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Trials May 2024Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several...
BACKGROUND
Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer.
METHODS
Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first.
DISCUSSION
This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness.
TRIAL REGISTRATION
Trial registered on Australian New Zealand Clinical Trials Registry.
REGISTRATION NUMBER
ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Neoplasms; Anxiety; Double-Blind Method; Randomized Controlled Trials as Topic; Affect; Hallucinogens; Treatment Outcome; Depression; Quality of Life; Methylphenidate; Time Factors; Male; Neoplasm Staging
PubMed: 38773523
DOI: 10.1186/s13063-024-08174-x -
Journal of Clinical Oncology : Official... May 2024
PubMed: 38771985
DOI: 10.1200/JCO.24.00707 -
Expert Opinion on Pharmacotherapy May 2024Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder characterized by impairing inattention and/or hyperactivity and impulsivity in... (Review)
Review
INTRODUCTION
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder characterized by impairing inattention and/or hyperactivity and impulsivity in children and adults. Although medications have been available to treat ADHD symptoms for decades, many are stimulant formulations. Stimulants, such as amphetamine and methylphenidate, are available in more than two dozen formulations, but all have similar adverse effects and carry a risk of misuse and dependence.
AREAS COVERED
In the United States (US), several nonstimulants are available to treat ADHD. Two, including atomoxetine and viloxazine extended-release (ER), are approved by the Food and Drug Administration for the treatment of ADHD in children and adults. Two others, clonidine ER and guanfacine ER, are only approved for children and adolescents in the US. Several other compounds are under investigation. Drugs in Phase 3 trials include centanafadine, solriamfetol, and L-threonic acid magnesium salt. Efficacy and safety data for nonstimulants is presented.
EXPERT OPINION
Although many effective formulations for the treatment of ADHD are available, more than 33% of children and 50% of adults discontinue treatment during the first year. The lack of individual drug response and tolerability are reasons many stop treatment. The development of new nonstimulants may offer hope for patients who need medication alternatives.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Adolescent; Adult; Delayed-Action Preparations
PubMed: 38771653
DOI: 10.1080/14656566.2024.2358987 -
Journal of Child and Adolescent... May 2024
PubMed: 38770608
DOI: 10.1089/cap.2024.0031 -
Journal of Alzheimer's Disease : JAD 2024Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD).
OBJECTIVE
We aimed to determine the efficacy and safety of pharmacologic and nutritional interventions for early AD.
METHODS
PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 1 September 2023. We included randomized controlled trials that evaluated the efficacy of interventions in early AD. Only interventions that demonstrated efficacy compared to placebo were included in the network meta-analysis (NMA). Then we performed frequentist fixed-effects NMA to rank the interventions. GRADE criteria were used to evaluate the level of evidence.
RESULTS
Fifty-eight trials including a total of 33,864 participants and 48 interventions were eligible for inclusion. Among the 48 interventions analyzed, only 6 (12.5%) treatments- ranging from low to high certainty- showed significant improvement in cognitive decline compared to placebo. High certainty evidence indicated that donanemab (standardized mean difference [SMD] -0.239, 95% confidence interval [CI] -0.343 to -0.134) and lecanemab (SMD -0.194, 95% CI -0.279 to -0.108) moderately slowed the clinical progression in patients with amyloid pathology. Additionally, methylphenidate, donepezil, LipiDiDiet, and aducanumab with low certainty showed significant improvement in cognitive decline compared to placebo. However, there was no significant difference in serious adverse events as reported between the six interventions and placebo.
CONCLUSIONS
Only 12.5% of interventions studied demonstrated efficacy in reducing cognitive impairment in early AD. Donanemab and lecanemab have the potential to moderately slow the clinical progression in patients with amyloid pathology. Further evidence is required for early intervention in AD.
Topics: Alzheimer Disease; Humans; Randomized Controlled Trials as Topic; Network Meta-Analysis
PubMed: 38759015
DOI: 10.3233/JAD-240161 -
Journal of Clinical Oncology : Official... May 2024To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer.
