presence in an office at a research or treatment site or if preferred by the participant online on a secure platform Written informed consent is collected The participants will be informed that participation is voluntary and that withdrawal from the study is possible at any time without implications for the treatment to which they were referred
The participants do not receive any monetary or other reimbursements gifts or rewards for their participation
Assignment to interventions randomization and concealment of treatment allocation
Following screening and baseline assessment participants will be randomized to either ST or TAU with a 11 allocation The randomization was stratified by depression severity moderate or severe HAM-D6 and childhood maltreatment Childhood Trauma Questionnaire CTQ dichotomized at baseline for the first 14 included patients however this was changed to stratification for site for the remainder of included patients The data management system Redcap Research Electronic Data Capture a secure web application for building and managing online surveys and databases will execute randomization
Adequate allocation concealment is secured by not performing the randomization until after baseline assessment and recruitment into the trial
After randomization the baseline assessor Assistant A will inform the relevant clinic about the treatment allocation Thus assistant A will be the only researcher knowledgeable about the results of randomization and will therefore not be involved in the outcome or follow-up assessments
Information from the electronic patient journals
After a participant has agreed to participate in the study written consent will be obtained from the participant for the research team to be able to access the participants electronic patient journals in order to obtain information about given psychotherapeutic psychopharmacological or other psychiatric treatment before or during the trial This information is used to be able to evaluate the participants degree of treatment resistance and the extent of given treatment as part of the scientific evaluation in relation to the studys purpose and further to be able to control and monitor for quality and adherence to treatment Also consent will be collected about being contacted in the case of treatment dropout in order to obtain information about the cause of the dropout
Plans to promote participant retention and complete follow-up
As a natural part of psychotherapeutic treatment study participants who utter doubt as to whether to stay in treatment will be invited by their therapist to a collaborative and motivational inquiry about their doubts Study participants who are absent from therapy sessions without notice will be contacted for a similar inquiry
At the 6- 12- and 24-month time points after baseline measurements the participants will be contacted by phone text message andor secure e-mail and asked to participate in a clinical assessment where they will also fill out the self-report measures If necessary the assessment can take place in the participants own home
Statistical analyses
The primary analysis will be based on the intention-to-treat principle with conservative imputation of missing outcomes The primary outcome HAMD-6 is treated as an interval-scaled normally distributed variable The efficacy of the therapies will be compared using a multilevel linear regression with therapy arm levels Schema TAU as the main effect of interest center and baseline depression symptom level as covariates and therapist as a random factor Missing outcomes for participants who dropped out of treatment will be multiply imputed based on the available data from participants that discontinued therapy but participated in follow-up assessments for the study retrieved dropouts For participants who completed therapy but did not participate in follow-up assessments outcomes will be multiply imputed based on the study completers with available data A statistical analysis plan will be finalized before breaking the blind this plan will specify the details of the imputation model
The therapy effect will be presented as the covariate-adjusted difference between the average outcomes in two therapy arms along with its 95 confidence interval Sensitivity analyses will be carried out for the subset of per-protocol participants with available outcome data Secondary outcomes will be analyzed in a similar way using generalized linear models depending on the type of the outcome eg multilevel logistic regression for the response rates Further sensitivity analyses will be carried out using non-linear regression models eg negative binomial regression to rule out bias due to ceiling or floor effects in the outcome
Exploratory analyses
Participants with childhood maltreatment and corresponding maladaptive schema could be hypothesized to benefit more from ST than participants with less severe experiences in childhood This will be analyzed by adding the interaction of maltreatment CTQ dichotomized therapy to the statistical model of the primary analysis and by estimating stratum specific therapy effects in participants with and without maltreatment experiences
Potential usefulness of the altered MSM-staging model will be evaluated by adding the MSM score as a predictor to the primary analysis and testing the increase in explained variance of the primary outcome and selected secondary outcomes and process variables dropout short- and long term follow-up data
