Savvy Psychopharmacology

High-dose stimulants for adult ADHD

Current Psychiatry. 2023 June;22(6):34-39 | doi: 10.12788/cp.0366

References

1. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006;163(4):716-723. doi:10.1176/ajp.2006.163.4.716

2. Sibley MH, Arnold LE, Swanson JM, et al. Variable patterns of remission from ADHD in the multimodal treatment study of ADHD. Am J Psychiatry. 2022;179(2):142-151. doi:10.1176/appi.ajp.2021.21010032

3. Cleveland KW, Boyle J, Robinson RF. Attention-deficit/hyperactivity disorder. In: Chisholm-Burns MA, Schwinghammer TL, Malone PM, et al, eds. Pharmacotherapy Principles & Practice. 6th ed. McGraw Hill; 2022. Accessed December 1, 2022. https://ppp.mhmedical.com/content.aspx?bookid=3114&sectionid=261474885

4. Steingard R, Taskiran S, Connor DF, et al. New formulations of stimulants: an update for clinicians. J Child Adolesc Psychopharmacol. 2019;29(5):324-339. doi:10.1089/cap.2019.0043

5. Faraone SV. The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018;87:255-270. doi:10.1016/j.neubiorev.2018.02.001

6. Markowitz JS, Patrick KS. The clinical pharmacokinetics of amphetamines utilized in the treatment of attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2017;27(8):678-689. doi:10.1089/cap.2017.0071

7. Mullen S. Medication Table 2: Attention Deficit Hyperactivity Disorder. In: English C, ed. CPNP Psychiatric Pharmacotherapy Review Course. 2022-2023 ed. College of Psychiatric and Neurologic Pharmacists; 2022.

8. Zhu HJ, Patrick KS, Yuan HJ, et al. Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. Am J Hum Genet. 2008;82(6):1241-1248. doi:10.1016/j.ajhg.2008.04.015

9. Xelstrym [package insert]. Miami, FL: Noven Pharmaceuticals, Inc.; 2022.

10. Padwal R, Brocks D, Sharma AM. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev. 2010;11(1):41-50. doi:10.1111/j.1467-789X.2009.00614.x

11. Childress AC, Komolova M, Sallee FR. An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations. Expert Opin Drug Metab Toxicol. 2019;15(11):937-974. doi:10.1080/17425255.2019.1675636

12. Markowitz JS, Melchert PW. The pharmacokinetics and pharmacogenomics of psychostimulants. Child Adolesc Psychiatr Clin N Am. 2022;31(3):393-416. doi:10.1016/j.chc.2022.03.003

13. Seaman JS, Bowers SP, Dixon P, et al. Dissolution of common psychiatric medications in a Roux-en-Y gastric bypass model. Psychosomatics. 2005;46(3):250-253. doi:10.1176/appi.psy.46.3.250

14. Ludvigsson M, Haenni A. Methylphenidate toxicity after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2016;12(5):e55-e57. doi:10.1016/j.soard.2016.03.015

15. Azran C, Langguth P, Dahan A. Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2017;13(7):1245-1247. doi:10.1016/j.soard.2017.03.003

16. Steffen KJ, Mohammad AS, Roerig JL, et al. Lisdexamfetamine pharmacokinetic comparison between patients who underwent Roux-en-Y gastric bypass and nonsurgical controls. Obes Surg. 2021;31(10):4289-4294. doi:10.1007/s11695-020-04969-4

17. Buxton ILO. Pharmacokinetics: the dynamics of drug absorption, distribution, metabolism, and elimination. In: Brunton LL, Knollmann BC, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. 14th ed. McGraw Hill; 2023. Accessed December 1, 2022. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2189&sectionid=166182905

18. DeMarco R, Rana R, Powell K, et al. How bariatric surgery affects psychotropic drug absorption. Current Psychiatry. 2022;21(8):39-44. doi:10.12788/cp.0271

