BIOMARKERS FOR ADHD

Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses.

Abstract

OBJECTIVE

To determine whether peripheral biochemical markers (biomarkers) might differentiate patients with attention-deficit/hyperactivity disorder (ADHD) from non-ADHD individuals.

METHOD

We conducted a systematic search and a series of meta-analyses of case-control studies comprising studies from 1969 to 2011.

RESULTS

We identified 210 studies in the following categories: 71 studies of the main metabolites and metabolism enzymes of monoaminergic neurotransmission pathway; 87 studies of environmental risk factors divided into heavy metals (18 studies), substance/chemical exposures (16 studies), and nutritional factors (trace elements: 29 studies; essential fatty acids: 24 studies); 22 studies of the hypothalamic-pituitary-adrenal axis (HPA) pathway; 31 studies indicated with “other”. After screening for the availability for meta-analyses of drug naïve/free case-control studies and Bonferroni correction, five comparisons were statistically significant (Norepinephrine [NE], 3-Methoxy-4-hydroxyphenylethylene glycol [MHPG], monoamine oxidase [MAO], Zinc [Zn], cortisol), five of the significant findings found support in studies of response to ADHD medications (NE, MHPG, MAO, b-phenylethylamine [PEA], cortisol), six in studies of symptoms severity (NE, MHPG, MAO, ferritin, Zn, cortisol) and three in studies of neurophysiological or cognitive functioning (lead-ferritin-Zn). No evidence of publication bias was found, whereas significant heterogeneity of effect sizes across studies was found for three of the five biomarkers that differentiated ADHD from control subjects. Suggestive associations were evidenced for neuropeptide Y (NPY), manganese, and dehydroepiandrosterone (DHEA).

CONCLUSIONS

This study provides evidence for several peripheral biomarkers as being associated with ADHD both in diagnosis and in treatment efficacy. Further studies are warranted to replicate these findings, to assess their specificity for ADHD, and to quantify the degree to which they are sufficiently precise to be useful in clinical settings.

https://www.ncbi.nlm.nih.gov/pubmed/23021477

Summary of Important Biomarkers in ADHD with Possible Clinical Importance

  • Cortisol
  • Ferritin
  • Lead
  • NE (Norepinephrine)
  • MAO (Monoamine oxidase)
  • MHPG (3-Methoxy-4-hydroxyphenylethylene glycol)
  • PEA (beta-phenylethylamine)
  • Zinc

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PSYCHOSOCIAL INTERVENTIONS FOR ADHD

American Academy of Paediatrics (AAP) Evidence-Based Child and Adolescent Psychosocial Interventions

Level 1 Best-Support Interventions for Attention & Hyperactivity Behaviors

Behavior Therapy and Medication, Biofeedback, Parent Management Training, Self-Verbalization

Level 2 Good-Support Interventions for Attention & Hyperactivity Behaviors

Contingency Management, Education, Parent Management Training (with Problem Solving, or with Teacher Psychoeducation), Physical Exercise (with or without Relaxation), Social Skills and Medication, Working Memory Training

Source: https://www.aap.org/en-us/Documents/resilience_anxiety_interventions.pdf

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Parent training for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 5 to 18 years. Cochrane Review

Authors’ Conclusions

Parent training may have a positive effect on the behaviour of children with ADHD. It may also reduce parental stress and enhance parental confidence. However, the poor methodological quality of the included studies increases the risk of bias in the results. Data concerning ADHD-specific behaviour are ambiguous. For many important outcomes, including school achievement and adverse effects, data are lacking. Evidence from this review is not strong enough to form a basis for clinical practice guidelines. Future research should ensure better reporting of the studyprocedures and results.

Reference: Zwi M, Jones H, Thorgaard C, York A, Dennis JA. Parent training interventions for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 5 to 18 years. Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No.: CD003018. DOI: 10.1002/14651858.CD003018.pub3.

Source: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009885.pub2/abstract

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Social skills training for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 5 to 18 years. Cochrane Review

Children with Attention Deficit Hyperactivity Disorder (ADHD) are hyperactive and impulsive, cannot maintain attention, and have difficulties with social interactions. This review looks at whether social skills training benefits children with ADHD in their social interactions. Eleven trials including a total of 747 participants met the inclusion criteria. This review suggests that there is little evidence for social skills training for children with ADHD at the moment. It is not possible to recommend or refute social skills training for children with ADHD. There is need for more randomised clinical trials, with low risk of bias and with a sufficient number of participants, investigating the efficacy of social skills training for children with ADHD. Authors’ conclusions: The review suggests that there is little evidence to support or refute social skills training for adolescents with ADHD. There is need for more trials, with low risk of bias and with a sufficient number of participants, investigating the efficacy of social skills training versus no training for both children and adolescents.

Reference: Storebø OJ, Skoog M, Damm D, Thomsen PH, Simonsen E, Gluud C. Social skills training for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 5 to 18 years. Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No.: CD008223. DOI: 10.1002/14651858.CD008223.pub2.

Source: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008223.pub2/abstract

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Family therapy for attention-deficit disorder or attention-deficit/hyperactivity disorder in children and adolescents. Cochrane Review

Authors’ Conclusions

Further research examining the effectiveness of family therapy versus a no-treatment control condition is needed to determine whether family therapy is an effective intervention for children with ADHD. There were no results available from studies investigating forms of family therapy other than behavioural family therapy.

Reference: Bjornstad GJ, Montgomery P. Family therapy for attention-deficit disorder or attention-deficit/hyperactivity disorder in children and adolescents. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD005042. DOI: 10.1002/14651858.CD005042.pub2.

Source: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005042.pub2/abstract

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NUTRIENT THERAPY FOR ADHD

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Overview

Attention Deficit/Hyperactivity Disorder (ADHD) in Children: Rationale for Its Integrative Management

Abstract

Attention Deficit/Hyperactivity Disorder (ADHD) is the most common behavioral disorder in children. ADHD is characterized by attention deficit, impulsivity, and sometimes overactivity (“hyperactivity”). The diagnosis is empirical, with no objective confirmation available to date from laboratory measures. ADHD begins in childhood and often persists into adulthood. The exact etiology is unknown; genetics plays a role, but major etiologic contributors also include adverse responses to food additives, intolerances to foods, sensitivities to environmental chemicals, molds, and fungi, and exposures to neurodevelopmental toxins such as heavy metals and organohalide pollutants. Thyroid hypofunction may be a common denominator linking toxic insults with ADHD symptomatologies. Abnormalities in the frontostriatal brain circuitry and possible hypofunctioning of dopaminergic pathways are apparent in ADHD, and are consistent with the benefits obtained in some instances by the use of methylphenidate (Ritalin®) and other potent psychostimulants. Mounting controversy over the widespread use of methylphenidate and possible life-threatening effects from its long-term use make it imperative that alternative modalities be implemented for ADHD management. Nutrient deficiencies are common in ADHD; supplementation with minerals, the B vitamins (added in singly), omega-3 and omega-6 essential fatty acids, flavonoids, and the essential phospholipid phosphatidylserine (PS) can ameliorate ADHD symptoms. When individually managed with supplementation, dietary modification, detoxification, correction of intestinal dysbiosis, and other features of a wholistic/integrative program of management, the ADHD subject can lead a normal and productive life.

Reference: Kidd PM. Attention Deficit/Hyperactivity Disorder (ADHD) in Children: Rationale for Its Integrative Management. Altern Med Rev. 2000 Oct;5(5):402-28. Review. PubMed PMID: 11056411.

Source: http://www.feingold.org/Research/PDFstudies/Kidd00.pdf

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Nutritional Supplements for the Treatment of Attention-Deficit Hyperactivity Disorder

Polyunsaturated fatty acid supplementation has demonstrated evidence of efficacy in meta-analysis of randomized, placebo-controlled trials in ADHD. The benefits of polyunsaturated fatty acid appear small compared to the effect sizes observed for traditional pharmacological treatments of ADHD. Some evidence suggests that polyunsaturated fatty acid formulations with higher eicosapentaenoic acid may be more effective in improving ADHD symptoms. Melatonin appears to be effective in treating chronic insomnia in children with ADHD but appears to have minimal effects in reducing core ADHD symptoms. Iron and zinc supplementation may have benefit in reducing ADHD symptoms in children with or at high risk of deficiency. Data demonstrating efficacy of iron, zinc or magnesium in non-nutrient deficient ADHD populations is lacking. Many other natural supplements are widely utilized in the United States despite minimal evidence of efficacy and possible side-effects.

Reference: Bloch MH, Mulqueen J. Nutritional Supplements for the Treatment of Attention-Deficit Hyperactivity Disorder. Child and adolescent psychiatric clinics of North America. 2014;23(4):883-897. doi:10.1016/j.chc.2014.05.002.

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170184/

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Phosphatidylserine

The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension.

Objective

To study the efficacy and safety of phosphatidylserine (PS) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone (PS-Omega3) in reducing attention-deficit/ hyperactivity disorder (ADHD) symptoms in children.

Method

A 15-week, double-blind, placebo-controlled phase followed by an open-label extension of additional 15 weeks. Two hundred ADHD children were randomized to receive either PS-Omega3 or placebo, out of them, 150 children continued into the extension. Efficacy was assessed using Conners’ parent and teacher rating scales (CRS-P,T), Strengths and Difficulties Questionnaire (SDQ), and Child Health Questionnaire (CHQ). Safety evaluation included adverse events monitoring.

