- Efficacy and safety of drugs for attention deficit hyperactivity disorder in children and adolescents: a network meta-analysis. [Journal Article]
- ECEur Child Adolesc Psychiatry 2018 Feb 19
- The aim of this study is to gather evidence of head-to-head double-blind randomized-controlled trials on the efficacy and safety of available treatments for attention deficit hyperactivity disorder (...
The aim of this study is to gather evidence of head-to-head double-blind randomized-controlled trials on the efficacy and safety of available treatments for attention deficit hyperactivity disorder (ADHD) in children and adolescents. A systematic review was conducted by two independent reviewers in ten electronic databases (PROSPERO register CRD42016043239). Methodological quality of included studies was evaluated according to the Jadad scale. Network meta-analyses were performed including double-blinded head-to-head trials comparing active allopathic drugs in patients (0-18 years old) diagnosed with ADHD. The results of efficacy and safety of atomoxetine (ATX), bupropion, buspirone (BSP), dexamphetamine, edivoxetine (EDX), guanfacine (GXR), lisdexamfetamine (LDX), methylphenidate (MPH), mixed amphetamine salts, modafinil, pindolol (PDL), reboxetine (RBX), selegiline, and venlafaxine were analyzed using ADDIS software v.1.16.5. Forty-eight trials were identified (n = 4169 participants), of which 12 were used for efficacy analysis and 33 for safety analysis. On the CGI-I scale, the analysis revealed that MPH was more effective than ATX and GXR. For the safety outcomes, according to drug ranks, LDX was more likely to cause sleep disorders (39%) as well as loss of appetite (65%) and behavior problems such as irritability (60%). BSP (71%) and EDX (44%) caused less appetite decrease. For behavioral effects, PDL was considered safest (50%). For any adverse events, RBX (89%) was the safest alternative. The lack of head-to-head trials properly reporting outcomes of interest limited some comparisons. Network meta-analysis offered a broader overview on the available treatments for ADHD, especially for safety issues, and contributes towards evidence gathering and clinical practice decisions. A core outcome set for ADHD should be designed to guide the conduction and report of clinical trials.
- Review of the evidence for the management of co-morbid Tic disorders in children and adolescents with attention deficit hyperactivity disorder. [Review]
- WJWorld J Clin Pediatr 2018 Feb 08; 7(1):36-42
- Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents, with prevalence ranging between 5% and 12% in the developed countries. Tic ...
Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents, with prevalence ranging between 5% and 12% in the developed countries. Tic disorders (TD) are common co-morbidities in paediatric ADHD patients with or without pharmacotherapy treatment. There has been conflicting evidence of the role of psychostimulants in either precipitating or exacerbating TDs in ADHD patients. We carried out a literature review relating to the management of TDs in children and adolescents with ADHD through a comprehensive search of MEDLINE, EMBASE, CINAHL and Cochrane databases. No quantitative synthesis (meta-analysis) was deemed appropriate. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and normal doses of psychostimulant use. Supratherapeutic doses of dextroamphetamine have been shown to exacerbate TD. Most tics are mild or moderate and respond to psychoeducation and behavioural management. Level A evidence support the use of alpha adrenergic agonists, including Clonidine and Guanfacine, reuptake noradrenenaline inhibitors (Atomoxetine) and stimulants (Methylphenidate and Dexamphetamines) for the treatment of Tics and comorbid ADHD. Priority should be given to the management of co-morbid Tourette's syndrome (TS) or severely disabling tics in children and adolescents with ADHD. Severe TDs may require antipsychotic treatment. Antipsychotics, especially Aripiprazole, are safe and effective treatment for TS or severe Tics, but they only moderately control the co-occurring ADHD symptomatology. Short vignettes of different common clinical scenarios are presented to help clinicians determine the most appropriate treatment to consider in each patient presenting with ADHD and co-morbid TDs.
- Pharmacological Treatment of Attention Deficit Hyperactivity Disorder During Pregnancy and Lactation. [Review]
- PRPharm Res 2018 Feb 06; 35(3):46
- CONCLUSIONS: The drugs used for the treatment of ADHD are apparently not teratogenic, but due to paucity of data, especially on the long-term neurodevelopmental outcome, the treating physician should reconsider the need of treatment during pregnancy. If needed, methylphenidate, amphetamines and bupropion are preferred drugs.
- Multi-spectroscopic characterization of bovine serum albumin upon interaction with atomoxetine. [Journal Article]
- JPJ Pharm Anal 2017; 7(3):148-155
- The quenching interaction of atomoxetine (ATX) with bovine serum albumin (BSA) was studied in vitro under optimal physiological condition (pH=7.4) by multi-spectroscopic techniques. The mechanism of ...
The quenching interaction of atomoxetine (ATX) with bovine serum albumin (BSA) was studied in vitro under optimal physiological condition (pH=7.4) by multi-spectroscopic techniques. The mechanism of ATX-BSA system was a dynamic quenching process and was confirmed by the fluorescence spectra and lifetime measurements. The number of binding sites, binding constants and other binding characteristics were computed. Thermodynamic parameters ∆H° and ∆S° indicated that intermolecular hydrophobic forces predominantly stabilized the drug-protein system. The average binding distance between BSA and ATX was studied by Försters theory. UV-absorption, Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD), synchronous spectra and three-dimensional (3D) fluorescence spectral results revealed the changes in micro-environment of secondary structure of protein upon the interaction with ATX. Displacement of site probes and the effects of some common metal ions on the binding of ATX with BSA interaction were also studied.
