Treatments for ADHD in Children and Adolescents: A Systematic Review.

CONTEXT: Effective treatment of attention-deficit/hyperactivity disorder (ADHD) is essential to improving youth outcomes. OBJECTIVES: This systematic review provides an overview of the available treatment options. DATA SOURCES: We identified controlled treatment evaluations in 12 databases published from 1980 to June 2023; treatments were not restricted by intervention content. STUDY SELECTION: Studies in children and adolescents with clinically diagnosed ADHD, reporting patient health and psychosocial outcomes, were eligible. Publications were screened by trained reviewers, supported by machine learning. DATA EXTRACTION: Data were abstracted and critically appraised by 1 reviewer and checked by a methodologist. Data were pooled using random-effects models. Strength of evidence and applicability assessments followed Evidence-based Practice Center standards. RESULTS: In total, 312 studies reported in 540 publications were included. We grouped evidence for medication, psychosocial interventions, parent support, nutrition and supplements, neurofeedback, neurostimulation, physical exercise, complementary medicine, school interventions, and provider approaches. Several treatments improved ADHD symptoms. Medications had the strongest evidence base for improving outcomes, including disruptive behaviors and broadband measures, but were associated with adverse events. LIMITATIONS: We found limited evidence of studies comparing alternative treatments directly and indirect analyses identified few systematic differences across stimulants and nonstimulants. Identified combination of medication with youth-directed psychosocial interventions did not systematically produce better results than monotherapy, though few combinations have been evaluated. CONCLUSIONS: A growing number of treatments are available that improve ADHD symptoms and other outcomes, in particular for school-aged youth. Medication therapies remain important treatment options but are associated with adverse events.

Correlates of Stimulant Use among People Who Use Heroin Undergoing Treatment in Out-Patient Facilities in France, 2010-2020.

Background: Polydrug use has been implicated in driving a "fourth wave" of the overdose crisis in North America, specifically through concurrent use of stimulants and opioids, especially fentanyl. In France, however, heroin has historically been and remains the easiest-to-access opioid, accounting for most drug treatment demand. Whether similar polydrug use is increasing in Western Europe remains understudied, despite severe health implications and potential inadequate public health responses.Methods: We take advantage of a nation-wide dataset containing information on all patients serviced in treatment centers in France from 2010 to 2020. We conduct Poisson regression to determine the main predictors of stimulant use among people who use heroin (PWUH) and opioids (PWUO) generally.Results: Heroin remains the primary opioid within drug treatment in France. A decreasing number of out-patients seeking treatment for heroin use has been accompanied by an increasing trend of stimulant use over time, most commonly with powder cocaine. Our results suggest a significant increase of crack cocaine use among the most vulnerable PWUH. Concurrent use of stimulants among PWUH was positively associated with use of alcohol, cannabis, unprescribed psychotropics and hallucinogens, and negatively with tobacco. Similar results were found for all in-treatment PWUO.Conclusions: Our results uncover heterogeneity in the profiles of PWUH that should be fully acknowledged to ensure better efficiency in substance use clinical practices and policy, while simultaneously drawing attention to trends in concurrent opioid-stimulant use outside North America. We advocate for an extension of the generalized risk framework and its implementation in prevention programs.

Association Between Stimulant Treatment and Substance Use Through Adolescence Into Early Adulthood.