Results

The key finding of the double-blind phase was the significant reduction in the Global:Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional (PE) subscale of the CHQ, both in the PS-Omega3 group. Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior, as well as mood and behavior-dysregulation, revealed a significant reduction in the ADHD-Index and hyperactive components. Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3. Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T, as compare to baseline scores. The treatment was well tolerated.

Conclusions

The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children. Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive, emotionally and behaviorally-dysregulated ADHD children.

Reference: Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman A. The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension. Eur Psychiatry. 2012 Jul;27(5):335-42. doi: 10.1016/j.eurpsy.2011.05.004. Epub 2011 Jul 31. PubMed PMID: 21807480.

Source: http://www.europsy-journal.com/article/S0924-9338(11)00095-2/abstract

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Safety of phosphatidylserine containing omega3 fatty acids in ADHD children: A double-blind placebo-controlled trial followed by an open-label extension

Objective

To evaluate the safety of phosphatidylserine (PS) enriched with omega3 fatty acids, mainly eicosapentaenoic (PS-Omega3) in children with attention-deficit hyperactivity disorder (ADHD).

Methods

Two hundred children diagnosed with ADHD were randomised to receive either PS-Omega3 (300 mg PS-Omega3/day) or placebo for 15 weeks. One hundred and fifty children continued into an open-label extension for an additional 15 weeks in which they all consumed PS-Omega3 (150 mg PS-Omega3/day). Standard blood biochemical and haematological safety parameters, blood pressure, heart rate, weight and height were evaluated. Adverse events and the Side Effect Rating Scale were also assessed.

Results

One hundred and sixty-two participants completed the double-blind phase. No significant differences were noted between the two study groups in any of the safety parameters evaluated. One hundred and forty participants completed the open-label phase. At the end of this phase, no significant changes from baseline were observed in any of the studied parameters among participants who consumed PS-Omega3 for 30 weeks.

Conclusions

Study results demonstrate that consumption of PS-Omega3 by children with ADHD, as indicated in a 30-week evaluation period, is safe and well tolerated, without any negative effect on body weight or growth.

Reference: Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman A. Safety of phosphatidylserine containing omega3 fatty acids in ADHD children: A double-blind placebo-controlled trial followed by an open-label extension. Eur Psychiatry. 2013 Aug;28(6):386-91. doi: 10.1016/j.eurpsy.2012.11.001. Epub 2013 Jan 9. PubMed PMID: 23312676.

Source: http://www.europsy-journal.com/article/S0924-9338(12)00137-X/abstract

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The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial

Background

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3–5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children.

Methods

Thirty six children, aged 4–14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day–1 PS (n = 19) for 2 months in a randomised, double-blind manner. Main outcome measures included: (i) ADHD symptoms based on DSM-IV-TR; (ii) short-term auditory memory and working memory using the Digit Span Test of the Wechsler Intelligence Scale for Children; and (iii) mental performance to visual stimuli (GO/NO GO task).

Results

PS supplementation resulted in significant improvements in: (i) ADHD (P < 0.01), AD (P < 0.01) and HD (P < 0.01); (ii) short-term auditory memory (P < 0.05); and (iii) inattention (differentiation and reverse differentiation, P < 0.05) and inattention and impulsivity (P < 0.05). No significant differences were observed in other measurements and in the placebo group. PS was well-tolerated and showed no adverse effects.

Conclusions

PS significantly improved ADHD symptoms and short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD.

Reference: Hirayama S, Terasawa K, Rabeler R, Hirayama T, Inoue T, Tatsumi Y, Purpura M, Jäger R. The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial. J Hum Nutr Diet. 2014 Apr;27 Suppl 2:284-91. doi: 10.1111/jhn.12090. Epub 2013 Mar 17. PubMed PMID: 23495677.

Source: http://www.europsy-journal.com/article/S0924-9338(12)00137-X/abstract

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Efficacy of EPA Enriched Phosphatidylserine-Omega-3 (Vayarin) on Children with ADHD (P7.336)

Objective

To determine if Vayarin is a plausible treatment for long-term ADHD management.

Background

The FDA approved medical food, Vayarin, is a phosphatidylserine-omega-3 that is EPA enriched and is intended to reduce ADHD symptoms. ADHD patient families are motivated to try non-stimulant medication therapy that might benefit the condition. Vayarin retails for $60 per month and lacks insurance coverage. Most families front the cost of treatment.

Design/Methods

Texas Child Neurology’s electronic health records (EHR) retrospectively identified 722 unique patients diagnosed with ADHD who had been prescribed Vayarin therapy for a potential of at least 3 months. Successful therapy was defined as continued treatment beyond 3 months and patient data was stratified into result groups based upon this premise. Information from chart review and telephone interview of parents garnered reasons for results of treatment. Quantification of therapy effect was based upon gathered information.

Results

Of the 722 unique patients, 300 patients met criteria for 3 months therapy. Co-treatment with stimulant medication occurred in 43.3%. Two-hundred forty-five (81.7%) continued Vayarin therapy beyond 3 months. Of these, 31.3% were definite beneficiaries of Vayarin. Another 29.7% reported some benefit. The remaining 20.7% reported no benefit but continued Vayarin regardless. A significant portion of the patient sample failed to use Vayarin for the required 3 months. Two-hundred and seven of the sample (28.7%) were lost to follow-up. Another 12.9% never filled the prescription. One-hundred twenty-two (16.9%) of the sample have incomplete information. Many of these are known to have quit Vayarin therapy prior to 3 months treatment (40.2%).

Conclusions

Vayarin is a novel therapy for ADHD that appears to be effective. Approximately 60% of the users who completed 3 months therapy reported benefit of treatment. A slow response time of 3 months is an impediment to successful management as only 41.6% of subjects prescribed Vayarin remained compliant for the duration. Cost and patient objection to Vayarin taste are prominent reasons for therapy failure.

Reference: Nguyen, Stephanie, Cindy Nguyen, Robert Chudnow, Van Miller, Anthony Riela, Gerald So, Patricia Mireles, and Lina Shah. 2014. “Efficacy of EPA Enriched Phosphatidylserine-Omega-3 (Vayarin) on Children with ADHD (P7.336).” Neurology 82 (10 Supplement): P7.336–P7.336.

Source: http://www.neurology.org/content/82/10_Supplement/P7.336.short

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PUFAs, Magnesium & Zinc

Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems - an observational cohort study.

Background

Polyunsaturated fatty acids are essential nutrients for humans. They are structural and functional components of cell membranes and pre-stages of the hormonally and immunologically active eicosanoids. Recent discoveries have shown that the long-chained omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also play an important role in the central nervous system. They are essential for normal brain functioning including attention and other neuropsychological skills.

Materials & Methods

In our large observational study we monitored 810 children from 5 to 12 years of age referred for medical help and recommended for consuming polyunsaturated fatty acids (PUFA) in combination with zinc and magnesium by a physician over a period of at least 3 months. The food supplement ESPRICO® (further on referred to as the food supplement) is developed on the basis of current nutritional science and containing a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc. Study objective was to evaluate the nutritional effects of the PUFA-zinc-magnesium combination on symptoms of attention deficit, impulsivity, and hyperactivity as well as on emotional problems and sleep related parameters. Assessment was performed by internationally standardised evaluation scales, i.e. SNAP-IV and SDQ. Tolerance (adverse events) and acceptance (compliance) of the dietary therapy were documented.

Results

After 12 weeks of consumption of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc most subjects showed a considerable reduction in symptoms of attention deficit and hyperactivity/impulsivity assessed by SNAP-IV. Further, the assessment by SDQ revealed fewer emotional problems at the end of the study period compared to baseline and also sleeping disorders. Mainly problems to fall asleep, decreased during the 12 week nutritional therapy. Regarding safety, no serious adverse events occurred. A total of 16 adverse events with a possible causal relationship to the study medication were reported by 14 children (1.7%) and only 5.2% of the children discontinued the study due to acceptance problems. Continuation of consumption of the food supplement was recommended by the paediatricians for 61.1% of the children.

Conclusion

Our results suggest a beneficial effect of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc consumption on attentional, behavioural, and emotional problems of children and adolescents. Thus, considering the behavioural benefit in combination with the low risk due to a good safety profile, the dietary supplementation with PUFA in combination with zinc and magnesium can be recommended.

Reference: Huss M, Völp A, Stauss-Grabo M. Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems – an observational cohort study. Lipids in Health and Disease. 2010;9:105. doi:10.1186/1476-511X-9-105.

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955638/

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Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Review

Author’s Conclusions

Overall, there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents. The majority of data showed no benefit of PUFA supplementation, although there were some limited data that did show an improvement with combined omega-3 and omega-6 supplementation. It is important that future research addresses current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, short follow-up times and other methodological weaknesses.

Reference: Gillies D, Sinn JKH, Lad SS, Leach MJ, Ross MJ. Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No.: CD007986. DOI: 10.1002/14651858.CD007986.pub2.

Source: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007986.pub2/citedby

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BOTANICAL MEDICINE FOR ADHD

Complementary medicines (herbal and nutritional products) in the treatment of Attention Deficit Hyperactivity Disorder (ADHD): A systematic review of evidence

Overview

Complementary and Alternative Medicines (CAMs) are frequently given to children and adolescents for reputed benefits in the treatment of hyperkinetic and concentration disorders such as Attention Deficit Hyperactivity Disorder (ADHD). In such vulnerable populations high quality evidence is required to support such claims. Aims The aim of the paper is to assess the current evidence of herbal and nutritional interventions for ADHD using a systematic search of clinical trials meeting an acceptable standard of evidence.

Methods

PubMed, PsycINFO, Cochrane Library and CINAHL were searched up to May 26th, 2011 for randomised, controlled clinical trials using CAM products as interventions to treat ADHD. A quality analysis using a purpose-designed scale, and an estimation of effect sizes (Cohen’s d) where data were available, were also calculated.

Results

The review revealed that 16 studies met inclusion criteria, with predominant evidentiary support found for zinc, iron, Pinus marinus (French maritime pine bark), and a Chinese herbal formula (Ningdong); and mixed (mainly inconclusive) evidence for omega-3, and l-acetyl carnitine. Current data suggest that Ginkgo biloba (ginkgo), and Hypercium perforatum (St. John’s wort) are ineffective in treating ADHD.

Conclusion

The research suggests only some CAMs may be beneficial in ADHD, thus clinicians need to be aware of the current evidence. Promising candidates for future research include Bacopa monniera (brahmi) and Piper methysticum (kava), providing potential efficacy in improving attentional and hyperkinetic disorders via a combination of cognitive enhancing and sedative effects.

Reference: Sarris J, Kean J, Schweitzer I, Lake J.Complementary medicines (herbal and nutritional products) in the treatment of Attention Deficit Hyperactivity Disorder (ADHD): A systematic review of evidence. Complement Ther Med. 2011 Aug;19(4):216-27. doi: 10.1016/j.ctim.2011.06.007. Epub 2011 Jul 26. Review. PubMed PMID: 21827936.

Source: http://www.complementarytherapiesinmedicine.com/article/S0965-2299(11)00087-2/abstract

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Ginkgo biloba in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. A randomized, placebo-controlled, trial.

Objective

To evaluate the efficacy of Ginkgo biloba as a complementary therapy for attention-deficit/hyperactivity disorder (ADHD).

Methods

Children and adolescents with ADHD received methylphenidate (20-30 mg/day) plus either G. biloba (80-120 mg/day) or placebo for 6 weeks. Parent and teacher forms of the ADHD Rating Scale-IV (ADHD-RS-IV) were completed at baseline, week 2, and week 6. Treatment response was defined as 27% improvement from baseline in the ADHD-RS-IV.

Results

Compared with placebo, more reduction was observed with G. biloba regarding ADHD-RS-IV parent rating inattention score (-7.74 ± 1.94 vs. -5.34 ± 1.85, P < 0.001) and total score (-13.1 ± 3.36 vs. -10.2 ± 3.01, P = 0.001) as well as teacher rating inattention score (-7.29 ± 1.90 vs. -5.96 ± 1.52, P = 0.004). Response rate was higher with G. biloba compared with placebo based on parent rating (93.5% vs. 58.6%, P = 0.002).

Conclusions

The G. biloba is an effective complementary treatment for ADHD. Further studies with longer treatment duration are warranted in this regard.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25925875

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Ginkgo biloba extract EGb 761 in Children with ADHD

Objective

The side effects, nonresponse, and prejudices against conventional pharmacological treatments call for complementary or alternative medical treatments (CAM) for ADHD. One possible treatment, at least for cognitive problems, might be the administration of Ginkgo biloba, though evidence is currently rare. This study tests the clinical efficacy of a Ginkgo biloba special extract (EGb 761®) and its correlation with brain electrical activity in children with ADHD combined type according to DSM-IV.

Methods

In this open clinical pilot study, EGb 761® was administered to 20 children with ADHD over 3 to 5 weeks. Dosage was increased to a maximum of 240 mg daily if attention problems persisted. Possible drug side effects were assessed using the Side Effect Rating Scale. Efficacy was assessed in a multilevel approach including clinical assessment, quality of life (QoL), as well as performance and preparatory brain-electrical activity evoked during a Continuous Performance Test (Cue-CNV in the CPT).

Results

A very low rate of mild adverse effects occurred during the observation period. Following EGb 761® administration, possible improvements in QoL, ADHD core symptoms as well as CPT performance were detected. Improved core symptoms were positively related to elevated CNV amplitude.

Conclusions

This preliminary evidence suggests that EGb 761® at a maximal dosage of 240 mg daily might be a clinically useful alternative treatment for children with ADHD, but further evidence is required before firm conclusions can be made.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25163996

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A Systematic Review and Meta-Analysis of Ginkgo biloba in Neuropsychiatric Disorders: From Ancient Tradition to Modern-Day Medicine.

Abstract

Ginkgo biloba (Gb) has demonstrated antioxidant and vasoactive properties as well as clinical benefits in several conditions such as ischemia, epilepsy, and peripheral nerve damage. Additionally, Gb is supposed to act as potential cognitive enhancer in dementia. So far, several trials have been conducted to investigate the potential effectiveness of Gb in neuropsychiatric conditions. However, the results of these studies remain controversial. We conducted a systematic review and a meta-analysis of three randomised controlled trials in patients with schizophrenia and eight randomised controlled trials in patients with dementia. Gb treatment reduced positive symptoms in patients with schizophrenia and improved cognitive function and activities of daily living in patients with dementia. No effect of Gb on negative symptoms in schizophrenic patients was found. The general lack of evidence prevents drawing conclusions regarding Gb effectiveness in other neuropsychiatric conditions (i.e., autism, depression, anxiety, attention-deficit hyperactivity disorder, and addiction). Our data support the use of Gb in patients with dementia and as an adjunctive therapy in schizophrenic patients.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23781271

Ginkgo biloba for attention-deficit/hyperactivity disorder in children and adolescents: a double blind randomized controlled trial.

Background

Although stimulants are highly effective in controlling the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), some children will not respond to, or are intolerant of stimulants. Thus, the desire for safe and effective nonstimulant medications has risen during the past several years. Ginkgo biloba has been suggested in the treatment of dementia and memory impairment. We hypothesized that G.biloba would be beneficial for treatment of ADHD, and this could be evaluated in a double blind, randomized, parallel group comparison of G.biloba (Ginko T.D. Tolidaru, Iran) and methylphenidate.

Methods

Fifty outpatients (39 boys and 11 girls) with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of Ginko T.D. at a dose of 80-120 mg/day depending on weight (80 mg/day for 30 kg) (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for 30 kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale- IV. Patients were assessed at baseline and at 21 and 42 days after the medication started.

Results

Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -6.52+/-11.43 (mean+/-S.D.) and -15.92+/-11.44 (mean+/-S.D.) for Ginko T.D. and methyphenidate, respectively for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -0.84+/-6.79 (mean+/-S.D.) and -14.04+/-8.67 (mean+/-S.D.) for Ginko T.D. and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the Ginko T.D. and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group.

Conclusion

The results of this study suggest that administration of G.biloba was less effective than methylphenidate in the treatment of ADHD.

Source: http://www.ncbi.nlm.nih.gov/pubmed/19815048

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PHARMACOTHERAPY FOR ADHD

Researchers urge caution in prescribing commonly used drug to treat ADHD Cochrane Review

Authors of new Cochrane Review remain uncertain about effect of widely used medicine on ADHD symptoms, despite large amount of research. Some evidence of increased sleeplessness and loss of appetite leads researchers to encourage more caution in use of methylphenidate. This new Cochrane Review includes data from 185 randomized controlled trials involving more than 12,000 children or adolescents. The studies were conducted mainly in the US, Canada, and Europe, included males and females from ages 3-18, and all compared methylphenidate with either a dummy pill or no intervention.

Source: http://www.cochrane.org/news/researchers-urge-caution-prescribing-commonly-used-drug-treat-adhd

Benefits and harms of methylphenidate for children and adolescents with ADHD. Cochrane Review

Authors’ Conclusions

The results of meta-analyses suggest that methylphenidate may improve teacher-reported ADHD symptoms, teacher-reported general behaviour, and parent-reported quality of life among children and adolescents diagnosed with ADHD. However, the low quality of the underpinning evidence means that we cannot be certain of the magnitude of the effects. Within the short follow-up periods typical of the included trials, there is some evidence that methylphenidate is associated with increased risk of non-serious adverse events, such as sleep problems and decreased appetite, but no evidence that it increases risk of serious adverse events. Better designed trials are needed to assess the benefits of methylphenidate. Given the frequency of non-serious adverse events associated with methylphenidate, the particular difficulties for blinding of participants and outcome assessors point to the advantage of large, ‘nocebo tablet’ controlled trials. These use a placebo-like substance that causes adverse events in the control arm that are comparable to those associated with methylphenidate. However, for ethical reasons, such trials should first be conducted with adults, who can give their informed consent. Future trials should publish depersonalised individual participant data and report all outcomes, including adverse events. This will enable researchers conducting systematic reviews to assess differences between intervention effects according to age, sex, comorbidity, type of ADHD and dose. Finally, the findings highlight the urgent need for large RCTs of non-pharmacological treatments.

Source: http://www.cochrane.org/CD009885/BEHAV_benefits-and-harms-methylphenidate-children-and-adolescents-attention-deficit-hyperactivity-disorder

Adderall Guidelines & Side Effects FDA

“AMPHETAMINES HAVE A HIGH POTENTIAL FOR ABUSE. ADMINISTRATION OF AMPHETAMINES FOR PROLONGED PERIODS OF TIME MAY LEAD TO DRUG DEPENDENCE AND MUST BE AVOIDED”

“The effectiveness of Adderall® for long-term use has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Adderall® for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.”

“Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.”

Source: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011522s040lbl.pdf

Ritalin for adult attention deficit hyperactivity disorder ADHD. Cochrane Review

Authors’ Conclusions

Data from randomized controlled trials suggest that immediate-release methylphenidate is efficacious for treating adults with ADHD with symptoms of hyperactivity, impulsivity, and inattentiveness, and for improving their overall clinical condition. Trial data suggest that adverse effects from immediate-release methylphenidate for adults with ADHD are not of serious clinical significance, although this conclusion may be limited, certainly in the case of weight loss, by the short duration of published studies.

Source: http://www.cochrane.org/CD005041/BEHAV_ritalin-for-adult-attention-deficit-hyperactivity-disorder-adhd

Amphetamines for attention deficit hyperactivity disorder in adults. Cochrane Review

Authors’ Conclusions

Amphetamines improved short-term ADHD symptom severity. MAS also increased retention in treatment. Amphetamines were associated with higher attrition due to adverse events. The short study length and the restrictive inclusion criteria limit the external validity of these findings. Furthermore, the possibility that the results of the included studies were biased was high, which could have led to an overestimation of amphetamine efficacy. Plain Language Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset psychiatric disorder that can persist into adulthood in up to 50% of patients. From a clinical point of view, ADHD is characterized by hyperactivity, mood instability, irritability, difficulties in maintaining attention, lack of organization and impulsive behaviours. The presence of other disorders occurring at the the same time is also common, especially mood disorders and substance abuse. It seems that amphetamines could reverse the underlying neurological problems that feature in ADHD, and so improve ADHD symptoms. We found seven studies, which enrolled 1091 patients. These studies compared amphetamines to placebo and three of them also compared amphetamines with other drugs: guanfacine, modafinil and paroxetine. Three amphetamine derivatives were investigated: dexamphetamine, lisdexamphetamine and mixed amphetamine salts (MAS). Treatment length ranged from two to 20 weeks. All amphetamines improved ADHD symptoms but overall they did not make people more likely to stay in treatment and were associated with a higher risk of treatment ending early due to adverse events. One type of amphetamine, mixed amphetamine salts, did, however, increase retention in treatment. We found no evidence that higher doses worked better than lower ones. We did not find any difference in effectiveness between immediate-release and sustained-release formulations. Therefore, it appears that short-term treatment with amphetamines reduces ADHD symptoms, but studies assessing the effects of amphetamines for longer periods of time are needed.

Source: http://www.cochrane.org/CD007813/BEHAV_amphetamines-for-attention-deficit-hyperactivity-disorder-in-adults

Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents.

Authors’ Conclusions

Most evidence on TCAs relates to desipramine. Findings suggest that, in the short term, desipramine improves the core symptoms of ADHD, but its effect on the cardiovascular system remains an important clinical concern. Thus, evidence supporting the clinical use of desipramine for the treatment of children with ADHD is low.

Source: http://www.cochrane.org/CD006997/BEHAV_tricyclic-antidepressants-for-attention-deficit-hyperactivity-disorder-adhd-in-children-and-adolescents

Efficacy and safety limitations of attention-deficit hyperactivity disorder pharmacotherapy in children and adults

“There have been major advances in the treatment and understanding of attention-deficit hyperactivity disorder (ADHD) in the last decade.”

“This article focuses on the evaluation of the efficacy and safety profiles of medications used for the management of ADHD. In assessing the various medical treatments for ADHD, certain issues and analyses have become important to address.” “Stimulants remain the US FDA-approved medical treatment of choice for patients with ADHD and are associated with an exceptional response rate.”

“Findings of the Multimodal Treatment of Children With ADHD study suggest that the combination of behavioural and medical therapy may benefit most patients.”

“Nonstimulant agents, such as atomoxetine (FDA-approved), and several non-approved agents, bupropion, guanfacine and clonidine, may offer necessary alternatives to the stimulants. This is especially important for patients who have comorbidities that are contraindicated for stimulant use based on medical issues and/or risk for stimulant abuse.”

“Typical psychiatric comorbidities in patients with ADHD include oppositional defiant disorder, conduct disorder, major depressive disorder, bipolar disorder, anxiety, substance abuse disorder, tic disorder, and Tourette’s syndrome.”

“Although relatively safe, both stimulants and atomoxetine have class-related warnings and contraindications and are associated with adverse effects that require consideration when prescribing.”

Source: http://www.ncbi.nlm.nih.gov/pubmed/19621975

ADHD and drug therapy: is it still a valid treatment?

“The purpose of this article is to discuss alternative treatments other than drug therapy for Attention-Deficit/Hyperactive Disorder (ADHD) in educational settings. There is an increasing body of knowledge that supports interventions for improving cognitive outcomes without the use of medication. The article explores the risks to ADHD children, shows the potential linkage between gifted children and ADHD, explores recent brain research, and examines various alternative treatment options. Information is presented on alternative treatments such as cognitive behavioral therapies, educational interventions, electroencephalograph (EEG) neuro-feedback, and diet.”

Source: http://www.ncbi.nlm.nih.gov/pubmed/15090116

Psychopharmacology of ADHD: children and adolescents.

“Medications can provide significant salutary effects for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Due to their well-established safety and efficacy, psychostimulants are generally considered first-line pharmacotherapy for most young patients with ADHD. Since psychostimulant treatment often requires frequent dosing and may be associated with unacceptable side effects and risks, other classes of medication have been studied as possible treatment alternatives. The most extensively researched nonstimulant medications are the tricyclic antidepressants. In addition, alpha2 agonists have also been shown to reduce symptoms of ADHD. However, concerns regarding potential cardiotoxicity have tempered the enthusiasm for both of these classes of medication. Newer antidepressants such as bupropion and venlafaxine may hold promise as treatments for ADHD.”

Source: http://www.ncbi.nlm.nih.gov/pubmed/9680052

Novel treatments for attention-deficit/hyperactivity disorder in children

“Optimal medications for children with attention-deficit/hyperactivity disorder (ADHD) would be effective, well tolerated, and long acting and not cause mood swings or worsen comorbid conditions. Current medications work on brain dopamine and/or norepinephrine systems, which are thought to be involved in ADHD. The medication class with the most evidence of efficacy in ADHD is stimulants, but they may be abused, are effective for only 4 to 12 hours, and may cause mood swings or increase tic severity. In recent years, alternative treatments have been explored. Tricyclic antidepressants have efficacy comparable to that of stimulants but may cause constipation, dry mouth, tremors, blood pressure changes, and potentially serious side effects including cardiac conduction and repolarization delays. Monoamine oxidase inhibitors may improve ADHD symptoms but are associated with severe dietary restrictions. Serotonin reuptake inhibitors have little or no effect in ADHD but may improve comorbid depression. Bupropion, although less effective than stimulants, may improve both ADHD symptoms and comorbid depression. Antihypertensive agents may improve impulsivity, hyperactivity, and comorbid tics but cause sedation or rebound hypertension. Atomoxetine, which is being developed for ADHD, reduces symptoms of ADHD without exacerbating comorbid conditions and is associated with only minor side effects, including subtle changes in blood pressure and heart rate. Before prescribing a treatment, physicians should consider the appropriateness and effectiveness of any medication for children with ADHD, who may be less tolerant of side effects and less able to monitor and express concerns about their well-being than adults.”

Source: http://www.ncbi.nlm.nih.gov/pubmed/9680052

A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes

Source: http://www.ncbi.nlm.nih.gov/pubmed/20051220

Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD

Authors’ conclusions

The results of meta-analyses suggest that methylphenidate may improve teacher-reported ADHD symptoms, teacher-reported general behaviour, and parent-reported quality of life among children and adolescents diagnosed with ADHD. However, the low quality of the underpinning evidence means that we cannot be certain of the magnitude of the effects. Within the short follow-up periods typical of the included trials, there is some evidence that methylphenidate is associated with increased risk of non-serious adverse events, such as sleep problems and decreased appetite, but no evidence that it increases risk of serious adverse events. Better designed trials are needed to assess the benefits of methylphenidate. Given the frequency of non-serious adverse events associated with methylphenidate, the particular difficulties for blinding of participants and outcome assessors point to the advantage of large, ‘nocebo tablet’ controlled trials. These use a placebo-like substance that causes adverse events in the control arm that are comparable to those associated with methylphenidate. However, for ethical reasons, such trials should first be conducted with adults, who can give their informed consent. Future trials should publish depersonalised individual participant data and report all outcomes, including adverse events. This will enable researchers conducting systematic reviews to assess differences between intervention effects according to age, sex, comorbidity, type of ADHD and dose. Finally, the findings highlight the urgent need for large RCTs of non-pharmacological treatments. Conclusions At the moment, the quality of the available evidence means that we cannot say for sure whether taking methylphenidate will improve the lives of children and adolescents with ADHD. Methylphenidiate is associated with a number of non-serious adverse events such as problems with sleeping and decreased appetite. Although we did not find evidence that there is an increased risk of serious adverse events, we need trials with longer follow-up to better assess the risk of serious adverse events in people who take methylphenidate over a long period of time. Given that methylphenidate is associated with adverse events, designing high quality trials is challenging. It can be easy for clinicians, researchers and participants to work out whether a child is in the experimental group (receiving methylphenidate) or in the control group (receiving the placebo). This is a serious risk of bias that can make us less confident in the results of a trial. One way to avoid this is to design trials that compare methylphenidate with a placebo that can produce similar adverse events, but which has no other active ingredient. These trials are known as ‘nocebo trials’. For ethical reasons, nocebo trials should first be undertaken with adults. Only if the results suggest that methylphenidate is effective for adults, should researchers consider recruiting children to trials with this design.