As mentioned ST is theorized to work through promoting the Healthy Adult Mode and Vulnerable Child Mode measured by the SMI-HA and SMI-VC In the case of a detected difference between treatments an exploratory mediation analysis will be performed to investigate the relative contribution of changes in SMI-HA and SMI-VC to the overall therapeutic outcome
Socioeconomic analysis
Analyses regarding the costs and effect of the longer ST intervention relative to socioeconomic aspects and interests will be performed using the Euro-QOL-5D as outcome measure
Harms and adverse event
The election of ST was made under the hypothesis that ST will be of particular benefit to CRTD-patients The treatment itself is not expected to have serious side effects however psychotherapy as well as the intake interview andor the filling out of questionnaires can induce temporary emotional stress when uncovering or with dense emotional issues If deterioration in the participants mental health occurs during the course of the study this will be naturally addressed with the participants therapist If it happens momentarily in the intake session the research assistants who will also have a Masters degree in Psychology will be handling this appropriately after training and under supervision by the project manager an authorized psychologist
Adverse events such as suicidal attempts admittance to a psychiatric ward or substantial self-harm are already routinely reported and addressed systematically with appropriate measures in the psychiatric secondary care system Such events will therefore be recorded as part of the study Finally the Negative Effects Questionnaire as a part of the secondary outcomes will address adverse events more broadly to qualify which events are potential harms of treatment and which are unrelated to treatment
Further as recommended by the European Medicines Agency subgroup analyses to detect symptom deterioration will be performed even in the case of no statistically significant difference between treatments This is to ensure that any subgroup with a differential negative effect of treatment is detected in order to provide contraindications towards a particular treatment for certain participants
Pilot study
Prior to the commencement of the trial a pilot study N4 will be performed to evaluate outcome measures relevance and applicability the procedure for inclusion of participants including an evaluation of participant flow and the therapist training program and implementation across treatment sites The pilot will inform the large-scale study and allow for smaller adjustments to ensure a smooth inclusion and treatment phase and the following of the time schedule The participants in the pilot study will all receive TAU after the intake interview
Data from the participants in the pilot study will not be included in the full-scale data analysis
Planned publications
A total of 5 articles are planned for the study articles 1-3 during the PhD and articles 4-5 during the post doc-period
1 Schema therapy for chronic treatment resistant depression - study protocol of a randomized controlled trial
2 Systematic review of schema therapy for mental disorders - reviewing the current evidence base
3 A randomized controlled superiority study of prolonged schema therapy vs TAU for chronic treatment resistant depression - symptoms functioning and patient-generated treatment goals
4 Follow-up of a randomized controlled study of schema therapy vs TAU for chronic treatment resistant depression
5 Chronicity and treatment resistance in patients with depression Proposition for a predictive staging model including psychotherapeutic treatment
The central aim of this study is to investigate whether Schema Therapy ST of longer duration up to 30 sessions outperforms the current treatment as usual TAU for patients with chronic and treatment resistant depression CTRD on depression outcomes at 12 months after baseline measurements as well as at 6 and 24 months time points after baseline It is hypothesized that the treatment effect in ST is mediated by changes in the psychological phenomenons called modes namely Healthy Adult Mode and Vulnerable Child Mode and that treatment effect is moderated by childhood adversity
A second aim is to expand the understanding of what constitutes a successful therapy by investigating relevant secondary outcomes at the same time points When dealing with chronic andor treatment resistant illnesses other success criteria such as level of functioning personal recovery or a completely different patient-generated outcome might be more obtainable than improvements in illness symptoms alone
The final aim for the study is to investigate and define the population of patients with CTRD It will be attempted to refine the Maudsley Staging Model for CTRD by including failed psychotherapy trials As a part of this it will be investigated whether patients with Treatment Resistant Depression TRD and Chronic Depression CD respectively can be adequately understood as exhibiting similar characteristics in symptoms and response to treatments
Background for study
CTRD-patients seem to differ substantially from non-CTRD patients in numerous respects factors such as adverse events in childhood higher prevalence of comorbid personality disorders as well as inhibiting personality features interpersonal behavior and cognitive styles
