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Drug and Alcohol Dependence Jul 2023Nicotine is commonly co-used with other psychostimulants. These high co-use rates have prompted much research on interactions between nicotine and psychostimulant drugs.... (Review)
Review
BACKGROUND
Nicotine is commonly co-used with other psychostimulants. These high co-use rates have prompted much research on interactions between nicotine and psychostimulant drugs. These studies range from examination of illicitly used psychostimulants such as cocaine and methamphetamine to prescription psychostimulants used to treat attention deficit hyperactivity disorder (ADHD) such as methylphenidate (Ritalin™) and d-amphetamine (active ingredient of Adderall™). However, previous reviews largely focus on nicotine interactions with illicitly used psychostimulants with sparse mention of prescription psychostimulants. The currently available epidemiological and laboratory research, however, suggests high co-use between nicotine and prescription psychostimulants, and that these drugs interact to modulate use liability of either drug. The present review synthesizes epidemiological and experimental human and pre-clinical research assessing the behavioral and neuropharmacological interactions between nicotine and prescription psychostimulants that may contribute to high nicotine-prescription psychostimulant co-use.
METHODS
We searched databases for literature investigating acute and chronic nicotine and prescription psychostimulant interactions. Inclusion criteria were that participants/subjects had to experience nicotine and a prescription psychostimulant compound at least once in the study, in addition to assessment of their interaction.
RESULTS AND CONCLUSIONS
Nicotine clearly interacts with d-amphetamine and methylphenidate in a variety of behavioral tasks and neurochemical assays assessing co-use liability across preclinical, clinical, and epidemiological research. The currently available research suggests research gaps examining these interactions in women/female rodents, in consideration of ADHD symptoms, and how prescription psychostimulant exposure influences later nicotine-related outcomes. Nicotine has been less widely studied with alternative ADHD pharmacotherapy bupropion, but we also discuss this research.
Topics: Female; Humans; Nicotine; Central Nervous System Stimulants; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Dextroamphetamine; Prescriptions
PubMed: 37216808
DOI: 10.1016/j.drugalcdep.2023.109906 -
The American Journal of Geriatric... Dec 2023The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) found that methylphenidate was effective in treating apathy with a small-to-medium effect size but showed...
OBJECTIVE
The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) found that methylphenidate was effective in treating apathy with a small-to-medium effect size but showed heterogeneity in response. We assessed clinical predictors of response to help determine individual likelihood of treatment benefit from methylphenidate.
DESIGN
Univariate and multivariate analyses of 22 clinical predictors of response chosen a priori.
SETTING
Data from the ADMET 2 randomized, placebo controlled multi-center clinical trial.
PARTICIPANTS
Alzheimer's disease patients with clinically significant apathy.
MEASUREMENTS
Apathy assessed with the Neuropsychiatric Inventory apathy domain (NPI-A).
RESULTS
In total, 177 participants (67% male, mean [SD] age 76.4 [7.9], mini-mental state examination 19.3 [4.8]) had 6-months follow up data. Six potential predictors met criteria for inclusion in multivariate modeling. Methylphenidate was more efficacious in participants without NPI anxiety (change in NPI-A -2.21, standard error [SE]:0.60) or agitation (-2.63, SE:0.68), prescribed cholinesterase inhibitors (ChEI) (-2.44, SE:0.62), between 52 and 72 years of age (-2.93, SE:1.05), had 73-80 mm Hg diastolic blood pressure (-2.43, SE: 1.03), and more functional impairment (-2.56, SE:1.16) as measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living scale.
CONCLUSION
Individuals who were not anxious or agitated, younger, prescribed a ChEI, with optimal (73-80 mm Hg) diastolic blood pressure, or having more impaired function were more likely to benefit from methylphenidate compared to placebo. Clinicians may preferentially consider methylphenidate for apathetic AD participants already prescribed a ChEI and without baseline anxiety or agitation.
Topics: Humans; Male; Aged; Female; Alzheimer Disease; Methylphenidate; Apathy; Activities of Daily Living; Dementia; Cholinesterase Inhibitors
PubMed: 37385898
DOI: 10.1016/j.jagp.2023.06.002 -
Expert Review of Neurotherapeutics 2023Emotional dysregulation (ED) symptoms are present in a considerable portion of patients with attention-deficit/hyperactivity disorder (ADHD). In recent years, an... (Review)
Review
INTRODUCTION
Emotional dysregulation (ED) symptoms are present in a considerable portion of patients with attention-deficit/hyperactivity disorder (ADHD). In recent years, an increasing number of studies investigated the effects of stimulant medications on ED in patients with ADHD.
