Does L-Methylfolate Supplement Methylphenidate Pharmacotherapy in Attention-Deficit/Hyperactivity Disorder?: Evidence of Lack of Benefit From a Double-Blind, Placebo-Controlled, Randomized Clinical Trial.
Administration, Oral
Adult
Attention Deficit Disorder with Hyperactivity
/ drug therapy
Autoantibodies
/ blood
Central Nervous System Stimulants
/ therapeutic use
Delayed-Action Preparations
/ therapeutic use
Diet Therapy
Dietary Supplements
Dopamine Uptake Inhibitors
/ administration & dosage
Dose-Response Relationship, Drug
Double-Blind Method
Drug Therapy, Combination
Executive Function
/ drug effects
Female
Folate Receptor 1
/ immunology
GTP Cyclohydrolase
/ genetics
Humans
Male
Methylphenidate
/ administration & dosage
Neuropsychological Tests
Pilot Projects
Tetrahydrofolates
/ adverse effects
Treatment Outcome
Young Adult
Journal
Journal of clinical psychopharmacology
ISSN: 1533-712X
Titre abrégé: J Clin Psychopharmacol
Pays: United States
ID NLM: 8109496
Informations de publication
Date de publication:
Historique:
entrez:
20
12
2018
pubmed:
20
12
2018
medline:
5
3
2019
Statut:
ppublish
Résumé
Interventions for attention-deficit/hyperactivity disorder (ADHD) may be inadequate for some patients. There is evidence that supplementation with L-methylfolate augments antidepressant agent effects and thus might also augment ADHD treatment effects by a common catecholaminergic mechanism. Forty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ADHD participated in a randomized, double-blind, placebo-controlled, 12-week trial of 15 mg of L-methylfolate in combination with osmotic-release oral system methylphenidate. Osmotic-release oral system methylphenidate was dose optimized over the first 6 weeks. We evaluated the effects on ADHD symptoms, self-report on the Behavior Rating Inventory of Executive Function of executive function, methylphenidate dosing, neuropsychological test measures, the Adult ADHD Self-report scale, emotional dysregulation, social adjustment, and work productivity, as well as moderating effects of body mass index, autoantibodies to folate receptors, and select genetic polymorphisms. L-Methylfolate was well tolerated, with no significant effect over placebo except improvement from abnormal measures on the mean adaptive dimension of the ASR scale (χ = 4.36, P = 0.04). Methylphenidate dosing was significantly higher in individuals on L-methylfolate over time (χ = 7.35, P = 0.007). Exploratory analyses suggested that variation in a guanosine triphosphate cyclohydrolase gene predicted association with higher doses of methylphenidate (P < 0.001). L-Methylfolate was associated with no change in efficacy on measures relevant to neuropsychiatric function in adults with ADHD, other than suggestion of reduced efficacy of methylphenidate. Further investigation would be required to confirm this effect and its mechanism and the genotype prediction of effects on dosing.
Sections du résumé
PURPOSE/BACKGROUND
OBJECTIVE
Interventions for attention-deficit/hyperactivity disorder (ADHD) may be inadequate for some patients. There is evidence that supplementation with L-methylfolate augments antidepressant agent effects and thus might also augment ADHD treatment effects by a common catecholaminergic mechanism.
METHODS
METHODS
Forty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ADHD participated in a randomized, double-blind, placebo-controlled, 12-week trial of 15 mg of L-methylfolate in combination with osmotic-release oral system methylphenidate. Osmotic-release oral system methylphenidate was dose optimized over the first 6 weeks. We evaluated the effects on ADHD symptoms, self-report on the Behavior Rating Inventory of Executive Function of executive function, methylphenidate dosing, neuropsychological test measures, the Adult ADHD Self-report scale, emotional dysregulation, social adjustment, and work productivity, as well as moderating effects of body mass index, autoantibodies to folate receptors, and select genetic polymorphisms.