With this knowledge ST may be a particularly promising treatment for CTRD as it targets both childhood adversity and particular inhibiting personality features Going to the root of problems ST can potentially have a more enduring effect on the presenting symptoms Also CTRD responds differently to psychotherapy than non-CTRD with smaller effects and with fewer sudden gains compared to non-chronic depression Longer duration of treatment also seems to be necessary a meta-analysis estimated a minimum of 18 sessions necessary to produce convincing results It is thus likely that a longer duration of ST therapy as opposed to the shorter TAU will still be cost-effective due to greater andor longer-lasting effects
Clinical practice varies widely in Denmark and internationally and the extent to which these patients are correctly diagnosed classified registered and referred to specialized prolonged CTRD treatment is unknown and probably not reflecting the true prevalence of CTRD-patients To some extent staging models encompass the differential features of CTRD but even the most elaborate and validated the Maudsley Staging Model MSM does not include treatment with psychotherapy as a variable The addition of former failed psychotherapy trials could possibly improve the predictive value on factors such as dropout short- and long-term effect of psychotherapy and effect of differential types of psychotherapy long duration ST vs TAU This could provide essential information for treatment selection as well as short- and even long-term prognosis
Study design
This is a multi-center two-arm parallel group assessor-blinded randomized controlled superiority study Participants will be allocated 1 1 to either 30 sessions of ST or to treatment as usual TAU for treating CTRD Both treatment conditions will include administration of medical treatment as appropriate following the usual treatment regimes in Danish secondary mental health services Data will be collected via interview and self-report at baseline prior to randomization and again at 6 12 and 24 months after baseline measurements
The treatment will take place at four psychiatric out-patient clinics in the Southern Odense and Capital CopenhagenNørrebro Frederiksberg Ballerup regions of Denmark
Schema therapists
The ST-therapists will be recruited on the basis of willingness to and availability for training 21 therapists will be trained in order to ensure enough available therapists in the case of therapist drop-out from the study As the risk for dropout of therapists has proven to be high privately practicing psychologists with schema therapy and prior psychiatric experience will be employed to provide treatment as needed on the sites
All therapists should have degrees within psychology medicine physiotherapy nursing or social work as well as prior psychotherapeutic experience After training in ST the therapists competency and adherence to the treatment protocol will be evaluated and therapists performing under the required level of competency will not be providing treatment in the study This is done by submission of one video recorded therapy session by each therapist with a current patient at the treatment site This patient is not part of the study intervention group and no further data is collected on the patient While the patient in the video will receive some sort of schema therapeutic intervention this is thought to be within the scope of the treatment that the patient would have otherwise received in treatment at the site The patient will be asked at the previous therapy session whether they would be willing to be video recorded at the next session for the purpose of the study A separate information sheet will be distributed for this purpose right before the initiation of recording
Throughout the study therapists will receive 15 hours of monthly supervision in groups of up to 10 therapists A selection of the therapy sessions for each therapist will be video-recorded and evaluated for adherence by research assistants A after the conclusion of intake assessments and B
Concomitant treatment
Psychopharmacological treatment and changes in medicine prescriptions are permitted by the psychiatrists working at the treatment sites since this is a part of the regular depression treatment in the Danish secondary psychiatric sector Medication use will be monitored via the electronic journal system Concomitant psychopharmacological or psychotherapeutic treatment outside of the treatment sites is discouraged but participants will still be included in the intent-to-treat-analyses Concomitant treatment will be registered as part of study data
Sample size
Sample size planning is based on previous studies that used the short form of the Hamilton Rating Scale for Depression HAM-D6 as their primary or secondary outcome In previous studies the standard deviation of HAM-D6 scores at end-of-treatment was around 35 within the intervention arms A difference of 2 units on the HAM-D6 ie d057 is considered clinically relevant this is the difference we would not like to miss in the comparison of the group averages at the 12 month measurement point On the HAM-D6 scale range 022 2 units correspond to an improvement on two of the six items depressed mood guilt feelings work and interest psychomotor retardation psychic anxiety general somatic symptoms At the conventional significance level of α005 two-tailed a total of N100 participants need to be randomized to detect the relevant group difference with 80 power