Importance: Possible associations between stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) and subsequent substance use remain debated and clinically relevant. Objective: To assess the association of stimulant treatment of ADHD with subsequent substance use using the Multimodal Treatment Study of ADHD (MTA), which provides a unique opportunity to test this association while addressing methodologic complexities (principally, multiple dynamic confounding variables). Design, Setting, and Participants: MTA was a multisite study initiated at 6 sites in the US and 1 in Canada as a 14-month randomized clinical trial of medication and behavior therapy for ADHD but transitioned to a longitudinal observational study. Participants were recruited between 1994 and 1996. Multi-informant assessments included comprehensively assessed demographic, clinical (including substance use), and treatment (including stimulant treatment) variables. Children aged 7 to 9 years with rigorously diagnosed DSM-IV combined-type ADHD were repeatedly assessed until a mean age of 25 years. Analysis took place between April 2018 and February 2023. Exposure: Stimulant treatment of ADHD was measured prospectively from baseline for 16 years (10 assessments) initially using parent report followed by young adult report. Main Outcomes and Measures: Frequency of heavy drinking, marijuana use, daily cigarette smoking, and other substance use were confidentially self-reported with a standardized substance use questionnaire. Results: A total of 579 children (mean [SD] age at baseline, 8.5 [0.8] years; 465 [80%] male) were analyzed. Generalized multilevel linear models showed no evidence that current (B [SE] range, -0.62 [0.55] to 0.34 [0.47]) or prior stimulant treatment (B [SE] range, -0.06 [0.26] to 0.70 [0.37]) or their interaction (B [SE] range, -0.49 [0.70] to 0.86 [0.68]) were associated with substance use after adjusting for developmental trends in substance use and age. Marginal structural models adjusting for dynamic confounding by demographic, clinical, and familial factors revealed no evidence that more years of stimulant treatment (B [SE] range, -0.003 [0.01] to 0.04 [0.02]) or continuous, uninterrupted stimulant treatment (B [SE] range, -0.25 [0.33] to -0.03 [0.10]) were associated with adulthood substance use. Findings were the same for substance use disorder as outcome. Conclusions and Relevance: This study found no evidence that stimulant treatment was associated with increased or decreased risk for later frequent use of alcohol, marijuana, cigarette smoking, or other substances used for adolescents and young adults with childhood ADHD. These findings do not appear to result from other factors that might drive treatment over time and findings held even after considering opposing age-related trends in stimulant treatment and substance use.

A gender-based secondary analysis of the ADAPT-2 combination naltrexone and bupropion treatment for methamphetamine use disorder trial.

BACKGROUND AND AIMS: Socio-cultural (gender) and biological (sex)-based differences contribute to psychostimulant susceptibility, potentially affecting treatment responsiveness among women with methamphetamine use disorder (MUD). The aims were to measure (i) how women with MUD independently and compared with men respond to treatment versus placebo and (ii) among women, how the hormonal method of contraception (HMC) affects treatment responsiveness. DESIGN: This was a secondary analysis of ADAPT-2, a randomized, double-blind, placebo-controlled, multicenter, two-stage sequential parallel comparison design trial. SETTING: United States. PARTICIPANTS: This study comprised 126 women (403 total participants); average age = 40.1 years (standard deviation = 9.6) with moderate to severe MUD. INTERVENTIONS: Interventions were combination intramuscular naltrexone (380 mg/3 weeks) and oral bupropion (450 mg daily) versus placebo. MEASUREMENTS: Treatment response was measured using a minimum of three of four negative methamphetamine urine drug tests during the last 2 weeks of each stage; treatment effect was the difference between weighted treatment responses of each stage. FINDINGS: At baseline, women used methamphetamine intravenously fewer days than men [15.4 versus 23.1% days, P = 0.050, difference = -7.7, 95% confidence interval (CI) = -15.0 to -0.3] and more women than men had anxiety (59.5 versus 47.6%, P = 0.027, difference = 11.9%, 95% CI = 1.5 to 22.3%). Of 113 (89.7%) women capable of pregnancy, 31 (27.4%) used HMC. In Stage 1 29% and Stage 2 5.6% of women on treatment had a response compared with 3.2% and 0% on placebo, respectively. A treatment effect was found independently for females and males (P < 0.001); with no between-gender treatment effect (0.144 females versus 0.100 males; P = 0.363, difference = 0.044, 95% CI = -0.050 to 0.137). Treatment effect did not differ by HMC use (0.156 HMC versus 0.128 none; P = 0.769, difference = 0.028, 95% CI -0.157 to 0.212). CONCLUSIONS: Women with methamphetamine use disorder receiving combined intramuscular naltrexone and oral bupropion treatment achieve greater treatment response than placebo. Treatment effect does not differ by HMC.

The Effects of Theta/Beta-based Neurofeedback Training on Attention in Children with Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-analysis.

