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The Australian and New Zealand Journal... Mar 2023There is an increasing interest in combining psilocybin or methylenedioxymethamphetamine with psychological support in treating psychiatric disorders. Although there... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
There is an increasing interest in combining psilocybin or methylenedioxymethamphetamine with psychological support in treating psychiatric disorders. Although there have been several recent systematic reviews, study and participant numbers have been limited, and the field is rapidly evolving with the publication of more studies. We therefore conducted a systematic review of PubMed, MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, Embase, and CINAHL for randomised controlled trials of methylenedioxymethamphetamine and psilocybin with either inactive or active controls.
METHODS
Outcomes were psychiatric symptoms measured by standardised, validated and internationally recognised instruments at least 2 weeks following drug administration, Quality was independently assessed using the Cochrane risk of bias assessment tool and Grading of Recommendations Assessment, Development and Evaluation framework.
RESULTS
There were eight studies on methylenedioxymethamphetamine and six on psilocybin. Diagnoses included post-traumatic stress disorder, long-standing/treatment-resistant depression, obsessive-compulsive disorder, social anxiety in adults with autism, and anxiety or depression in life-threatening disease. The most information and strongest association was for the change in methylenedioxymethamphetamine scores compared to active controls in post-traumatic stress disorder ( = 4; standardised mean difference = -0.86; 95% confidence interval = [-1.23, -0.50]; < 0.0001). There were also small benefits for social anxiety in adults with autism. Psilocybin was superior to wait-list but not niacin (active control) in life-threatening disease anxiety or depression. It was equally as effective as escitalopram in long-standing depression for the primary study outcome and superior for most of the secondary outcomes in analyses uncorrected for multiple comparisons. Both agents were well tolerated in supervised trials. Trial quality varied with only small proportions of potential participants included in the randomised phase. Overall certainty of evidence was low or very low using the Grading of Recommendations Assessment, Development and Evaluation framework.
CONCLUSION
Methylenedioxymethamphetamine and psilocybin may show promise in highly selected populations when administered in closely supervised settings and with intensive support.
Topics: Adult; Child; Humans; Cognitive Behavioral Therapy; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; Developmental Disabilities; Anxiety Disorders
PubMed: 35285280
DOI: 10.1177/00048674221083868 -
Brain Sciences Nov 2022cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving... (Review)
Review
BACKGROUND
cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials.
OBJECTIVES
we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two authors screened studies' titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes.
RESULTS
Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes.
LIMITATIONS
Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy.
CONCLUSIONS
There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.
PubMed: 36421870
DOI: 10.3390/brainsci12111546 -
Journal of the American College of... Aug 2020Although the prevalence of attention-deficit/hyperactivity disorder (ADHD) has been stable over the past 3 decades, prescriptions of sympathomimetic stimulants have...
Although the prevalence of attention-deficit/hyperactivity disorder (ADHD) has been stable over the past 3 decades, prescriptions of sympathomimetic stimulants have steadily increased in the United States. This study consisted of a systematic review of PubMed articles screened for ADHD medications and potential cardiovascular toxicity as well as nondrug strategies for managing ADHD. The cumulative body of data showed that ADHD medications cause modest elevations in resting heart rate and blood pressure. Other adverse effects reported with ADHD stimulants included arrhythmia, nonischemic cardiomyopathy, Takotsubo cardiomyopathy, and sudden death. However, such reports did not imply causation, and there was a paucity of randomized trial evidence addressing long-term safety of ADHD medications, particularly among adults. Further studies are essential to clarify the risks and benefits of ADHD stimulant medications and to explore nonpharmacological options, including regular exercise and omega-3 fatty acids, which could be helpful for improving ADHD symptoms.