The number of randomized participants should be increased to account for clustering and dropout The therapy is administered individually not in groups therefore cluster effects are expected to be low intra-cluster correlation 001 but not zero because several participants are treated by the same therapist Dropout is assumed to be substantial in this patient population and should be compensated in the sample size calculation even if the main analysis uses imputation of missing data
With a cluster size of around 5 participants per therapist and accounting for a dropout of approximately 20 the total sample size should be increased to a total of 129 participants randomized 11 in each intervention arm
Recruitment participant information and consent
When referred to psychiatric treatment in the Mental Health Services Capital and Southern Regions of Denmark all new patients routinely go through a treatment intake interview At this interview the sites clinicians will also evaluate the possible participants eligibility for the study
Interested individuals are then contacted by the research team who will give further verbal and written information about the study by telephone and e-mail If the participant is still interested and eligible a minimum of 24 hours is given before the baseline interview to consider whether they would like to participate or not The baseline assessment interview takes place in a quiet setting either with physical presence in an office at a research or treatment site or if preferred by the participant online on a secure platform Written informed consent is collected The participants will be informed that participation is voluntary and that withdrawal from the study is possible at any time without implications for the treatment to which they were referred
The participants do not receive any monetary or other reimbursements gifts or rewards for their participation
Assignment to interventions randomization and concealment of treatment allocation
Following screening and baseline assessment participants will be randomized to either ST or TAU with a 11 allocation The randomization was stratified by depression severity moderate or severe HAM-D6 and childhood maltreatment Childhood Trauma Questionnaire CTQ dichotomized at baseline for the first 14 included patients however this was changed to stratification for site for the remainder of included patients The data management system Redcap Research Electronic Data Capture a secure web application for building and managing online surveys and databases will execute randomization
Adequate allocation concealment is secured by not performing the randomization until after baseline assessment and recruitment into the trial
After randomization the baseline assessor Assistant A will inform the relevant clinic about the treatment allocation Thus assistant A will be the only researcher knowledgeable about the results of randomization and will therefore not be involved in the outcome or follow-up assessments
Information from the electronic patient journals
After a participant has agreed to participate in the study written consent will be obtained from the participant for the research team to be able to access the participants electronic patient journals in order to obtain information about given psychotherapeutic psychopharmacological or other psychiatric treatment before or during the trial This information is used to be able to evaluate the participants degree of treatment resistance and the extent of given treatment as part of the scientific evaluation in relation to the studys purpose and further to be able to control and monitor for quality and adherence to treatment Also consent will be collected about being contacted in the case of treatment dropout in order to obtain information about the cause of the dropout
Plans to promote participant retention and complete follow-up
As a natural part of psychotherapeutic treatment study participants who utter doubt as to whether to stay in treatment will be invited by their therapist to a collaborative and motivational inquiry about their doubts Study participants who are absent from therapy sessions without notice will be contacted for a similar inquiry
At the 6- 12- and 24-month time points after baseline measurements the participants will be contacted by phone text message andor secure e-mail and asked to participate in a clinical assessment where they will also fill out the self-report measures If necessary the assessment can take place in the participants own home
Statistical analyses
The primary analysis will be based on the intention-to-treat principle with conservative imputation of missing outcomes The primary outcome HAMD-6 is treated as an interval-scaled normally distributed variable The efficacy of the therapies will be compared using a multilevel linear regression with therapy arm levels Schema TAU as the main effect of interest center and baseline depression symptom level as covariates and therapist as a random factor Missing outcomes for participants who dropped out of treatment will be multiply imputed based on the available data from participants that discontinued therapy but participated in follow-up assessments for the study retrieved dropouts For participants who completed therapy but did not participate in follow-up assessments outcomes will be multiply imputed based on the study completers with available data A statistical analysis plan will be finalized before breaking the blind this plan will specify the details of the imputation model
