CNS Drugs

, Volume 24, Issue 10, pp 805–810

Abuse-Deterrent and Tamper-Resistant Opioid Formulations

What is their Role in Addressing Prescription Opioid Abuse?
  • Jennifer P. Schneider
  • Michele Matthews
  • Robert N. Jamison
Leading Article


About one in every three individuals will experience chronic pain in their lifetime, and opioids are known to be an effective means to treat this condition. Much attention, however, has been given to the fact that prescription opioid analgesics are some of the most frequently abused drugs, and misuse is prominent in patients with chronic pain. Several new opioid formulations that are designed to prevent or deter the abuse of opioids are currently in development, and two have been approved for marketing (morphine sulphate co-formulated with naltrexone hydrochloride [Embeda®] and a new formulation of the extended-release oxycodone [OxyContin®]).

In this article, we review the various types of abuse-deterrent and tamper-resistant formulations in clinical development. We believe that continued advances in opioid formulations can help mitigate risk for those with legitimate need for pain control, but only if used rationally in the context of good clinical practice.


  1. 1.
    Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD: a systematic review and meta-regression analysis. Am J Psychiatry 2007; 164: 942–8PubMedCrossRefGoogle Scholar
  2. 2.
    American Academy of Pediatrics (AAP). Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics 2000; 105: 1158–70CrossRefGoogle Scholar
  3. 3.
    Biederman J, Faraone SC. Attention-deficit hyperactivity disorder. Lancet 2005; 367: 237–48CrossRefGoogle Scholar
  4. 4.
    Klassen AF, Miller A, Fine S. Health-related quality of life in children and adolescents who have a diagnosis of attention-deficit/hyperactivity disorder. Pediatrics 2004; 114: e541–7PubMedCrossRefGoogle Scholar
  5. 5.
    Corkum P, Tannock R, Moldofsky H. Sleep disturbances in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1998; 37: 637–46PubMedCrossRefGoogle Scholar
  6. 6.
    Sung V, Hiscock H, Sciberras E, et al. Sleep problems in children with attention-deficit/hyperactivity disorder: prevalence and the effect on the child and family. Arch Pediatr Adolesc Med 2008; 162: 336–42PubMedCrossRefGoogle Scholar
  7. 7.
    Lecendreux M, Cortese S. Sleep problems associated with ADHD: a review of current therapeutic options and recommendations for the future. Expert Rev Neurother 2007; 7: 1799–806PubMedCrossRefGoogle Scholar
  8. 8.
    Owens J, Sangal RB, Sutton VK, et al. Subjective and objective measures of sleep in children with attention-deficit/ hyperactivity disorder. Sleep Med 2009; 10: 446–56PubMedCrossRefGoogle Scholar
  9. 9.
    Van der Heijden KB, Smits MG, Gunning WB. Sleep-related disorders in ADHD: a review. Clin Pediatr (Phila) 2005; 44: 201–10CrossRefGoogle Scholar
  10. 10.
    Bullock GL, Schall U. Dyssomnia in children diagnosed with attention deficit hyperactivity disorder: a critical review. Aust N Z J Psychiatry 2005; 39: 373–7PubMedCrossRefGoogle Scholar
  11. 11.
    Kirov R, Banaschewski T, Uebel H, et al. REM-sleep alterations in children with tic disorder and attention-deficit/ hyperactivity disorder comorbidity: impact of hypermotor symptoms. Eur Child Adolesc Psychiatry 2007; 16 Suppl. 1: 45–50PubMedCrossRefGoogle Scholar
  12. 12.
    Kirov R, Kinkelbur J, Banaschewski T, et al. Sleep patterns in children with attention-deficit/hyperactivity disorder, tic disorder, and comorbidity. J Child Psychol Psychiatry 2007; 48: 561–70PubMedCrossRefGoogle Scholar
  13. 13.
    Konofal E, Lecendreux M, Bouvard MP, et al. High levels of nocturnal activity in children with attention-deficit hyperactivity disorder: a video analysis. Psychiatry Clin Neurosci 2001; 55: 97–103PubMedCrossRefGoogle Scholar
  14. 14.