Topics: Attention Deficit Disorder with Hyperactivity; Cardiovascular Diseases; Cardiovascular System; Central Nervous System Stimulants; Humans
PubMed: 32792083
DOI: 10.1016/j.jacc.2020.05.081 -
Cureus May 2021Stimulants have been used throughout human history for a variety of reasons. High levels of stress and the demanding nature of medical school make their usage among... (Review)
Review
Stimulants have been used throughout human history for a variety of reasons. High levels of stress and the demanding nature of medical school make their usage among medical students particularly common. The most prevalent stimulant used by students is coffee, followed by tea and other forms of caffeine like sugary energy drinks. In addition, amphetamine-based medications for treating attention deficit hyperactivity disorder (ADHD) have been increasing in popularity, which many students take illicitly. Students report taking various forms of stimulants to promote cognitive enhancement, prolong wakefulness and retain focus for long periods of time. Moderate doses of caffeine and amphetamines would lead to enhanced alertness and concentration. However, large increases in dosage or frequency would lead to an increased risk of toxicity and adverse effects. The positive outcomes from stimulant consumption are often overshadowed by the negative side effects and incorrect dosage. Thus, it appears that usage of stimulants should be limited, in favor of a more sustainable approach to cognitive enhancement. This review analyzes the use of stimulants among the medical student community, consequences of misuse and discussed the healthy and organic approaches to lessen the stress and improve academic performance. This article also discusses the mechanisms of action, acceptable doses, additives, ingredients of stimulants commonly used by medical students for cognitive enhancement and the implications of long-term use as the stress of practicing medicine extends well beyond the medical school years.
PubMed: 34178492
DOI: 10.7759/cureus.15163 -
Journal of Child Psychology and... Jun 2021Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The... (Meta-Analysis)
Meta-Analysis
Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis.
BACKGROUND
Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta-analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation.
METHODS
We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha-2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random-effects model.
RESULTS
Twenty-five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent-rated: standardized mean difference [SMD] = -.63, 95%CI = -.95,-.30; teacher-rated: SMD = -.81, 95%CI = -1.43,-.19) and inattention (parent-rated: SMD = -.36, 95%CI = -.64,-.07; teacher-rated: SMD = -.30, 95%CI = -.49,-.11). Atomoxetine reduced inattention (parent-rated: SMD = -.54, 95%CI = -.98,-.09; teacher/investigator-rated: SMD = -0.38, 95%CI = -0.75, -0.01) and parent-rated hyperactivity (parent-rated: SMD = -.49, 95%CI = -.76,-.23; teacher-rated: SMD = -.43, 95%CI = -.92, .06). Indirect evidence for significant reductions in hyperactivity with second-generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events.
CONCLUSIONS
Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long-term continuation is undertaken to help guide clinical decision-making regarding treatment of co-occurring ADHD symptoms in children and youth with ASD.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Central Nervous System Stimulants; Child; Guanfacine; Humans; Methylphenidate
PubMed: 32845025
DOI: 10.1111/jcpp.13305 -
Obesity Reviews : An Official Journal... Nov 2021Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice.... (Review)
Review
Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice. This systematic literature review aimed to identify real-world (RW) evidence for AOMs to treat adults ( ≥ 18 years) with obesity or overweight (BMI ≥ 27 kg/m ). Searches conducted in MEDLINE, Embase, Health Technology Assessment (HTA) Database, National Health Service (NHS) Economic Evaluation Database, and Cochrane Central Register of Controlled Trials for studies of relevant FDA-approved AOMs yielded 41 publications. Weight loss (WL) was consistently observed, with 14% to 58.6% of patients achieving ≥ 5% WL on orlistat, phentermine/topiramate, naltrexone/bupropion, phentermine, or liraglutide in studies of 3-6 months' duration where this was measured. When cardiometabolic risk factors were assessed, AOMs reduced or had no impact on blood pressure, lipids, or glycemia. RW data on the impact of AOMs on existing obesity-related comorbidities and mortality were generally lacking. AOMs were associated with various adverse events, but these were of mild to moderate severity and no unexpected safety signals were reported. A pattern of poor adherence and persistence with AOMs was observed across studies. Overall, the review confirmed the effectiveness of AOMs in RW settings but demonstrated large gaps in the evidence base.
