Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis–related fatigue

Background: Fatigue is the most common symptom of MS and has no effective pharmacotherapy. Objective: To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue. Methods: In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models. Results: In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (−0.10 point; 95% confidence interval (CI): −0.32, 0.12; p = 0.40). We observed a trend in reduced FSS scores at 1 week (−5.2 points; 95% CI: −10.4, 0.14; p = 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (−13.5 point; 95% CI: −25.0, −1.98; p = 0.04). Conclusions: Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS.

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Acute Effects of Ketamine Infusion on Postoperative Mood Scores in Patients Undergoing Dilation and Curettage: A Randomized Double-Blind Controlled Study

Anesthesiology Research and Practice ◽

10.1155/2021/6674658 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Raham Hasan Mostafa ◽

Ahmed Mohamed Khamis ◽

Ashraf Nabil Saleh ◽

Yehia Mamdouh Hassan Mekki ◽

Mohamed Mohamed Kamal ◽

...

Keyword(s):

Low Dose ◽

Controlled Trial ◽

Acute Effect ◽

Controlled Study ◽

Control Group ◽

Double Blind ◽

Ketamine Infusion ◽

Dilation And Curettage ◽

Post Infusion ◽

The Impact

Background. Emotional and psychological effects following abortion are more common than physical side effects and can range from mild regret to more serious complications such as depression. In the last decade, it has been suggested that low dose of ketamine is a fast-acting antidepressant. Purpose. The aim of this study was to investigate the impact of intraoperative ketamine infusion on postoperative mood score in patients undergoing Dilation and Curettage (D&C) under spinal anesthesia. We hypothesized that a single low-dose administration of ketamine infusion during D&C surgery can improve mood scores in the immediate postoperative period. Methods. A prospective, randomized, double-blind, parallel-group, placebo-controlled trial. The study included a total of 60 patients, ≥18 years, physical status ASA II, with up to 12-week gestation undergoing elective D&C surgery. Patients were divided randomly into a ketamine group (group K) and a control group (group C). In group K, 0.4 mg/kg ketamine was given as a continuous infusion over 20 min intraoperatively. Main Outcome Measure. Profile of Mood States (POMS) was recorded preoperatively and 2 hours postoperatively. Results. There were no differences in preoperative POMS between the two groups. Mean postoperative POMS of group K was lower than that of group C indicating mood improvement. Ketamine group patients showed higher sedation score and increased, although self-limiting, psychedelic phenomena than the control group. Conclusion. Observed data here support an acute effect of ketamine on mood but any further claim will be speculative. Further future studies exploring postoperative mood scores after 24 hours post-infusion are needed. This trial is registered with PACTR201907779292947.

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Pharmacologic Therapy for Multiple Sclerosis–Related Fatigue

International Journal of MS Care ◽

10.7224/1537-2073-7.1.22 ◽

2005 ◽

Vol 7 (1) ◽

pp. 22-27 ◽

Cited By ~ 1

Author(s):

Jay H. Rosenberg

Keyword(s):

Multiple Sclerosis ◽

Sleep Disturbances ◽

Well Being ◽

Pharmacologic Therapy ◽

Controlled Trials ◽

Common Symptom ◽

Impact Scale ◽

Moderate Fatigue ◽

The Central Nervous System ◽

Fatigue Severity

Fatigue is the most common symptom of multiple sclerosis and is perhaps the symptom with the most devastating impact on patient well-being. It is reported by 75% to 95% of individuals, and more than half describe it as the worst symptom of the disease. The mechanisms underlying the development of fatigue remain unclear; although fatigue is believed to be a primary symptom of MS (ie, related to the demyelinating processes of the disease), fatigue may also occur secondarily to factors such as sleep disturbances, depression, or the effects of medications. The highly variable presentation of MS and the number of agents used for disease modification and symptom management make it important for potential contributors to MS-related fatigue to be identified and managed appropriately. If fatigue continues despite elimination or adequate management of secondary causes, pharmacologic therapy may be required. Several agents have been reported to improve MS-related fatigue; however, only three have been investigated in controlled trials. Amantadine has been studied in several small controlled trials, and appears to be effective in one quarter to one third of those with mild-to-moderate fatigue. It has shown efficacy on a number of scales, including the Visual Analog Scale for Fatigue (VAS-F) and the MS-Specific Fatigue Scale (MS-FS). The central nervous system (CNS) stimulant pemoline has demonstrated limited benefit in clinical trials and is often poorly tolerated, especially in higher doses. Recently, the wake-promoting agent modafinil has been shown to significantly improve MS-related fatigue on a number of commonly used fatigue assessment scales, including the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS).

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Fatigue Is Associated with Poor Sleep in People with Multiple Sclerosis and Cognitive Impairment

Multiple Sclerosis International ◽

10.1155/2014/872732 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Michelle H. Cameron ◽

Vanessa Peterson ◽

Eilis A. Boudreau ◽

Ashley Downs ◽

Jesus Lovera ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Sleep Quality ◽

Cross Sectional Study ◽

Poor Sleep ◽

Common Symptom ◽

Cross Sectional ◽

Impact Scale ◽

Quality Sleep ◽

Fatigue Severity

Background. Fatigue is the most common symptom in people with multiple sclerosis (MS). Poor sleep also occurs in this population.Objective. The objective of this study was to determine the relationship between fatigue and sleep quality in people with MS and cognitive impairment.Method. This cross-sectional study assessed relationships among fatigue, assessed with the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS), sleep quality assessed with the Pittsburg Sleep Quality Index (PSQI), and demographics in 121 people with MS and cognitive impairment.Results. Fatigue was significantly correlated with poor sleep quality (MFIS:F=15.60,P<0.01; FSS:F=12.09,P<0.01). FSS scores were also significantly correlated with the PSQI subscore for daytime dysfunction and MFIS scores were significantly correlated with disability, age, and the PSQI subscores for sleep quality, sleep duration, and daytime dysfunction.Conclusions. This study demonstrates a relationship between fatigue and sleep quality in individuals with MS and cognitive impairment.

