Clinical trial NCT02200406: Desvenlafaxine in Opioid-Dependent Patients
Official title: An Open-Label Pilot Study of Desvenlafaxine for Opioid-Dependent Patients With Comorbid Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Opioid Dependence
Methadone Treatment
Keywords: Desvenlafaxine
Opioid-dependent
Addiction
Depression
Methadone
Comorbidity
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2014-07-25
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

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

Primary outcomes:
measure: Tolerability: Systematic Assessment for Treatment Emergent Events (SAFTEE)
timeFrame: 8 weeks
Secondary outcomes:
measure: effect of Desvenlafaxine on depressive symptoms
timeFrame: 8 weeks
measure: effect of Desvenlafaxine on depressive symptoms
timeFrame: 8 weeks
measure: Response to treatment
timeFrame: 8 weeks
measure: Feasibility: Proportion of persons screened who are eligible and enrolled
timeFrame: Baseline
measure: Treatment adherence
timeFrame: 8 weeks
measure: Effect of Desvenlafaxine administration on QT/QTc interval prolongation
timeFrame: 4 weeks
measure: Feasibility: Proportion of scheduled study visits completed and biological samples collected
timeFrame: 8 weeks
measure: Potential for drug interactions between methadone and antidepressants - Effect of Desvenlafaxine on methadone serum level (pharmacokinetic variability)
timeFrame: 4 weeks
measure: Methadone dose adjustments
timeFrame: 2 - 4 weeks
Other outcomes:
measure: Substance use
timeFrame: 8 weeks
measure: Effect of Desvenlafaxine on anxiety
timeFrame: 8 weeks
measure: Effect of Desvenlafaxine on blood pressure and heart rate
timeFrame: 8 weeks
measure: Effect of Desvenlafaxine on opioid craving
timeFrame: 8 weeks
measure: Effect of Desvenlafaxine on quality of life
timeFrame: 8 weeks
measure: Effect of Desvenlafaxine on disability
timeFrame: 8 weeks
measure: Effect of Desvenlafaxine on suicidal behaviour
timeFrame: 8 weeks
measure: Effect of Desvenlafaxine on testosterone level
timeFrame: 4 weeks
Locations:
city: Montréal
country: Canada
facility: Centre de recherche du Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Didier Jutras-Aswad, M.D., M.Sc.
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Suzanne Brissette, M.D., M.Sc.
role: STUDY_CHAIR
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Julie Bruneau, M.D., M.Sc.
role: STUDY_CHAIR
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Paul Lespérance, M.D., M.Sc.
role: STUDY_CHAIR
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Clairélaine Ouellet-Plamondon, M.D.
role: STUDY_CHAIR
References:
citation: El Hage C, Ghabrash MF, Dubreucq S, Brissette S, Lesperance F, Lesperance P, Ouellet-Plamondon C, Bruneau J, Jutras-Aswad D. A pilot, open-label, 8-week study evaluating desvenlafaxine for treatment of major depression in methadone-maintained individuals with opioid use disorder. Int Clin Psychopharmacol. 2018 Sep;33(5):268-273. doi: 10.1097/YIC.0000000000000223.