Topics: Adult; Anti-Obesity Agents; Humans; Orlistat; Phentermine; State Medicine; Weight Loss
PubMed: 34423889
DOI: 10.1111/obr.13326 -
Diabetes, Obesity & Metabolism Sep 2023To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight. (Meta-Analysis)
Meta-Analysis
AIM
To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight.
MATERIALS AND METHODS
We performed a systematic review of drugs approved for treating obesity and overweight. We searched MEDLINE, Embase and CENTRAL through 26 February 2023. Random-effects network meta-analysis was applied.
RESULTS
A total of 168 trials (97 938 patients) were included. There was no evidence that drugs approved for weight management had different associations with cardiovascular death (69 trials, 59 037 participants). Naltrexone/bupropion was associated with lower cardiovascular mortality than placebo (odds ratio [OR], 0.62 [95% CI: 0.39, 0.99]; low certainty evidence). All drugs were associated with greater weight loss at 12 months than placebo (33 trials, 37 616 participants), mainly semaglutide (mean difference [MD], -9.02 kg [95% CI: -10.42, -7.63]; moderate certainty) and phentermine/topiramate (MD, -8.10 kg [95% CI: -10.14, -6.05]; high certainty); and with greater waist circumference reduction at 12 months than placebo (24 trials, 35 733 participants), mainly semaglutide (MD, -7.84 cm [95% CI: -9.34, -6.34]; moderate certainty) and phentermine/topiramate (MD, -6.20 cm [95% CI: -7.46, -4.94]; high certainty). Semaglutide and phentermine/topiramate were associated with lower or no difference in the odds of treatment withdrawal compared with all other drugs (87 trials, 70 860 participants).
CONCLUSIONS
Among adults with obesity or overweight, semaglutide and phentermine/topiramate were associated with greater body weight loss and waist circumference reduction at 12 months than all other drugs, and lower or no significant difference in risks of withdrawal. There was no evidence that drugs approved for weight management had different associations with cardiovascular death.
Topics: Adult; Humans; Overweight; Topiramate; Network Meta-Analysis; Randomized Controlled Trials as Topic; Obesity; Phentermine
PubMed: 37254688
DOI: 10.1111/dom.15138 -
European Journal of Neurology Sep 2021Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based...
BACKGROUND AND AIM
Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children.
METHODS
The European Academy of Neurology (EAN), European Sleep Research Society (ESRS) and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach.
RESULTS
A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong), methylphenidate, amphetamine derivates (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) excessive daytime sleepiness in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivates (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions.
CONCLUSION
The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.
Topics: Adult; Cataplexy; Child; Humans; Modafinil; Narcolepsy; Sleep; Sodium Oxybate
PubMed: 34173695
DOI: 10.1111/ene.14888 -
Journal of Clinical Sleep Medicine :... Sep 2021This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children.
INTRODUCTION
This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children.
METHODS
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths to each recommendation, based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force provided a summary of the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations.
RECOMMENDATIONS
The following recommendations are intended to guide clinicians in choosing a specific treatment for central disorders of hypersomnolence in adults and children. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the individual patient's values and preferences to determine the best course of action. Under each disorder, strong recommendations are listed in alphabetical order followed by the conditional recommendations in alphabetical order. The section on adult patients with hypersomnia because of medical conditions is categorized based on the clinical and pathological subtypes identified in ICSD-3. The interventions in all the recommendation statements were compared to no treatment.
1
We recommend that clinicians use modafinil for the treatment of narcolepsy in adults. (STRONG).
2
We recommend that clinicians use pitolisant for the treatment of narcolepsy in adults. (STRONG).
3
We recommend that clinicians use sodium oxybate for the treatment of narcolepsy in adults. (STRONG).
