Exploring Clinical Subgroups of Participants with Major Depressive Disorder that may Benefit from Adjunctive Minocycline Treatment

Objective@#To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). @*Methods@#This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. @*Results@#There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. @*Conclusion@#Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications.

Improved Antidepressant Remission in Major Depression via a Pharmacokinetic Pathway Polygene Pharmacogenetic Report

OBJECTIVE: Major depressive disorder (MDD) is projected to be a leading cause of disability globally by 2030. Only a minority of patients remit with antidepressants. If assay of polymorphisms influencing central nervous system (CNS) bioavailability could guide prescribers to more effectively dose patients, remission rates may improve and the burden of disease from MDD reduce. Hepatic and blood brain barrier (BBB) polymorphisms appear to influence antidepressant CNS bioavailability. METHODS: A 12-week prospective double blind randomized genetically guided versus unguided trial of antidepressant dosing in Caucasian adults with MDD (n=148) was conducted. RESULTS: Subjects receiving genetically guided prescribing had a 2.52-fold greater chance of remission (95% confidence interval [CI]=1.71-3.73, z=4.66, p<0.0001). The number needed to genotype (NNG)=3 (95% CI=1.7-3.5) to produce an additional remission. CONCLUSION: These data suggest that a pharmacogenetic dosing report (CNSDose(R)) improves antidepressant efficacy. The effect size was sufficient that translation to clinical care may arise if results are independently replicated.