Buprenorphine Used With Treatment Resistant Depression in Older Adults

• Status: Completed
• Trial end date: 2018-04-30
• Target enrollment: 0
• Participant gender: All

Summary

The investigators are conducting a research study to learn about the safety and benefit of using a medication called buprenorphine for patients with difficult to treat depression. This research study is testing whether combining two medications will be effective in treating depression when initial treatment with just one antidepressant does not relieve the depressive symptoms; this is what is called "difficult to treat depression" or "treatment resistant depression". The two medications the investigators are using are: an anti-depressant medication called venlafaxine extended release (venlafaxine XR), which is the generic form of Effexor, and buprenorphine. Buprenorphine is a medication that is FDA approved for the treatment of opioid dependence. The investigators are testing whether adding buprenorphine to venlafaxine XR enhances treatment response.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborator: Reckitt Benckiser LLC
• Treatments: Buprenorphine; Venlafaxine Hydrochloride

Criteria

Inclusion Criteria for Main Study:

1. Age > or = to 50 years.

2. Major depressive disorder (MDD), single or recurrent, as diagnosed by the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID-IV).

3. Montgomery Asberg Depression Rating Scale (MADRS) >/= to 15.

4. Has or agrees to establish a clinical relationship with primary care physician (PCP).

5. Availability of an informant (e.g., emergency contact).

Exclusion Criteria:

1. Inability to provide informed consent.

2. Depressive symptoms not severe enough (i.e., MADRS < 15) at the baseline assessments

3. Dementia, as defined by Mini Mental State Exam (3MS) < 84 and clinical evidence of dementia (e.g., memory impairment, executive dysfunction, agnosia, apraxia, aphasia, with functional impairment).

4. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the SCID.

5. Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and confirmed by study physician interview.

6. Drinking 15 or more drinks per week or consuming 5 or more drinks on any one occasion in the past week.

7. High risk for suicide (e.g., active SI and/or current/recent intent or plan) and unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases.

8. Contraindication to venlafaxine XR or BPN as determined by PCP and study physician including history of intolerance of either venlafaxine XR or BPN in the study target dosage range (venlafaxine XR at up to 300 mg/day; BPN at up to 2 mg/day).

9. Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English).

10. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

11. Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. This will be determined based on information from the patient's personal physician and study physician's clinical judgment. Referral to the patient's personal physician or to a general practitioner will be made in these cases.

12. Subjects taking psychotropic medications that cannot be safely tapered and discontinued prior to study initiation. The following exceptions are allowed if they have been taken at a stable dose for at least 4 weeks prior to study entry and there is not a plan to change the dose during the next 28 weeks: benzodiazepines up to 2 mg/d lorazepam equivalent; other sedative-hypnotics (e.g., zolpidem, zaleplon, eszopiclone); gabapentin if prescribed for non-psychiatric indication (e.g., neuropathy).

13. History of opioid abuse or dependence.

14. Severe pain, defined as > 7 on 0-10 numeric rating scale for pain.

15. Concomitant use of strong or moderate CYP3A4 inhibitor (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem).

16. Refusal to stop all opioids (to avoid precipitating opioid withdrawal).

17. Hepatic impairment

18. Estimated Glomerular Filtration Rate (GFR) < 20 ml/min.

19. Inability/refusal to identify a person as an emergency contact.

20. Pregnancy