The therapy effect will be presented as the covariate-adjusted difference between the average outcomes in two therapy arms along with its 95 confidence interval Sensitivity analyses will be carried out for the subset of per-protocol participants with available outcome data Secondary outcomes will be analyzed in a similar way using generalized linear models depending on the type of the outcome eg multilevel logistic regression for the response rates Further sensitivity analyses will be carried out using non-linear regression models eg negative binomial regression to rule out bias due to ceiling or floor effects in the outcome
Exploratory analyses
Participants with childhood maltreatment and corresponding maladaptive schema could be hypothesized to benefit more from ST than participants with less severe experiences in childhood This will be analyzed by adding the interaction of maltreatment CTQ dichotomized therapy to the statistical model of the primary analysis and by estimating stratum specific therapy effects in participants with and without maltreatment experiences
Potential usefulness of the altered MSM-staging model will be evaluated by adding the MSM score as a predictor to the primary analysis and testing the increase in explained variance of the primary outcome and selected secondary outcomes and process variables dropout short- and long term follow-up data
As mentioned ST is theorized to work through promoting the Healthy Adult Mode and Vulnerable Child Mode measured by the SMI-HA and SMI-VC In the case of a detected difference between treatments an exploratory mediation analysis will be performed to investigate the relative contribution of changes in SMI-HA and SMI-VC to the overall therapeutic outcome
Socioeconomic analysis
Analyses regarding the costs and effect of the longer ST intervention relative to socioeconomic aspects and interests will be performed using the Euro-QOL-5D as outcome measure
Harms and adverse event
The election of ST was made under the hypothesis that ST will be of particular benefit to CRTD-patients The treatment itself is not expected to have serious side effects however psychotherapy as well as the intake interview andor the filling out of questionnaires can induce temporary emotional stress when uncovering or with dense emotional issues If deterioration in the participants mental health occurs during the course of the study this will be naturally addressed with the participants therapist If it happens momentarily in the intake session the research assistants who will also have a Masters degree in Psychology will be handling this appropriately after training and under supervision by the project manager an authorized psychologist
Adverse events such as suicidal attempts admittance to a psychiatric ward or substantial self-harm are already routinely reported and addressed systematically with appropriate measures in the psychiatric secondary care system Such events will therefore be recorded as part of the study Finally the Negative Effects Questionnaire as a part of the secondary outcomes will address adverse events more broadly to qualify which events are potential harms of treatment and which are unrelated to treatment
Further as recommended by the European Medicines Agency subgroup analyses to detect symptom deterioration will be performed even in the case of no statistically significant difference between treatments This is to ensure that any subgroup with a differential negative effect of treatment is detected in order to provide contraindications towards a particular treatment for certain participants
Pilot study
Prior to the commencement of the trial a pilot study N4 will be performed to evaluate outcome measures relevance and applicability the procedure for inclusion of participants including an evaluation of participant flow and the therapist training program and implementation across treatment sites The pilot will inform the large-scale study and allow for smaller adjustments to ensure a smooth inclusion and treatment phase and the following of the time schedule The participants in the pilot study will all receive TAU after the intake interview
Data from the participants in the pilot study will not be included in the full-scale data analysis
Planned publications
A total of 5 articles are planned for the study articles 1-3 during the PhD and articles 4-5 during the post doc-period
1 Schema therapy for chronic treatment resistant depression - study protocol of a randomized controlled trial
2 Systematic review of schema therapy for mental disorders - reviewing the current evidence base
3 A randomized controlled superiority study of prolonged schema therapy vs TAU for chronic treatment resistant depression - symptoms functioning and patient-generated treatment goals
4 Follow-up of a randomized controlled study of schema therapy vs TAU for chronic treatment resistant depression
5 Chronicity and treatment resistance in patients with depression Proposition for a predictive staging model including psychotherapeutic treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None