Source: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009885.pub2/abstract

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HORMONE THERAPY & HORMONAL CORRELATES IN ADHD

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Thyroid Hormones

Behavioral effects of liothyronine (L-T3) in children with attention deficit hyperactivity disorder in the presence and absence of resistance to thyroid hormone

Abstract

Evidence that the thyroid may play a role in the pathogenesis of attention deficit hyperactivity disorder (ADHD) comes from observations that 48% to 73% of children with the syndrome of resistance to thyroid hormone (RTH) have ADHD. Casual observations in subjects with RTH have suggested that treatment with thyroid hormone may improve the symptoms of ADHD. The aim of this study was to determine whether thyroid hormone has a beneficial effect on the behavior of children with RTH. A prospective, randomized, double-blinded, placebo-controlled, cross-over study was conducted to evaluate the effect of the rapid acting thyroid hormone, liothyronine (L-T3), on the behavior of 8 children with ADHD + RTH, and 9 children with ADHD and normal thyroid function (ADHD Only). Parent and teacher ratings of hyperactivity (Conners scale) and a computerized continuous performance test (CPT) were used as objective measures of hyperactivity, attention and impulsivity. L-T3 had no effect on Conners Hyperactivity Index in 7 of 9 children with ADHD Only; it caused improvement and deterioration in 1 subject each. In contrast, the rating in 5 of 8 subjects with ADHD + RTH showed improvement, whereas 3 of 8 subjects remained unchanged. L-T3 was associated with increased commission errors in 5 of 8 children with ADHD Only and decreased commission errors in 4 of 7 with ADHD + RTH. In children with RTH and ADHD, particularly those that exhibit hyperactivity, L-T3 in supraphysiological doses may be beneficial in reducing hyperactivity and impulsivity. In the majority of children with ADHD who do not have RTH, L-T3 treatment has no effect or may be detrimental.

Reference:Weiss RE, Stein MA, Refetoff S. Behavioral effects of liothyronine (L-T3) in children with attention deficit hyperactivity disorder in the presence and absence of resistance to thyroid hormone. Thyroid. 1997 Jun;7(3):389-93. PubMed PMID: 9226208.

Source: http://www.ncbi.nlm.nih.gov/pubmed/?term=Behavioral+effects+of+liothyronine+(L-T3)+in+children+with+attention+deficit+hyperactivity+disorder+in+the+presence+and+absence+of+resistance+to+thyroid+hormone

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Thyroid hormones correlate with symptoms of hyperactivity but not inattention in attention deficit hyperactivity disorder.

Abstract The diagnostic validity of dividing attention deficit hyperactivity disorder (ADHD) into two distinct subgroups, one with and one without hyperactivity, is controversial since there have been no physiological differences demonstrated between these two subgroups. In this study, the relationship between thyroid hormones and symptoms of hyperactivity was examined in subjects with resistance to thyroid hormone (RTH) and their unaffected family members. Clinical data were collected on 152 subjects; 75 subjects with RTH and 77 family members without RTH. Each subject was assessed using DSM-III-R criterion based, structured psychiatric interviews, and Total T3 (TT3), Total T4 (TT4) and TSH concentrations were measured. The total number of ADHD symptoms were assigned to either inattention or hyperactivity subgroups using DSM-III-R criteria. The total number of ADHD symptoms were then reassigned to inattention or hyperactivity/impulsivity subgroups using DSM-IV criteria. Pearson R correlation coefficients were calculated separately for the RTH and unaffected family members groups in order to determine the relationships between TSH, TT3 and TT4 concentrations, and the DSM-III-R and DSM-IV symptom categories of ADHD in both groups. TSH concentrations were not significantly correlated with any of the symptom categories in either group. However, in the RTH group, both TT3 and TT4 concentrations were significantly and positively correlated with total symptoms of ADHD (DSM-III-R) as well as symptoms of inattention (DSM-III-R) and symptoms of hyperactivity (DSM-III-R). When DSM-IV criteria were used, which reassigns symptoms of impulsivity from the inattention to the hyperactivity category, only the positive correlation between TT3 and TT4 concentrations and symptoms of hyperactivity/impulsivity (DSM-IV) remained significant. In the group of unaffected family members, the relationship between TT3 concentrations and symptoms of hyperactivity/impulsivity (DSM-IV) was the only significant correlation. The data support the hypothesis that thyroid hormones may provide a physiological basis for the dichotomy between symptoms of inattention and symptoms of hyperactivity, particularly when DSM-IV criteria are applied.

Reference: Hauser P, Soler R, Brucker-Davis F, Weintraub BD. Thyroid hormones correlate with symptoms of hyperactivity but not inattention in attention deficit hyperactivity disorder. Psychoneuroendocrinology. 1997 Feb;22(2):107-14. PubMed PMID: 9149332.

Source: http://www.ncbi.nlm.nih.gov/pubmed/9149332

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Neurocognitive characteristics of individuals with resistance to thyroid hormone: comparisons with individuals with attention-deficit hyperactivity disorder.

Abstract Previous studies have demonstrated an association between resistance to thyroid hormone (RTH) and attention-deficit hyperactivity disorder (ADHD). To determine if the neurocognitive characteristics in individuals with RTH are similar to those observed in ADHD, 12 children with RTH from 7 families were matched to 12 children with ADHD without RTH. Subjects were administered standardized intellectual, developmental, and school achievement tests. Parent and teacher ratings of children’s hyperactivity and attention were similar for both groups, as were measures of attention, impulsivity, and verbal IQ. Children with RTH displayed lower nonverbal intelligence (performance IQ = 85) and academic achievement (> 1-2 SD below the mean) when compared with those with ADHD only (performance IQ = 99; achievement within 2 SD). Although children with RTH have behavioral characteristics similar to those with ADHD, their significantly weaker abilities of perceptual-organization and lower school achievement suggest a more severe neurobehavioral impairment than ADHD.

Reference: Stein MA, Weiss RE, Refetoff S. Neurocognitive characteristics of individuals with resistance to thyroid hormone: comparisons with individuals with attention-deficit hyperactivity disorder. J Dev Behav Pediatr. 1995 Dec;16(6):406-11. PubMed PMID: 8746549.

Source: http://www.ncbi.nlm.nih.gov/pubmed/8746549

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Oxytocin

Decreased levels of serum oxytocin in pediatric patients with Attention Deficit/Hyperactivity Disorder

Abstract Attention Deficit/Hyperactivity Disorder (ADHD) and autism spectrum disorder (ASD) are highly comorbid, and both disorders share executive function deficits. Accumulating evidence suggests that ASD patients have significantly lower peripheral oxytocin (OXT) levels compared with their normal counterparts, and that the repetitive behavior seen in ASD is related to abnormalities in the OXT system. In this study, we investigated whether serum levels of OXT are altered in pediatric patients with ADHD. We measured serum OXT levels: drug naive ADHD (n=23), medicated ADHD (n=13), and age- and sex- matched, neurotypical controls (n=22). Patients were evaluated using the ADHD-RS. Serum levels of OXT in total subjects with ADHD were significantly decreased compared with those of neurotypical controls, and serum levels of OXT in drug naive ADHD patients were significantly lower than those in medicated ADHD patients. Interestingly, there was a significant negative correlation between serum OXT levels and ADHD-RS total scores, as well as ADHD-RS inattentive scores in all ADHD patients. In conclusion, this study suggests that decreased levels of OXT may play a role in the pathophysiology of patients with ADHD and its inherent inattentiveness.

Source: http://www.ncbi.nlm.nih.gov/pubmed/26168929

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WORKING MEMORY TRAINING FOR ADHD

Will working memory training generalize to improve off-task behavior in children with attention-deficit/hyperactivity disorder

Computerized working memory and executive function training programs designed to target specific impairments in executive functioning are becoming increasingly available, yet how well these programs generalize to improve functional deficits in disorders, such as attention-deficit/hyperactivity disorder (ADHD), beyond the training context is not well-established. The aim of this study was to examine the extent to which working memory (WM) training in children with ADHD would diminish a core dysfunctional behavior associated with the disorder, “off-task” behavior during academic task performance. The effect of computerized WM training (adaptive) was compared to a placebo condition (nonadaptive) in a randomized, double-blind, placebo-controlled design in 26 children (18 males; age, 7 to 14 years old) diagnosed with ADHD. Participants completed the training in approximately 25 sessions. The Restricted Academic Situations Task (RAST) observational system was used to assess aspects of off-task behavior during the completion of an academic task. Traditional measures of ADHD symptoms (Conners’ Parent Rating Scale) and WM ability (standardized WM tests) were also collected. WM training led to significant reductions in off-task ADHD-associated behavior on the RAST system and improvement on WM tests. There were no significant differences between groups in improvement on parent rating scales. Findings lend insight into the generalizability of the effects of WM training and the relation between deficits in WM and off-task behavioral components of ADHD. These preliminary data suggest WM training may provide a mechanism for indirectly altering academic performance in children with ADHD.