    Chervin RD, Archbold KH, Dillon JE, et al. Inattention, hyperactivity, and symptoms of sleep-disordered breathing. Pediatrics 2002; 109: 449–56PubMedCrossRefGoogle Scholar
  15. 15.
    Chervin RD, Archbold KH, Dillon JE, et al. Associations between symptoms of inattention, hyperactivity, restless legs, and periodic leg movements. Sleep 2002; 25: 213–8PubMedGoogle Scholar
  16. 16.
    Cortese S, Konofal E, Lecendreux M, et al. Restless legs syndrome and attention-deficit/hyperactivity disorder: a review of the literature. Sleep 2005; 28: 1007–13PubMedGoogle Scholar
  17. 17.
    Konofal E. Relationship between ADHD and sleep disturbances. Advances ADHD 2008; 2: 85–94Google Scholar
  18. 18.
    Cortese S, Faraone SV, Konofal E, et al. Sleep in children with attention-deficit/hyperactivity disorder: meta-analysis of subjective and objective studies. J Am Acad Child Adolesc Psychiatry 2009; 48: 894–908PubMedGoogle Scholar
  19. 19.
    Johnson EO, Breslau N, Roth T, et al. Psychometric evaluation of daytime sleepiness and nocturnal sleep onset scales in a representative community sample. Biol Psychiatry 1999; 45: 764–70PubMedCrossRefGoogle Scholar
  20. 20.
    Gelman VS, King NJ. Wellbeing of mothers with children exhibiting sleep disturbance. Austrian J Psychol 2001; 53: 18–22CrossRefGoogle Scholar
  21. 21.
    Walters AS, Mandelbaum DE, Lewin DS, et al. Dopaminergic therapy in children with restless legs/periodic limb movements in sleep and ADHD: Dopaminergic Therapy Study Group. Pediatr Neurol 2000; 22: 182–6PubMedCrossRefGoogle Scholar
  22. 22.
    Chervin RD, Ruzicka DL, Giordani BJ, et al. Sleep-disordered breathing, behavior, and cognition in children before and after adenotonsillectomy. Pediatrics 2006; 117: e769–78PubMedCrossRefGoogle Scholar
  23. 23.
    Huang YS, Guilleminault C, Li HY, et al. Attention-deficit/hyperactivity disorder with obstructive sleep apnea: a treatment outcome study. Sleep Med 2007; 8: 18–30PubMedCrossRefGoogle Scholar
  24. 24.
    Wei JL, Mayo MS, Smith HJ, et al. Improved behavior and sleep after adenotonsillectomy in children with sleep-disordered breathing. Arch Otolaryngol Head Neck Surg 2007; 133: 974–9PubMedCrossRefGoogle Scholar
  25. 25.
    Faries DE, Yalcin I, Harder D, et al. Validation of the ADHD Rating Scale as a clinician administered and scored instrument. J Atten Disord 2001; 5: 39–47CrossRefGoogle Scholar
  26. 26.
    Ivanenko A, Crabtree VM, Obrien LM, et al. Sleep complaints and psychiatric symptoms in children evaluated at a pediatric mental health clinic. J Clin Sleep Med 2006 15; 2: 42–8PubMedGoogle Scholar
  27. 27.
    Ivanenko A, Johnson K. Sleep disturbances in children with psychiatric disorders. Semin Pediatr Neurol 2008; 15: 70–8PubMedCrossRefGoogle Scholar
  28. 28.
    Liu X, Buysse DJ, Gentzler AL, et al. Insomnia and hyper-somnia associated with depressive phenomenology and comorbidity in childhood depression. Sleep 2007; 30: 83–90PubMedGoogle Scholar
  29. 29.
    Quine L. Sleep problems in children with mental handicap. J Ment Defic Res 1991; 35 (Pt 4): 269–90PubMedGoogle Scholar
  30. 30.
    Douglass AB, Bornstein R, Nino-Murcia G, et al. The Sleep Disorders Questionnaire: I. Creation and multivariate structure of SDQ. Sleep 1994; 17: 160–7Google Scholar
  31. 31.
    Chervin RD, Hedger K, Dillon JE, et al. Pediatric Sleep Questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Med 2000; 1: 21–32PubMedCrossRefGoogle Scholar
  32. 32.
