Clinical Trial of the Effectiveness of Metacognitive Therapy in the Treatment of Patients With Major Depressive Disorder
Clinical Trial of the Effectiveness of Metacognitive Therapy in the Treatment of Patients With Major Depressive Disorder
The main aim of this study is to (1) evaluate the effectiveness of metacognitive therapy for
 major depressive disorder. Additional aims are to (2) investigate patterns of change and the
 mechanisms of action involved during treatment, and to (3) examine the impact of
 meta-cognitions in the treatment and relapse prevention of depression.
Major depressive disorder is a disabling condition which adversely affects a person's family,
 work or school life, sleeping and eating habits, and general health.

 Cognitive-behavioral therapy (CBT) is a recommended treatment for depression, with a large
 number of clinical trials supporting its efficacy. However, despite the success of CBT
 relative to other treatments, only 40-58 % of patients receiving CBT may be classified as
 recovered using clinical significant change assessed by the Beck Depression Inventory.
 Moreover, research demonstrates that only between one-third and one quarter of patients
 receiving CBT remain recovered at 18 months follow-up.

 A new treatment approach to MDD is Meta-Cognitive Therapy. In this treatment approach, MDD is
 conceptualized as being maintained by rumination and meta-cognitions. Treatment seeks to
 challenge and change specific meta-cognitions and rumination, through behavioural experiments
 and verbal reattribution. No randomized controlled studies have compared the effectiveness of
 MCT to a waiting-list condition for MDD. Related to this, no study has examined the specific
 elements of therapy that are hypothesized to be of most importance for changing rumination,
 leading to positive treatment outcomes.

 The purpose of this trial is to investigate the efficacy of Wells' MCT for Major Depressive
 Disorder (MDD). Another aim will be to examine the in-treatment processes associated with
 positive treatment outcomes.

 The study will be a randomized controlled, trial comprising 50 patients with a primary
 diagnosis of major depressive disorder (DSM-IV; APA, 1994). Experienced diagnosticians will
 assess all patients by using structural interviews such as SCID-I, SCID II and the Hamilton
 Rating Scale for Depression.

 All patients will be randomized in blocks to two groups in order to compare the following
 conditions: MCT and a wait list control condition. After the waiting period of 10 weeks, the
 patients in the wait-list condition will be allocated to the treatment condition. Both
 between-subjects and within-subjects comparisons will be conducted.

 The research trial will be conducted at the outpatient-clinic at the Department of
 Psychology, Norwegian University of Science and Technology in Trondheim, Norway.

 Questions that will be addressed:

 1. Are the effects of MCT possible to replicate by a separate research group (other
 clinical groups than those that developed the method)?

 2. Is MCT better than a waitlist condition?

 3. Is change in positive and negative appraisals of rumination predictive of treatment
 outcome?

 4. What is the effect size of MCT for depression? How is the relapse prevention of MCT?

 5. Does the treatment have an effect on co-morbid anxiety disorder (s)?

 6. What treatment elements predict outcome in MCT?

 7. What effect does the treatment have on stable personality traits linked to depression
 and anxiety (e.g., neuroticism)?

 The meta-cognitive treatment program is based on Wells' manual. The patients who are
 receiving meta-cognitive therapy will be treated up to maximum 10 sessions, with weekly
 session of 45-60 minute duration.

 In the first treatment session, an idiosyncratic case formulation based on the MCT model of
 depression is built and shared with each patient. Socialization to the model then follows,
 which emphasizes how rumination and a high level of self focus (e.g., focusing on negative
 thoughts and feelings) maintains depression. At the end of the first treatment session,
 attention training (ATT) is introduced as a method of counteracting excessive self-focus, and
 to help patients' switch to a meta-cognitive mode of processing. ATT is an auditory attention
 task consisting of three stages; selective attention, attention switching and divided
 attention. The task takes approximately 10 minutes, and once practiced in session, patients
 are asked to implement ATT daily as a homework assignment. In-session practice of ATT is used
 throughout treatment.

