|
Title
|
|
|
|
The search for novel treatments for major depressive disorder
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Major depressive disorder (MDD) is a severe recurrent psychiatric disorder that affects over 300 million people globally and is a recurrent psychiatric condition. Treatment for MDD involves mainly pharmacotherapy and psychotherapy but is often inadequate, with a significant portion of patients not achieving complete remission. Residual symptoms such as fatigue and cognitive dysfunction frequently persist. After a first episode, up to 85% of patients experience recurrence. This thesis examines new strategies to address these unmet needs in treating MDD. Different research projects focusing on various aspects of the pathophysiology and treatment of MDD will be presented. Chapters 2 and 3 present a study on the effects of inflammatory stress (i.e., a typhoid vaccine), psychosocial stress (i.e., Trier Social Stress Test), and their combination on mood, biomarkers, and cognition in women with recurrent depression in (partial) remission and healthy controls. The study found that inflammatory stress without psychosocial stress worsened mood in patients but not in controls. Only in patients was the inflammatory stressor also associated with changes in cognitive function, including an increase in negative emotional bias. Chapter 4 examines the pro-cognitive effects of nicotine in healthy young and elderly volunteers, finding nicotine had no effects in young volunteers and no or worsening effects in elderly volunteers. However, a secondary analysis revealed that the effects were dependent on baseline function, with people with lower baseline function having more positive effects of nicotine. Chapters 5 and 6 focus on existing treatments for specific depression subtypes. Chapter 5 presents a case where ketamine anaesthesia successfully treated depression resistant to electroconvulsive therapy, suggesting that ketamine can be a potential augmentation strategy. Chapter 6 discusses bupropion's efficacy in seasonal affective disorder. The evidence is most robust for preventive use in the winter months. MDD is a complex disorder, and there is a need for further research into its pathophysiology and treatment. Investigations into anti-inflammatory drugs, cytokine inhibitors, and minocycline for MDD treatment show promise but require more research. The potential for targeting the cholinergic system for treating cognitive dysfunction in depression remains unexplored. Esketamine is approved for treatment-resistant depression, and in patients resistant to ECT, the combination with ketamine anaesthesia can be considered based on the case report. Bupropion is effective in preventing seasonal affective disorder and can be used for this purpose in routine clinical practice. |
| |
|
Language
|
|
|
|
English
| |
|
Publication
|
|
|
|
Antwerpen
:
Universiteit Antwerpen, Faculteit Geneeskunde en Gezondheidswetenschappen
,
2024
| |
|
ISBN
|
|
|
|
978-94-6506-130-6
| |
|
DOI
|
|
|
|
10.63028/10067/2061820151162165141
| |
|
Volume/pages
|
|
|
|
211 p.
| |
|
Note
|
|
|
|
:
Sabbe, Bernard G.C. [Supervisor]
:
Hulstijn, Wouter [Supervisor]
:
Morrens, Manuel [Supervisor]
| |
|
Full text (open access)
|
|
|
|
| |
|