Neurofeedback training is a common treatment option for attention deficit hyperactivity disorder (ADHD). Given theta/beta-based neurofeedback (T/B NF) training targets at the electrophysiological characteristics of children with ADHD, benefits for attention may be expected. PsycINFO, PubMed, ScienceDirect, Scopus, and Web of Science were searched through December 31, 2020. Studies were evaluated with Risk of Bias tools. Within-group effects based on Pre- and Post-treatment comparisons of the Intervention Group, and Between-group effects based on the between-group differences from Pre-treatment to Post-treatment were calculated. Nineteen studies met selection criteria for systematic review, 12 of them were included in meta-analysis. Within-group effects were medium at Post-treatment and large at Follow-up. Between-group analyses revealed that T/B NF was superior to waitlist control and physical activities, but not stimulant medication. Results showed that T/B NF has benefits for attention in children with ADHD, however, cautions should be taken when interpreting the findings.

The effect of Rosa canina L. and a polyherbal formulation syrup in patients with attention-deficit/hyperactivity disorder: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood and adolescence. A number of these patients do not respond to the current pharmacological treatments and there may also be drug side effects. This study aims to determine the efficacy and safety of two herbal medicine products, including Rosa canina L. (RC) and a polyherbal formulation (PHF) syrup, on the clinical manifestations of ADHD in children and adolescents. METHODS: Ninety ADHD patients based on DSM-5 diagnostic criteria will be randomly assigned equally into three groups: (1) RC syrup + methylphenidate (MP), (2) PHF syrup + MP, and (3) placebo + MP according to the inclusion criteria (30 subjects in each group). The syrup dosage is 5cc every 8 h, and MP will have a stabilized dose for 8 weeks during the study. Moreover, Conner's questionnaires will be completed by the teacher and parents before the intervention and then every 4 weeks. Also, the Child Symptom Inventory-fourth edition (CSI-4) and temperament questionnaires will be completed before the intervention and every 4 weeks until 2 months. DISCUSSION: This trial is the first experiment to determine the effects of RC and PHF syrups on the clinical manifestations of ADHD in children and adolescents. Our findings provide new insight into the effect of these herbal products on the clinical manifestations of ADHD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20190923044855N1 . Registered on 14 January 2020. The trial was registered at https://www.irct.ir/ .

Editorial: Accumulating Evidence for the Benefit of Micronutrients for Children With Attention-Deficit/Hyperactivity Disorder.

The first paper indicating that a central nervous system stimulant (amphetamine) could be beneficial for children with attention-deficit/hyperactivity disorder (ADHD)-like behavioral symptoms appeared in 1937.1 Over the subsequent 80 years, a range of additional stimulant (methylphenidate) and nonstimulant (atomoxetine, clonidine, guanfacine, and, most recently, viloxazine) drugs have been approved to treat children and adolescents with ADHD. These drug treatments have been the subject of a large number of randomized controlled trails (RCTs). A network meta-analysis found that using clinician ratings, amphetamine, methylphenidate, and atomoxetine were all significantly superior to a placebo.2 These findings suggest that in the short-term at least, these treatments are effective-data are sparse on the efficacy of longer-term drug treatment. However, there are longstanding worries about the use of such drug treatments with children. In particular there are concerns over possible adverse impact on growth. There are also less tangible, but important, concerns of parents as the whether it is appropriate to subject their children to the modification of behavior by drugs.3 For these reasons, there is an urgent need to develop nonpharmacological treatments for children and adolescents with ADHD. One such nonpharmacological treatment is dietary supplementation with micronutrients. In this issue of the Journal, Johnstone et al.4 present a study of micronutrients showing that, under the stringent conditions of an RCT, micronutrients substantially benefit the well-being of young people with ADHD and irritability (risk ratio [RR] = 2.97; 97.5% CI = 1.50-5.90).

Exploring the Effects of Pharmacological, Psychosocial, and Alternative/Complementary Interventions in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Meta-Regression Approach.

