Skip to main content

Advertisement

Log in

Long-term changes in management following n-of-1 trials of stimulants in attention-deficit/hyperactivity disorder

  • Clinical Trial
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

Our objective was to evaluate the long-term impact of n-of-1 trials—within-patient randomised, double-blind, cross-over comparisons of stimulant versus placebo or stimulant—on ADHD management.

Methods

Telephone surveys at 3, 6 and 12 months. Main outcome measures included (1) changes in treatment before and after the n-of-1 trial, (2) congruence of management at follow-up with trial result, (3) reasons for any non-congruence, and (4) persistence of the joint patient-doctor decision over 12 months. Patients were children with clinically diagnosed ADHD, aged 5–16 years.

Results

A total of 76 patients were followed up; 12 months’ data were available for 67 (88%). Management changed from baseline for 46, 48 and 51% at 3, 6 and 12 months respectively. Most responders, 21/37 (57%), remained on the same stimulant at 12 months, compared to 9/24 (37%) non-responders. Of the remaining non-responders, 15/24 (62%) either switched (2/24, 8%) or ceased stimulants (13/24, 54%). The rate of congruence with the test result was 45/65 (69%) at 3 months, 44/67 (66%) at 6 months and 40/67 (60%) at 12 months. Persistence with the post-trial decision over 12 months was high (79–85%) whether the decision was to continue or to cease stimulants.

Conclusions

Although not conclusive because there was no control group, our results suggest that n-of-1 trials may improve rational treatment of ADHD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sawyer MG, Rey JM, Graetz BW, Clark JJ, Baghurst PA (2002) Use of medication by young people with attention-deficit/hyperactivity disorder. Med J Aust 177:21–25

    PubMed  Google Scholar 

  2. Spencer T, Biederman J, Wilens T, Harding M, O’Donnell D, Griffin S (1996) Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad Child Adolesc Psych 35:409–432

    Article  CAS  Google Scholar 

  3. Nikles J, Mitchell G, Del Mar C, Clavarino A, McNairn N (2006) An n-of-1 trial service in clinical practice: testing the effectiveness of stimulants for attention-deficit/hyperactivity disorder. Pediatrics 117(6):2040–2046

    Article  PubMed  Google Scholar 

  4. Duggan CM, Mitchell G, Nikles CJ, Glasziou PP, Del Mar CB, Clavarino A (2000) Managing ADHD in general practice: N of 1 trials can help! Aust Fam Physician 29:1205–1209

    PubMed  CAS  Google Scholar 

  5. Barbaresi WJ (1996) Primary care approach to the diagnosis and management of attention-deficit/hyperactivity disorder. Mayo Clinic Proc 71:463–471

    Article  PubMed  CAS  Google Scholar 

  6. Hale JB, Hoeppner JA, DeWitt MB, Coury DL, Ritacco DG, Trommer B (1998) Evaluating medication response in ADHD: cognitive, behavioural, and single-subject methodology. J Learn Disabil 31:595–607

    PubMed  CAS  Google Scholar 

  7. Kamien M (1998) The use of an N-of-1 randomised clinical trial in resolving therapeutic doubt. Aust Fam Physician 27:S103–105

    PubMed  Google Scholar 

  8. Kent MA, Camfield CS, Camfield PR (1999) Double-blind methylphenidate trials: practical, useful and endorsed by families. Arch Pediatr Adolesc Med 153:1292–1296

    PubMed  CAS  Google Scholar 

  9. McBride MC (1988) An individual double-blind crossover trial for assessing methylphenidate response in children with attention-deficit/hyperactivity disorder. J Pediatr 113:137–145

    Article  PubMed  CAS  Google Scholar 

  10. Van Reekum R, Links PS (1994) N-of-1 study: methylphenidate in a patient with borderline personality disorder and attention-deficit/hyperactivity disorder. Can J Psychiatr 39:186–187

    Google Scholar 

  11. Varley CK, Trupin EW (1983) Double-blind assessment of stimulant medication for attention deficit disorder: a model for clinical application. Am J Orthopsychiatr 53:542–547

    Article  CAS  Google Scholar 

  12. Bussing R, Zima BT, Mason D, Hou W, Garvan CW, Forness S (2005) Use and persistence of pharmacotherapy for elementary school students with attention-deficit/hyperactivity disorder. Am J Orthopsychiatr 15:78–87