PURPOSE
To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer.
METHODS
This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood.
RESULTS
One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, -0.95 to 4.90; = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, -1.35 [95% CI, -2.41 to -0.30]). There were no differences in mortality or serious adverse events.
CONCLUSION
After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.
PubMed: 38757263
DOI: 10.1200/JCO.23.02639 -
European Child & Adolescent Psychiatry May 2024Fetal Alcohol Spectrum Disorders (FASD) refer to physical, cognitive, and behavioural symptoms in an individual whose mother consumed alcohol during pregnancy. It is the...
Fetal Alcohol Spectrum Disorders (FASD) refer to physical, cognitive, and behavioural symptoms in an individual whose mother consumed alcohol during pregnancy. It is the leading cause of non-genetic avoidable mental disability, with an estimated worldwide prevalence of 1%. Attention Deficit Hyperactivity Disorder (ADHD) diagnostic criteria are met for 50-80% of patients with FASD. Methylphenidate (MPH) is the first-line pharmacological treatment for ADHD. This study aims to explore the lived experience of children with FASD taking MPH and their caregivers to adapt prescribing modalities by considering different ways to administer the drugs. We hope to improve the therapeutic alliance between the children and their caregivers by gaining an insiders' view of the medication perception. Semi-structured interviews with children and their caregivers were conducted in this qualitative study. Data collection by purposive sampling continued until we reached theoretical sufficiency. Data were analysed using interpretative phenomenological analysis. We conducted 16 semi-structured interviews: 8 with the children aged 7-12, 5 boys and 3 girls and 8 with their caregivers. The analysis showed that inadequate palatability and capsule form experiences were the leading causes of children's non-adherence to the treatment. MPH appeared to be a valuable aid for caregivers even if they had concerns about its potential toxicity. However, it is necessary to identify caregivers' expectations concerning MPH to adapt the prescription in terms of choice of specialty and intake modalities. Regular support was required to reduce caregivers' fears of dependence, personality transformation and long-term adverse effects. Information on palatability should be given when prescribing MPH to children with ADHD as well as its possible side effects or toxicity. It highlights the need for further studies of the experience of palatability of drugs prescribed to children. When prescribing a treatment, children should be more involved in medical counselling and it is necessary to understand the child's perspectives to co-construct common representations for better therapeutical adherence.
PubMed: 38755318
DOI: 10.1007/s00787-024-02457-z -
The International Journal of... Jun 2024The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor...
BACKGROUND
The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor for cognitive control, but the degree of how much gain control may be enhanced underlies a physical limit.
METHODS
To investigate whether methylphenidate (MPH) and transcranial direct current stimulation (tDCS) share common underlying mechanisms and cognitive effects, we administered MPH and anodal tDCS (atDCS) over the right inferior frontal gyrus both separately and combined, while healthy adult participants (n = 104) performed a response selection and inhibition task. The recorded EEG data were analyzed with a focus on theta band activity, and source estimation analyses were conducted.
RESULTS
The behavioral data show that MPH and atDCS revealed interactive effects on the ability to inhibit responses. Both MPH and atDCS modulated task-related theta oscillations in the supplementary motor area when applied separately, making a common underlying mechanism likely. When both stimulation methods were combined, there was no doubling of effects in the supplementary motor area but a shift to inferior frontal areas in the cortical network responsible for theta-driven processing.
CONCLUSIONS
The results indicate that both MPH and atDCS likely share a common underlying neuronal mechanism, and interestingly, they demonstrate interactive effects when combined, which are most likely due to the physical limitations of gain control increases. The current study provides critical groundwork for future combined applications of MPH and non-invasive brain stimulation.
Topics: Humans; Transcranial Direct Current Stimulation; Male; Female; Adult; Young Adult; Methylphenidate; Inhibition, Psychological; Theta Rhythm; Electroencephalography; Central Nervous System Stimulants; Prefrontal Cortex; Motor Cortex
PubMed: 38742426
DOI: 10.1093/ijnp/pyae023 -
Frontiers in Pediatrics 2024The organization of healthcare pathways for neurodevelopmental disorders (NDD) relies on different levels of expertise depending on the complexity of these disorders....
