1.Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?
Samantha E. RUSSELL ; Anna L. WROBEL ; Melanie M. ASHTON ; Alyna TURNER ; Mohammadreza MOHEBBI ; Michael BERK ; Sue COTTON ; Seetal DODD ; Chee H. NG ; Gin S. MALHI ; Olivia M. DEAN
Clinical Psychopharmacology and Neuroscience 2023;21(3):457-465
Objective:
Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder.
Methods:
Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (+4 weeks discontinuation).Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined.
Results:
There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning.
Conclusion
There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.
2.The Impact of N-acetylcysteine on Major Depression: Qualitative Observation and Mixed Methods Analysis of Participant Change during a 12-week Randomised Controlled Trial
Samantha E. RUSSELL ; David R. SKVARC ; Mohammadreza MOHEBBI ; David CAMFIELD ; Linda K. BYRNE ; Alyna TURNER ; Melanie M. ASHTON ; Michael BERK ; Seetal DODD ; Gin S. MALHI ; Sue M. COTTON ; Ashley I. BUSH ; Olivia M. DEAN
Clinical Psychopharmacology and Neuroscience 2023;21(2):320-331
Objective:
N -acetylcysteine (NAC) is a novel therapeutic agent with multiple mechanisms of action in the central nervous system and a favourable side effect profile. Clinical evidence indicates that adjunctive NAC may reduce the severity of depressive symptoms in individuals with major depressive disorder (MDD).
Methods:
A 12-week randomised controlled trial of 2,000 mg/day adjunctive NAC for MDD found no significant improvement at the primary endpoint (week 12) but did see improvements at the post-discontinuation interview (week 16). Within the context of patient-centered treatment, mixed-methods qualitative analysis was also included to explore factors that may determine individual responses to adjunctive NAC treatment. These data were drawn, under blinded conditions, from clinician notes recorded in the case report form. Using the DSM-5 symptom profile for MDD as the initial framework, themes were developed and explored. Frequencies were compared between placebo and NAC groups.
Results:
Per protocol analysis of individual themes across the six interviews revealed group differences in favour of NAC for overall depressive affect, optimism, relationships and reduced functional impairment.
Conclusion
This study provides further evidence for the utility of the mixed methods approach complimenting the primary findings using traditional quantitative analyses, as well as being able to capture additional, often more subtle, evidence of individual symptom-level change that reflects improvement in functional abilities in response to NAC supplementation. The use of mixed methods to explore outcomes from psychiatric studies should be considered in future to work towards improved patient-centred care and both confirm quantitative findings and generate novel hypotheses.
3.Exploring Clinical Subgroups of Participants with Major Depressive Disorder that may Benefit from Adjunctive Minocycline Treatment
Gerard ANMELLA ; Alcy MEEHAN ; Melanie ASHTON ; Mohammadreza MOHEBBI ; Giovanna FICO ; Chee H. NG ; Michael MAES ; Lesley BERK ; Michele De PRISCO ; Ajeet B. SINGH ; Gin S. MALHI ; Michael BERK ; Seetal DODD ; Diego HIDALGO-MAZZEI ; Iria GRANDE ; Isabella PACCHIAROTTI ; Andrea MURRU ; Eduard VIETA ; Olivia M. DEAN
Clinical Psychopharmacology and Neuroscience 2024;22(1):33-44
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.