Motivational Interviews for Depression in Primary Care

Setting Denver Health is an integrated healthcare system. During the time period that the
trial was conducted, 2010 to 2012, Denver Health comprised eight federally qualified
community health facilities serving primarily uninsured and Medicaid patients in Denver,
Colorado, USA. The mainstay treatment for depression was antidepressant medication only, as
access to specialty mental health counseling or psychiatric services was not readily
available at the participating primary care facilities during the time frame of the trial.

Randomization and Masking We recruited seven primary care facilities housing 10 independent
care teams (clusters). Three facilities had two teams each, and four had one team. Although
staff and providers from different facilities and teams attend role-specific training
together and may share managers, each team has unique support staff, providers, and patient
panels. We used a blocked design to limit the possibility of patients crossing over from a
team assigned to one randomization group to one in the other group (contamination). Because
of a negative association between minority race/ ethnicity and depression diagnosis and
treatment receipt, we stratified the teams by the race/ ethnicity of the respective patient
populations at each facility (plurality Hispanic, non-Hispanic black, or non-Hispanic white).
Prior to randomization, we blocked eight of 10 teams into four pairs within strata because
they: (a) shared the same facility (three facilities with two teams each); or (b) were from
closely located neighborhoods (two facilities with one team each).

Outcome assessors who obtained written consent, conducted the baseline depression assessment,
and collected clinical outcomes were blinded to cluster allocation and were not involved in
other study procedures. Patient participants were blinded to group assignment. Participating
providers were not blinded.

Protocol Change Prior to recruiting patients into the intention-to-treat (ITT) groups, we
changed the primary outcome at the trial registration site on 4/29/10 from the outcome
specified in the original 2008 protocol, "adherence to antidepressant medication", to
"remission from depression." However, detecting remission, defined as an event where
depressive symptoms fall below a clinically significant level for a prolonged period, entails
weekly or bi-weekly outcome assessments (Nierenberg, 2001; Rush et al., 2006). Limited study
resources precluded closely spaced outcome assessments over 36 weeks. Therefore, to better
understand trajectories of clinical outcome for the primary care patients assigned to teams
staffed by providers trained to discuss depression with Motivational Interviewing versus
those patients assigned to teams staffed by untrained providers, measures of both continuous
depressive symptoms and a binary outcome measure (Patient Health Questionnaire-9 (PHQ-9)
score < 5) were calculated for each group at 6, 12, and 36 weeks.

Primary Care Providers In May 2009, the research team emailed 53 providers from 13 primary
care teams (eligible clusters) in eight facilities with an invitation to participate in a
study of "training for a new counseling method for treating depression." Inclusion criteria
included working at least 1.5 days per week in outpatient care, previous experience treating
depression, and availability for a one-day baseline MI training on 7/25/09. We obtained
consent from providers prior to randomization.

Patients During the recruitment phase, the research team called sequential eligible patients
2 to 3 days prior to scheduled visits with participating providers. The team assessed for
initial exclusion criteria and invited those not excluded to complete an audio-recorded
partial waiver of consent and stage-I depression screen, the Patient Health Questionnaire-2
(PHQ-2). Prior to the visit, a recruiter met patients scoring 2 or higher on either item of
the PHQ-2, described the study, obtained written informed consent, and invited consenting
patients to complete the PHQ-9.

Patients were excluded if they were attending a one-time disability qualification
examination, had no personal phone, were homeless, were treated for depression with
antidepressant medication within the previous 3 months, were currently in therapy provided by
a mental health specialist, had impaired memory, had a life-threatening physical disease,
expressed severe suicidal ideation, were pregnant or breastfeeding, or exhibited alcohol/
drug dependence, bipolar disorder or current psychosis assessed with a diagnostic schedule.

The recruiter notified the provider and patient prior to the clinical encounter when patients
scored 10 or higher on the PHQ-9, signifying 'probable major depression' . A board-certified
psychiatrist, blinded to patient allocation, diagnosed depression and determined additional
exclusion criteria. Patients diagnosed with a major depressive episode, not excluded for
other reasons, and completing a subsequent baseline telephone interview within 8 days, were
enrolled as the Intention-To-Treat (ITT) sample.

Intervention - MI with Standard Management of Depression The MI training approach included
interactive learning for the core MI skills. An 8-hour classroom training on 7/25/09
consisted of a brief overview of MI, videos and discussion of core MI skills and "MI Spirit,"
as well as skill-building practice. Providers learned how to use "OARS" and summaries to
elicit change talk, how to implement the elicit-provide-elicit technique, and how to craft
action plans with patients. Providers practiced using 0-10 Ruler questions to assess and
increase patient importance and confidence in changing.

The training was designed according to Arkowitz and Burkes' (2008) recommendation for a
three-component framework when using MI to discuss depression. In this framework, the
provider first helps explore the patient's negative emotions through reflective listening.
Second, the provider uncovers contributors to the negative emotions. Third, the patient's own
ideas about how to handle their negative emotions are elicited.

To optimize treatment integrity, 4-hour refresher sessions were offered after 4 and 12
months. Over the first 14 months, feedback was provided via email and face-to face regarding
audio-taped encounters (total two to four feedbacks per provider).

Control - Standard Management of Depression Alone All providers randomized to either
intervention or to control received a 1-hour slideshow and the "American Psychiatric
Association Practice Guideline for the Treatment of Major Depressive Disorder" (APA
depression guideline) (2010). The resources recommended antidepressant medications and
psychotherapy as evidence-based treatments for depression.

Measurements Baseline Descriptors. In addition to demographics, provider information included
training (M.D. versus mid-level) and certification (Family Practitioner, General Internist,
Physician's Assistant, or Nurse Practitioner), and years of clinical experience. Patient
descriptors included generalized anxiety disorder (past 6 months), federal poverty level, and
previous suicidal behavior.

Treatment Variables. Time spent discussing depression at the index visit was assessed from
audio-recorded encounters. Two measures of follow-up over 36 weeks, total primary care visits
dichotomized at the median and at least three or more visits with documented discussion of
mental health were abstracted from the electronic medical record. Receipt of antidepressant
medication and specialty mental health counseling was also determined.

Statistical Analysis Missing Data. Total missingness and whether missingness was differential
by group or cluster was assessed. Little's likelihood ratio test was used to test the
hypothesis that data is Missing Completely at Random (MCAR). To determine plausibility of
Missing at Random (MAR), correlations between baseline or auxiliary variables and missingness
by group at each time point were calculated.

Prior to performing the ITT analyses, Multiple Imputation through Chained Equations (MICE)
was conducted to deal with missing data. The Fully Conditional Specification algorithm in the
SAS MI procedure was used to generate 30 imputed datasets. The effects of the intervention on
depressive symptoms and on remission were determined on each imputed data set. MI repetition
results were combined to generate final estimates of parameters and confidence intervals for
depressive symptoms. Rubin's rules were used to combine the parameter estimates and errors
into a single set of results.

Treatment Outcomes. Analyses of treatment outcomes were run by ITT. Generalized linear mixed
effects models, adjusted for clustering of patients within care team, were used to examine
differences in outcomes by randomization group. Whereas randomization was stratified by class
(race/ ethnicity), the interaction between class and treatment group as well as class itself
were included in all multivariate analyses.

Main Effects. Main outcome analyses were run by ITT utilizing imputed datasets. General
linear mixed effects models, or generalized models for a binary outcome, were used to examine
whether the group x time interactions for outcomes depressive symptoms and remission were
significant. The general linear mixed model assumed unstructured variance-covariance
matrices, maximum likelihood (method = ML) estimation, and adjusted for clustering of
patients within care teams and repeated measures within patients. Whereas the random effect
of clustering patients within care teams on remission in the adjusted model was zero,
patients were not clustered within care teams in the generalized model for the binary
outcome.

Moderator hypothesis: A hypothesis concerning moderator variables was included in the
Colorado Multiple Institutional Review Board (COMIRB) protocol for the trial. In the protocol
approved with a COMIRB stamp on 2/3/10, specific aim #2 was "ii. Specific Aim #2: Aim 2 is to
explore for moderators and mediators of the effect of AMI-TAD on adherence and outcome. We
hypothesize that higher baseline patient self-efficacy will differentially increase the
effect of AMI-TAD with SCD." AMI-TAD is an earlier abbreviated name for the the MI training
intervention.

Inclusion Criteria:

1. Women and men aged 18 or older presenting at one of the seven DHH study clinics with a
new treatment episode for depression will be considered for the study.

2. The PHQ-9 is used to define depression category with a sensitivity and specificity for
MDD of at least 88%. Patients must have PHQ-9≥10 to ensure sufficient severity to
warrant intervention.

3. A new treatment episode is defined as no treatment with an antidepressant medication
for emotional problems over the previous 90 days, nor evidence-based psychotherapy for
depression.

4. The subjects must have major depression as determined by diagnostic schedule.

Exclusion Criteria:

1. Receipt of an antidepressant medication in the previous 90 days other than a low-dose
TCA for pain or Trazodone for sleep (e.g. amitriptyline ≤ 50 mg a day or Trazodone ≤
100 mg at night).

2. Current interpersonal or cognitive behavioral psychotherapy that focuses on
depression.

3. Female subjects who are either pregnant or nursing.

4. Subjects with drug or alcohol dependency or abuse (except for nicotine or caffeine)
within the preceding 6 months.

5. High risk for suicide.

6. Inability to communicate in English.

7. No personal telephone or homeless.

8. Lifetime bipolar disorder.

9. Psychosis.

10. Subjects with a lifetime history of autism, mental retardation, or pervasive
developmental disorders.

11. Subjects with uncorrected hypothyroidism or hyperthyroidism.

12. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory,
cardiovascular (including ischemic heart disease), endocrinologic, neurologic,
immunologic, or hematologic disease.