BACKGROUND: There have been various therapies for attention-deficit/hyperactivity disorder (ADHD), but the previous meta-analysis of ADHD efficacy remains unclear. This study aims to systemically meta-regress the effect sizes (ES) of psychostimulant pharmacotherapy (methylphenidate and lisdexamfetamine), non-stimulant pharmacotherapy (atomoxetine and alpha-2 agonists), psychosocial therapy (parental behavioral therapy [PBT]), combination therapy (psychostimulant plus PBT), and alternative/complementary interventions to determine the right treatment for ADHD. METHODS: We searched various ADHD interventions from the MEDLINE and PubMed databases (National Center for Biotechnology Information) between January 1, 1980, and July 30, 2018. Following the meta-analysis of random effects, the meta-regression analyses were used to explore factors potentially influencing treatment efficacy. The confounding variables included type of treatment, type of study, age, type of symptom scale used, and year of publication. RESULTS: A total of 107 trials (n = 9883 participants) were included. After adjustment, compared with the psychostimulant therapy (28 trial, 2134 participants), non-stimulant pharmacotherapy (28 trials, 4991 participants) and alternative/complement intervention (25 trials, 1195 participants) were less effective by the ES of -0.384 (P = .004) and -0.419 (P = .028), respectively. However, compared with psychostimulant, PBT (19 trials, 1122 participants; ES = -0.308, P = .095) and the combination of psychostimulant and PBT (7 trials, 441participants; ES = -0.196, P = .209) did not differ significantly. CONCLUSIONS: Psychostimulant therapy surpassed non-stimulant pharmacotherapy and alternative/complement intervention. Psychostimulant therapy, PBT, and the combination of psychostimulant therapy and PBT appear to be similar in efficacy according to this meta-regression.

Adjuvant effects of vitamin A and vitamin D supplementation on treatment of children with attention-deficit/hyperactivity disorder: a study protocol for a randomised, double-blinded, placebo-controlled, multicentric trial in China.

INTRODUCTION: Approximately 7.2% of children in the world suffer from attention-deficit/hyperactivity disorder (ADHD). Due to the availability of the osmotic-release oral-system methylphenidate, ADHD currently has a remission rate of up to 30.72%. Nevertheless, it has been reported that patients with ADHD tend to exhibit vitamin A and vitamin D deficiency, which may aggravate the symptoms of ADHD. This study aims to determine the effect of vitamin A and vitamin D supplementation as adjunctive therapy to methylphenidate on the symptoms of ADHD. METHODS AND ANALYSIS: This is a parallel, prospective, interventional multicentric study. Patients will be enrolled from the southern, central and northern parts of China. A target of 504 patients will be followed for 8 weeks. They will be allocated into three groups (vitamin AD, vitamin D and placebo) and administered the interventions accordingly. Data on changes in the symptoms of ADHD as well as changes in the serum concentrations of vitamin A and vitamin D will be recorded. Both responders and nonresponders based on the sociodemographic and clinical data will also be described to mitigate selection bias. ETHICS AND DISSEMINATION: This study is performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Children's Hospital of Chongqing Medical University, China (approval number: (2019) IRB (STUDY) number 262). The results of the trial will be reported in peer-reviewed scientific journals and academic conferences regardless of the outcomes. TRIAL REGISTRATION NUMBER: NCT04284059.

Modafinil Decreased Thalamic Activation in Auditory Emotional Processing: A Randomized Controlled Functional Magnetic Resonance Imaging Study.

BACKGROUND: Modafinil improves wakefulness and attention, is approved in Japan for treatment of narcolepsy, and was reported to be effective for attention-deficit/hyperactivity disorder. However, it was reported to induce emotional instability, including mania, depression, and suicidal ideation. Such side effects may be related to changes in cognitive behavior caused by the effects of modafinil on emotional recognition. However, the effects of modafinil on the neural basis of emotional processing have not been fully verified. We used functional magnetic resonance imaging to investigate the effects of modafinil on the neural basis of auditory emotional processing. METHODS: This study adopted a placebo-controlled within-subject crossover design. Data from 14 participants were analyzed. The effects of modafinil on cerebral activation and task performance during an emotional judgement task were analyzed. RESULTS: Task accuracy decreased significantly and response time of emotional judgement was significantly delayed by modafinil, as compared with placebo. Right thalamic activation in auditory emotional processing was significantly less in the modafinil condition than in the placebo condition. In addition, reduction of right thalamic activation by modafinil was positively correlated with accuracy of emotional judgement. CONCLUSIONS: Our findings suggest that modafinil acts on the right thalamus and changes behavior and brain function associated with auditory emotional processing. These results indicate that modafinil might change emotional recognition by reducing emotional activation related to social communication.

