Lisdexamfetamine Dimesylate Augmentation in Adults With Persistent Executive Dysfunction After Partial or Full Remission of Major Depressive Disorder

Major depressive disorder (MDD) and alcohol use disorder (AUD) are leading causes of disability, and patients are frequently affected by both conditions. This comorbidity is known to confer worse outcomes and greater illness severity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation method that has demonstrated antidepressant effects. However, the study of rTMS for patients with MDD and commonly associated comorbidities, such as AUD, has been largely overlooked, despite significant overlap in clinical presentation and neurobiological mechanisms. This narrative review aims to highlight the interrelated aspects of the literature on rTMS for MDD and rTMS for AUD. First, we summarize the available evidence on the effectiveness of rTMS for each condition, both most studied through stimulation of the dorsolateral prefrontal cortex (DLPFC). Second, we describe common symptom constructs that can be modulated by rTMS, such as executive dysfunction, that are transdiagnostic across these disorders. Lastly, we describe promising approaches in the personalization and optimization of rTMS that may be applicable to both AUD and MDD. By bridging the gap between research efforts in MDD and AUD, rTMS is well positioned to be developed as a treatment for the many patients who have both conditions concurrently.

Download Full-text

A randomised, placebo-controlled 24-week study evaluating adjunctive brexpiprazole in patients with major depressive disorder

Acta Neuropsychiatrica ◽

10.1017/neu.2018.23 ◽

2018 ◽

Vol 31 (1) ◽

pp. 27-35 ◽

Cited By ~ 10

Author(s):

Michael Bauer ◽

Nanco Hefting ◽

Annika Lindsten ◽

Mette Krog Josiassen ◽

Mary Hobart

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Treatment Period ◽

Study Design ◽

Primary Endpoint ◽

Inadequate Response ◽

Madrs Total Score ◽

Open Label ◽

Major Depressive ◽

Full Remission

AbstractObjectiveTo evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.MethodsThe study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation. Patients with early response to open-label ADT were withdrawn at Week 6. Patients fulfilling criteria for inadequate response were randomised to ADT+brexpiprazole 1–3 mg/day, or ADT+placebo. The primary endpoint was full remission: Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≤10 and ≥50% decrease from randomisation (i.e. baseline) in MADRS total score for at least 8 consecutive weeks.ResultsThe primary efficacy analysis failed to show a statistically significant difference between the proportions of patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from baseline to Week 6 in MADRS total score showed no difference between ADT+brexpiprazole and ADT+placebo (−0.4; p=0.3259). The most frequent treatment-emergent adverse event (TEAE) in patients receiving ADT+brexpiprazole was weight increased (9.5% vs. 5.0% in ADT+placebo). The incidence of TEAEs leading to withdrawal in the randomised treatment period was 6.3% in the ADT+brexpiprazole group and 3.4% in the ADT+placebo group.ConclusionAdjunctive brexpiprazole did not differentiate from ADT+placebo on the primary endpoint of full remission. A number of design elements in this previously untried study design may have contributed to the study result. Brexpiprazole was well tolerated.

Download Full-text

Longitudinal diffusion weighted imaging of limbic regions in patients with major depressive disorder after 6 years and partial to full remission

Psychiatry Research Neuroimaging ◽

10.1016/j.pscychresns.2019.04.004 ◽

2019 ◽

Vol 287 ◽

pp. 75-86 ◽

Cited By ~ 1

Author(s):

Kelly Doolin ◽

Sinaoife Andrews ◽

Angela Carballedo ◽

Hazel McCarthy ◽

Erik O'Hanlon ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Diffusion Weighted Imaging ◽

Longitudinal Diffusion ◽

Major Depressive ◽

Full Remission ◽

Diffusion Weighted ◽

Limbic Regions

Download Full-text

The Relationship Between the Gut Microbiome-Immune System-Brain Axis and Major Depressive Disorder

Frontiers in Neurology ◽

10.3389/fneur.2021.721126 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jane A. Foster ◽

Glen B. Baker ◽

Serdar M. Dursun

Keyword(s):

Nervous System ◽

Major Depressive Disorder ◽

Immune System ◽

Depressive Disorder ◽

Gut Microbiome ◽

Antidepressant Drugs ◽

Short Chain Fatty Acids ◽

Major Depressive ◽

Signaling Systems ◽

Full Remission

Major depressive disorder (MDD) is a prominent cause of disability worldwide. Current antidepressant drugs produce full remission in only about one-third of MDD patients and there are no biomarkers to guide physicians in selecting the best treatment for individuals. There is an urgency to learn more about the etiology of MDD and to identify new targets that will lead to improved therapy and hopefully aid in predicting and preventing MDD. There has been extensive interest in the roles of the immune system and the gut microbiome in MDD and in how these systems interact. Gut microbes can contribute to the nature of immune responses, and a chronic inflammatory state may lead to increased responsiveness to stress and to development of MDD. The gut microbiome-immune system-brain axis is bidirectional, is sensitive to stress and is important in development of stress-related disorders such as MDD. Communication between the gut and brain involves the enteric nervous system (ENS), the autonomic nervous system (ANS), neuroendocrine signaling systems and the immune system, and all of these can interact with the gut microbiota. Preclinical studies and preliminary clinical investigations have reported improved mood with administration of probiotics and prebiotics, but large, carefully controlled clinical trials are now necessary to evaluate their effectiveness in treating MDD. The roles that several gut microbe-derived molecules such as neurotransmitters, short chain fatty acids and tryptophan play in MDD are reviewed briefly. Challenges and potential future directions associated with studying this important axis as it relates to MDD are discussed.

Download Full-text