    Owens JA, Spirito A, McGuinn M. The Children’s Sleep Habits Questionnaire (CSHQ): psychometric properties of a survey instrument for school-aged children. Sleep 2000; 23: 1043–51PubMedGoogle Scholar
  33. 33.
    National Sleep Foundation. Sleep diary [online]. Available from URL: [Accessed 2008 Nov 24]
  34. 34.
    National Institutes of Health. Star sleeper for kids [online]. Available from URL: [Accessed 2008 Nov 24]
  35. 35.
    Mindell JA, Owens JA. A clinical guide to pediatric sleep: diagnosis and management of sleep problems. Baltimore (MD): Lippincott Williams & Wilkins, 2003Google Scholar
  36. 36.
    Morgenthaler TI, Lee-Chiong T, Alessi C, et al. Standards of Practice Committee of the American Academy of Sleep Medicine: practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep 2007; 30: 1445–59Google Scholar
  37. 37.
    Van der Heijden KB, Smits MG, Van Someren EJ, et al. Idiopathic chronic sleep onset insomnia in attention-deficit/ hyperactivity disorder: a circadian rhythm sleep disorder. Chronobiol Int 2005; 22: 559–70PubMedCrossRefGoogle Scholar
  38. 38.
    Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003; 4: 101–19Google Scholar
  39. 39.
    Cortese S, Lecendreux M, Bernardina BD, et al. Attention-deficit/hyperactivity disorder, Tourette’s syndrome, and restless legs syndrome: the iron hypothesis. Med Hypotheses 2008; 70: 1128–32PubMedCrossRefGoogle Scholar
  40. 40.
    Bruni O, Ottaviano S, Guidetti V, et al. The Sleep Disturbance Scale for Children (SDSC): construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence. J Sleep Res 1996; 5: 251–61PubMedCrossRefGoogle Scholar
  41. 41.
    Chervin RD, Hedger KM. Clinical prediction of periodic leg movements during sleep in children. Sleep Med 2001; 2: 501–10PubMedCrossRefGoogle Scholar
  42. 42.
    Archbold KH. Sleep disorders and attention-deficit hyperactivity disorder in children: a missing differential diagnosis. J Am Psychiatr Nurses Assoc 2006; 12: 216–24CrossRefGoogle Scholar
  43. 43.
    Owens JA, Dalzell V. Use of the ‘BEARS’ sleep screening tool in a pediatric residents’ continuity clinic: a pilot study. Sleep Med 2005; 6: 63–9PubMedCrossRefGoogle Scholar
  44. 44.
    Morin CM, Espie CA. Insomnia: a clinical guide to assessment and treatment. New York: Springer, 2003Google Scholar
  45. 45.
    Cohen-Zion M, Ancoli-Israel S. Sleep in children with attention-deficit hyperactivity disorder (ADHD): a review of naturalistic and stimulant intervention studies. Sleep Med Rev 2004; 8: 379–402PubMedCrossRefGoogle Scholar
  46. 46.
    Gruber R, Sadeh A, Raviv A. Instability of sleep patterns in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2000; 39: 495–501PubMedCrossRefGoogle Scholar
  47. 47.
    Hvolby A, Jorgensen J, Bilenberg N. Actigraphic and parental reports of sleep difficulties in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 2008; 162: 323–9PubMedCrossRefGoogle Scholar
  48. 48.
    Weiss MD, Wasdell MB, Bomben MM, et al. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry 2006; 45: 512–9PubMedGoogle Scholar
  49. 49.
    Van Veen MM, Kooij JJ, Boonstra AM, et al. Delayed circadian rhythm in adults with attention-deficit/ hyperactivity disorder and chronic sleep-onset insomnia. Biol Psychiatry 2010; 67(11): 1091–6PubMedCrossRefGoogle Scholar
  50. 50.
    Pliszka S, for the AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007; 46: 894–921PubMedCrossRefGoogle Scholar
  51. 51.
    Stein MA, Weiss M, Leventhal BL. ADHD by night: sleep problems and ADHD medications. Child Adolesc Pharmacol News 2007; 12: 1–5CrossRefGoogle Scholar
  52. 52.
