Antidepressants Causing Adverse Effects in Therapeutic Use
Conditions
Keywords
Pharmacogenomics, Primary care physicians
Brief summary
This is a 6-month randomized, wait-listed, controlled pilot trial conducted in 6 department of family medicine (DFM) clinics at the University of Michigan (UM). Physicians practicing at a UM DFM clinical site who are willing to utilize pharmacogenomic (PGx) test results to manage antidepressant use will be enrolled. Patients of these DFM physicians who are adults with a new prescription for a target antidepressant will also be enrolled.
Detailed description
This is a 6-month randomized, wait-listed, controlled pilot trial conducted in 6 department of family medicine (DFM) clinics at the University of Michigan (UM). We will enroll physicians practicing at a UM DFM clinical site who are willing to utilize PGx test results in conjunction with treating patients prescribed certain antidepressants. We will also enroll patients of these DFM physicians who are adults with a new prescription for an antidepressant (within the past 4 weeks) including patients who have switched to a new antidepressant from another antidepressant or have added on a new antidepressant to current antidepressant therapy. Patients are excluded if taking an antidepressant for more than 4 weeks or if they have had PGx testing in the past. Patients will be randomized to either an intervention or control group. Patients in the intervention group will have PGx test results available soon after enrollment while the control patients will have test results available 3 months after the first visit. All patients will complete a baseline, 3-, and 6-month assessment; control patients will have an additional 9-month assessment. Data to be collected include symptoms and severity (PHQ-8, GAD7), functional health status (SF-12), PGx knowledge, work status changes, demographic information, physician and emergency department visits, adverse effects, and medication alterations and adherence.
Interventions
DIAGNOSTIC_TESTPGx test
A laboratory developed genetic test that differentiates common and uncommon alleles in genes that have been previously identified as being involved in either the metabolism or response of drugs used in the treatment of depression and/or anxiety. The results are provided as a report that contains information related to the allele status of the patient's genes, translates this into a phenotype, and relates this phenotype to recommendation classes for drugs.
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Physician participants Inclusion criteria: * Be a practicing physician at a University of Michigan Department of Family Medicine clinic * Be willing to use PGx test results for their patients enrolled in the study * Be willing to allow study staff to contact their patients * Self-report that they are willing to prescribe antidepressants
Exclusion criteria
-Do not meet inclusion criteria Patient Participants Inclusion: * Be a patient of a participating physician * Have a new prescription for one of the following antidepressant medications: citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Rapiflux, Sarafem, Selfemra), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR), sertraline (Zoloft), duloxetine (Cymbalta, Irenka), venlafaxine (Effexor), venlafaxine XR (Effexor XR), nortriptyline (Aventyl, Pamelor), bupropion (Forfivo XL, Wellbutrin, Wellbutrin SR, Wellbutrin XL), mirtazapine (Remeron, Remeron Soltab), or vortioxetine (Trintellix) * Be willing to undergo PGx testing via single tube blood draw Exclusion: * Do not speak English * Have previously undergone PGx testing * Are unable to provide their own consent to participate in the study * Have been taking the new antidepressant prescription for longer than 4 weeks (prior to screening)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants Prescribed Antidepressant Medication | Baseline, 3 months, 6 months, and 9 months | Count of participants who have been prescribed antidepressant medications which are not contraindicated |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Symptom Severity - Patient Health Questionnaire (PHQ-8) | Baseline and 6 months | Change in PHQ-8 scores. The PHQ-8 is an 8-item participant-report measure for screening for depression and for establishing depression severity. The total score ranges from 0-24, with a higher score indicating greater depression symptom severity. |
| Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7) | Baseline and 6 months | The GAD-7 is a self-administered assessment for general anxiety disorder. The total score for the seven items ranges from 0 to 21. Higher values represent a worse outcome. |
| Change in Adherence to Refills and Medication Scale (ARMS) Scores | Baseline and 6 months | Change in medication adherence: The Adherence to Refills and Medication was scored by summing together the 14 items after first reversing the final item to be consistent in direction with the others. Individuals were allowed to have up to 2 missing values present which were imputed with the mean of the remaining answered items, only a handful of individuals answered 13 of the 14 questions resulting in a single item within their scale being imputed across the time periods. The questionnaire has 14 items with each item being recorded on a four-point Likert scale. The total score ranges from 14-56 with the lower score indicating better adherence. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Acceptability of PGx Testing | Baseline and 6 months | Acceptability of PGx testing in primary care among persons taking a target antidepressant and primary care physicians who care for them |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Delayed Intervention (Control Arm) Participants in this arm will have PGx test results made available to physicians 3 months after study enrollment
PGx test: A laboratory developed genetic test that differentiates common and uncommon alleles in genes that have been previously identified as being involved in either the metabolism or response of drugs used in the treatment of depression and/or anxiety. The results are provided as a report that contains information related to the allele status of the patient's genes, translates this into a phenotype, and relates this phenotype to recommendation classes for drugs. | 26 |
| PGx Test Participants in this arm will have PGx test results made available to physicians as soon available after enrollment.
