PMID- 37770309
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240416
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 45
IP  - 12
DP  - 2023 Dec
TI  - Adverse Events During Dosing of Delayed-release/Extended-release Methylphenidate: 
      Learnings From the Open-label Phase of a Registration Trial and a Real-world 
      Postmarketing Surveillance Program.
PG  - 1212-1221
LID - S0149-2918(23)00354-5 [pii]
LID - 10.1016/j.clinthera.2023.09.009 [doi]
AB  - PURPOSE: Delayed-release/extended-release methylphenidate (DR/ER-MPH) (formerly 
      HLD200) is an evening-dosed agent used for the treatment of 
      attention-deficit/hyperactivity disorder. Postmarketing surveillance data from 
      approximately 74,000 patients exposed to DR/ER-MPH (up to June 17, 2022) were 
      reported and compared with the open-label, treatment-optimization phase of a 
      Phase III clinical trial to derive possible learnings on how to approach adverse 
      events (AEs) that emerge during dose titration. METHODS: An analysis of AEs 
      spontaneously reported to Ironshore in postmarketing surveillance included, where 
      available, age, dose, timing, and discontinuations. Data were summarized using 
      descriptive statistics. FINDINGS: A total of 395 children, adolescents, and 
      adults reported 601 AEs in postmarketing surveillance. Five AEs were classified 
      as serious. AEs preceded drug use discontinuation in 172 patients. Many AEs 
      occurred early (52% were reported within 30 days) and at lower doses (54% were 
      reported at 20 to 40 mg), similar to the trial data. Reported AEs included those 
      similar in type but orders of magnitude lower in number than those from the 
      clinical trial. IMPLICATIONS: No new safety concerns were revealed in this 
      real-world setting compared with the safety profile identified in DR/ER-MPH trial 
      data. In real-world practices, clinicians tended to discontinue DR/ER-MPH 
      treatment after AE onset, whereas trial investigators continued to optimize 
      treatment and found that AEs were generally tolerable, suggesting that health 
      care practitioners may consider developing strategies to manage tolerability 
      issues with DR/ER-MPH treatment on AE emergence rather than immediately 
      discontinuing use of the drug to provide optimal therapeutic benefit. 
      CLINICALTRIALS: gov identifier: NCT02493777.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Katzman, Martin A
AU  - Katzman MA
AD  - S.T.A.R.T. Clinic for Mood and Anxiety Disorders, Toronto, Ontario, Canada; 
      Northern Ontario School of Medicine, Sudbury, Ontario, Canada; Lakehead 
      University, Thunder Bay, Ontario, Canada; Adler Graduate Professional School, 
      Toronto, Ontario, Canada. Electronic address: mkatzman@startclinic.ca.
FAU - Otcheretko, Victor
AU  - Otcheretko V
AD  - Ironshore, Grand Cayman, Cayman Islands.
FAU - Po, Michelle D
AU  - Po MD
AD  - Ironshore, Grand Cayman, Cayman Islands.
FAU - Uchida, Cassandra L
AU  - Uchida CL
AD  - Ironshore, Grand Cayman, Cayman Islands.
FAU - Incledon, Bev
AU  - Incledon B
AD  - Ironshore, Grand Cayman, Cayman Islands.
LA  - eng
SI  - ClinicalTrials.gov/NCT02493777
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230927
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 207ZZ9QZ49 (Methylphenidate)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Delayed-Action Preparations)
SB  - IM
MH  - Adult
MH  - Child
MH  - Adolescent
MH  - Humans
MH  - *Methylphenidate
MH  - *Central Nervous System Stimulants
MH  - Delayed-Action Preparations/adverse effects
MH  - *Attention Deficit Disorder with Hyperactivity/drug therapy
MH  - Administration, Oral
MH  - Treatment Outcome
MH  - Double-Blind Method
OTO - NOTNLM
OT  - Adverse events
OT  - Attention-deficit/hyperactivity disorder
OT  - Methylphenidate
OT  - Postmarketing surveillance
COIS- Declaration of Competing Interest M.A.K. is a speaker and/or adviser for Abbvie, 
      Alefia Cannabis, Allergan, Bausch Health, Biron, Canopy, Eisai, Elvium, Lundbeck, 
      Janssen, Eli Lilly, Novartis, Merck, Otsuka, Pfizer, Purdue, Sante Cannabis, 
      Sunovion, Takeda, and Tilray. He has also supported clinical trials and/or 
      research studies for Abbvie, Alefia, Biron, Canopy, Lundbeck, Janssen, Eli Lilly, 
      Pfizer, and Takeda. M.A.K. did not receive remuneration for authoring this 
      manuscript, and he is not a consultant nor has he received research funding from 
      Ironshore. V.O., M.D.P., C.L.U., and B.I. are employees of Ironshore. The authors 
      have indicated that they have no other conflicts of interest regarding the 
      content of this article.
EDAT- 2023/09/29 00:42
MHDA- 2023/12/17 09:44
CRDT- 2023/09/28 21:54
PHST- 2023/07/27 00:00 [received]
PHST- 2023/09/06 00:00 [revised]
PHST- 2023/09/11 00:00 [accepted]
PHST- 2023/12/17 09:44 [medline]
PHST- 2023/09/29 00:42 [pubmed]
PHST- 2023/09/28 21:54 [entrez]
AID - S0149-2918(23)00354-5 [pii]
AID - 10.1016/j.clinthera.2023.09.009 [doi]
PST - ppublish
SO  - Clin Ther. 2023 Dec;45(12):1212-1221. doi: 10.1016/j.clinthera.2023.09.009. Epub 
      2023 Sep 27.