stimulants – American ME and CFS Society

Patient-Reported Treatment Outcomes in ME/CFS and Long COVID

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are persistent multi-system illnesses affecting many patients. With no known effective FDA-approved treatments for either condition, patient-reported outcomes of treatments are invaluable for guiding management strategies in patient care and generating new avenues for research. Here, we present the results of an ME/CFS and Long COVID treatment survey with responses from 3,925 patients.

We assessed the experiences of these patients with more than 150 treatments, as well as their demographics, symptoms, and comorbidities. Patients with each condition who participated in the study shared similar symptom profiles, including all the core symptoms of ME/CFS, e.g., 89.7% of ME/CFS and 79.4% of Long COVID reported post-exertional malaise (PEM). Treatments with the greatest perceived benefits were identified, which had varied effects on different core symptoms.

In addition, treatment responses were significantly correlated (R² = 0.68) between the two patient groups. Patient subgroups with distinct profiles of symptoms and comorbidities showed varied responses to treatments, e.g., a POTS-dominant cluster benefiting from autonomic modulators and a cognitive-dysfunction cluster from CNS stimulants.

This study underscores the symptomatic and therapeutic similarities between ME/CFS and Long COVID and highlights the commonalities and nuanced complexities of infection-associated chronic diseases and related conditions. Insights from patient-reported experiences, in the absence of approved treatments, provide urgently needed real-world evidence for targeted therapies in patient care and for developing future clinical trials.

Source: Martha Eckey, Peng Li, Braxton Morrison, Ronald W Davis, Wenzhong Xiao. Patient-Reported Treatment Outcomes in ME/CFS and Long COVID. medRxiv 2024.11.27.24317656; doi: https://doi.org/10.1101/2024.11.27.24317656 https://www.medrxiv.org/content/10.1101/2024.11.27.24317656v1.full-text (Full text)

Challenges of memory enhancers

Abstract:

40 per cent of people over the age of 65 experience some form of memory loss, called as the age related memory impairment. This might be due to hormone and proteins (Growth factors) which repair the brain cells decline with age. Certain conditions such as age, stress, disease and excessive emotional response may lead to loss of memory, loss of learning ability and altered mood and behaviour. These conditions may be treated by using nootropic agents which can help to improve learning abilities and memory.

Source: Chaudhry, Sunil. Challenges of memory enhancers. Annals of Geriatric Education and Medical Sciences; 2020/08/22. https://www.agems.in/article-details/11990 (Full text)

KPAX002 as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a prospective, randomized trial

Abstract:

Mitochondrial dysfunction and a hypometabolic state are present in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). KPAX002 consists of low-dose methylphenidate hydrochloride to treat a hypometabolic state combined with key micronutrients intended to broadly support mitochondrial function.

The objective of this study was to evaluate KPAX002 as a treatment for fatigue and concentration disturbance symptoms in ME/CFS subjects. This phase 2 randomized, double-blinded, placebo-controlled trial was conducted at 4 sites in the United States. A total of 135 subjects with ME/CFS were randomly assigned to either KPAX002 (n=67) or placebo (n=68) for 12 weeks of treatment. The primary endpoint was change in the Checklist Individual Strength (CIS) total score from baseline to Week 12. Secondary measurements included visual analog scales for fatigue and concentration disturbance symptoms.

In the intent-to-treat population, the mean reduction in the CIS total score from baseline to week 12 for the KPAX002 and placebo groups was -16.9 (± 23.52) and -13.8 (± 22.15), respectively (95% confidence interval, -11.1, 4.0; P=0.359). On the visual analog scale for fatigue, the mean reduction from baseline to week 12 was -18.2 mm (± 25.05) and -11.1 mm (± 22.08) for the KPAX002 and placebo groups, respectively (95% confidence interval, -11.5, 2.3; P=0.189). The two groups demonstrating the most robust response to KPAX002 were subjects with more severe ME/CFS symptoms at baseline (P=0.086) and subjects suffering from both fatigue and pain (P=0.057). The incidence of adverse events was not statistically different between the two groups.

Treatment with KPAX002 resulted in a reduction in fatigue and concentration disturbance symptoms in multiple analyses. Two key subgroups of patients whose response approached statistical significance were identified.

