None listed
Conditions
Brief summary
A combination of currently approved drugs dextromethorphan and bupropion (D+B) was recently approved by the FDA for the treatment of depression. This combination differs from conventional antidepressants in that improvements in mood occur more rapidly after starting treatment, within 1-2 weeks. Dextromethorphan is a cough suppressant used in many cough and cold medicines. Bupropion is a medication used to help people stop smoking; in many other countries it is approved as an antidepressant. Psychotherapy (talking treatment) can also help in the treatment of depression. One of the recommended psychotherapies is Behavioural Activation Therapy (BAT). Our study aims to see if combining BAT with D+B can help treat depression and prevent relapse once D+B treatment finishes. We hypothesis that treatment with D+B is likely to help with participants' depressed mood in the short-term-within 1 week of dosing and combining D+B with BAT psychotherapy will improve outcomes and prevent relapse once D+B treatment ends.
Interventions
In this study, all patients will receive Dextromethorphan + Bupropion (D+B) for 8 weeks, with approximately half randomized to receive 12 sessions of Behavioral Activation Therapy (BAT) as well. All participants will receive D+ B (50 mg + 150 mg) once daily for 3 days, followed by twice daily for the remainder of the study. In Day 1, initial dosing with D+B will be in the clinic to establish tolerance. Subsequently, we would give patients take home tablets. All participants will receive nursing
In this study, all patients will receive Dextromethorphan + Bupropion (D+B) for 8 weeks, with approximately half randomized to receive 12 sessions of Behavioral Activation Therapy (BAT) as well. All participants will receive D+ B (50 mg + 150 mg) once daily for 3 days, followed by twice daily for the remainder of the study. In Day 1, initial dosing with D+B will be in the clinic to establish tolerance. Subsequently, we would give patients take home tablets. All participants will receive nursing contact and oversight on dosing days in clinic and by telephone as needed over the study period. Mood ratings and assessments of safety and tolerability will be collected at each visit. Safety data will be monitored for at least 2 hours after initial D+B dosing and at visits 3-6. Adverse events will be monitored throughout the study. Safety data will consist of a baseline assessment of general well-being, including systems enquiry, vital signs (blood pressure, heart rate, and temperature). At initial dosing, vital signs (blood pressure, heart rate, respiratory rate, O2 saturation) will be obtained pre-dose, 30, 60 and 120 mins post dosing. At visits 3-6, vital signs will be recorded once. To monitor adherence to the intervention, participants will be given enough medicine for the duration from one visit to the next visit. BAT consists of 12 sessions provided at twice-weekly intervals for 4 weeks, then weekly intervals for 4 weeks (8 weeks in total). BAT will be provided in a clinic or via Zoom, depending on participant’s preference. BAT content includes psychoeducation about depression and the BAT model, values, goal setting, scheduling pleasant and mastery activities, negotiating support from others, dealing with rumination and worry, skills training as needed (e.g. problem solving, assertive communication) and managing early signs of relapse. BAT will include an initial focus on symptom reduction followed by maintenance of improvements and behavioural change to prevent relapse. BAT sessions will be scheduled within 24 hours of D+B dosing. This timing is intended to benefit from the anticipated improved mental state following D+B treatment and to enhance the potential for change. The approximate duration of BAT sessions is 50 Minutes. BAT will be provided by a psychologist. Supervision of the BAT therapist and fidelity checks of BAT delivery will occur.
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
• Male or female aged between 18 and 65 years • In good general health • Capable of understanding and signing an informed consent. Good general use of English. • Participants will receive the DSM-5 MINI Diagnostic Interview at screening to provide conventional DSM-5 diagnoses and will have moderate to severe treatment-resistant depression (TR-MDD). We will also quantify the severity of treatment resistance using the Maudsley staging method. At screening, patients will have a MADRS score of greater than or equal to 20, reflecting depression of at least moderate severity. • Participants will be required to be on stable medication treatment (or no treatment) for at least 1 month prior to screening for the study and commit to remaining on the same medication during active treatment to ensure treatment withdrawal or dose changes do not confound study effects.
Exclusion criteria
• Evidence of severe acute or chronic medical conditions (e.g. diabetes, ischaemic heart disease, chronic obstructive airways disease, cerebrovascular disease). • Past or current diagnoses of schizophrenia, bipolar disorder, or current psychotic symptoms; moderate-severe personality disorder • Female patients who are intending to become pregnant or breastfeeding • Current or recent significant suicidal ideation (Score of greater than or equal to 4 on the MADRS suicide item). • Current or recent (past 6 months) substance use disorder. • Current or prior history of seizures. • Prior history of serious head injury or other neurological condition resulting in ongoing cognitive impairment. • Receiving active psychotherapy for MDD (supportive psychotherapy can be placed on hold during the study) • Having received a course of BAT in the last 12 months; previous non-response to BAT or D+B treatment. • Treatment with Electroconvulsive Therapy (ECT) in the last 6 months. • Current or prior diagnosis of bulimia or anorexia nervosa. • Use of a Monoamine Oxidase Inhibitor (MAOI) within 14 days of study entry. • Known hypersensitivity to bupropion and/or dextromethorphan. • Current use of medications that are strong inhibitors (e.g. ticlodipine, voriconazole) or inducers (e.g. evafirenz, carbamazepine, artemisinin, rifampin) of CYP2B6. • Current use of medications that are strong inhibitors (e.g. fluoxetine, tiparoxetine, quinidine) of CYP2D6.
Outcome results
None listed