RESULTS
RESULTS
L-Methylfolate was well tolerated, with no significant effect over placebo except improvement from abnormal measures on the mean adaptive dimension of the ASR scale (χ = 4.36, P = 0.04). Methylphenidate dosing was significantly higher in individuals on L-methylfolate over time (χ = 7.35, P = 0.007). Exploratory analyses suggested that variation in a guanosine triphosphate cyclohydrolase gene predicted association with higher doses of methylphenidate (P < 0.001).
CONCLUSIONS
CONCLUSIONS
L-Methylfolate was associated with no change in efficacy on measures relevant to neuropsychiatric function in adults with ADHD, other than suggestion of reduced efficacy of methylphenidate. Further investigation would be required to confirm this effect and its mechanism and the genotype prediction of effects on dosing.
Identifiants
pubmed: 30566416
doi: 10.1097/JCP.0000000000000990
pii: 00004714-201901000-00006
pmc: PMC6750952
mid: NIHMS1048525
doi:
Substances chimiques
Autoantibodies
0
Central Nervous System Stimulants
0
Delayed-Action Preparations
0
Dopamine Uptake Inhibitors
0
FOLR1 protein, human
0
Folate Receptor 1
0
Tetrahydrofolates
0
Methylphenidate
207ZZ9QZ49
GTP Cyclohydrolase
EC 3.5.4.16
5-methyltetrahydrofolate
TYK22LML8F
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
28-38Subventions
Organisme : NIDA NIH HHS
ID : K12 DA000357
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH118478
Pays : United States
Références
J Atten Disord. 2017 Apr;21(6):487-493
pubmed: 24994877
Neuropsychopharmacology. 2006 Nov;31(11):2376-83
pubmed: 16855530
J Reprod Immunol. 2008 Oct;79(1):85-92
pubmed: 18804286
Compr Psychiatry. 1996 Nov-Dec;37(6):393-401
pubmed: 8932963
Aging (Milano). 1993 Feb;5(1):63-71
pubmed: 8257478
J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62
pubmed: 14399272
Int J Food Sci Nutr. 2016 Nov;67(7):733-4
pubmed: 27346490
Br J Psychiatry. 2007 May;190:402-9
pubmed: 17470954
Psychol Med. 1992 Nov;22(4):871-6
pubmed: 1283223
Lancet. 1990 Aug 18;336(8712):392-5
pubmed: 1974941
Biol Psychiatry. 1999 Nov 1;46(9):1234-42
pubmed: 10560028
Am J Psychiatry. 2011 Jun;168(6):617-23
pubmed: 21498464
Am J Psychiatry. 2006 Apr;163(4):716-23
pubmed: 16585449
J Biol Chem. 1981 Sep 25;256(18):9684-92
pubmed: 6169714
Curr Drug Metab. 2012 Oct;13(8):1184-95
pubmed: 22746304
Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):365-375
pubmed: 19676101
Birth Defects Res A Clin Mol Teratol. 2016 Aug;106(8):685-95
pubmed: 27166990
Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15424-9
pubmed: 19706381
Psychiatry Res. 1994 Jul;53(1):13-29
pubmed: 7991729
Nature. 1980 Oct 30;287(5785):852-3
pubmed: 6253816
Am J Clin Nutr. 2011 Jul;94(1):322S-331S
pubmed: 21593508
J Clin Psychiatry. 2008 Sep;69(9):1352-3
pubmed: 19193337
Am J Psychiatry. 2007 Jun;164(6):942-8
pubmed: 17541055
Innov Clin Neurosci. 2011 Jan;8(1):19-28
pubmed: 21311704
J Clin Psychiatry. 2009;70 Suppl 5:12-7
pubmed: 19909688
Iran J Psychiatry. 2013 Aug;8(3):108-12
pubmed: 24454418
Child Adolesc Psychiatr Clin N Am. 2000 Jan;9(1):77-97
pubmed: 10674191
J Clin Psychiatry. 2006 Apr;67(4):524-40
pubmed: 16669717
Biol Psychiatry. 2000 Jul 1;48(1):9-20
pubmed: 10913503