 In the next sessions, treatment focuses on a careful identification of rumination, and on
 modifying related positive and negative beliefs. Verbal reattribution strategies are used to
 modify negative beliefs concerning the uncontrollable nature of rumination. This is followed
 by training patients in 'detached mindfulness', coupled with rumination postponement
 experiments which challenge the belief that rumination is uncontrollable. Patients are asked
 whether they have ever noticed their negative thoughts, but chosen to not engage with them.
 In this context, engagement means rumination, analysis of the thought, cognitive avoidance or
 any form of further processing of the thought. Patients may still be motivated to use
 rumination as a coping strategy if positive beliefs about rumination remain. To counteract
 positive beliefs, an analysis of the advantages and disadvantages of rumination is undertaken
 to demonstrate that rumination maintains depression and is not an effective method of coping.

 The final treatment sessions focused on relapse prevention and further modification of
 positive and negative meta-cognitive beliefs, including erroneous beliefs about the
 recurrence of emotion and deviations in mood. Relapse prevention further involves the
 development of a therapy blueprint which includes a written and diagrammatic formulation of
 the meta-cognitive model of depression. A detailed account of the main therapeutic strategies
 used during treatment is provided, along with a specific plan for the patient to implement in
 guiding their thinking and behavioral style in responses to future negative moods. Patients
 are encouraged to implement these strategies to maintain and strengthen the gains made over
 the course of treatment.

 The treatment will be administered according to the originators published treatment protocols
 for MCT. Independent assessors will assess adherence and quality of treatment.

 Independent experts will assess the quality of treatment by inspection of a sampling of
 video-recorded treatments. Using checklists session-by-session will ensure adherence of the
 therapy. Responsible investigator and supervisors will be using video of all treatment
 sessions to assess adherence to the treatment condition.

 1. All patients referred to the university clinic will be consecutively assessed at intake
 (SCID-I + II, HDRS-17). Based on diagnosis and criteria for inclusion and exclusion, the
 patients will be asked to volunteer to participate in the study and confirm by signing a
 form of consent.

 2. Patients will be randomized to one of two conditions.

 3. Patients will be asked to self-rate symptoms on a battery of self-report questionnaires.

 4. Meta-cognitive therapy will be given to patients in group 1, while group 2 is a waiting
 list control. Waiting list controls will be rated but not treated and will wait for
 treatment for 10 weeks.

 5. After 10 weeks the waiting list controls will transferred to the treatment group.

 6. The patients will be assessed prior to treatment, by 10 weeks in treatment, and at six
 months and at , one and two years of follow-up.

 7. Reassessment of the diagnosis and symptom severity is made by post-treatment.

 Criteria for recovery will be: Jacobsen criteria of a minimum change and patients crossing
 the cut-off point on two measures: The HDRS-17 and BDI. Other outcome measures will include:

 -  Reduction of depressive symptoms as measured by self-report questionnaires

 -  Number of patients with no MDD diagnosis based on SCID-I after treatment

 -  Relapse rate during six months and at , one and two years follow-up

 The proportion of responders as measured by the HDRS-17 and BDI and those who no longer
 fulfil the conditions for a MDD diagnosis at post-treatment and by 6 months and one and two
 years follow-up.

 The secondary efficacy variables will be the proportion of responders at post-treatment and
 six months and by , one and two years follow-up as measured by the other symptom measures. In
 addition, the proportions of responders as measured by MDD-S and the relapse rates during two
 one years of follow-up are selected to be one of the secondary efficacy variables.

 A comparison between the two groups of patients will be conducted at post-treatment and there
 will be 6 month and at one- and two years of follow up for the treatment condition. The null
 hypothesis is assumed. A within group analyses will be conducted in order to estimate effect
 sizes and significant clinical change estimates.

 Participants will be randomized in blocks of 17 patients divided on three conditions in a 1:2
 ratio. Two factors are controlled for in the randomization. First, gender, second the number
 of previous depressive episodes (DSM-IV, APA 1994). A computer provided by NTNU will generate
 the randomization list.
Inclusion Criteria:

 -  Major depressive disorder

 -  18 years or older

 -  Signed written informed consent prior to entry in the study

 Exclusion Criteria:

 -  Known somatic disease

 -  Psychosis

 -  Current suicide intent

 -  PTSD

 -  Cluster A or cluster B personality disorder

 -  Substance dependence

 -  Not willing to accept random allocation

 -  Not willing to withdraw psychotropic medication for a period of 4 weeks prior to entry
 to the trial