    Stein MA. Unravelling sleep problems in treated and untreated children with ADHD. J Child Adolesc Psycho-pharmacol 1999; 9: 157–68CrossRefGoogle Scholar
  53. 53.
    Day HD, Abmayr SB. Parent reports of sleep disturbances in stimulant-medicated children with attention-deficit hyperactivity disorder. J Clin Psychol 1998; 54: 701–16PubMedCrossRefGoogle Scholar
  54. 54.
    Kent JD, Blader JC, Koplewicz HS, et al. Effects of late-afternoon methylphenidate administration on behavior and sleep in attention-deficit hyperactivity disorder. Pediatrics 1995; 96: 320–5PubMedGoogle Scholar
  55. 55.
    O’Brien LM, Ivanenko A, Crabtree VM, et al. The effect of stimulants on sleep characteristics in children with attention deficit/hyperactivity disorder. Sleep Med 2003; 4: 309–16PubMedCrossRefGoogle Scholar
  56. 56.
    Sangal RB, Owens J, Allen AJ, et al. Effects of atomoxetine and methylphenidate on sleep in children with ADHD. Sleep 2006; 29: 1573–85PubMedGoogle Scholar
  57. 57.
    Schwartz G, Amor LB, Grizenko N, et al. Actigraphic monitoring during sleep of children with ADHD on methylphenidate and placebo. J Am Acad Child Adolesc Psychiatry 2004; 43: 1276–82PubMedCrossRefGoogle Scholar
  58. 58.
    Kratochvil CJ, Lake M, Pliszka SR, et al. Pharmacological management of treatment-induced insomnia in ADHD. J Am Acad Child Adolesc Psychiatry 2005; 44: 499–501PubMedCrossRefGoogle Scholar
  59. 59.
    Ahmann PA, Waltonen SJ, Olson KA, et al. Placebo-controlled evaluation of ritalin side effects. Pediatrics 1993; 91: 1101–6PubMedGoogle Scholar
  60. 60.
    Stein MA, Blondis TA, Schnitzler ER, et al. Methylphenidate dosing: twice daily versus three times daily. Pediatrics 1996; 98: 748–56PubMedGoogle Scholar
  61. 61.
    Carlson GA, Kelly KL. Stimulant rebound: how common is it and what does it mean? J Child Adolesc Psycho-pharmacol 2003; 13: 137–42CrossRefGoogle Scholar
  62. 62.
    Golan N, Shahar E, Ravid S, et al. Sleep disorders and daytime sleepiness in children with attention-deficit/ hyperactive disorder. Sleep 2004; 27: 261–6PubMedGoogle Scholar
  63. 63.
    Lecendreux M, Konofal E, Bouvard M, et al. Sleep and alertness in children with ADHD. J Child Psychol Psychiatry 2000; 41: 803–12PubMedCrossRefGoogle Scholar
  64. 64.
    Oosterloo M, Lammers GJ, Overeem S, et al. Possible confusion between primary hypersomnia and adult attention-deficit/hyperactivity disorder. Psychiatr Res 2006; 143: 293–7CrossRefGoogle Scholar
  65. 65.
    Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14: 540–5PubMedGoogle Scholar
  66. 66.
    Biederman J, Pliszka SR. Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents. J Pediatr 2008; 152: 394–9PubMedCrossRefGoogle Scholar
  67. 67.
    Wigal SB, Biederman J, Swanson JM, et al. Efficacy and safety of modafinil film-coated tablets in children and adolescents with or without prior stimulant treatment for attention deficit/hyperactivity disorder: pooled analysis of 3 randomized, double-blind, placebo controlled studies. Prim Care Companion J Clin Psychiatry 2006; 8: 352–60PubMedGoogle Scholar
  68. 68.
    Amiri S, Mohammadi MR, Mohammadi M, et al. Modafinil as a treatment for attention-deficit/hyperactivity disorder in children and adolescents: a double blind, randomized clinical trial. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 145–9PubMedCrossRefGoogle Scholar
  69. 69.
    Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs 2008; 68: 1803–39PubMedCrossRefGoogle Scholar
  70. 70.
    Harsh JR, Easley A, LeBourgeois MK. An instrument to measure children’s sleep hygiene [abstract]. Sleep 2002; 25: A316Google Scholar
  71. 71.
    Hryshko-Mullen AS, Broeckl LS, Haddock CK, et al. Behavioral treatment of insomnia: the Wilford Hall Insomnia Program. Mil Med 2000; 165: 200–7PubMedGoogle Scholar
  72. 72.
    LeBourgeois MK, Giannotti F, Cortesi F, et al. The relationship between reported sleep quality and sleep hygiene in Italian and American adolescents. Pediatrics 2005; 115(1 Suppl. ): 257–65PubMedCrossRefGoogle Scholar
  73. 73.
    American Academy of Sleep Medicine. Sleep hygiene: the healthy habits of good sleep, 2008 [online]. Available from URL: [Accessed 2009 Dec 18]
  74. 74.
    Mastin DF, Bryson J, Corwyn R. Assessment of sleep hygiene using the Sleep Hygiene Index. J Behav Med 2006; 29: 223–7PubMedCrossRefGoogle Scholar
  75. 75.
    Jan JE, Owens JA, Weiss MD, et al. Sleep hygiene for children with neurodevelopmental disabilities. Pediatrics 2008; 122: 1343–50PubMedCrossRefGoogle Scholar
  76. 76.
    Currie SR, Wilson KG, Pontefract AJ, et al. Cognitive-behavioral treatment of insomnia secondary to chronic pain. J Consult Clin Psychol 2000; 68: 407–16PubMedCrossRefGoogle Scholar
  77. 77.
    Morawetz D. Insomnia and depression: which comes first? Sleep Res Online 2003; 5: 77–81Google Scholar
  78. 78.
    Smith MT, Huang MI, Manber R. Cognitive behavior therapy for chronic insomnia occurring within the context of medical and psychiatric disorders. Clin Psychol Rev 2005; 25: 559–92PubMedCrossRefGoogle Scholar
  79. 79.
    Efron D, Jarman F, Barker M. Side effects of methylpheni-date and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Pediatrics 1997; 100(4): 662–6PubMedCrossRefGoogle Scholar
  80. 80.
    Sikich L, Frazier JA, McClellan J, et al. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study. Am J Psychiatry 2008; 165: 1420–31PubMedCrossRefGoogle Scholar
  81. 81.
    Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009; 302: 1765–73PubMedCrossRefGoogle Scholar
  82. 82.
    Weiss M, Panagiotopoulos D, Giles L, et al. A naturalistic study of predictors and risks of atypical antipsychotic use in an attention-deficit/hyperactivity disorder clinic. J Child Adolesc Psychopharmacol 2009; 19: 575–82PubMedCrossRefGoogle Scholar
  83. 83.
    Van der Heijden KB, Smits MG, Van Someren EJ, et al. Prediction of melatonin efficacy by pretreatment dim light melatonin onset in children with idiopathic chronic sleep onset insomnia. J Sleep Res 2005; 14: 187–94PubMedCrossRefGoogle Scholar
  84. 84.
    Van der Heijden KB, Smits MG, Van Someren EJ, et al. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad Child Adolesc Psych 2007; 46: 233–41CrossRefGoogle Scholar
  85. 85.
    Corkum P, Moldofsky H, Hogg-Johnson S, et al. Sleep problems in children with attention-deficit/hyperactivity disorder: impact of subtype, comorbidity, and stimulant medication. J Am Acad Child Adolesc Psychiatry 1999; 38: 1285–93PubMedCrossRefGoogle Scholar
  86. 86.
    Hoebert M, van der Heijden KB, van Geijlswijk IM, et al. Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia. J Pineal Res 2009 Aug; 47(1): 1–7PubMedCrossRefGoogle Scholar
  87. 87.
    National Sleep Foundation. Melatonin and sleep [online]. Available from URL: [Accessed 2008 Nov 24]

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Jennifer P. Schneider
    • 1
  • Michele Matthews
    • 2
    • 3
  • Robert N. Jamison
    • 3
  1. 1.Arizona Community PhysiciansTucsonUSA
  2. 2.Massachusetts College of Pharmacy and Health SciencesBostonUSA
  3. 3.Pain Management Center, Departments of Anesthesia and PsychiatryBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  4. 4.Pain Management Center, Brigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

Personalised recommendations