Source: http://www.ncbi.nlm.nih.gov/pubmed/22752960

Cogmed WM training: reviewing the reviews.

Does Cogmed working-memory training (CWMT) work? Independent groups of reviewers have come to what appears to be starkly different conclusions to this question, causing somewhat of a debate within scientific and popular media. Here, various studies, meta-analyses, and reviews of the Cogmed research literature will be considered to provide an overview of our present understanding regarding the effects of CWMT. These will particularly be considered in light of two recent critical reviews published by Melby-Lervåg and Hulme ( 2013 ) and Shipstead, Hicks, and Engle ( 2012 ) and their arguments and conclusions assessed against current available evidence. Importantly we describe how the conclusions drawn by Melby-Lervåg and Hulme appear to contradict their own findings. In fact, the results from their meta-analysis show highly significant effects of working-memory (WM) training on improving visuospatial WM and verbal WM (both ps < .001). In addition, analyses of long-term follow-ups show that effects on visuospatial WM remain significant over time (again at p < .001). Thus, the analyses show that WM is indeed improved using WM training, and the highest effect sizes are achieved using CWMT (compared with other training programs). We also conclude that there is current evidence from several studies using different types of outcome measures that shows attention can be improved following CWMT. In a little more than a decade, there is evidence that suggests that Cogmed has a significant impact upon visual-spatial and verbal WM, and these effects generalize to improved sustained attention up to 6 months. We discuss the evidence for improvements in academic abilities and conclude that although some promising studies are pointing to benefits gained from CWMT, more controlled studies are needed before we can make strong and specific claims on this topic. In conclusion, we find that there is a consensus in showing that WM capacity and attention is improved following CWMT. Due to the importance of WM and attention in everyday functioning, this is, on its own, of great potential value.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25010082

Long-term far-transfer effects of working memory training in children with ADHD: a randomized controlled trial

ADHD affects working memory (WM) and other executive functions (EFs) and thereby negatively impacts school performance, clinical symptoms and functional impairment. The main aim of this study was to analyse the efficacy of computerized WM training (CWMT/Cogmed Working Memory Training) on EF (Executive Function) rating scales. A secondary objective was to assess its efficacy on performance-based measures of EF (PBMEF), learning, clinical symptoms and functional impairment. 66 children with combined-type ADHD between 7 and 12 years of age from the Child and Adolescent Psychiatric Unit (Spain) were included in this randomized, double-blind, placebo-controlled, parallel-group clinical trial. The participants were randomized (1:1) to an experimental group (EG) (CWMT) (n = 36) or a control group (CG) (placebo training). Assessments were conducted at baseline (T0), 1-2 weeks (T1), and 6 months post-intervention (T2) with the administration of EF rating scales, PBMEF, measures of academic achievement, and questionnaires regarding clinical symptoms and functional impairment. Participants, parents, teachers and professionals who performed the cognitive assessments were blinded. Adjusted multiple linear regression analysis showed significant improvements in EF scales-parent version, from T1 to T2, on the metacognition index [p = 0.03, d’ = -0.78 (95 % CI -1.28 to -0.27)] and on WM (also significant at T2-T0) and plan/organize subscales. Significant improvements were also noted in EF scales-teacher version, from T0 to T1 and T2, on the metacognitive index [p = 0.05, d’ = -0.37 (95 % CI -0.86 to 0.12) T1-T0, p = 0.02, d’ = -0.81 (95 % CI -1.31 to -0.30) T2-T0] and on the initiate, WM, monitor and shift subscales. There were also significant improvements in PBMEF, ADHD symptoms, and functional impairment. CWMT had a significant impact on ADHD deficits by achieving long-term far-transfer effects.

Source: http://www.ncbi.nlm.nih.gov/pubmed/26669692

Cognitive training for children with ADHD: a randomized controlled trial of cogmed working memory training and 'paying attention in class'.

The goal of this randomized controlled trial was to replicate and extend previous studies of Cogmed Working Memory Training (CWMT) in children with Attention-deficit/hyperactivity disorder (ADHD). While a large proportion of children with ADHD suffer from academic difficulties, only few previous efficacy studies have taken into account long term academic outcome measures. So far, results regarding academic outcome measures have been inconsistent. Hundred and two children with ADHD between the age of 8 and 12 years (both medicated and medication naïve) participated in current randomized controlled trial. Children were randomly assigned to CWMT or a new active combined working memory- and executive function compensatory training called ‘Paying Attention in Class.’ Primary outcome measures were neurocognitive functioning and academic performance. Secondary outcome measures contained ratings of behavior in class, behavior problems, and quality of life. Assessment took place before, directly after and 6 months after treatment. Results showed only one replicated treatment effect on visual spatial working memory in favor of CWMT. Effects of time were found for broad neurocognitive measures, supported by parent and teacher ratings. However, no treatment or time effects were found for the measures of academic performance, behavior in class or quality of life. We suggest that methodological and non-specific treatment factors should be taken into account when interpreting current findings. Future trials with well-blinded measures and a third ‘no treatment’ control group are needed before cognitive training can be supported as an evidence-based treatment of ADHD. Future research should put more effort into investigating why, how and for whom cognitive training is effective as this would also potentially lead to improved intervention- and study designs.

Source: http://journal.frontiersin.org/article/10.3389/fpsyg.2015.01081/full

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Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (Cogmed™) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts.

Source: http://www.ncbi.nlm.nih.gov/pubmed/26138580

Cognitive training for children with ADHD: A randomized controlled trial of cogmed working memory training and 'paying attention in class

The goal of this randomized controlled trial was to replicate and extend previous studies of Cogmed Working Memory Training (CWMT) in children with Attention-deficit/hyperactivity disorder (ADHD). While a large proportion of children with ADHD suffer from academic difficulties, only few previous efficacy studies have taken into account long term academic outcome measures. So far, results regarding academic outcome measures have been inconsistent. Hundred and two children with ADHD between the age of 8 and 12 years (both medicated and medication naïve) participated in current randomized controlled trial. Children were randomly assigned to CWMT or a new active combined working memory- and executive function compensatory training called ‘Paying Attention in Class.’ Primary outcome measures were neurocognitive functioning and academic performance. Secondary outcome measures contained ratings of behavior in class, behavior problems, and quality of life. Assessment took place before, directly after and 6 months after treatment. Results showed only one replicated treatment effect on visual spatial working memory in favor of CWMT. Effects of time were found for broad neurocognitive measures, supported by parent and teacher ratings. However, no treatment or time effects were found for the measures of academic performance, behavior in class or quality of life. We suggest that methodological and non-specific treatment factors should be taken into account when interpreting current findings. Future trials with well-blinded measures and a third ‘no treatment’ control group are needed before cognitive training can be supported as an evidence-based treatment of ADHD. Future research should put more effort into investigating why, how and for whom cognitive training is effective as this would also potentially lead to improved intervention- and study designs.

Source: http://www.ncbi.nlm.nih.gov/pubmed/26284005

A randomized clinical trial of Cogmed Working Memory Training in school-age children with ADHD: a replication in a diverse sample using a control condition

Background

Cogmed Working Memory Training (CWMT) has received considerable attention as a promising intervention for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children. At the same time, methodological weaknesses in previous clinical trials call into question reported efficacy of CWMT. In particular, lack of equivalence in key aspects of CWMT (i.e., contingent reinforcement, time-on-task with computer training, parent-child interactions, supportive coaching) between CWMT and placebo versions of CWMT used in previous trials may account for the beneficial outcomes favoring CWMT.

Methods

Eighty-five 7- to 11-year old school-age children with ADHD (66 male; 78%) were randomized to either standard CWMT (CWMT Active) or a well-controlled CWMT placebo condition (CWMT Placebo) and evaluated before and 3 weeks after treatment. Dependent measures included parent and teacher ratings of ADHD symptoms; objective measures of attention, activity level, and impulsivity; and psychometric indices of working memory and academic achievement (Clinical trial title: Combined cognitive remediation and behavioral intervention for the treatment of Attention-Deficit/Hyperactivity Disorder; http://clinicaltrials.gov/ct2/show/NCT01137318).

Results

CWMT Active participants demonstrated significantly greater improvements in verbal and nonverbal working memory storage, but evidenced no discernible gains in working memory storage plus processing/manipulation. In addition, no treatment group differences were observed for any other outcome measures.

Conclusions

When a more rigorous comparison condition is utilized, CWMT demonstrates effects on certain aspects of working memory in children with ADHD; however, CWMT does not appear to foster treatment generalization to other domains of functioning. As such, CWMT should not be considered a viable treatment for children with ADHD.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24117656

Commentary:Working memory training and ADHD - where does its potential lie? Reflections on Chacko et al. (2014).

