Comorbid Obesity and Depression With an Anti-inflammatory Medication

This is a single-centre feasibility using minocycline (200mg/daily) in participants with comorbid obesity and major depressive disorder (MDD). The study aims to investigate the feasibility and acceptability of this proof-of-concept study in comorbid obesity and depression, selected for elevated inflammation, using adjunctive minocycline treatment. We will test, in a 12-week feasibility, proof-of-concept study, whether individuals with comorbid obesity and treatment-resistant depression will complete an 8-week course of daily minocycline alongside their regular antidepressant treatment, complete biomarker measurements (e.g., blood, saliva, MRI), and complete other outcome measurements (e.g., questionnaires, interviews). Enrolment and retention rates will be monitored over the 12-week period. The acceptability and suitability of all assessment measures will be examined. Participant feedback of their activities will determine the acceptability of this study, and assist refinement of the design in preparation for a future RCT. The study will also aim to provide insight into the feasibility of using biomarkers of inflammation, as well as pathways affected by minocycline, towards the design of a future RCT in individuals with comorbid obesity and depression. Objective: Determine the feasibility and acceptability of this protocol in comorbid obesity and depression using minocycline as adjunctive treatment. Minocycline dosing regimen: After successful completion of the Screening Visit (Visit 1), eligible subjects will be invited for the Baseline (Visit 2) when they will be provided with the first bottle of minocycline (oral capsules) lasting 4 weeks. At the 4-week mark, subjects will return to the clinic to complete Visit 3 and associated visit procedures, including returning the medication bottle and any remaining capsules. Upon returning the bottle, the pharmacy will dispense a second bottle for the subject, once again containing minocycline for 4 weeks. In total, subjects will be taking minocycline for 8 weeks. The dose of 200mg will be taken once daily. Study schedule: Following consent, participants will be screened to ensure eligibility according to the inclusion and exclusion criteria as well as a small number of assessments (including safety bloods to check liver and kidney functioning) and questionnaires on mood, medical, and psychiatric history. Furthermore, we will ask each participant's general practitioner (GP) for a summary of the participant's medical records (including current and past medications). For females, a pregnancy test will be done at all visits to ensure that they are not pregnant. A small amount of blood (no more than 10ml, or about 2 teaspoons) will be taken to check your levels of inflammation and some other tests to look at overall health and confirm CRP levels are suitably elevated (at least 3mg/L). If following the screening, participants are deemed eligible, they will be invited for a baseline and then Week 4, Week 8, and Week 12 visits. Simultaneously, eligible participants will be sent a saliva sample collection kit in the post to complete at home and bring with them to their next visit. In this kit will be 6 tubes, saliva collection instructions, and a diary to track your sample collections. At the Baseline (visit 2) visit, we will repeat some of the questionnaires from the previous visit along with some new questionnaires, including some that ask about past stressful events, how they have been feeling since the last visit, and whether any medications have changed. A sample of blood (no more than 50ml, or 3 tablespoons) will be collected to check inflammation levels. At this visit, participants will also undergo their first brain MRI scan lasting approximately an hour. During this visit, participants will be given their first bottle of minocycline by a study doctor. Participants will take 2 capsules (each 100mg) orally, once a day in the mornings with breakfast, for 28 consecutive days, alongside their usual antidepressant. A diary to track the use of minocycline, any side effects or illness, and any medications taken will be provided too, as well as the 2nd saliva sample collection kit to be completed at home. At Week 4 (visit 3), after 28 days (±3 days) of taking minocycline, participants will return to the clinic for their next assessment. The assessment and blood collection will be the same as those completed at Baseline. No MRI will be conducted here. Participants will also be given their 2nd bottle of minocycline, dose the same as before, to take for another 28 consecutive days. As before, participants should continue taking their antidepressant normally alongside this and continue completing their diary to track the use of minocycline, any side effects, and any other drugs taken. With these, a saliva sample collection kit will again be provided to complete at home. At Week 8 (visit 4), after another 28 days (±3 days) of taking minocycline, participants will return for their final in-person visit to the clinic. All assessments, including the MRI, will be the same as those conducted at the Baseline visit. The remaining minocycline will be returned to the research team and no new bottle will be dispensed - this is the end of the minocycline administration. Finally, at Week 12, participants will be contacted by phone to complete the final set of questionnaires - the same set completed in person at the previous visits. No blood or saliva samples will be collected at this time point.