Effects of methylphenidate on sensory and sensorimotor gating of initially psychostimulant-naïve adult ADHD patients.

Deficient information processing in ADHD theoretically results in sensory overload, which in turn may underlie its symptoms. If this sensory overload is caused by deficient filtering of environmental stimuli, then one would expect finding deficits in P50 gating and prepulse inhibition of the startle reflex (PPI). Previous reports on these measures in ADHD have shown inconsistent findings, which may have been caused by either medication use or comorbidity (e.g. ASD). The primary aim of this study was therefore to explore P50 suppression and PPI in adult, psychostimulant-naïve patients with ADHD without major comorbidity, and to examine the effects of 6 weeks treatment with methylphenidate (MPH) on these measures. A total of 42 initially psychostimulant-naive, adult ADHD patients without major comorbidity and 42 matched healthy controls, were assessed for their P50 gating, PPI, and habituation/sensitization abilities at baseline and after 6 weeks of treatment with methylphenidate. Although six weeks of treatment with MPH significantly reduced symptomatology as well as improved daily life functioning in our patients, it neither significantly affected PPI, P50 suppression nor sensitization, but habituation unexpectedly decreased. The absence of PPI and P50 suppression deficits in our patients in the psychostimulant-naïve state indicates no gating deficits. In turn, this suggests that the difficulties to inhibit distraction of attention by irrelevant stimuli that many patients with (adult) ADHD report, have a different origin than the theoretical causes of sensory overload frequently reported in studies on patients with schizophrenia.

The Efficacy of Acupuncture Treatment for Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to assess the efficacy of acupuncture for treating attention deficit hyperactivity disorder (ADHD) in children and adolescents. PATIENTS AND METHODS: Systematic review and meta-analysis including randomized controlled trials that compared the effects of acupuncture treatment (AT) with pharmacotherapy (methylphenidate hydrochloride, MPH) among patients with ADHD. A total of 12 electronic databases were searched from inception until February 3, 2020. The main outcomes were the effective rate and post-treatment hyperactivity scores. We also assessed the incidence of adverse events and follow-up course. RESULTS: A total of 10 studies involving 876 patients were included in this study. The meta-analysis revealed that AT yielded a significantly higher effective rate than MPH (odds ratio 2.239, 95% CI 1.438-3.487, p < 0.001, 8 studies), and that AT can reduce the hyperactivity scores to a lesser degree than MPH (standardized mean difference = -0.882, 95% CI -1.295 to -0.469, p < 0.001, 3 studies). Two studies reported no adverse events in the AT group, while one study suggested that AT can reduce adverse drug reactions. Furthermore, 3 studies concluded that the effects of AT were maintained, even after completion of treatment. CONCLUSION: This study suggests that AT may be more beneficial than MPH therapy for ADHD patients. However, the evidence may be highly limited, especially considering the outcome of hyperactivity scores with the high risk of bias, very low GRADE, and small number of studies. Thus, further studies of rigorous design and high quality are needed to confirm and strengthen the results, especially in the Western part of the world. Additionally, well-designed randomized controlled trials that evaluate adverse events and include a long-term follow-up should be conducted to determine the efficacy, safety, and side effects of AT for ADHD in children and adolescents.

Sleep disturbance in patients with cancer: a feasibility study of multimodal therapy.