4
We recommend that clinicians use solriamfetol for the treatment of narcolepsy in adults. (STRONG).
5
We suggest that clinicians use armodafinil for the treatment of narcolepsy in adults. (CONDITIONAL).
6
We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL).
7
We suggest that clinicians use methylphenidate for the treatment of narcolepsy in adults. (CONDITIONAL).
8
We recommend that clinicians use modafinil for the treatment of idiopathic hypersomnia in adults. (STRONG).
9
We suggest that clinicians use clarithromycin for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
10
We suggest that clinicians use methylphenidate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
11
We suggest that clinicians use pitolisant for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
12
We suggest that clinicians use sodium oxybate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
13
We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL).
14
We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to dementia with Lewy bodies in adults. (CONDITIONAL).
15
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL).
16
We suggest that clinicians use sodium oxybate for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL).
17
We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL).
18
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL).
19
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL).
20
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL).
21
We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).
22
We suggest that clinicians use sodium oxybate for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).
CITATION
Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. . 2021;17(9):1881-1893.
Topics: Adult; Child; Disorders of Excessive Somnolence; Humans; Idiopathic Hypersomnia; Modafinil; Narcolepsy; Sleep; United States
PubMed: 34743789
DOI: 10.5664/jcsm.9328 -
Psychopharmacology Aug 2020Agonist-based pharmacologic intervention is an accepted approach in treatment of opioid and tobacco use disorders. (Meta-Analysis)
Meta-Analysis
RATIONALE
Agonist-based pharmacologic intervention is an accepted approach in treatment of opioid and tobacco use disorders.
OBJECTIVES
We conducted a systematic review and meta-analysis to evaluate usefulness of an agonist approach as treatment of (psycho)stimulant use disorder (PSUD).
METHODS
We reviewed PubMed/Medline, LILACS, and ClinicalTrials.gov databases searching for randomized, double-blind, placebo-controlled, parallel-design studies evaluating outcomes of individuals treated for cocaine- or amphetamine-type substance use disorder. We combined results of all trials that included the following prescription psychostimulants (PPs): modafinil, methylphenidate, or amphetamines (mixed amphetamine salts, lisdexamphetamine, and dextroamphetamine). The combined sample consisted of 2889 patients. Outcomes of interest included the following: drug abstinence (defined as 2-3 weeks of sustained abstinence and the average maximum days of consecutive abstinence), percentage of drug-negative urine tests across trial, and retention in treatment. We conducted random-effects meta-analyses and assessed quality of evidence using the GRADE system.
RESULTS
Thirty-eight trials were included. Treatment with PPs increases rates of sustained abstinence [risk ratio (RR) = 1.45, 95% confidence interval (CI) = (1.10, 1.92)] and duration of abstinence [mean difference (MD) = 3.34, 95% CI = (1.06, 5.62)] in patients with PSUD, particularly those with cocaine use disorder (very low-quality evidence). Prescription amphetamines were particularly efficacious in promoting sustained abstinence in patients with cocaine use disorder [RR = 2.44, 95% CI = (1.66, 3.58)], and higher doses of PPs were particularly efficacious for treatment of cocaine use disorder [RR = 1.95, 95% CI = (1.38, 2.77)] (moderate-quality evidence). Treatment with prescription amphetamines also yielded more cocaine-negative urines [MD = 8.37%, 95% CI = (3.75, 12.98)]. There was no effect of PPs on the retention in treatment.
CONCLUSION
Prescription psychostimulants, particularly prescription amphetamines given in robust doses, have a clinically significant beneficial effect to promote abstinence in the treatment of individuals with PSUD, specifically the population with cocaine use disorder.
Topics: Amphetamine; Central Nervous System Stimulants; Cocaine; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Modafinil; Prescription Drugs; Randomized Controlled Trials as Topic; Substance-Related Disorders; Treatment Outcome
PubMed: 32601988
DOI: 10.1007/s00213-020-05563-3