PGx test: A laboratory developed genetic test that differentiates common and uncommon alleles in genes that have been previously identified as being involved in either the metabolism or response of drugs used in the treatment of depression and/or anxiety. The results are provided as a report that contains information related to the allele status of the patient's genes, translates this into a phenotype, and relates this phenotype to recommendation classes for drugs. | 25 |
| Physicians Physicians who practiced at 1 of the 6 UM Family Medicine clinics. | 24 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | For Physician arm only; those physicians who did not have patients who participated | 0 | 0 | 7 |
| Overall Study | Lost to Follow-up | 3 | 6 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Delayed Intervention (Control Arm) | PGx Test | Total | Physicians |
|---|---|---|---|---|
| Age, Continuous | 39.2 years STANDARD_DEVIATION 13.2 | 42.0 years STANDARD_DEVIATION 14.6 | 40.5 years STANDARD_DEVIATION 13.9 | — |
| Age of Physicians, Continuous | — | — | 41.83 years STANDARD_DEVIATION 10.47 | 41.83 years STANDARD_DEVIATION 10.47 |
| Education <4 yrs College | 8 Participants | 11 Participants | 19 Participants | 0 Participants |
| Education Bachelor's Degree | 7 Participants | 6 Participants | 13 Participants | 0 Participants |
| Education Graduate | 11 Participants | 8 Participants | 43 Participants | 24 Participants |
| Employment Employed | 19 Participants | 17 Participants | 60 Participants | 24 Participants |
| Employment Unemployed | 7 Participants | 8 Participants | 15 Participants | 0 Participants |
| Income 100k+ | 9 Participants | 10 Participants | 19 Participants | — |
| Income <50k | 7 Participants | 8 Participants | 15 Participants | — |
| Income 50k-99k | 10 Participants | 7 Participants | 17 Participants | — |
| Marital Status Married | 11 Participants | 15 Participants | 26 Participants | — |
| Marital Status Not Married | 15 Participants | 10 Participants | 25 Participants | — |
| Number of Children At Least One | 12 Participants | 12 Participants | 24 Participants | — |
| Number of Children No Children | 14 Participants | 13 Participants | 27 Participants | — |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 2 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 19 Participants | 61 Participants | 19 Participants |
| Region of Enrollment United States | 26 Participants | 25 Participants | 75 Participants | 24 Participants |
| Sex/Gender, Customized Female | 13 Participants | 14 Participants | 43 Participants | 16 Participants |
| Sex/Gender, Customized Male | 13 Participants | 10 Participants | 31 Participants | 8 Participants |
| Sex/Gender, Customized Other | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Smoking Status Non-Smoker | 25 Participants | 23 Participants | 48 Participants | — |
| Smoking Status Smoker | 1 Participants | 2 Participants | 3 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 25 |
| other Total, other adverse events | 0 / 26 | 0 / 25 |
| serious Total, serious adverse events | 0 / 26 | 0 / 25 |
Outcome results
Primary
Count of Participants Prescribed Antidepressant Medication
Count of participants who have been prescribed antidepressant medications which are not contraindicated
Time frame: Baseline, 3 months, 6 months, and 9 months
Population: Per protocol, only control arm patients were to have a 9 month assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Delayed Intervention (Control Arm) | Count of Participants Prescribed Antidepressant Medication | Month 6 | 6 Participants |
| Delayed Intervention (Control Arm) | Count of Participants Prescribed Antidepressant Medication | Month 3 | 5 Participants |
| Delayed Intervention (Control Arm) | Count of Participants Prescribed Antidepressant Medication | Month 9 | 5 Participants |
| Delayed Intervention (Control Arm) | Count of Participants Prescribed Antidepressant Medication | Baseline | 5 Participants |
| PGx Test | Count of Participants Prescribed Antidepressant Medication | Month 3 | 8 Participants |
| PGx Test | Count of Participants Prescribed Antidepressant Medication | Baseline | 8 Participants |
| PGx Test | Count of Participants Prescribed Antidepressant Medication | Month 6 | 8 Participants |
Secondary
Change in Adherence to Refills and Medication Scale (ARMS) Scores
Change in medication adherence: The Adherence to Refills and Medication was scored by summing together the 14 items after first reversing the final item to be consistent in direction with the others. Individuals were allowed to have up to 2 missing values present which were imputed with the mean of the remaining answered items, only a handful of individuals answered 13 of the 14 questions resulting in a single item within their scale being imputed across the time periods. The questionnaire has 14 items with each item being recorded on a four-point Likert scale. The total score ranges from 14-56 with the lower score indicating better adherence.
Time frame: Baseline and 6 months
Population: ARMs data is unavailable for 10 participants in the control arm and 8 participants in the PGx Test arm because of missing data at 6 months or loss to follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delayed Intervention (Control Arm) | Change in Adherence to Refills and Medication Scale (ARMS) Scores | baseline | 17.1 score on a scale | Standard Deviation 3.3 |
| Delayed Intervention (Control Arm) | Change in Adherence to Refills and Medication Scale (ARMS) Scores | 6 month | 17 score on a scale | Standard Deviation 2.5 |
| PGx Test | Change in Adherence to Refills and Medication Scale (ARMS) Scores | baseline | 17.4 score on a scale | Standard Deviation 3.2 |
| PGx Test | Change in Adherence to Refills and Medication Scale (ARMS) Scores | 6 month | 16.6 score on a scale | Standard Deviation 3.2 |
Comparison: baseline to 6 month comparisonp-value: 0.947t-test, 2 sided
Secondary
Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7)
The GAD-7 is a self-administered assessment for general anxiety disorder. The total score for the seven items ranges from 0 to 21. Higher values represent a worse outcome.
Time frame: Baseline and 6 months
Population: Because GAD-7 data is unavailable for 8 participants in the control arm and 7 participants in the PGx Test arm because of missing data at 6 months or loss to follow-up, the data is presented for those participants who had both data points so comparisons between the two time points are appropriate.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delayed Intervention (Control Arm) | Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7) | baseline | 9.1 score on a scale | Standard Deviation 6.2 |
| Delayed Intervention (Control Arm) | Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7) | Month 6 | 6.1 score on a scale | Standard Deviation 5 |
| PGx Test | Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7) | baseline | 6.9 score on a scale | Standard Deviation 5.6 |
| PGx Test | Change in Symptom Severity - General Anxiety Disorder - 7 (GAD 7) | Month 6 | 5.2 score on a scale | Standard Deviation 4.9 |
Comparison: Baseline p value to six monthp-value: 0.0327t-test, 2 sided
Comparison: baseline to 6 month comparison p valuep-value: 0.2088t-test, 2 sided
Secondary
Change in Symptom Severity - Patient Health Questionnaire (PHQ-8)
Change in PHQ-8 scores. The PHQ-8 is an 8-item participant-report measure for screening for depression and for establishing depression severity. The total score ranges from 0-24, with a higher score indicating greater depression symptom severity.
Time frame: Baseline and 6 months
Population: PHQ-8 data is unavailable for 8 participants in the control arm and 7 participants in the PGx Test arm because of missing data at 6 months or loss to follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delayed Intervention (Control Arm) | Change in Symptom Severity - Patient Health Questionnaire (PHQ-8) | Baseline | 9.0 score on a scale | Standard Deviation 4.4 |
| Delayed Intervention (Control Arm) | Change in Symptom Severity - Patient Health Questionnaire (PHQ-8) | 6 month | 7.5 score on a scale | Standard Deviation 4.3 |
| PGx Test | Change in Symptom Severity - Patient Health Questionnaire (PHQ-8) | Baseline | 8.6 score on a scale | Standard Deviation 6.1 |
| PGx Test | Change in Symptom Severity - Patient Health Questionnaire (PHQ-8) | 6 month | 5.8 score on a scale | Standard Deviation 5.4 |
Comparison: Baseline and 6 month valuesp-value: 0.0115t-test, 2 sided
Comparison: baseline to 6 month comparisonp-value: 0.027t-test, 2 sided
Other Pre-specified
Acceptability of PGx Testing
Acceptability of PGx testing in primary care among persons taking a target antidepressant and primary care physicians who care for them
Time frame: Baseline and 6 months