BACKGROUND: Our aim was to determine feasibility and effect sizes of bright light therapy (BLT), melatonin (MLT), methylphenidate (MP) and eight combinations (BLT+MLT+MP, BLT+MLT, BLT+MP, BLT alone, MLT+MP, MLT alone, MP alone, placebo for BLT, MLT and MP) defined as multimodal therapy (MMT), to improve sleep quality (SQ) (Pittsburgh Sleep Quality Index (PSQI)) from baseline to day 15. We also examined the effects of MMT on insomnia, fatigue, depression, quality of life and actigraphy. METHODS: Patients with advanced cancer with poor SQ (PSQI ≥5) were eligible. Using a double-blind randomised factorial study design, patients were randomised into 1 of the 8 arms for 2 weeks. Feasibility and effect sizes were assessed. RESULTS: 81% (54/67) of randomised patients completed the study. There were no differences in the demographics and SQ between groups. The adherence rates for BLT, MLT and MP were 93%, 100% and 100%, respectively. BLT+MLT+placebo of MP; BLT+placebo of MLT+placebo of MP; BLT+MLT+MP showed an effect size (Cohen's d) for change in PSQI scores of 0.64, 0.57 and 0.63, respectively. PSQI change using linear regression showed BLT (n=29) has effect size of 0.46, p=0.017; MLT (n=26), 0.24, p=0.20; MP (n=26), 0.06, p=0.46. No significant differences were observed in scores for insomnia, fatigue, depression, quality of life and actigraphy. There were no differences in adverse events by groups(p=0.80). CONCLUSIONS: The use of MMT to treat SQ disturbance was feasible. BLT+MLT showed the most promising effect size in improvement in SQ, and additional larger studies are needed. TRIAL REGISTRATION NUMBER: NCT01628029.

L-Threonic Acid Magnesium Salt Supplementation in ADHD: An Open-Label Pilot Study.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is estimated to affect up to 5% of adults worldwide. Preclinical work demonstrates that L-Threonic Acid Magnesium Salt (LTAMS) administration is associated with neurobiological and neurofunctional effects that could offer clinical benefits in ADHD treatment.Methods: Participants were 15 adults with ADHD of moderate severity. Subjects received up to 12 weeks of open-label LTAMS administered as MMFS302 and MMFS202. The study was approved by the Institutional Review Board and posted on ClinicalTrails.Gov (NCT02558790).Results: 47% of subjects met our criteria of response attaining a CGI-Improvement score ≤2 and AISRS total reduction ≥25%. Significant improvement was seen in the AISRS, CGI-I, and the shifting subscale of the BRIEF. Changes in IQ and WASI-II performance were favorable and significant in the study population.Conclusion: LTAMS supplementation was found to be effective and well tolerated. Nearly half of participants met our definition of ADHD symptom clinical response. These results support the need to further evaluate this compound in larger samples under double-blind conditions.

What Do Meta-Analyses Have to Say About the Efficacy of Neurofeedback Applied to Children With ADHD? Review of Previous Meta-Analyses and a New Meta-Analysis.

Objective: We reviewed previously published meta-analyses of neurofeedback applied to children with ADHD and conducted a new meta-analysis of randomized controlled trials (RCTs) that updates previous results and incorporates methodological modifications. Method: Searches were carried out through PubMed, Sage, PsycINFO, SpringerLink, and Psicodoc. We used Hedges' (adjusted) g and a random-effects model. To assess heterogeneity, Q and I2 were calculated. We performed different analyses depending on the control groups, ADHD symptoms, pre- and/or posttreament data used and symptom evaluator. Results: We reviewed seven meta-analyses, and 17 studies were incorporated into the meta-analysis. RCTs support the efficacy of neurofeedback applied to ADHD when most proximal evaluators assess symptoms. Neurofeedback significantly improves inattention symptoms when possibly blinded evaluators assess symptoms. The preliminary results suggest that stimulant medication is more effective than neurofeedback. Conclusion: New RCTs that establish links between ADHD symptom measurements, subjects' learning after neurofeedback, and neurophysiological measures could improve the quality of the conclusions.

A central role for apathy in the effectiveness of interventions for cancer-related fatigue.