- Clinical trials in autism spectrum disorder: evidence, challenges and future directions. [Journal Article]
- COCurr Opin Neurol 2018 Jan 31
- CONCLUSIONS: Several compounds have evidence for the treatment of co-occurring symptoms in children and youth with ASD, although pharmacological interventions for core symptoms are still lacking. Identifying the various biologies underling ASD and developing biomarkers that stratify biologically homogeneous populations are both necessary to realize the promise of precision medicine in ASD.
- Fatigue in Patients with Major Depressive Disorder: Prevalence, Burden and Pharmacological Approaches to Management. [Review]
- CDCNS Drugs 2018 Jan 30
- Fatigue is a frequently reported symptom in major depressive disorder, occurring in over 90% of patients. Clinical presentations of fatigue within major depressive disorder encompass overlapping phys...
Fatigue is a frequently reported symptom in major depressive disorder, occurring in over 90% of patients. Clinical presentations of fatigue within major depressive disorder encompass overlapping physical, cognitive and emotional aspects. While this review addresses the epidemiology, burden, functional impact and management of fatigue in major depressive disorder, the main focus is on available pharmacotherapy options and their comparative efficacies. Our review of the effects of pharmacological treatments on fatigue in major depressive disorder found that medications with dopaminergic and/or noradrenergic action such as modafinil, flupenthixol and atomoxetine were most effective in improving symptoms of fatigue and low energy. However, significant variation across studies in assessment tools and study inclusion/exclusion criteria may have contributed to inconsistent findings. The efficacy of non-pharmacological interventions is also discussed, including light therapy and exercise.
- Selective noradrenaline reuptake inhibitors for schizophrenia. [Review]
- CDCochrane Database Syst Rev 2018 Jan 25; 1:CD010219
- CONCLUSIONS: Our results provide tentative very low quality evidence that compared to placebo, NRIs (specifically reboxetine) may have a benefit on the negative symptoms of schizophrenia. Limited evidence also suggests that NRIs have no effect on the positive symptoms of schizophrenia or cognitive functioning. NRIs appear generally well tolerated with no real differences in adverse effects such as nausea noted between NRIs and placebo. However, these results are based on short-term follow-up and are poor quality - there is need for more good-quality evidence. A large RCT of reboxetine over a longer period of time, focusing specifically on negative and cognitive symptoms as well as more detailed and comprehensive reporting of outcomes, including adverse events, is required.
- [A strategy for increasing the efficiency of psychopharmacological treatment of hyperkinetic behavior disorder with pantogam]. [Journal Article]
- ZNZh Nevrol Psikhiatr Im S S Korsakova 2017; 117(11. Vyp. 2):75-79
- CONCLUSIONS: A short-term positive therapeutic dynamics was observed when introducing hopantenic acid (pantogam) augmentation strategy to existing atomoxetine therapy. Qualitative improvements in children's state were found not only in the ability to control symptoms but also in their social functioning levels and quality of life. The proposed therapeutic strategy can help to improve treatment outcomes for children with certain clinical forms of hyperkinetic behavior disorder.
- Case report: Cytochrome P450 implications for comorbid ADHD and OCD pharmacotherapy. [Journal Article]
- JCJ Child Adolesc Psychiatr Nurs 2018 Jan 19
- CONCLUSIONS: Genetic testing as a prescriptive tool is not indicated for all medications; however, potential drug-drug interactions, narrow therapeutic drug index, and side effect toxicity contribute to the need for testing. An understanding of CYP450 metabolism and drug interaction as well as metabolism phenotypes should inform prescribing and dosing psychotropic medications.
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- Treatment with the noradrenaline re-uptake inhibitor atomoxetine alone and in combination with the α2-adrenoceptor antagonist idazoxan attenuates loss of dopamine and associated motor deficits in the LPS inflammatory rat model of Parkinson's disease. [Journal Article]
- BBBrain Behav Immun 2018 Jan 12
- The impact of treatment with the noradrenaline (NA) re-uptake inhibitor atomoxetine and the α2-adrenoceptor (AR) antagonist idazoxan in an animal model of Parkinson's disease (PD) was assessed. Concu...
The impact of treatment with the noradrenaline (NA) re-uptake inhibitor atomoxetine and the α2-adrenoceptor (AR) antagonist idazoxan in an animal model of Parkinson's disease (PD) was assessed. Concurrent systemic treatment with atomoxetine and idazoxan, a combination which serves to enhance the extra-synaptic availability of NA, exerts anti-inflammatory and neuroprotective effects following delivery of an inflammatory stimulus, the bacterial endotoxin, lipopolysaccharide (LPS) into the substantia nigra. Lesion-induced deficits in motor function (akinesia, forelimb-use asymmetry) and striatal dopamine (DA) loss were rescued to varying degrees depending on the treatment. Treatment with atomoxetine following LPS-induced lesion to the substantia nigra, yielded a robust anti-inflammatory effect, suppressing microglial activation and expression of the pro-inflammatory cytokine TNF-α whilst increasing the expression of neurotrophic factors. Furthermore atomoxetine treatment prevented loss of tyrosine hydroxylase (TH) positive nigral dopaminergic neurons and resulted in functional improvements in motor behaviours. Atomoxetine alone was sufficient to achieve most of the observed effects. In combination with idazoxan, an additional improvement in the impairment of contralateral limb use 7 days post lesion and a reduction in amphetamine-mediated rotational asymmetry 14 days post-lesion was observed, compared to atomoxetine or idazoxan treatments alone. The results indicate that increases in central NA tone has the propensity to regulate the neuroinflammatory phenotype in vivo and may act as an endogenous neuroprotective mechanism where inflammation contributes to the progression of DA loss. In accordance with this, the clinical use of agents such as NA re-uptake inhibitors and α2-AR antagonists may prove useful in enhancing the endogenous neuroimmunomodulatory potential of NA in conditions associated with brain inflammation.