    Google Scholar 

  13. Sanchez RJ, Crismon ML, Barner JC, Bettinger T, Wilson JP (2005) Assessment of adherence measures with different stimulants among children and adolescents. Pharmacotherapy 25:909–917

    Article  PubMed  Google Scholar 

  14. Clowes JA, Peel NF, Eastell R (2004) The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89:1117–1123

    Article  PubMed  CAS  Google Scholar 

  15. Firestone P (1982) Factors associated with children’s adherence to stimulant medication. Am J Orthopsychiatr 52:447–457

    Article  CAS  Google Scholar 

  16. Thiruchelvam D, Charach A, Schachar RJ (2001) Moderators and mediators of long-term adherence to stimulant treatment in children with ADHD. J Am Acad Child Adolesc Psych 40:922–928

    Article  CAS  Google Scholar 

  17. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th. edn. American Psychiatric Association, Arlington, VA

    Google Scholar 

  18. Conners CK, Sitarenios G, Parker JD, Epstein JN (1998a) The revised Conners’ Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity. J Abnorm Child Psychol 26(4):257–268

    Article  CAS  Google Scholar 

  19. Conners CK, Sitarenios G, Parker JDA, Epstein JN (1998b) Revision and restandardisation of the Conners Teacher Rating Scale (CTRS-R): factor structure, reliability, and criterion validity. J Abnorm Child Psychol 26:279–291

    Article  CAS  Google Scholar 

  20. Conners CK, Wells KC, Parker JD, Sitarenios G, Diamond JM, Powell JW (1997) A new self-report scale for assessment of adolescent psychopathology: factor structure, reliability, validity, and diagnostic sensitivity. J Abnorm Child Psychol 25(6):487–497

    Article  PubMed  CAS  Google Scholar 

  21. DuPaul GJ (1998) ADHD rating scale-IV: checklists, norms, and clinical interpretation. Guilford, New York

    Google Scholar 

  22. McQuay HJ, Carroll D, Jadad AR, Glynn CJ, Jack T, Moore RA, Wiffeh PJ (1994) Dextromorphan for the treatment of neuropathic pain: a double-blind randomised controlled crossover trial with integral n-of-1 design. Pain 59:127–133

    Article  PubMed  CAS  Google Scholar 

  23. Patel A, Jaeschke R, Guyatt GH, Keller JL, Newhouse MT (1991) Clinical usefulness of n-of-1 randomized controlled trials in patients with non-reversible chronic airflow limitation. Am Rev Respir Dis 144:962–964

    PubMed  CAS  Google Scholar 

  24. Pope JE, Prashker M, Anderson J (2004) The efficacy and cost effectiveness of N of 1 studies with diclofenac compared to standard treatment with nonsteroidal antiinflammatory drugs in osteoarthritis. J Rheumatol 31:40–9

    Google Scholar 

  25. Wegman AC, van der Windt DA, de Haan M, Deville WL, Fo CT, de Vries TP (2003) Switching from NSAIDs to paracetamol: a series of n of 1 trials for individual patients with osteoarthritis. Ann Rheumatic Dis 62:1156–1161

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Thanks to the General Practice Evaluation Program, the Department of Health and Aged Care, Queensland Medical Laboratory (QML) and the Royal Australian College of General Practitioners for funding; QML and Mater Misericordiae Health Services, Brisbane, for delivering the service; Paul Glasziou for the initial concept; Cate Duggan, Tina Janamian, Peter Coxeter, Kate Del Mar, Sharyn Herzig, Julie King, Jacob Carter, Donna-Marie Preston, Robyn Brown, Brenda Rosser, and Grace McBride for research assistance; and the participants. Jane Nikles held a National Health and Medical Research Council Scholarship 210364.

Disclosure

The authors have no financial relationships to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. Jane Nikles.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nikles, C.J., Mitchell, G.K., Del Mar, C.B. et al. Long-term changes in management following n-of-1 trials of stimulants in attention-deficit/hyperactivity disorder. Eur J Clin Pharmacol 63, 985–989 (2007). https://doi.org/10.1007/s00228-007-0361-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-007-0361-x

Keywords

Navigation