Clinical trial NCT05503966: Combining Antidepressants and Attention Bias Modification in Depression
Official title: Combining Antidepressants and Attention Bias Modification in Depression: a Randomized Controlled Trial in Primary Care
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depressive Disorder
Keywords: Major Depressive Disorder
Attentional Bias Modification
Primary Health Care
Lead sponsor: University of Oslo
Sponsor class: OTHER
Collaborators: name: University of Oxford
First posted: 2022-08-17
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a three-armed, double-blinded, pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants (SSRI ABM group) in primary care compared to standard antidepressant treatment (SSRI TAU group). The third group will in addition to TAU be engaged in answering all the questionnaires and perform all the tasks, but without ABM, thus controlling for being engaged in some cognitive activity (SSRI Active comparison group).
Primary purpose: TREATMENT

Brief summary: Background: Major depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care (PHC) in the municipalities and represent a challenging group. Attentional Bias Modification (ABM) training in combination with antidepressants (SSRIs) could be an effective treatment. The overall aim of this study is to test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in PHC will result in further improvement of symptoms compared to treatment with antidepressants alone (treatment as usual, TAU) and as compared to an active comparison condition.

Methods: A total of 246 patients with a diagnosis of MDD will be included in this study. The study is a three-armed pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants in primary care (ABM condition) compared to standard antidepressant treatment (TAU condition). In a third group participants will complete the same schedule of intermediate assessments as the ABM condition in addition to TAU , but no ABM, thus controlling for the non-training-specific aspects of the ABM condition (SSRI Active comparison group).

Discussion:

The clinical outcome of this study may help develop easy accessible, low cost treatment of depression in PHC. Moreover, the study aims to broaden our knowledge of optimal treatment for patients with a MDD by providing adjunct treatment to facilitate recovery and long term gain

Detailed description: Major Depressive Disorder (MDD) is a debilitating disorder that affects 15% of the population and is a leading cause of disability worldwide. The economic burden of MDD is enormous, with estimates of direct/indirect costs of $210.2 billion/year in the US alone.

Although both psychotherapy and antidepressant medications are effective, it is not uncommon for a patient with MDD to have temporary symptom reduction after treatment but require an extended amount of time for full restoration of function. A large proportion of MDD patients are treated in PHC in the municipalities and represent a challenging group to treat effectively. At the same time, it is known that early treatment and coordinated follow-up can be efficient even without costly specialist interventions or hospital treatment. Thus, improved treatment of MDD in municipalities represents a tremendous opportunity for improvement of public health and well being in the general population.

Considerable progress has been made in characterizing mechanisms underlying depression vulnerability and this may be harnessed to improve future treatment strategies. The ability to deal effectively with stress and life events is influenced by the ability of the brain to rapidly adapt, which in turn is a function of synaptic plasticity. Further, it has been hypothesized that the capacity of synapses for functional and structural change plays an important role in the pathophysiology and treatment of mood disorders. These dysfunctional neural mechanisms are affected by antidepressants and increased synaptic plasticity may be one of the therapeutic mechanisms. However, enhancing plasticity alone may not lead to a sufficient treatment response in all individuals affected by depression. Indeed, the entrenched attentional biases seen in depression, such as the tendency to focus on and recall negative information, may persist and be further entrenched by changes in the neural underpinnings of learning and memory. Furthermore, negative attention biases are associated with persistence of sad mood in major depressive disorder. However, selective biases in attention can potentially be modified by a simple computerized technique: The Attention Bias Modification Task (ABM).

While some studies have reported an effect of ABM in depression, definitive conclusions have been limited by small samples and poor trial methodology in many studies. However, recently a large RCT study showed that ABM training led to significantly greater decrease in clinician-rated symptoms of depression as compared to the control condition. ABM induced a change in AB towards relatively more positive stimuli for participants that also showed greater symptom reduction. A secondary network analysis indicated that ABM primarily influenced the symptom "interest" which could mediate both symptoms, social support, functioning and quality of life. Furthermore, a sub-sample was included in a brain imaging study revealing that the ABM active group showed reduced activation in the amygdala and the anterior cingulate cortex when passively viewing negative images compared to the sham group. Other studies have also found that experimentally modifying negatively biased attention reduces depressive symptoms. However, some studies have showed that ABM is not significantly better in improving depressive symptoms as compared to sham.

