Desvenlafaxine in Opioid-Dependent Patients

Phase 4

Completed

• Conditions: Depression; Opioid Dependence; Methadone Treatment
• Interventions: Drug: Desvenlafaxine

• Registration Number: NCT02200406
• Lead Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Brief Summary

Background: Although substitution therapy has been shown to be highly effective to retain opioid-dependent patients in treatment and reduce drug use, this population is afflicted by numerous conditions including depression. Unfortunately, studies published thus far have reported inconsistent or no difference in response between placebo therapy and antidepressants such as selective serotonin reuptake inhibitors. Objective: To assess the feasibility of Desvenlafaxine (DESV) administration among opioid-dependent subjects and explore its effect on depressive symptoms. Methods: Open-label pilot trial of 8 weeks of DESV 50-100 mg/day in 20 methadone-maintained individuals with comorbid depressive symptoms at the Centre hospitalier de l'Université de Montréal. Significance: This pilot study will lay down the foundation on which a larger multisite clinical trial could be conducted to examine DESV as new treatment for opioid-dependent population with comorbid depression.

Detailed Description

To assess the feasibility, tolerability and acceptability of 8 weeks of Desvenlafaxine (DESV) administration among opioid-dependent subjects in a methadone-maintenance program, we will collect detailed information on compliance to DESV treatment, side effects, methadone plasma levels, methadone dose changes and QTc measures.

To explore the effects of DESV on depressive symptoms among opioid-dependent subjects on methadone-maintenance treatment. The severity and symptoms of depression will be evaluated by using the MADRS, the HRDS, and the CGI scale.

To explore the effects of DESV on substance use, anxiety, craving, quality of life and suicidal risk.

Study Timeline

• Study Start: 2014-07
• Study First Submitted: 2014-07-22
• Study First Submitted QC: 2014-07-23
• Study First Posted: 2014-07-25
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2017-08
• Last Update Submitted: 2020-10-21
• Last Update Posted: 2020-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• DSM-IV-TR criteria for opioid dependence;
• Subject is on methadone treatment in the substitution program for at least 4 weeks;
• Subject is aged between 18 and 65 years old;
• subject meets the DSM-V TR criteria for major depressive episode, according to the study psychiatrist and confirmed by the Mini International Neuropsychiatric Interview (MINI);
• Subject reports a score of 20 or higher on the MADRS;
• Subject is eligible for and consents to the study;
• subject is able to give valid, informed consent;
• subject is able to speak and read French or English (grade-nine level of language required)

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Exclusion Criteria

• Unstable medical illness, defined as any medical illness which has not been well-controlled with standard-of-care medications;
• Severe psychiatric condition (e.g., current acute psychosis, past or current hypomania/mania) based on the MINI;
• Pregnancy or breastfeeding;
• Inability to use a medically acceptable form of contraception throughout the study duration. A medically acceptable form of contraception is either: (1) contraceptive pill or intrauterine device or depot hormonal preparation (ring, injection, implant); and/or (2) a barrier method of contraception such as diaphragm, sponge with spermicide or condom;
• Subject currently takes another antidepressant;
• Treatment with Desvenlafaxine at any time in the past;
• Known hypersensitivity to venlafaxine;
• Subject is undergoing psychotherapies for current depression (support therapy or counseling are allowed);
• Subject failed to respond to two or more Health-Canada-approved antidepressants during current episode;
• Unstable Axis-II personality disorder or other Axis-II disorder which has been the primary focus of treatment in the past 3 months, as ascertained by a study psychiatrists;
• Medical diagnosis of kidney and/or liver failure

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Desvenlafaxine	Desvenlafaxine	* Open-label pilot study * Desvenlafaxine will be administered during 56 consecutive days * Desvenlafaxine will be administered in the morning at a 50 mg dose during weeks 1 and 2, and at 50-100 mg doses (based on the study psychiatrist's judgment) during the 6 following weeks.

Primary Outcome Measures

Name	Time	Method
Tolerability: Systematic Assessment for Treatment Emergent Events (SAFTEE)	8 weeks	Safety and adverse effects with the Systematic Assessment for Treatment Emergent Events (SAFTEE)

Secondary Outcome Measures

Name	Time	Method
Treatment adherence	8 weeks	Compliance will be evaluated at each in-person follow-up visit. Treatment adherence will be calculated as the total number of tablets dispensed minus the number returned, divided by the total number of tablets dispensed
Feasibility: Proportion of persons screened who are eligible and enrolled	Baseline	Proportion of persons screened who are eligible and enrolled
Effect of Desvenlafaxine administration on QT/QTc interval prolongation	4 weeks	It will be assessed by electrocardiograms (upper limit for safety should be 500ms).
Methadone dose adjustments	2 - 4 weeks	Change from baseline in methadone dose. Each dose adjustment occurring during the trial will be noted at each follow-up visit
Response to treatment	8 weeks	A favorable response will be defined as a score of 1 or 2 (very much or much improved) on the Clinical Global Impression CGI-I subscale
Feasibility: Proportion of scheduled study visits completed and biological samples collected	8 weeks	Proportion of scheduled study visits completed and biological samples collected
effect of Desvenlafaxine on depressive symptoms	8 weeks	Responders will be determined by a 50% reduction in the Montgomery-Asberg Depression Scale (MADRS) scores, and remitters will be determined based on scores of 10.
Potential for drug interactions between methadone and antidepressants - Effect of Desvenlafaxine on methadone serum level (pharmacokinetic variability)	4 weeks	Change from baseline in methadone serum level. We will assessed the methadone serum level at baseline and after a month of treatment.

Trial Locations

Locations (1)

Centre de recherche du Centre Hospitalier de l'Université de Montréal; 🇨🇦 Montréal, Quebec, Canada