AREAS COVERED
A narrative review of the literature on stimulant treatment for ED is provided, including controlled and observational clinical studies conducted on pediatric and adult samples and neurobiological investigations. Positive effects of stimulants on irritability have been demonstrated in children. Comorbidity with disruptive behavior disorders (DBD) and disruptive mood dysregulation disorder does not prevent stimulant effectiveness. Methylphenidate has also been found to reduce temper problems, affective instability, and emotional over-reactivity in adults with ADHD, although with variable effect sizes. A variety of adverse emotional effects have been reported, especially at high doses and in special populations. However, several possible confounders of treatment-emergent ED have been highlighted. Finally, according to neuroimaging studies, stimulants may mitigate emotional processing anomalies associated with ADHD.
EXPERT OPINION
The findings are consistent with models including ED within the core features of ADHD. Stimulant treatment should be prioritized over antipsychotics in ADHD-DBD. It remains to be elucidated whether other medications may be more effective in specific populations with ADHD and/or ED.
Topics: Adult; Humans; Child; Attention Deficit Disorder with Hyperactivity; Methylphenidate; Central Nervous System Stimulants; Attention Deficit and Disruptive Behavior Disorders; Irritable Mood
PubMed: 37747111
DOI: 10.1080/14737175.2023.2263645 -
Journal of Attention Disorders Dec 2022Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research.
OBJECTIVE
Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research.
METHOD
Controlled trials of adult ADHD measuring emotional behavior were included if another study offered a comparable analysis of the same treatment method. Standardized Mean Difference (SMD) of effects were calculated, and the size of effects for emotional and non-emotional ADHD behavior were compared.
RESULTS
13 out of 14 studies of methylphenidate, atomoxetine, and lisdexamfetamine demonstrated significant improvement in emotional behavior measures, with small to high SMDs. The proportional effect on emotional versus non-emotional behavior ranged from 46% to 110% for methylphenidate, 56% to 129% for atomoxetine, and 36% to 96% for lisdexamfetamine.
CONCLUSION
Psychopharmacological treatments for ADHD are likely to improve emotional behavior, and available scales are sensitive to these effects. Studies dedicated to treatment of this domain of function can further refine clinical approaches.
Topics: Adult; Humans; Atomoxetine Hydrochloride; Lisdexamfetamine Dimesylate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Treatment Outcome
PubMed: 35822610
DOI: 10.1177/10870547221110926 -
The Lancet. Psychiatry Feb 2024
Topics: Child; Humans; Adolescent; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; World Health Organization
PubMed: 38245023
DOI: 10.1016/S2215-0366(23)00395-4 -
The Lancet. Psychiatry Feb 2024
Topics: Child; Humans; Adolescent; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; World Health Organization
PubMed: 38245022
DOI: 10.1016/S2215-0366(23)00392-9 -
International Journal of Molecular... Aug 2023Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, although the aetiology of ADHD is not yet understood. One... (Review)
Review
Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, although the aetiology of ADHD is not yet understood. One proposed theory for developing ADHD is N-methyl-D-aspartate receptors (NMDARs) dysfunction. NMDARs are involved in regulating synaptic plasticity and memory function in the brain. Abnormal expression or polymorphism of some genes associated with ADHD results in NMDAR dysfunction. Correspondingly, NMDAR malfunction in animal models results in ADHD-like symptoms, such as impulsivity and hyperactivity. Currently, there are no drugs for ADHD that specifically target NMDARs. However, NMDAR-stabilizing drugs have shown promise in improving ADHD symptoms with fewer side effects than the currently most widely used psychostimulant in ADHD treatment, methylphenidate. In this review, we outline the molecular and genetic basis of NMDAR malfunction and how it affects the course of ADHD. We also present new therapeutic options related to treating ADHD by targeting NMDAR.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Receptors, N-Methyl-D-Aspartate; Methylphenidate; Brain; Central Nervous System Stimulants
PubMed: 37629164
DOI: 10.3390/ijms241612983 -
Neurourology and Urodynamics Sep 2023Giggle incontinence (GI) is a rare form of urinary incontinence that occurs during or immediately after laughing due to involuntary and complete bladder emptying. Few...