In addition to explore mechanisms of neuroplasticity, in parallel research there has also been interest in understanding the effects of antidepressant drugs on psychological processes involved in depression. Thus, a number of studies for more than a decade have documented that SSRIs modify biases in emotional processing, thus they work by modifying the same underlying basic mechanism that are the focus when applying ABM procedures. Emotional processing is influenced early in the treatment and independently of change in subjective mood, and these effects have been shown in depressed subjects as well as in healthy volunteers. Most of these studies investigated the effects of a single dose of an SSRI compared with placebo. However, it has been showed that antidepressants as prescribed in the community also increases processing for positive information.

A logical next step is to combine SSRIs as prescribed in primary health with an ABM procedure. Combining pharmacological and psychological regimes are gold standard treatment options in both depression and anxiety and is not associated with baseline severity.Treatments, such as cognitive behavioral therapy (CBT) might also change attentional biases, but by implementing an ABM procedure we will more readily target these biases directly. By combining ABM with today's treatment options, we could potentially increase treatment efficacy and shorten treatment duration. Furthermore, ABM has the advantage of being entirely deliverable on a digital platform without the need for therapist interaction.

The main aim of this study is to test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in PHC will result in a clinically important improvement of symptoms compared to treatment with antidepressants alone (TAU), and as compared to an active comparison condition. Secondary aims are to investigate possible effects of the combined treatment on anxiety symptoms, emotional blunting, rumination, perceived stress, psychosocial functioning/work and suicidal risk. Thirdly, a number of potential moderators will also be investigated.

Eligibility criteria: Inclusion Criteria:

* Major Depressive Disorder
* BDI II \> 14
* Age 18 - 65 years
* Ability to understand and speak a Scandinavian language
* Willingness and ability to give informed consent

Exclusion Criteria:

* Current or past neurological illness
* Traumatic brain injury
* Current alcohol and/or substance dependency disorders
* Psychotic disorders
* Bipolar disorder type 1,
* Developmental disorders and mental retardation.

Primary outcomes:
measure: Hamilton Depression Rating Scale
timeFrame: 8 weeks after baseline.
measure: Beck Depression Inventory II
timeFrame: 8 weeks after baseline.
Secondary outcomes:
measure: Beck Depression Inventory II
timeFrame: Follow-up 12 weeks after baseline.
measure: Beck Depression Inventory II
timeFrame: Follow-up 6 months after baseline
measure: Generalized Anxiety Disorder-7
timeFrame: 8 weeks after baseline.
measure: Generalized Anxiety Disorder-7
timeFrame: 12 weeks after baseline.
measure: Generalized Anxiety Disorder-7
timeFrame: 6 months after baseline
measure: Oxford Depression Questionnaire
timeFrame: 8 weeks after baseline
measure: Oxford Depression Questionnaire
timeFrame: 12 weeks after baseline.
measure: Oxford Depression Questionnaire
timeFrame: 6 months after baseline
measure: Rumination Response Scale
timeFrame: 8 weeks after baseline.
measure: Rumination Response Scale
timeFrame: 12 weeks after baseline
measure: Rumination Response Scale
timeFrame: 6 months after baseline
measure: The Perceived Stress Scale
timeFrame: 8 after baseline
measure: The Perceived Stress Scale
timeFrame: 12 weeks after baseline
measure: The Perceived Stress Scale
timeFrame: 6 months after baseline
measure: The Work and Social Adjustment Scale
timeFrame: 8 weeks after baseline.
measure: The Work and Social Adjustment Scale
timeFrame: 12 weeks after baseline.
measure: The Work and Social Adjustment Scale
timeFrame: 6 months after baseline.
measure: Bergen Insomnia Scale
timeFrame: 8 weeks after baseline.
measure: Bergen Insomnia Scale
timeFrame: 12 weeks after baseline.
measure: Bergen Insomnia Scale
timeFrame: 6 months after baseline.
measure: Beck depression Inventory II (Suicid item)
timeFrame: 8 weeks after baseline.
measure: Beck depression Inventory II (Suicid item)
timeFrame: 12 weeks after baseline.
measure: Beck depression Inventory II (Suicid item)
timeFrame: 6 months after baseline.
measure: Dot probe
timeFrame: 8 weeks after baseline.
measure: Dot probe
timeFrame: 12 weeks after baseline
measure: Dot probe
timeFrame: 6 months after baseline.
measure: Facial Expression Rating Task
timeFrame: 8 weeks after baseline
measure: Facial Expression Rating Task
timeFrame: 12 weeks after baseline
measure: Facial Expression Rating Task
timeFrame: 6 months after baseline
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Jan Ivar Røssberg
state: Nydalen
Study officials:
affiliation: Universitetet i Oslo/Oslo universitetssykehus
name: Jan I Røssberg, PhD
role: PRINCIPAL_INVESTIGATOR
References: