Purpose:
Cancer and depression commonly occur together, and each worsens the other. We conducted a
large psychotherapy study treating depression in breast cancer patients, showing that
psychotherapy lowers symptoms. Surprisingly, no studies have compared depression-focused
psychotherapy to antidepressant medication for patients with breast cancer and depression. We
applied to the National Cancer Institute for a large, cross-national grant. Reviewers asked
us to first demonstrate that patients would accept either psychotherapy or medication as
treatment.
Thanks to funding from the Columbia Herbert Irving Cancer Center, we will test this study
approach. We will randomly assign 20 patients with both non-metastatic breast cancer and
major depression to 12 weeks of tele-therapy (by Zoom) with either interpersonal
psychotherapy or a serotonin reuptake inhibitor. We expect patients in both treatments to
report improvement in depression symptoms. We will also measure C-reactive protein, a blood
test of inflammation elevated in both cancer and depression, which may predict medication
response.
Study summary:
Screening. All patients with non-metastatic, Stage I-III breast cancer who are undergoing
care at HICCC will be offered the PHQ-9, a brief, reliable, widely used depression screener.
This provides an opportunity to assess depression prevalence in the HICCC population.
Patients who screen positive for likely major depression (PHQ-9 score ≥10; sensitivity 88%,
specificity 88%)26 will be offered further evaluation and an explanation of the study.
Independent evaluators trained to reliability will assess patient eligibility. Inclusion
criteria: 1) Age ≥18 and <80; 2) diagnosis of diagnosis of Stage I-III breast cancer (<10
years from diagnosis), based on patient report and HICCC chart; 3) MDD episode without
psychotic features on Structured Clinical Interview for DSM-5 (SCID-528); 4) 24-item Ham-D27
score ≥18; 5) written informed consent. Men and women are eligible. Exclusion criteria: 1)
Psychosis (by SCID-5 interview); 2) current moderate/severe substance use disorder (mild
substance disorder is not an exclusion) (by SCID-5); 3) acute suicidal risk (Ham-D suicide
item score >2); 4) history of non-response to (>6 week) trials of venlafaxine (≥225 mg/d) and
escitalopram (≥20 mg/d); 5) history of non-response to IPT (>4 sessions); 6) receiving
current medication or psychotherapy treatment for depression; 7) acute medical instability
(too physically debilitated to participate in trial) or delirium; 8) inability to complete
self-administered questionnaires in English; 9) current enrollment in a therapeutic oncology
trial; 10) known metastases. Eligible patients who consent will be randomly assigned in 1:1
ratio to 12 weeks of IPT or SRI (venlafaxine XR or escitalopram, based on treatment history).
Study-eligible patients will be interviewed by a research assistant using an open-ended
inventory of patient willingness and disinclination to participate in the study based on
factors including treatment preference, tele-therapy preference, cell phone and computer
broadband access, socioeconomic status and family burden, work conflicts, interpersonal
support, and outside depression treatment. We will tabulate the number of patients already
receiving antidepressant treatments, whose non-participation would not reflect on treatment
acceptability or study participation.
Treatments. As both treatments were initially intended to be delivered as tele-therapy in the
multi-site SWOG grant proposal, they are well adapted to the Covid-19 era.9 All treatment
sessions and all assessments (unless patient is visiting the HICCC in person and prefers
this) will be conducted via HIPAA-secure Zoom. Tele-therapy has become standard treatment
during the pandemic9 and may ease access for already burdened BC patients. Tele-therapy may
improve current undertreatment of MDD among patients with BC.
IPT is a well-defined, manualized, repeatedly proven treatment for depression.14,29 Dr.
Markowitz, a leading IPT researcher with multiple NIH grant experience, including with
tele-therapy,9,30 will supervise already trained IPT therapists based on recorded
HIPAA-secure Zoom sessions. IPT defines depression as a treatable medical illness that is not
the patient's fault, and which often arises in the context of distressing life events - such
as the diagnosis of breast cancer, and the effect of cancer and its treatment on body image.
In 12 50-minute weekly sessions, IPT helps patients understand and accept their feelings in
an environmental context and to use their emotions to handle the crisis and build protective
social support.
Pharmacotherapy. Dr. Hellerstein, a clinical trials veteran, will provide expert supervision,
supplementing a manualized medication approach.31 In our experience, venlafaxine (VLX) and
escitalopram (ESC) are the two antidepressants best tolerated and least likely to interfere
with oncotherapy for patients with MDD and breast cancer. Having minimal CYP2D6 inhibition
and hence interfering less with tamoxifen and aromatase inhibitor metabolism, VLX makes sense
as first choice; ESC mildly inhibits 2D6. Tele-sessions lasting 20-30 minutes will occur
weekly for two weeks, then biweekly through week 12. Clinicians will raise doses as tolerated
to ensure efficacy, assessing side effects by checklist, to a maximum of velafaxine XR 300 mg
or escitalopram 30 mg daily. Pharmacotherapists will not conduct psychotherapy.
Assessments will be conducted at baseline, midpoint, and end of treatment (weeks 0, 6, and
12) by raters reliably trained on instruments and blinded to treatment assignment.
Self-reports will be conducted online using REDCap. Treatment sessions will be recorded for
therapist adherence rating using the established CSPRS-6 scale.32 In addition to the rating
instruments, the PI and co-PI will tele-interview all patients post-treatment to determine
their level of and reasons for treatment satisfaction and dissatisfaction, and will debrief
all study clinicians to determine their views of patient treatment acceptability, comfort,
and satisfaction.
The study will employ standard observer and self-report assessments. The PROMIS-2936 assesses
not only psychiatric and medical symptom domains but quality of life and meaning and purpose,
factors that might potentially distinguish treatment effects. We have previously used such
scales to evaluate treatment trials, and similarly expect high levels in this study:
clinician treatment fidelity (>95%), patient treatment preference, and patient satisfaction
(>80% scores). We have allocated in the study budget $50 compensation for patients who
complete their week 12 evaluations.
Data analysis. 1. Descriptive statistics such as means with standard deviation, proportions,
and counts will be reported to characterize BC patients that will be screened. 2. Point
prevalence of depression at HICCC for patients with Stage I-III BC will be calculated. 3.
Qualitative analysis will be used to report reasons eligible patients would participate in or
decline the study. Zero-Inflated Poisson regression will be used to model both study
participants and eligible BC patients who decline the study. 4. Paired t-test or Fisher's
exact test will be used to compare outcome changes between baseline and end of study.
Proportion responding (≥50% Ham-D-24 decrease from pre-treatment Ham-D-24) and remission rate
(Ham-D-24 ≤7) will be the outcomes of interests.
Criteria:
Inclusion Criteria:
- diagnosis of diagnosis of Stage I-III breast cancer (<10 years from diagnosis)
- episode of major depressive disorder without psychotic features on Structured Clinical
Interview for DSM-5 (SCID-5)
- 24-item Hamilton Depression Rating Scale score ≥18
- written informed consent
Exclusion Criteria:
- Psychosis (by SCID-5 interview)
- current moderate/severe substance use disorder (mild substance disorder is not an
exclusion)
- acute suicidal risk
- history of non-response to (>6 week) trials of venlafaxine (≥225 mg/d) and
escitalopram (≥20 mg/d);
- history of non-response to IPT (>4 sessions
- receiving current medication or psychotherapy treatment for depression
- acute medical instability (too physically debilitated to participate in trial) or
delirium
- inability to complete self-administered questionnaires in English
- current enrollment in a therapeutic oncology trial
- known metastases