Investigating the effectiveness of oral ketamine on pain, mood and quality of life in treatment resistant chronic pain

IntroductionChronic pain is defined as pain lasting longer than 3 months. This often causes persistent emotional distress and functional disability that is refractory to conventional treatments. Emerging evidence suggests that oral Ketamine therapy may have a specific role in managing treatment-resistant chronic pain. This study aimed to assess the effectiveness of oral ketamine within a tertiary chronic pain management clinic.MethodsThis study was a clinic-based retrospective descriptive study of 79 patients with a broad range of chronic pain diagnoses and treated with oral ketamine over a period up to 12 years. Changes in pain, mood and quality of life (QoL) were assessed using a numerical pain severity score, the Brief Pain Inventory (BPI), the Public Health Questionnaire (PHQ-9) and American Chronic Pain Association Quality of Life (QoL) scale.Results73 patients were accessible for follow-up (mean daily dose and treatment duration were 193.84 mg and 22.6 months respectively). Pain scores decreased (p < 0.0001) on both numerical scores (41.6% decrease) and BPI scoring (mean decrease 2.61). Mood improved (p < 0.0001) across both PHQ-9 and BPI measurements. Patients also reported less difficulty with daily activities and improved QoL. The most common adverse reaction was drowsiness (21.9%), with 30.1% reporting no adverse reactions from Ketamine.DiscussionThis work adds to the growing body of evidence that under the supervision of a pain specialist, oral ketamine therapy may be a safe, tolerable and effective treatment for chronic pain conditions which have not responded to other management options. Further research is required to produce a more accurate understanding of its chronic use. Key messageThis real-world study shows that patients being treated with oral ketamine for chronic pain report decreased severity of pain, improved mood and increased quality of life across all conditions

The hippocampus, amygdala and their principal output tracts in major depressive disorder

Major depressive disorder is a common, debilitating illness. Despite its high prevalence rate and global disease burden, the biological mechanisms underlying this disorder remain largely unknown. Evidence points towards the involvement of the limbic system deep within the brain. This system processes memory, emotion and arousal, all of which are affected by depression symptoms. Two key regions in the limbic system are the hippocampus and the amygdala. The hippocampus is important for memory formation, with the left hippocampus particularly important for episodic memory. The previously well-documented changes in this structure in depression may account for the common global memory and cognition impairments found in this condition. The amygdala has been shown to be fundamental to the generation and recognition of emotional responses, with the right side demonstrating more involvement in negative emotional responses compared to the left side, which processes more positive emotions. Although evidence exists for a role of this structure in depression, this evidence is less extensive than that of the hippocampus. Both of these structures have widespread connections across the entire brain and each has a clearly defined major white matter bundle, or output tract, that connects each structure to its principal downstream effectors. These tracts are the fornix, which conveys processed memory information from the hippocampus, and the stria terminalis, which conducts emotionally-laden output from the amygdala. Both these tracts terminate in the basal forebrain and hypothalamus, regions important for pleasure and stress responses, respectively. There is limited evidence for the involvement of both of these tracts in depression. Using advanced volumetric and diffusion neuroimaging methods, combined with novel bespoke analyses of these images, this study has found noteworthy differences in all four structures in a well-characterised group of eighty-three patients with depression compared to eighty controls. Hippocampal differences were found to be confined to the core processing areas, more so on the left. There was evidence of an extension of pathology in patients with recurrent depression when compared to first presentation patients who exhibited more restrictive structural changes. The amygdala showed an exaggeration in the normal right-left volume imbalance, driven by enlargement of right stress-associated centromedial output areas. Through measurement of the cortisol awakening response in a subset of participants, the right amygdala revealed an association with abnormal stress responses in depression. Both the fornix and the stria terminalis showed localised differences along distinct sections of their tracts suggestive of abnormal axonal connectivity in depression. The aforementioned centromedial areas of the amygdala were found to be predictors of a depression diagnosis. These amygdala areas and a specific substructure within the hippocampus, the CA1 region, were also found to be predictors of disease duration in depression. These findings reinforce a role for these four limbic regions in depression. The lateralised volume differences in each of these structures could account for many of the symptoms of depression, including low mood, anhedonia and cognitive disturbance found in the disorder. While these results are preliminary, they demonstrate the utility of my novel analyses by revealing deeper and more site-specific differences in depression. These findings place altered hippocampal and amygdala volumes at the centre of a limbic network influencing memory, emotion and arousal in depression. Further studies, refining these techniques and exploring the upstream and downstream components of these structures are already underway

Reduced hippocampal volume in adolescents with psychotic experiences: A longitudinal population-based study

