810
Views
23
CrossRef citations to date
0
Altmetric
Review

Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder

&
Pages 463-474 | Received 17 Sep 2015, Accepted 25 Jan 2016, Published online: 07 Mar 2016

References

  • Efron D, Sciberras E, Anderson V, et al. Functional status in children with ADHD at age 6-8: a controlled community study. Pediatrics. 2014;134(4):e992–e1000.
  • Biederman J, Petty CR, Woodworth KY, et al. Adult outcome of attention-deficit/hyperactivity disorder: a controlled 16-year follow-up study. J Clin Psychiatry. 2012;73(7):941–950.
  • Willcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics. 2012;9(3):490–499.
  • Wolraich M, Brown L, Brown RT, et al. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011;128(5):1007–1022.
  • Pliszka S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894–921.
  • Lang HC, Scheffler RM, Hu TW. The discrepancy in attention deficit hyperactivity disorder (ADHD) medications diffusion: 1994-2003–a global pharmaceutical data analysis. Health Policy. 2010;97(1):71–78.
  • Express Scripts. The Express scripts 2012 drug trend report; [cited 2015 Aug 17]. Available from: http://www.drugtrendreport.com/docs/DTR_FULLPDF-1029.pdf
  • Express scripts. The 2014 drug trend report; [ cited 2015 Aug 17]. Available from: http://lab.express-scripts.com/drug-trend-report/
  • Top 25 psychiatric medication prescriptions for 2013. [ cited 2016 Jan 23]. Available from: http://psychcentral.com/lib/top-25-psychiatric-medication-prescriptions-for-2013/
  • Silva RR, Muniz R, Pestreich L, et al. Dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2008;47(2):199–208.
  • Wigal T, Brams M, Gasior M, et al. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design. Behav Brain Funct. 2010;6:34.
  • Faraone SV, Glatt SJ. A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes. J Clin Psychiatry. 2010;71(6):754–763.
  • Kelsey DK, Sumner CR, Casat CD, et al. Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder, including an assessment of evening and morning behavior: a double-blind, placebo-controlled trial. Pediatrics. 2004;114(1):e1–8.
  • STRATTERA capsules for oral use. Prescribing information; Apr 2015; Lilly USA, LLC, Indianapolis, IN.
  • KAPVAY (clonidine hydrochloride) extended-release tablets, for oral use. Prescribing Information; St. Michael, Barbados: Concordia Pharmaceuticals, Inc; 2015.
  • INTUNIV (guanfacine) extended-release tablets, for oral use. Prescribing Information; Feb 2015; Wayne, PA: Shire US Inc.
  • Polaha J, Dalton WT 3rd, Lancaster BM. Parental report of medication acceptance among youth: implications for everyday practice. South Med J. 2008;101(11):1106–1112.
  • Childress A, Desousa NJ, Incledon B, et al. The single dose pharmacokinetics of HLD200: A modified release methylphenidate (MPH) formulation in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Poster presented at the American Professional Society of ADHD and Related Disorders Annual Meeting; 2015 Jan 16–18, Washington (DC).
  • McDonnell M, Childress A, Wigal S, et al. A phase III, 6-week, open-label, dose optimization study of HLD200 in children with attention-deficit hyperactivity disorder. Poster presented at the American Psychiatric Association 168th Annual Meeting; 2015 May 16–20; Toronto, Canada.
  • Highland therapeutics announces positive top-line data from phase III trial. [ cited 2016 Jan 23]. Available from: http://www.highlandtherapeutics.com/pdf/Highland_Announces_Phase_III_Data_FINAL.pdf
  • Wigal SB, Wigal TL. The laboratory school protocol: its origin, use, and new applications. J Atten Disord. 2006;10(1):92–111.
  • Quinn D, Bode T, DeSousa NJ, et al. A phase-2 pharmacokinetic study of a modified release formulation of dextroamphetamine following evening administration to adolescents and children with ADHD. American Professional Society of ADHD and Related Disorders Annual Meeting; 2015 Jan 16–18; Washington (DC).