Source: Jose G Montoya, Jill N Anderson, Danya L Adolphs, Lucinda Bateman, Nancy Klimas, Susan M Levine, Donn W Garvert, Jon D Kaiser. KPAX002 as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a prospective, randomized trial. Int J Clin Exp Med 2018;11(3):2890-2900 www.ijcem.com /ISSN:1940-5901/IJCEM0065685 (Full article)

Long-term methylphenidate intake in chronic fatigue syndrome

Abstract:

OBJECTIVE: Concentration disturbances are frequent in chronic fatigue syndrome (CFS). In a placebo-controlled double-blind crossover study, methylphenidate over 4 weeks was superior to placebo in the relief of fatigue and concentration disturbance. This observational study describes the effect of long-term methylphenidate intake on fatigue, concentration, and daily life activities, as reported by the patients themselves.

METHODS: A questionnaire was sent to all CFS patients who were prescribed methylphenidate at the general internal medicine department of a university hospital between August 2004 and February 2007, for possible improvement of concentration difficulties and fatigue.

RESULTS: Out of 194 consecutive patients, 149 (76.8%) sent the questionnaire back. At the time of the questionnaire, 65.3% had stopped the intake of methylphenidate, 34.7% still took it daily or occasionally. Among the patients who continued methylphenidate, 48% reported an at least 50% improvement of fatigue, and 62% reported an at least 50% improvement of concentration difficulties. This continued intake of methylphenidate resulted in more working hours in these patients. Side effects (agitation, palpitations, and dry mouth) were reported significantly more in patients who had stopped methylphenidate than in those who still took it.

CONCLUSION: The long-term intake of methylphenidate by CFS patients with concentration difficulties has a positive effect in about one out of three patients.

Source: Blockmans D, Persoons P. Long-term methylphenidate intake in chronic fatigue syndrome. Acta Clin Belg. 2016 Dec;71(6):407-414. Epub 2016 Jun 27. https://www.ncbi.nlm.nih.gov/pubmed/27351244

A prospective, proof-of-concept investigation of KPAX002 in chronic fatigue syndrome

Abstract:

Stimulant drugs and various micronutrient interventions have previously been studied in chronic fatigue syndrome (CFS) but they have never been studied in combination. This proof of concept investigation seeks to examine the clinical effects and safety profile of KPAX002 (a combination of methylphenidate hydrochloride and mitochondrial support nutrients) in patients with CFS.

Fifteen patients diagnosed with CFS by 1994 Fukuda criteria were recruited and treated with KPAX002 to explore a potential synergistic effect of this combination. Fatigue and concentration disturbance symptoms were measured at baseline, 4 weeks, and 12 weeks using two clinically validated tools: Checklist Individual Strength (CIS) and Visual Analog Scale (VAS).

The primary outcome objective was a decrease in the total CIS score of ≥25% in at least 50% of the subjects. The mean total CIS score decreased by 36.4 points (34%) at 12 weeks (P<0.0001), corresponding to a ≥25% decrease in 87% of the participants.

Treatment with KPAX002 was well tolerated and significantly improved fatigue and concentration disturbance symptoms in greater than 50% of patients with CFS. These results were statistically significant. This combination treatment is worthy of additional investigation.

Source: Kaiser JD. A prospective, proof-of-concept investigation of KPAX002 in chronic fatigue syndrome. Int J Clin Exp Med. 2015 Jul 15;8(7):11064-74. eCollection 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565289/ (Full article)

Chronic fatigue syndrome: 3 cases and a discussion of the natural history of attention-deficit/hyperactivity disorder

Abstract:

Fatigue is commonly reported in the primary care setting; however, its cause is often unclear. This article presents 3 cases involving patients with chronic fatigue syndrome who responded poorly to treatment. After clinical evaluation, all patients were found to meet criteria for attention-deficit/hyperactivity disorder (ADHD) and underwent a standard regimen of a psychostimulant medication.

After treatment with psychostimulants, the 3 patients reported improved symptoms of fatigue and pain, and cognitive and core ADHD symptoms. These cases suggest that ADHD and chronic fatigue syndrome (and possibly fibromyalgia) share a common underlying mechanism. This article presents a model suggesting that over time, ADHD (predominantly inattentive type) develops into a syndrome of chronic fatigue and pain. These cases indicate that fatigue may be an important presenting symptom of adult ADHD. These cases also suggest the need for additional research to determine the prevalence of ADHD in patients who present with fatigue, and, in those meeting criteria for ADHD, the responsiveness of fatigue to psychostimulant treatment.