INTRODUCTION AND AIMS
The organization of healthcare pathways for neurodevelopmental disorders (NDD) relies on different levels of expertise depending on the complexity of these disorders. NDDs affect between 8% and 15% of children. Historically, national recommendations and healthcare planning measures were initially devoted to autism spectrum disorders and were gradually extended to Attention deficit hyperactivity disorder (ADHD) and specific learning and development disorders. Private doctors play an increasing role in these pathways at different levels of care due to difficulties in organization, particularly in the health and social sector. The aim of this work was to evaluate the contribution of second-line private doctors in the diagnosis and care of children affected by NDD.
METHODS
A first series of surveys in 2016 evaluated the level of commitment of primary care pediatricians; this online national survey was repeated in 2023 among 1,430 members of the French Association of Ambulatory Pediatrics (Association Française de Pédiatrie Ambulatoire: AFPA) to assess their training, current and future involvement, and activity in NDD care. Analysis was performed by the main author using Epi-Info software.
RESULTS
The study identified in 2023 214 second-line private doctors (14% of all pediatricians in activity), of which 185 agreed to appear in a directory published the same year by the AFPA to facilitate referrals from other professionals. Sex ratio of responders is usual for paediatricians: 79.5%/20.5% (F/M), with a distribution among ages showing a slight increase of the age range between age 51-60 (30.5%). Our data indicate that in France in 2022, second-line private doctors made 48%-53% of NDD diagnoses, 24%-26.4% of follow-up consultations and declare to be accountable for 21% of initial prescriptions for Methylphenidate. Among these second-line doctors, 40% had completed a post-university degree on NDD, 74.3% had completed professional development training (PDT) and 85.2% had completed either or both types of training. Most doctors participating in the survey wanted to improve their level of practice, suggesting that in five years, the number of second-line private doctors will increase by 20% to 244 despite 24 planned retirements within the same period. This data probably underestimates the role of private doctors in NDD diagnosis, follow-up, and initial Methylphenidate prescriptions given the unfavourable working conditions (no financial compensation for long appointments, difficulty accessing paramedical and psychological assessments).
CONCLUSIONS
Our data confirms that diagnosis and care coordination in the various presentations of NDD may rely on different types of practices and specializations: medical and social professionals, mental health professionals, but also a growing body of medical doctors involved in developmental and behavioural pediatrics. This data and reflection will be helpful for organizing healthcare in France or in other countries. Main study limitation relies in the self-declaration of MD's involvement in NDD and could not evaluate the activity of employed MD's from the social and medico social sector, nor be based on the national databases for prescription. It remains however the first attempt of characterization of medical activity at the national level in France for NDD.
PubMed: 38725981
DOI: 10.3389/fped.2024.1269198 -
Frontiers in Pharmacology 2024Mounting evidence from animal models and human studies indicates that psychostimulants can significantly affect social behaviors. This is not surprising considering that... (Review)
Review
Mounting evidence from animal models and human studies indicates that psychostimulants can significantly affect social behaviors. This is not surprising considering that the neural circuits underlying the regulation and expression of social behaviors are highly overlapped with those targeted by psychostimulants, which in most cases have strong rewarding and, consequently, addictive properties. In the present work, we provide an overview regarding the effects of illicit and prescription psychostimulants, such as cocaine, amphetamine-type stimulants, methylphenidate or modafinil, upon social behaviors such as social play, maternal behavior, aggression, pair bonding and social cognition and how psychostimulants in both animals and humans alter them. Finally, we discuss why these effects can vary depending on numerous variables such as the type of drug considered, acute long-term use, clinical recreational consumption, or the presence or absence of concomitant risk factors.
PubMed: 38725665
DOI: 10.3389/fphar.2024.1364630