Impaired medication absorption after bariatric surgery

Medication malabsorption following bariatric surgery is a significant concern. In a systematic review of 22 studies, Padwal et al¹⁰ found that in one-third of these studies, decreased absorption following bariatric surgery may be present in patients taking medications that have poor absorption, high lipophilicity, or enterohepatic recirculation. Childress et al¹¹ found that methylphenidate IR and dextroamphetamine/amphetamine are both well absorbed, with bioavailability percentages of 100% and 90%, respectively. Additional research shows both stimulants have rapid absorption rates but relatively poor bioavailability.¹² In one study analyzing the dissolution of common psychiatric medications, methylphenidate was shown to dissolve slightly more in the Roux-en-Y gastric bypass surgery model (80 mg) compared to controls (70 mg).¹³ One case indicated potential methylphenidate toxicity following Roux-en-Y gastric bypass surgery,¹⁴ while another suggested impaired absorption following the same procedure.¹⁵ A case-control design study assessing the impact of Roux-en-Y gastric bypass surgery on the pharmacokinetic properties of lisdexamfetamine found no significant differences between the Roux-en-Y group (n = 10) and nonsurgical controls (n = 10). The investigators concluded that while data suggest adjusting lisdexamfetamine dosing following Roux-en-Y gastric bypass surgery is unnecessary, there may be interindividual differences, and individualized dosing regimens may be needed.¹⁶

When managing patients who might be experiencing medication malabsorption, it may be helpful to use dosage forms that avoid disintegration, acidic environments, and slow dissolution. Because they are more rapidly absorbed and not susceptible to disintegration and dissolution, liquid formulations are recommended.¹⁷ For medications that are not available as a liquid, an IR formulation is recommended.¹⁸

Using nonoral routes of administration that avoid the anatomical changes of the gastrointestinal tract should be considered for patients who have undergone Roux-en-Y gastric bypass surgery.¹⁷ The methylphenidate transdermal patch, a medication delivery system that avoids gut and hepatic first-pass metabolism, can improve medication bioavailability, reduce dose frequency, and stabilize medication delivery. It is available in 4 sizes/dosages: 10 mg/9 hours, 15 mg/9 hours, 20 mg/9 hours, and 30 mg/9 hours. Methylphenidate is delivered at a steady rate based upon patch size. The onset of action of the patch is approximately 2 hours, and patients should wear the patch for 9 hours, then remove it. Methylphenidate will still be absorbed up to 2 to 3 hours after patch removal. Appropriate application and removal of the patch is important for optimal effectiveness and to avoid adverse effects.⁴

In March 2022, the FDA approved a dextroamphetamine transdermal patch.⁹ It is available in 4 sizes/dosages: 4.5 mg/9 hours, 9 mg/9 hours, 13.5 mg/9 hours, and 18 mg/9 hours.⁹ Like the methylphenidate transdermal patch, the onset of action is approximately 2 hours, and it is recommended that patients wear it for 9 hours.⁹

CASE CONTINUED

Ms. H emphasizes her desire to maintain functionality in all areas of life, while her care team reiterates the risks of continuing to take high-dose stimulants. Both Ms. H and her care team acknowledge that stimulant usage could be worsening her anxiety, and that Roux-en-Y gastric bypass surgery may be a possible explanation for her dosing challenges.

Continue to: Following consultation with the pharmacist...

References

4. Steingard R, Taskiran S, Connor DF, et al. New formulations of stimulants: an update for clinicians. J Child Adolesc Psychopharmacol. 2019;29(5):324-339. doi:10.1089/cap.2019.0043

9. Xelstrym [package insert]. Miami, FL: Noven Pharmaceuticals, Inc.; 2022.

12. Markowitz JS, Melchert PW. The pharmacokinetics and pharmacogenomics of psychostimulants. Child Adolesc Psychiatr Clin N Am. 2022;31(3):393-416. doi:10.1016/j.chc.2022.03.003

13. Seaman JS, Bowers SP, Dixon P, et al. Dissolution of common psychiatric medications in a Roux-en-Y gastric bypass model. Psychosomatics. 2005;46(3):250-253. doi:10.1176/appi.psy.46.3.250

14. Ludvigsson M, Haenni A. Methylphenidate toxicity after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2016;12(5):e55-e57. doi:10.1016/j.soard.2016.03.015

15. Azran C, Langguth P, Dahan A. Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2017;13(7):1245-1247. doi:10.1016/j.soard.2017.03.003

18. DeMarco R, Rana R, Powell K, et al. How bariatric surgery affects psychotropic drug absorption. Current Psychiatry. 2022;21(8):39-44. doi:10.12788/cp.0271

High-dose stimulants for adult ADHD

References

Impaired medication absorption after bariatric surgery

CASE CONTINUED

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