  • Wigal SB, Childress A, Wigal T, et al. Adolescent ADHD symptom improvement with triple-bead mixed amphetamine salts. Presented at the 54th Annual Meeting of the American Academy of Child and Adolescent Psychiatry; 2007 Oct 25; San Diego, CA.
  • Spencer TJ, Adler LA, Weisler RH, et al. Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: a randomized, double-blind, multicenter, placebo-controlled study. J Clin Psychiatry. 2008;69(9):1437–1448.
  • DuPaul GJ, Power T, Anastopoulos A, et al. ADHD rating scale-IV: checklists, norms, and clinical interpretation. New York: Guilford Press; 1998.
  • Childress A, Stark JG, Sikes C, et al. The pharmacokinetic properties of a novel extended-release oral disintegrating tablet formulation of methylphenidate in children and adolescents with ADHD. Poster presented at the American Academy of Child and Adolescent Psychiatry 62nd Annual Meeting; 2015 Oct 30; San Antonio, TX.
  • Childress A, Kollins SH, Cutler AJ,et al. A new formulation of methylphenidate phase 3 study of the efficacy and tolerability of an extended-release orally disintegrating tablet in children 6-12 years of age with ADHD. Poster presented at the American Academy of Child and Adolescent Psychiatry 62nd Annual Meeting; 2015 Oct 30; San Antonio, TX.
  • Stark J, McMahen R, Tengler M, et al. Oral bioavailability/bioequivalence of a novel investigational extended-release, oral-disintegrating tablet formulation (XR-ODT) of amphetamine for attention-deficit/hyperactivity disorder (ADHD). Presented at the American Academy of Child & Adolescent Psychiatry 2013 Annual Meeting; 2013 Oct 24; Orlando, FL.
  • DYANAVELTM XR (amphetamine) extended-release oral capsules,CII. Highlights of prescribing information. Tris Pharma, Inc; 2015 Oct [cited 2016 Jan 23]. Available from: http://www.trispharma.com/DXRUSPI.pdf
  • QUILLICHEW ERTM (methylphenidate hydrochloride) extended-release chewable tablets, for oral use, CII. Highlights of prescribing information. Manufactured by: Tris Pharma, Inc, Monmouth Junction, NJ 08852; [cited 2016 Jan 23]. Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=2577
  • Pfizer receives U.S. FDA approval of new quillichew ER™ (methylphenidate hydrochloride) extended-release chewable tablets CII. [cited Jan 23 2016]. Available from: http://www.pfizer.com/news/press-release/press-release
  • Study to evaluate safety & efficacy of d-amphetamine transdermal system compared to placebo in children & adolescents With ADHD. [cited 2016 Jan 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01711021?term=d-ats&rank=1
  • Noven announces positive phase 2 results of investigational d-amphetamine transdermal system For ADHD. [ cited 2016 Jan 23]. Available from: http://www.noven.com/PR072213.php
  • PRC-063 in an ADULT workplace environment. [ cited Jan 23 2016]. Available from: https://clinicaltrials.gov/ct2/show/NCT02225639?term=prc063&rank=3
  • Faraone SV, Biederman J, Spencer TJ, et al. Comparing the efficacy of medications for ADHD using meta-analysis. MedGenMed. 2006;8(4):4.
  • Jain R, Segal S, Kollins SH, et al. Clonidine extended-release tablets for pediatric patients with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2011;50(2):171–179.
  • Sallee FR, McGough J, Wigal T, et al. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2009;48(2):155–165.
  • Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry. 2002;159(11):1896–1901.
  • Hodgkins P, Shaw M, Coghill D, et al. Amfetamine and methylphenidate medications for attention-deficit/hyperactivity disorder: complementary treatment options. Eur Child Adolesc Psychiatry. 2012;21(9):477–492.
  • Jin L, Xu W, Krefetz D, et al. Clinical outcomes from an open-label study of edivoxetine use in pediatric patients with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2013;23(3):200–207.
  • Kielbasa W, Quinlan T, Jin L, et al. Pharmacokinetics and pharmacodynamics of edivoxetine (LY2216684), a norepinephrine reuptake inhibitor, in pediatric patients with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2012;22(4):269–276.
  • Lin DY, Kratochvil CJ, Xu W, et al. A randomized trial of edivoxetine in pediatric patients with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2014;24(4):190–200.
  • Koblan KS, Hopkins SC, Sarma K, et al. Dasotraline for the treatment of attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled, proof-of-concept trial in adults. Neuropsychopharmacology. 2015;40(12):2745–2752. doi:10.1038/npp.2015.124.
  • Dasotraline pediatric ADHD study. [ cited 2016 Jan 23]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02428088?term=dasotraline&rank=1
  • Dasotraline adult ADHD study. [cited 2016 Jan 23]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02276209?term=dasotraline&rank=2
  • Bymaster FP, Golembiowska K, Kowalska M, et al. Pharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB-1020: implications for treatment of attention-deficit hyperactivity disorder. Synapse. 2012;66(6):522–532.
  • Wilens TE, Cutler AJ, Childress A, et al. A pilot study of a novel monoamine triple reuptake inhibitor, EB-1020 SR, in the treatment of attention-deficit/hyperactivity disorder in adult males. Society of Biological Psychiatry 2014 Annual Meeting. 2014 May 8–10, New York.
  • Robertson BA, Shram MJ, Schoedel KA. Early stage assessment of the abuse potential of centanafadine, a triple reuptake inhibitor: preclinical and clinical study results. American College of Neuropsychopharmacology 53rd Annual Meeting. 2014 Dec 7–11; Phoenix (AZ).
  • Manor I, Ben-Hayun R, Aharon-Peretz J, et al. A randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of extended-release metadoxine in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2012;73(12):1517–1523.
  • Fornai F, Grazia Alessandri M, Bonuccelli U, et al. Effect of metadoxine on striatal dopamine levels in C57 black mice. J Pharm Pharmacol. 1993;45(5):476–478.
  • CAARS™conners’ adult ADHD rating scales. [ cited 2016 Jan 23]. Available from: http://www.mhs.com/product.aspx?gr=cli&id=overview&prod=caars
  • The MEASURE study - a phase 3 study of MDX 1400 mg daily compared with placebo in adults with ADHD. [ cited 2016 Jan 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02477748?term=metadoxine&rank=13
  • Hashimoto K, Sasaki T. Old drug tipepidine as new hope for children with ADHD. Aust N Z J Psychiatry. 2015;49(2):181–182.
  • Sasaki T, Hashimoto K, Tachibana M et al. Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study. Neuropsychiatr Dis Treat. 2014;10:147–151.
  • Tipepidine in children with attention deficit/hyperactivity disorder (AD/HD): a double-blind, placebo-controlled trial. [ cited 2016 Jan 23]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02305134?term=tipepidine&rank=1
  • Vidt DG. Mechanism of action, pharmacokinetics, adverse effects, and therapeutic uses of amiloride hydrochloride, a new potassium-sparing diuretic. Pharmacotherapy. 1981;1(3):179–187.
  • Product monograph: MIDAMORR antikaliuretic agent with diuretic properties. Vaughan (ON):AA Pharma Inc; 2010 [cited 2016 Jan 23]. Available from http://www.aapharma.ca/downloads/en/PIL/midamor_pm.pdf
  • Amiloride hydrochloride as an effective treatment for ADHD. [cited 2016 Jan 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01733680
  • Zayats T, Athanasiu L, Sonderby I, et al. Genome-wide analysis of attention deficit hyperactivity disorder in norway. PLoS One. 2015;10(4):e0122501.
  • Zhang-James Y, Middleton FA, Sagvolden T, et al. Differential expression of SLC9A9 and interacting molecules in the hippocampus of rat models for attention deficit/hyperactivity disorder. Dev Neurosci. 2012;34(2–3):218–227.
  • Stahl SM. L-methylfolate: a vitamin for your monoamines. J Clin Psychiatry. 2008;69(9):1352–1353.
  • Papakostas GI, Shelton RC, Zajecka JM, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012;169(12):1267–1274.
  • Wolraich ML, Lambert W, Doffing MA, et al. Psychometric properties of the vanderbilt ADHD diagnostic parent rating scale in a referred population. J Pediatr Psychol. 2003;28(8):559–567.
  • Quillin R High dose L-methylfolate as novel therapy in ADHD. Abstract Presented at the Amercian Academy of Pediatrics National Conference; 2013 Oct 26–29; Orlando, FL.
  • L-methylfolate supplementation to OROS-methylphenidate pharmacotherapy in ADHD adults. [cited 23 Jan 2016]. Available from: https://clinicaltrials.gov/show/NCT01853280
  • Adler LA, Gorny SW. Pilot study of droxidopa with carbidopa in adults with ADHD. J Atten Disord. 2015 Apr 23. pii:1087054715580393. [Epub ahead of print].
  • Preliminary data from exploratory phase II study demonstrates significant activity of droxidopa in adult attention deficit hyperactivity disorder (ADHD) [Internet]. In: GlobeNewswire. 2011 [cited 2016 Feb 19]. Available from: http://files.shareholder.com/downloads/CHTP/2719542466x0x485689/b9b73a99-c322-458b-a8e8-809af9d92e42/CHTP_News_2011_7_26_News_Releases.pdf.
  • Spencer TJ, Adler LA, Meihua Q, et al. Validation of the adult ADHD investigator symptom rating scale (AISRS). J Atten Disord. 2010;14(1):57–68.
  • Keks NA, Hope J. Culhane C. Vortioxetine: A multimodal antidepressant or another selective serotonin reuptake inhibitor? Australas Psychiatry. 2015;23(3):210–213.
  • Investigating the effect of vortioxetine in adult ADHD patients. [cited 2016 Jan 23]. Available from: https://clinicaltrials.gov/show/NCT02327013
  • Pinna A. Adenosine A2A receptor antagonists in Parkinson’s disease: progress in clinical trials from the newly approved istradefylline to drugs in early development and those already discontinued. CNS Drugs. 2014;28(5):455–474.
  • Safety, tolerability, PK & efficacy of V81444 in volunteers with attention deficit/hyperactivity disorder (ADHD). [cited 2016 Jan 23]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT02253745?term=v81444&rank=2
  • Promising results of phase Ib/II proof-of-concept study in attention deficit hyperactivity disorder (ADHD) with V81444. [cited 2016 Jan 23]. Available from: http://www.vernalis-research.com/respubs/research-press-releases/680-promising-results-of-phase-ib-ii-proof-of-concept-study-in-attention-deficit-hyperactivity-disorder-adhd-with-v81444
  • Moorthy G, Sallee F, Gabbita P, et al. Safety, tolerability, and pharmacokinetics of 2-pyridylacetic acid, a major metabolite of betahistine, in phase 1 dose escalation study in subjects with ADHD. Biopharm Drug Dispos. 2015;36(7):429–439. doi:10.1002/bdd.1955.
  • Leurs R, Bakker RA, Timmerman H, et al. The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005;4(2):107–120.
  • Weisler RH, Pandina GJ, Daly EJ, et al. Randomized clinical study of a histamine H3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs. 2012;26(5):421–434.
  • Safety and effectiveness study of JNJ-31001074 in adults with attention-deficit/hyperactivity disorder. [ Cited 2016 Jan 23]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT00566449?term=bavisant&rank=1
  • Herring WJ, Wilens TE, Adler LA, et al. Randomized controlled study of the histamine H3 inverse agonist MK-0249 in adult attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2012;73(7):e891–e898.
  • PF-03654746/H3 receptor antagonist. [ Cited 2016 Jan 23]. Available from: https://ncats.nih.gov/files/PF-03654746.pdf
  • Wilens TE, Klint T, Adler L, et al. A randomized controlled trial of a novel mixed monoamine reuptake inhibitor in adults with ADHD. Behav Brain Funct. 2008;4:24.