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Relationship between Fatigue and Physical Activity in a Polish Cohort of Multiple Sclerosis Patients

Medicina ◽

10.3390/medicina56120726 ◽

2020 ◽

Vol 56 (12) ◽

pp. 726

Author(s):

Michalina Rzepka ◽

Mateusz Toś ◽

Michał Boroń ◽

Katarzyna Gibas ◽

Ewa Krzystanek

Keyword(s):

Physical Activity ◽

Multiple Sclerosis ◽

Severe Depression ◽

Neurological Impairment ◽

Common Symptom ◽

Metabolic Equivalents ◽

Impact Scale ◽

Relapsing Remitting ◽

Fatigue Severity ◽

Multiple Sclerosis Patients

Background and objectives: Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS). It can be defined as a subjective lack of physical and mental energy. The aim of this study was to evaluate the frequency and severity of fatigue in patients with MS and its relationship with overall physical activity and disease-related disability. Materials and Methods: The study included 100 patients with a clinical relapsing-remitting form of MS. Patients with severe depression were excluded. Neurological impairment was rated using the Expanded Disability Status Scale (EDSS). Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS), with FSS scores greater than 36 indicating patients with fatigue. Physical activity was evaluated with the International Physical Activity Questionnaire (IPAQ) and categorized on three levels: low, moderate, and high, using standard metabolic equivalents (MET). Results: The average FSS and MFIS scores were (mean ± SD) 31.3 ± 15.2 and 30.1 ± 17.0, respectively. The mean EDSS score was 2.5 ± 1.5. 42%. Patients were classified as fatigued based on FSS. Fatigued patients had higher mean EDSS scores than non-fatigued (3.0 ± 1.6 vs. 2.2 ± 1.4, respectively, p = 0.002). Low, moderate, and high levels of physical activity were reported in 35%, 20%, and 45% of patients, respectively. Higher scores of fatigue in FSS and MFIS were inversely correlated with the intensity of physical activity (r = −0.38, p < 0.001 and r = −0.33, p < 0.001, respectively). Conclusions: In patients with MS, fatigue is a common symptom. Patients with lower physical activity and greater MS-related disability have a higher severity of fatigue, which negatively affects cognitive, psychosocial, and physical functioning.

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Low Dose Perioperative Ketamine Infusion and it's Effect on Postoperative Pain Score, Sedation Score and Narcotic Consumption in Patients Undergoing Spine Surgery: A Prospective Randomized Double Blind Control Trial.

Case Medical Research ◽

10.31525/ct1-nct04259476 ◽

2020 ◽

Author(s):

Keyword(s):

Postoperative Pain ◽

Pain Score ◽

Spine Surgery ◽

Low Dose ◽

Sedation Score ◽

Double Blind ◽

Ketamine Infusion ◽

Postoperative Pain Score

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Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial

Indian Pediatrics ◽

10.1007/s13312-021-2255-x ◽

2021 ◽

Vol 58 (7) ◽

pp. 617-623

Author(s):

Ramachandran Rameshkumar ◽

Ponnarmeni Satheesh ◽

Puneet Jain ◽

Jagadeesh Anbazhagan ◽

Shilpa Abraham ◽

...

Keyword(s):

Diabetic Ketoacidosis ◽

Low Dose ◽

Standard Dose ◽

Controlled Trial ◽

Double Blind

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Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain: A Randomized Double-Blind Clinical Trial

Chronic Stress ◽

10.1177/2470547020981670 ◽

2020 ◽

Vol 4 ◽

pp. 247054702098167

Author(s):

Alisher R. Dadabayev ◽

Sonalee A. Joshi ◽

Mariam H. Reda ◽

Tamar Lake ◽

Mark S. Hausman ◽

...

Keyword(s):

Posttraumatic Stress Disorder ◽

Chronic Pain ◽

Posttraumatic Stress ◽

Outcome Measures ◽

Low Dose ◽

Stress Disorder ◽

Double Blind ◽

Impact Of Event Scale ◽

Event Scale ◽

Ketamine Infusion

Objective To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions. Methods We compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in CP patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, one day and seven days after the infusion. A planned sample size of 40 patients randomly assigned to treatment order was estimated to provide 80% power to detect a hypothesized treatment difference after the infusion. Main Outcome and Measures: The primary outcome measures were change in PTSD symptom severity assessed with the Impact of Event Scale–Revised (IES-R) and Visual Analogue Scale (VAS) for pain administered by a study clinician 24 hours post infusion. Secondary outcome measures included Impact of Event Scale–Revised (IES-R), VAS and Brief Pain Inventory (Short Form) for pain 1 week after the infusion. Results Both treatments offered comparable improvement of PTSD and CP symptoms that persisted for 7 days after the infusion. Patients with comorbid PTSD and CP experienced less dissociative side effects compared to the CP group. Surprisingly, ketorolac infusion resulted in dissociative symptoms in CP patients only. Conclusions This first prospective study comparing effects of subanesthetic ketamine versus ketorolac infusions for comorbid PTSD and CP, suggests that both ketamine and ketorolac might offer meaningful and durable response for both PTSD and CP symptoms.

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