Source: Young JL. Chronic fatigue syndrome: 3 cases and a discussion of the natural history of attention-deficit/hyperactivity disorder. Postgrad Med. 2013 Jan;125(1):162-8. doi: 10.3810/pgm.2013.01.2631. https://www.ncbi.nlm.nih.gov/pubmed/23391682

Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study

Abstract:

The purpose of this study was to assess the efficacy of lisdexamfetamine dimesylate (LDX) for the treatment of executive functioning deficits in adults (ages 18-60) with chronic fatigue syndrome (CFS). The study’s primary outcome measure was the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). Secondary outcome measures were standardized assessments of fatigue, pain and global functioning.

Twenty-six adults who met criteria for CFS and had clinically significant executive functioning deficits were randomly assigned to a flexible morning dose (30, 50, 70 mg/day) of either placebo or LDX for a 6-week trial. The data were analyzed with standard analysis of variance (ANOVA) procedures. Participants in the LDX group showed significantly more positive change in BRIEF-A scores (Mchange=21.38, SD=15.85) than those in the placebo group (Mchange=3.36, SD=7.26).

Participants in the active group also reported significantly less fatigue and generalized pain relative to the placebo group. Although future studies with LDX should examine whether these benefits generalize to larger, more diverse samples of patients, these results suggest that LDX could be a safe and efficacious treatment for the executive functioning deficits often associated with CFS. The possibility that dopaminergic medications could play an important role addressing the symptoms of CFS is also discussed.

Source: Young JL. Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study. Psychiatry Res. 2013 May 15;207(1-2):127-33. doi: 10.1016/j.psychres.2012.09.007. Epub 2012 Oct 9. https://www.ncbi.nlm.nih.gov/pubmed/23062791

Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate

Abstract:

Chronic fatigue syndrome (CFS) is a distinct entity belonging to the group of persistent fatigue that can be challenging to diagnose and to treat. It is characterized by a combination of prolonged fatigue, other nonspecific somatic manifestations and neuropsychological symptoms, including difficulties with concentration, short-term memory and thinking, as well as impaired attention and slowed processing speed. Neurostimulants increasing dopamine and norepinephrine activity, such as bupropion, dextroamphetamine and recently immediate-release methylphenidate have been advocated to improve neurocognitive deficits. The use of immediate-release methylphenidate in CFS has been shown in one small study. Using the positive results of this study and the well-known beneficial effects of the drug on a range of similar cognitive symptoms in attention-deficit/hyperactivity disorder, this perspective addresses CFS and other related disorders and provides a discussion on the potential promising role of methylphenidate in the therapeutic armamentarium of CFS.

Source: Valdizán Usón JR, Idiazábal Alecha MA. Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate. Expert Rev Neurother. 2008 Jun;8(6):917-27. Doi: 10.1586/14737175.8.6.917. https://www.ncbi.nlm.nih.gov/pubmed/18505357

Does methylphenidate reduce the symptoms of chronic fatigue syndrome?

Abstract:

PURPOSE: Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life.

SUBJECTS AND METHODS: A double-blind randomized placebo-controlled crossover study was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and March 2004 at the outpatient department of a university hospital referral center for chronic fatigue syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 x 10 mg/day, followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed by methylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual Strength (CIS) and a Visual Analogue Scale (VAS).

RESULTS: Fatigue scores fell significantly during methylphenidate intake in comparison with baseline (mean difference: -0.7, P = .010 for VAS; mean difference: -11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: -1.0, P = .001 for VAS; mean difference: -9.7, P <.0001 for CIS). Concentration disturbances, measured with a VAS improved significantly under methylphenidate treatment compared with baseline (mean difference: -1.3, P <.0001) and compared with placebo (mean difference: -1.1, P <.0001). A clinical significant effect (> or =33% improvement or CIS < or =76) on fatigue was achieved in 17% of patients, who were considered responders; on concentration in 22% of patients.

CONCLUSIONS: Methylphenidate at a dose of 2 x 10 mg/day is significantly better than placebo in relieving fatigue and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are needed to investigate the long-term effects of this treatment.

Source: Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006 Feb;119(2):167.e23-30. https://www.ncbi.nlm.nih.gov/pubmed/16443425