Aims Smaller hippocampal volumes are among the most consistently reported neuroimaging findings in schizophrenia. However, little is known about hippocampal volumes in people who report psychotic experiences. This study investigated differences in hippocampal volume between young people without formal diagnoses who report psychotic experiences (PEs) and those who do not report such experiences. This study also investigated if any differences persisted over two years. Methods A nested case-control study of 25 adolescents (mean age 13.5 years) with reported PEs and 25 matched controls (mean age 13.36 years) without PEs were drawn from a sample of 100 local schoolchildren. High-resolution T1-weighted anatomical imaging and subsequent automated cortical segmentation (Freesurfer 6.0) was undertaken to determine total hippocampal volumes. Comprehensive semi-structured clinical interviews were also performed including information on PEs, mental diagnoses and early life stress (bullying). Participants were invited for a second scan at two years. Results 19 adolescents with PEs and 19 controls completed both scans. Hippocampal volumes were bilaterally lower in the PE group compared to the controls with moderate effects sizes both at baseline [left hippocampus p = 0.024 d = 0.736, right hippocampus p = 0.018, d = 0.738] and at 2 year follow up [left hippocampus p = 0.027 d = 0.702, right = 0.048 d = 0.659] throughout. These differences survived adjustment for co-morbid mental disorders and early life stress. Conclusions Psychotic experiences are associated with total hippocampal volume loss in young people and this volume loss appears to be independent of possible confounders such as co-morbid disorders and early life stress

A comprehensive regional neurochemical theory in depression: a protocol for the systematic review and meta-analysis of 1H-MRS studies in major depressive disorder

Abstract Background Magnetic resonance spectroscopy (MRS) is a non-invasive analytical technique that investigates the presence and concentrations of brain metabolites. In the context of major depressive disorder (MDD), MRS has revealed regional biochemical changes in GABA, glutamate, and choline across different brain compartments. Technical and methodological advances in MRS data acquisition, in particular proton-based 1H-MRS, have resulted in a significant increase in the incidence of reports utilizing the technique for psychiatric disorder research and diagnosis. The most recent comprehensive meta-analysis reviewing MRS in MDD stems from 2006. Using contemporary systemic reviews and meta-analysis, the aim is to first test a neurochemical circuit-based theory of depression and then to determine if clinical scores relate to metabolite concentrations before and during treatment. Methods Region-specific metabolite changes in MDD will be assessed by systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria will include participant age (18 to 65), English language studies, known regions of interest, and detailed documentation of 1H-MRS procedures. Reported brain regions will be standardized according neuroanatomical expertise allowing increased power of the meta-analysis. Regions of interest will initially include the hippocampus, thalamus, prefrontal cortex, anterior and posterior cingulate gyri, parietal lobe, and basal ganglia. Exclusion criteria will include comorbid psychiatric illness and drug use. Two independent reviewers will undertake all data extraction, while a third reviewer will check for reviewer discrepancies. Statistical analysis will be performed using STATA supplemented by Metan software and SPSS. Discussion This data will shed new light on the biochemical basis of depression in different brain regions, thereby highlighting the potential of MRS in identifying biomarkers and generating models of MDD and treatment response. Systematic review registration PROSPERO CRD4201809149

Investigating the effectiveness of oral ketamine on pain, mood and quality of life in treatment resistant chronic pain

Introduction: Chronic pain is defined as pain lasting longer than 3 months. This often causes persistent emotional distress and functional disability that is refractory to conventional treatments. Emerging evidence suggests that oral Ketamine therapy may have a specific role in managing treatment-resistant chronic pain. This study aimed to assess the effectiveness of oral ketamine within a tertiary chronic pain management clinic. Methods: This study was a clinic-based retrospective descriptive study of 79 patients with a broad range of chronic pain diagnoses and treated with oral ketamine over a period up to 12 years. Changes in pain, mood and quality of life (QoL) were assessed using a numerical pain severity score, the Brief Pain Inventory (BPI), the Public Health Questionnaire (PHQ-9) and American Chronic Pain Association Quality of Life (QoL) scale. Results: 73 patients were accessible for follow-up (mean daily dose and treatment duration were 193.84 mg and 22.6 months respectively). Pain scores decreased (p p Discussion: This work adds to the growing body of evidence that under the supervision of a pain specialist, oral ketamine therapy may be a safe, tolerable and effective treatment for chronic pain conditions which have not responded to other management options. Further research is required to produce a more accurate understanding of its chronic use. Key message: This real-world study shows that patients being treated with oral ketamine for chronic pain report decreased severity of pain, improved mood and increased quality of life across all conditions.</p