INTRODUCTION
Giggle incontinence (GI) is a rare form of urinary incontinence that occurs during or immediately after laughing due to involuntary and complete bladder emptying. Few studies in the literature report that methylphenidate can be effective in treatment of this condition.
OBJECTIVE
The aim of this study is to characterize children with GI and evaluate their response to methylphenidate, as well as describe treatment duration, dosage of methylphenidate, relapse rates after discontinuation of medication, and side effects.
METHODS
Medical records and 48-h frequency-volume charts from children treated with methylphenidate for GI in the period January 2011-July 2021 were retrospectively analyzed.
RESULTS
Eighteen children were diagnosed with GI and fulfilled inclusion criteria. Fifteen patients were included in analysis, as 3 out of 18 children decided not to take the methylphenidate that was prescribed. In total, 14 out of the 15 GI patients treated with methylphenidate experienced clinical effect. All patients included in the study had methylphenidate prescribed in a dose range of 5-20 mg daily. Treatment duration ranged from 30 to 1001 days, with a median of 152 days (IQR 114, 243.5). Ten children experienced complete response and two of those reported symptom relapse after discontinuation of the methylphenidate. Only mild and short-lasting side effects were reported by two patients.
DISCUSSION
Our study demonstrates that methylphenidate is an effective treatment in children diagnosed with GI. Side effects are mild and uncommon.
Topics: Humans; Child; Methylphenidate; Retrospective Studies; Urinary Incontinence; Treatment Outcome; Laughter
PubMed: 37376840
DOI: 10.1002/nau.25232 -
The Journal of Clinical Psychiatry Feb 2022Apathy is a common and important yet often ignored neuropsychiatric symptom of Alzheimer's disease (AD). Cholinesterase inhibitors and memantine, used to treat AD,... (Review)
Review
Apathy is a common and important yet often ignored neuropsychiatric symptom of Alzheimer's disease (AD). Cholinesterase inhibitors and memantine, used to treat AD, appear ineffective against apathy. A meta-analysis of 4 randomized, placebo-controlled trials (RCTs) found that psychostimulants significantly attenuated apathy ratings in AD. However, the pooled sample size in this meta-analysis was just 156, and one of the trials was a 2-week crossover study with a large effect. A large RCT (n = 200) has now been published. This study found that methylphenidate (MPH; 20 mg/d) was superior to placebo in the attenuation of apathy scores in patients with possible or probable, mild to moderate AD; the advantage was evident by the end of the second month of treatment and remained evident to the end of 6 months. The effect size at 6 months was small (Cohen = 0.37). In this RCT, disappointingly, MPH was not superior to placebo on secondary outcomes, including informant-rated apathy, dependence, activities of daily living, quality of life, and neurocognitive performance; caregiver burden was not formally studied. Speculatively, the psychosocial intervention provided to all participants in this RCT may have boosted response in the placebo group, thereby attenuating differences in outcomes between the MPH and placebo groups. A reasonable conclusion is that whereas MPH may attenuate the severity of apathy in patients with AD across as long as 6 months, the absence of improvements in measures of dependence, activities of daily living, and quality of life suggest that this effect of MPH on apathy may not be clinically significant. An unanswered question is whether the benefits of MPH may be clinically significant in real world practice settings in which the delivery of behavioral interventions is not feasible.
Topics: Activities of Daily Living; Aged; Alzheimer Disease; Apathy; Central Nervous System Stimulants; Humans; Methylphenidate; Quality of Life
PubMed: 35120284
DOI: 10.4088/JCP.22f14398 -
Journal of the American Academy of... Dec 2020Stimulants are the first-line medication for attention-deficit/hyperactivity disorder (ADHD), and methylphenidate (MPH) is the first choice in Europe, with good efficacy...
Stimulants are the first-line medication for attention-deficit/hyperactivity disorder (ADHD), and methylphenidate (MPH) is the first choice in Europe, with good efficacy and acceptable tolerability in a short-term course during childhood and adolescence. ADHD is, however a chronic condition, and patients can receive pharmacological treatment for a long period of time with understandable concerns related to long-term risks. Beside the well-known mild and transient adverse effects (ie, sleep disturbance, nervousness, anorexia, headache, and abdominal pain), in the last decade, emphasis has been placed on several less common, but potentially more serious, effects occurring with prolonged use, and in particular on a possible drug-related impact of medications on growth and pubertal maturation.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Europe; Humans; Methylphenidate; Time; Young Adult
PubMed: 33065204
DOI: 10.1016/j.jaac.2020.10.002