OBJECTIVE: Cancer-related fatigue (CRF) affects a substantial number of cancer patients and survivors. Recommendations for CRF treatments are largely based on results of randomized controlled trials. The interpretability of such results is limited to patients eligible and willing to participate in these trials. We aimed to address this limitation in a retrospective study of patients seen at a CRF clinic in a comprehensive cancer center. The objectives were to (a) determine the effectiveness of clinician-initiated interventions for CRF and identify their mediators and (b) describe the frequency and effectiveness of patient-initiated physical activity (PA) behavior for alleviating CRF and identify determinants of this PA. METHODS: Data (patient-reported somatic and mood symptoms; clinical data; clinician-documented changes in medication and behavior) from n = 213 patients collected as part of the clinic's standard of care at initial clinical consult and follow-up 4 to 11 weeks later were included. Effects of clinician-initiated interventions and patient-initiated PA on change in fatigue were analyzed using linear models. RESULTS: Of all clinician-initiated interventions, only psychostimulant start was recorded frequent enough for further investigation and was associated with reduced fatigue; this association was mediated by a reduction in apathy. PA was also associated with reduced fatigue severity. PA initiation/increase after consult was associated with lower apathy at consult. CONCLUSIONS: These results demonstrate a major role for patient apathy in the effectiveness and initiation of CRF-targeting interventions. Behavioral therapies focusing on reduction in apathy should be considered as initial treatment of CRF in those with substantial apathy.

Treatment of stimulant use disorder: A systematic review of reviews.

AIMS: Stimulant use disorder contributes to a substantial worldwide burden of disease, although evidence-based treatment options are limited. This systematic review of reviews aims to: (i) synthesize the available evidence on both psychosocial and pharmacological interventions for the treatment of stimulant use disorder; (ii) identify the most effective therapies to guide clinical practice, and (iii) highlight gaps for future study. METHODS: A systematic database search was conducted to identify systematic reviews and meta-analyses. Eligible studies were those that followed standard systematic review methodology and assessed randomized controlled trials focused on the efficacy of interventions for stimulant use disorder. Articles were critically appraised using an assessment tool adapted from Palmeteer et al. and categorized for quality as 'core' or 'supplementary' reviews. Evidence from the included reviews were further synthesized according to pharmacological or non-pharmacological management themes. RESULTS: Of 476 identified records, 29 systematic reviews examining eleven intervention modalities were included. The interventions identified include: contingency management, cognitive behavioural therapy, acupuncture, antidepressants, dopamine agonists, antipsychotics, anticonvulsants, disulfiram, opioid agonists, N-Acetylcysteine, and psychostimulants. There was sufficient evidence to support the efficacy of contingency management programs for treatment of stimulant use disorder. Psychostimulants, n-acetylcysteine, opioid agonist therapy, disulfiram and antidepressant pharmacological interventions were found to have insufficient evidence to support or discount their use. Results of this review do not support the use of all other treatment options. CONCLUSIONS: The results of this review supports the use of contingency management interventions for the treatment of stimulant use disorder. Although evidence to date is insufficient to support the clinical use of psychostimulants, our results demonstrate potential for future research in this area. Given the urgent need for effective pharmacological treatments for stimulant use disorder, high-quality primary research focused on the role of psychostimulant medications for the treatment of stimulant use disorder is needed.

[Pharmacotherapy of attention deficit hyperactivity disorder in adults]. / Medikamentöse Therapie der Aufmerksamkeitsdefizit­/Hyperaktivitätsstörung im Erwachsenenalter.

Pharmacotherapy is a central component in the context of an overall therapeutic concept in the treatment of adults with attention deficit hyperactivity disorder (ADHD). In this concept psychosocial interventions with psychoeducation or specific psychotherapy measures also play an important role. In adults three compounds are currently approved for the pharmacological treatment of ADHD in Germany. The long-acting stimulants retarded methylphenidate preparations and lisdexamfetamine can be prescribed. Alternatively, the adrenergic uptake inhibitor atomoxetine can be used. In several meta-analyses good effectiveness and tolerance of these drugs on ADHD psychopathology has been shown. They also improve ADHD-related disorders of emotional regulation capability and disorganization in everyday life. Importantly, an improvement in everyday functionality and quality of life under medication could also be shown in several studies. In this review the evidence for pharmacotherapy of ADHD and its implementation into treatment of adult patients is presented.

Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

OBJECTIVE: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions. CONCLUSIONS: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.