Chacko et al.’s investigation of the clinical utility of WM training to alleviate key symptoms of ADHD is timely and substantial, and marks a significant point in cognitive training research. Cogmed Working Memory Training (CWMT) involves intensive practice on multiple memory span tasks that increase in difficulty as performance improves with practice. Relative to a placebo version in which the span level of the memory tasks are kept at a low fixed level, Chacko et al. () found that CWMT boosted the performance of children with ADHD on short-term memory (STM) tasks similar to trained activities. Complex WM span measures sharing little overlap with the structure of training activities were not enhanced. Neither did active CWMT ameliorate classic symptoms of ADHD such as parent or teacher ratings of attentional problems, or direct measures of motor impulsivity and sustained attention. Reading, spelling, comprehension or mathematics scores similarly showed no response to training.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24438534

Cogmed Working Memory Training for youth with ADHD: a closer examination of efficacy utilizing evidence-based criteria

The current review applied the evidence-based treatment criteria espoused by the Society for Clinical Child and Adolescent Psychology (Silverman & Hinshaw, 2008 ) to specifically evaluate the short-term and longer term efficacy of Cogmed Working Memory Training (CWMT) as a treatment for youth with Attention-Deficit/Hyperactivity Disorder (ADHD). Utilizing a systematic literature search, 7 studies that employed the school-age version of CWMT were identified for this review. The data reviewed herein suggest mixed findings regarding the benefit of CWMT for youth with ADHD. Two randomized controlled studies have demonstrated that CWMT led to improvements in neuropsychological outcomes and parent-rated ADHD symptoms relative to wait-list control and placebo treatment conditions. Another study demonstrated effects of CWMT relative to a placebo condition on an analog observation of behavior during an academic task, although this study did not find an effect of CWMT on parent-rated ADHD. Finally, an additional study utilizing an active comparison control condition did not find incremental benefits of CWMT on parent- or teacher-rated ADHD. Critical issues in interpreting existing studies include lack of alignment between demonstrated outcomes and the hypothesized model of therapeutic benefit of CWMT, issues with equivalence of control conditions, and individual differences that may moderate treatment response. Collectively, the strengths and limitations of the studies reviewed suggest that CWMT is best defined as a Possibly Efficacious Treatment for youth with ADHD. We suggest future directions for research and conclude with clinical implications of our findings for the treatment of youth with ADHD.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23668397

Working memory training in young children with ADHD: a randomized placebo-controlled trial.

Background

Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are available. To this end, a triple-blind, randomized, placebo-controlled study was designed to assess the efficacy of Cogmed Working Memory Training (CWMT) in young children with ADHD.

Methods

Fifty-one children (5-7 years) with a DSM-IV-TR diagnosis of ADHD (without current psychotropic medication) were randomly assigned to the active (adaptive) or placebo (nonadaptive) training condition for 25 sessions during 5 weeks. The compliance criterion (>20 sessions) was met for 47 children. The primary outcome measure concerned the core behavioural symptoms of ADHD, measured with the ADHD Rating Scale IV (ADHD-RS). Secondary outcome measures were neurocognitive functioning, daily executive functioning, and global clinical functioning. The influence of the increase in difficulty level (Index-Improvement) for the treatment group was also analysed. Clinical trial registration information – ‘Working Memory Training in Young ADHD Children’; www.clinicaltrials.gov; NCT00819611.

Results

A significant improvement in favour of the active condition was found on a verbal working memory task (p = .041; adapted Digit Span WISC-III, backward condition). However, it did not survive correction for multiple testing. No significant treatment effect on any of the primary or other secondary outcome measurements was found. The Index-Improvement significantly contributed to ADHD-RS and the Behavior Rating Inventory of Executive Function, both rated by the teacher, but revealed no significant group difference.

Conclusions

This study failed to find robust evidence for benefits of CMWT over the placebo training on behavioural symptoms, neurocognitive, daily executive, and global clinical functioning in young children with ADHD.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24628438

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NEUROFEEDBACK/BIOFEEDBACK FOR ADHD

Editorial: Neurofeedback in ADHD

“Neurofeedback as a therapeutic intervention has been most comprehensively investigated for the treatment of attention-deficit/hyperactivity disorder (ADHD)”

“The current controversy regarding the efficacy of neurofeedback in ADHD is centered on the fundamental question of how it should be evaluated: namely, in accordance with the APA guidelines (used to evaluate psychological treatments), or along the lines of drug treatments (requiring double-blind placebo controlled designs).”

“As is clear from the historical studies mentioned above, neurofeedback is built on the foundations of learning theory. Therefore, it is crucial to dissociate “neurofeedback as a treatment” from “neurofeedback as entertainment.” The “neurofeedback as entertainment” is an approach popularized by many modern devices such as the Mattel Mindflex (keep a ball in the air using your brain activity) or consumer-grade EEG units such as the Emotiv Epoc which run brain-training “apps.”

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626559/

Neurofeedback:

Abstract

Current research has shown that neurofeedback, or EEG biofeedback as it is sometimes called, is a viable alternative treatment for Attention Deficit Hyperactivity Disorder (ADHD). The aim of this article is to illustrate current treatment modalities(s), compare them to neurofeedback, and present the benefits of utilizing this method of treatment to control and potentially alleviate the symptoms of ADHD. In addition, this article examines the prevalence rates and possible etiology of ADHD, the factors associated with ADHD and brain dysfunction, the current pharmacological treatments of ADHD, Ritalin, and the potential risks and side effects. Behavior modification and cognitive behavioral treatment for ADHD is discussed as well. Lastly, a brief history of the study of neurofeedback, treatment successes and clinical benefits, comparisons to medication, and limitations are presented.

Source: http://www.ncbi.nlm.nih.gov/pubmed/16385424

Nonpharmacological treatments for ADHD: a meta-analytic review

Objective

The authors replicated and expanded on Fabiano et al.’s meta-analysis of behavioral treatments for ADHD, systematically comparing the efficacy of 7 nonpharmacological interventions.

Method

A total of 14 controlled treatment studies conducted post-1994-evaluating behavior modification, neurofeedback therapy, multimodal psychosocial treatment, school-based programs, working memory training, parent training, and self-monitoring-were identified, primarily by searching electronic English-language databases. The results were meta-analyzed: mean-weighted effect sizes for the treatment outcomes of 625 participants (382 treatment, 243 controls) were calculated, and moderator analyses examined contributions of gender, ADHD subtype, and treatment “dosage” to outcome.

Results

Behavior modification and neurofeedback treatments were most supported by this evidence. Interventions were generally more efficacious for girls, and least efficacious for the “combined” ADHD subtype. The authors found no dose or age effects.

Conclusion

Based on the small, published literature, this study supports some nonpharmacological interventions for ADHD, and indicates directions for more evaluation research into psychological treatments.

Source: http://www.ncbi.nlm.nih.gov/pubmed/16385424

Efficacy of Neurofeedback Versus Pharmacological Support in Subjects with ADHD.

Abstract

Behavioral training in neurofeedback has proven to be an essential complement to generalize the effects of pharmacological support in subjects who have attention deficit with hyperactivity disorder (ADHD). Therefore, this investigation attempts to analyze the efficacy of neurofeedback compared with pharmacological support and the combination of both. Participants were 131 students, classified into four groups: control (did not receive neurofeedback or pharmacological support), neurofeedback group, pharmacological support group, and combined group (neurofeedback + pharmacological support). Participants’ executive control and cortical activation were assessed before and after treatment. Results indicate that the combined group obtained more benefits and that the neurofeedback group improved to a greater extent in executive control than the pharmacological support group. It is concluded that this kind of training may be an alternative to stimulate activation in subjects with ADHD.

Source: http://www.ncbi.nlm.nih.gov/pubmed/26290167

The effects of individual upper alpha neurofeedback in ADHD: an open-label pilot study.

Abstract

Standardized neurofeedback (NF) protocols have been extensively evaluated in attention-deficit/hyperactivity disorder (ADHD). However, such protocols do not account for the large EEG heterogeneity in ADHD. Thus, individualized approaches have been suggested to improve the clinical outcome. In this direction, an open-label pilot study was designed to evaluate a NF protocol of relative upper alpha power enhancement in fronto-central sites. Upper alpha band was individually determined using the alpha peak frequency as an anchor point. 20 ADHD children underwent 18 training sessions. Clinical and neurophysiological variables were measured pre- and post-training. EEG was recorded pre- and post-training, and pre- and post-training trials within each session, in both eyes closed resting state and eyes open task-related activity. A power EEG analysis assessed long-term and within-session effects, in the trained parameter and in all the sensors in the (1-30) Hz spectral range. Learning curves over sessions were assessed as well. Parents rated a clinical improvement in children regarding inattention and hyperactivity/impulsivity. Neurophysiological tests showed an improvement in working memory, concentration and impulsivity (decreased number of commission errors in a continuous performance test). Relative and absolute upper alpha power showed long-term enhancement in task-related activity, and a positive learning curve over sessions. The analysis of within-session effects showed a power decrease (“rebound” effect) in task-related activity, with no significant effects during training trials. We conclude that the enhancement of the individual upper alpha power is effective in improving several measures of clinical outcome and cognitive performance in ADHD. This is the first NF study evaluating such a protocol in ADHD. A controlled evaluation seems warranted due to the positive results obtained in the current study.