  • CHOP research institute hosts major genomics conference. Bench to bedside. (The Children’s Hospital of Philadelphia, Cincinnati, 2012) [ Cited 2016 Jan 23]. Available from: http://www.research.chop.edu/forms/btob/Oct12BtoB.pdf
  • Oka M, Itoh Y, Shimidzu T, et al. Involvement of metabotropic glutamate receptors in Gi- and Gs-dependent modulation of adenylate cyclase activity induced by a novel cognition enhancer NS-105 in rat brain. Brain Res. 1997;754(1–2):121–130.
  • Oka M, Itoh Y, Tatsumi S, et al. A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture. Naunyn Schmiedebergs Arch Pharmacol. 1997;356(2):189–196.
  • Placebo-controlled trial with GlyTI-M among children with attention deficit hyperactivity disorder (ADHD). [ Cited 2016 Jan 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT01725737?term=GlyTI-M&rank=1
  • Dwoskin LP, Crooks PA. A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse. Biochem Pharmacol. 2002;63(2):89–98.
  • Martin CA, Nuzzo PA, Ranseen JD, et al. Lobeline effects on cognitive performance in adult ADHD. J Atten Disord. 2013. doi:10.1177/108705471349779.
  • ND0801 for cognitive disorders. [ Cited 2016 Jan 23]. Available from: http://www.pharmaceuticalonline.com/doc/neuroderm-initiates-phase-2-study-of-nd0801-0001
  • A study of ND0801 in attention deficit/hyperactivity disorder (ADHD). [ Cited 2016 Jan 23]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT01174355?term=nd0801&rank=1
  • Thase ME, Youakim JM, Skuban A, et al. Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study. J Clin Psychiatry. 2015;76(9):1232–1240. doi:10.4088/JCP.14m09689.
  • Howland RH. Brexpiprazole: another multipurpose antipsychotic drug? J Psychosoc Nurs Ment Health Serv. 2015;53(4):23–25.
  • Study of the safety and efficacy of OPC-34712 as a complementary therapy in the treatment of adult attention deficit/hyperactivity disorder (STEP-A). [ Cited 2016 Jan 23]. Available from: https://clinicaltrials.gov/show/NCT01074294
  • A pivotal efficacy trial to evaluate HLD200 in children with ADHD in a naturalistic setting. [ Cited 2016 Jan 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02520388?term=hld200&rank=1
  • Childress A, Sallee FR. Pozanicline for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Investig Drugs. 2014;23(11):1585–1593.
  • Vohora D, Bhowmik M. Histamine H3 receptor antagonists/inverse agonists on cognitive and motor processes: relevance to Alzheimer’s disease, ADHD, schizophrenia, and drug abuse. Front Syst Neurosci. 2012;6:72.
  • Brioni JD, Esbenshade TA, Garrison TR, et al. Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer’s disease. J Pharmacol Exp Ther. 2011;336(1):38–46.
  • Kiser DP, Rivero O, Lesch KP. Annual research review: the (epi)genetics of neurodevelopmental disorders in the era of whole-genome sequencing–unveiling the dark matter. J Child Psychol Psychiatry. 2015;56(3):278–295.
  • Mastronardi CA, Pillai E, Pineda DA, et al. Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate. Mol Psychiatry. 2015 Nov 24. doi:10.1038/mp.2015.172. [Epub ahead of print].
  • Cherkasova MV, Faridi N, Casey KF, et al. Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD. Neuropsychopharmacology. 2014;39(6):1498–1507.
  • Cherkasova MV, Hechtman L. Neuroimaging in attention-deficit hyperactivity disorder: beyond the frontostriatal circuitry. Can J Psychiatry. 2009;54(10):651–664.
  • Del Campo N, Fryer TD, Hong YT, et al. A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment. Brain. 2013;136(Pt 11):3252–3270.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.