Source: http://www.ncbi.nlm.nih.gov/pubmed/25199660

A decade of EEG Theta/Beta Ratio Research in ADHD: a meta-analysis.

Objective

Many EEG studies have reported that ADHD is characterized by elevated Theta/Beta ratio (TBR). In this study we conducted a meta-analysis on the TBR in ADHD.

Method

TBR data during Eyes Open from location Cz were analyzed from children/adolescents 6-18 years of age with and without ADHD.

Results

Nine studies were identified with a total of 1253 children/adolescents with and 517 without ADHD. The grand-mean effect size (ES) for the 6-13 year-olds was 0.75 and for the 6-18 year-olds was 0.62. However the test for heterogeneity remained significant; therefore these ESs are misleading and considered an overestimation. Post-hoc analysis found a decreasing difference in TBR across years, explained by an increasing TBR for the non-ADHD groups.

Conclusion

Excessive TBR cannot be considered a reliable diagnostic measure of ADHD, however a substantial sub-group of ADHD patients do deviate on this measure and TBR has prognostic value in this sub-group, warranting its use as a prognostic measure rather than a diagnostic measure.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23086616

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OTHER THERAPIES FOR ADHD

Meditation therapies for attention-deficit/hyperactivity disorder (ADHD). Cochrane Review

Authors’ Conclusions

As a result of the limited number of included studies, the small sample sizes and the high risk of bias, we are unable to draw any conclusions regarding the effectiveness of meditation therapy for ADHD. The adverse effects of meditation have not been reported. More trials are needed.

Source: http://www.cochrane.org/CD006507/BEHAV_meditation-therapies-for-attention-deficithyperactivity-disorder-adhd

Acupuncture for ADHD in children and adolescents. Cochrane Review

Authors’ Conclusions

A comprehensive search showed that there is no evidence base of randomised or quasi-randomised controlled trials to support the use of acupuncture as a treatment for ADHD in children and adolescents. Due to the lack of trials, we cannot reach any conclusions about the efficacy and safety of acupuncture for ADHD in children and adolescents. This review highlights the need for further research in this area in the form of high quality, large scale, randomised controlled trials.

Source: http://www.cochrane.org/CD007839/BEHAV_acupuncture-for-adhd-in-children-and-adolescents

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ADHD & SUBSTANCE ABUSE RISK

Attention-deficit/hyperactivity disorder and early-onset substance abuse disorders.

“In recent years, there has been an increased recognition of the common comorbidity of attention-deficit/ hyperactivity disorder (ADHD) and substance use disorder (SUD) among adolescents and adults. ADHD can be an important factor in the pathogenesis and maintenance of SUD; moreover, retrospective studies suggest that treating ADHD during childhood may prevent the development of SUD. In addition, treatment of ADHD among adults, and possibly adolescents, with SUD can reduce their risk of relapse. Theoretical mechanisms that may explain the relationship between ADHD and SUD are explored in this paper. Current research and recommended clinical practices related to the diagnosis and treatment of ADHD with SUD in adolescents are discussed as well. More research is needed to definitively assess the effectiveness and safety of medications in this population of youths with ADHD and SUD.”

Source: http://www.ncbi.nlm.nih.gov/pubmed/16262592

Childhood ADHD and risk for substance dependence in adulthood: a longitudinal, population-based study

“Adolescents with attention-deficit/hyperactivity disorder (ADHD) are known to be at significantly greater risk for the development of substance use disorders (SUD) compared to peers. Impulsivity, which could lead to higher levels of drug use, is a known symptom of ADHD and likely accounts, in part, for this relationship.”

“Our study found preliminary evidence that adults with childhood ADHD are more susceptible than peers to developing drug dependence, a disorder associated with neurological changes in the brain. The relationship between ADHD and alcohol dependence appears to be more complex.”

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146503/

Adolescent Substance Use in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD) (MTA) as a Function of Childhood ADHD, Random Assignment to Childhood Treatments, and Subsequent Medication.

“Medication for ADHD did not protect from, nor contribute to, visible risk of substance use or SUD by adolescence…” “These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication.”

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589108/

ADHD, stimulant treatment in childhood and subsequent substance abuse in adulthood - a naturalistic long-term follow-up study

The purpose of the study was to estimate the risk of substance use disorder (SUD) and alcohol abuse in adulthood among children and adolescents with attention-deficit hyperactivity disorder (ADHD) compared to the background population. Furthermore, to examine whether the age at initiation and duration of stimulant treatment in childhood predicts SUD and alcohol abuse in adulthood. 208 youths with ADHD (183 boys; 25 girls) were followed prospectively. Diagnoses of SUD and alcohol abuse were obtained from The Danish Psychiatric Central Register. The relative risk (RR) of SUD and alcohol abuse for cases with ADHD, compared to the background population was 7.7 (4.3-13.9) and 5.2 (2.9-9.4), respectively. Female gender, conduct disorder in childhood and older age at initiation of stimulant treatment increased the risk of later SUD and alcohol abuse. Our results warrant increased focus on the possibly increased risk of substance abuse in females with ADHD compared to males with ADHD.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24090624

A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders.

“Adolescent and adult patients with ADHD are at increased risk for SUD (substance abuse disorder), as well as a number of other psychiatric disorders. Psychostimulant agents like methylphenidate [Ritalin] (MPH) and mixed amphetamine salts (MAS)[Adderall] are effective first-line pharmacotherapies for ADHD; however, they are Schedule II controlled substances with a potential for abuse.”

“Evidence suggests that treatment of ADHD during childhood with stimulant agents may reduce the risk of developing SUD later on.” [Note: this evidence is inconclusive and there is also evidence which shows exactly the opposite]

“Treatment initiation during adolescence or young adulthood also has been linked to increased risk of polydrug use and non-medical stimulant use, a pattern of behavior consistent with a risk of SUD development. Treatment plans for patients with ADHD and co-morbid SUD should include behavioral interventions, careful monitoring, and when appropriate, pharmacotherapy.”

Source: http://www.ncbi.nlm.nih.gov/pubmed/18384709

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ADULT ADHD

The complexity of ADHD: diagnosis and treatment of the adult patient with comorbidities

“Popular culture propagates the myth that ADHD recedes with age; this is not the case.””Adults with ADHD show significant comorbidities with depressive disorders, anxiety disorders, substance use, oppositional defiant disorder, personality disorders, sleep problems, and learning disabilities. However, symptoms that result from ADHD, such as mood symptoms or lability, are often mistaken for comorbid disorders.”

“Effect sizes of approved medicines at approved doses are half those seen in children. Adults may also need longer duration of medication effects than children. Short-acting stimulants are likely to result in poorer adherence and have a higher risk for diversion or abuse.”

“Psychosocial interventions may be beneficial in treating both ADHD and comorbidities.”

Comment: Psychosocial Interventions according the American Academy of Pediatrics Level 1 interventions include: Behaviour Therapy, Biofeedback, Parent Management Training, Self-Verbalization.

Source: http://www.ncbi.nlm.nih.gov/pubmed/17667893

A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes.

Conclusions

Although both stimulant and nonstimulant medications are effective for treating ADHD in adults, stimulant medications show greater efficacy for the short durations of treatment characteristic of placebo-controlled studies. We found no significant differences between short- and long-acting stimulant medications. Study design features vary widely among studies and can confound indirect comparisons unless addressed statistically as we have done in this study.

Source: http://www.ncbi.nlm.nih.gov/pubmed/20051220

  • Level/Grade of Evidence: Prioritize higher level evidence over lower level evidence in selecting the most appropriate treatment or intervention: Meta-analysis/Systematic Review > Randomized Controlled Trial > Cohort Studies > Case Reports > Expert Opinion.
  • Time & Cost: Consider the time and cost involved with a treatment.
  • Risks & Benefits: Consider the risks, benefits and side effects of a treatment, including short-term and long-term.
  • Complex Interventions: Research usually examines a single treatment or intervention and may overlook the possible benefits of synergistically combining several different treatments or interventions.
  • Lack of Evidence: A lack of evidence is different than evidence showing something is not efficacious. A lack of evidence means more research is required before a definitive conclusion can be made. Many complimentary and alternative treatments (CAM) fall in this category.
  • Sponsorship Bias: Industry sponsored pharmaceutical studies are two-four times more likely to show favorable results for a drug than are non-industry sponsored studies.
  • Publication Bias: Failing to publish negative or questionable results while publishing only positive results is known as publication bias. Systematic reviews and meta-analyses, which constitute the gold standard in research, usually only analyze published studies and not those which were withheld from publication. If studies showing negative or questionable results have been withheld due to publication bias then the gold standard in research will not reflect the whole truth. For example, among 74 studies on antidepressants registered with the FDA a total of 37 studies with positive results were published. Only one study viewed as positive was not published. 22 studies on antidepressant medications registered with the FDA with negative or questionable results were not published or published in a way that conveyed a possible positive outcome (reversal or spin). Only 3 studies with negative or questionable outcomes were published.Turner et al. 2008 (NEJM) Publication bias may result in an overestimation of treatment efficacy and underestimation of side effects or adverse reactions.