Methylphenidate for the Treatment of Parkinson Disease and Other Neurological Disorders

AbstractMethylphenidate (MPH) is a central nervous system stimulant derived from an amphetamine and acts as a potent inhibitor of catecholamine reuptake and increases dopamine levels in the brain. Methylphenidate is widely used for the treatment of children and adults with attention deficit hyperactivity disorder. Because the dopaminergic system is critical to the pathological process in Parkinson disease (PD), it has been suggested that MPH, which increases dopaminergic stimulation at the postsynaptic receptor level, may provide symptomatic relief in PD patients. This article reviews those studies that have evaluated the potential of MPH to treat the motor and cognitive aspects of PD, summarizes the evidence for clinical use in other neurological diseases, and briefly reviews the physiological mechanisms whereby MPH may bring about its therapeutic effects. Methylphenidate does seem to be useful for ameliorating cognitive, affective, and motor deficits in PD and in other neurological patients; however, additional studies are needed before MPH can be routinely prescribed as an adjunct therapy in these populations.

[1]  G. Scriba.  Sean C. Sweetman (Ed.): Martindale: The Complete Drug Reference , 2011 .

[2]  J. Nutt,et al.  Methylphenidate Increases the Motor Effects of L-Dopa in Parkinson's Disease: A Pilot Study , 2001, Clinical neuropharmacology.

[3]  J. Nutt,et al.  The dopamine transporter: Importance in Parkinson's disease , 2004, Annals of neurology.

[4]  R. Mutani,et al.  Analgesic action of methylphenidate on parkinsonian sensory symptoms. Mechanisms and pathophysiological implications. , 1988, Archives of neurology.

[5]  J. Biederman,et al.  Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. , 2005, The Journal of clinical psychiatry.

[6]  Álvaro Camacho,et al.  Methylphenidate for α-interferon induced depression , 2006 .

[7]  T. Bai.  Adrenergic Agonists and Antagonists , 2009 .

[8]  A. Porta,et al.  Early Abnormalities of Vascular and Cardiac Autonomic Control in Parkinson’s Disease Without Orthostatic Hypotension , 2007, Hypertension.

[9]  F. Petty,et al.  Methylphenidate May Treat Apathy Independent of Depression , 2005, The Annals of pharmacotherapy.

[10]  M. Rappley,et al.  Clinical practice. Attention deficit-hyperactivity disorder. , 2005, The New England journal of medicine.

[11]  Treatment of ADHD in children with tics: a randomized controlled trial. , 2002, Neurology.

[12]  P. Wender,et al.  ADHD in adults. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[13]  J. Swanson,et al.  National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: 24-month outcomes of treatment strategies for attention-deficit/hyperactivity disorder. , 2004, Pediatrics.

[14]  R. Grunau,et al.  Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 Weeks' postconceptional Age. , 2001, Pediatrics.

[15]  N. Volkow,et al.  Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. , 1998, The American journal of psychiatry.

[16]  D. Segal,et al.  Effects of Methylphenidate on Extracellular Dopamine, Serotonin, and Norepinephrine: Comparison with Amphetamine , 1997, Journal of neurochemistry.

[17]  E. Bruera,et al.  Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  D. Abernethy,et al.  Pharmacokinetics and Clinical Effectiveness of Methylphenidate , 1999, Clinical pharmacokinetics.

[19]  K. Blennow,et al.  Decreased monoamine metabolites in frontotemporal dementia and Alzheimer’s disease , 1998, Neurobiology of Aging.

[20]  B. Sahakian,et al.  Effects of methylphenidate on cognition and apathy in normal pressure hydrocephalus: A case study and review , 2005, British journal of neurosurgery.

[21]  L. Friberg,et al.  The striatum in a putative cerebral network activated by verbal awareness in normals and in ADHD children , 1998, European journal of neurology.

[22]  Jeffrey M. Hausdorff,et al.  Dual tasking, gait rhythmicity, and Parkinson's disease: Which aspects of gait are attention demanding? , 2005, The European journal of neuroscience.

[23]  R. Gardner,et al.  Mattis Dementia Rating Scale: internal reliability study using a diffusely impaired population. , 1981, Journal of clinical neuropsychology.

[24]  R. Inoue,et al.  A juvenile case of frontotemporal dementia: Neurochemical and neuropathological investigations , 1995, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[25]  T. Robbins,et al.  Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia , 2006, Neuropsychopharmacology.

[26]  N. Hanna,et al.  A phase II study of methylphenidate for the treatment of fatigue , 2006, Supportive Care in Cancer.

[27]  J. Swanson,et al.  Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies. , 2003, Archives of general psychiatry.

[28]  Kiyoharu Inoue,et al.  Cardiovascular dysautonomia in de novo Parkinson's disease , 2006, Journal of the Neurological Sciences.

[29]  C. Reynolds,et al.  Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial. , 2006, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[30]  S. Faraone,et al.  Meta-Analysis of the Efficacy of Methylphenidate for Treating Adult Attention-Deficit/Hyperactivity Disorder , 2004, Journal of clinical psychopharmacology.

[31]  D. M. Feeney,et al.  Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. , 1982, Science.

[32]  Yu-Shin Ding,et al.  Therapeutic Doses of Oral Methylphenidate Significantly Increase Extracellular Dopamine in the Human Brain , 2001, The Journal of Neuroscience.

[33]  E. Bruera,et al.  Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  E. Bruera,et al.  The use of methylphenidate in patients with incident cancer pain receiving regular opiates. A preliminary report , 1992, Pain.

[35]  L. Toussaint,et al.  Methylphenidate in early poststroke recovery: a double-blind, placebo-controlled study. , 1998, Archives of physical medicine and rehabilitation.

[36]  L. Jerome.  Treatment of attention-deficit hyperactivity disorder. , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[37]  G. Uhl,et al.  Parkinsonian patients report blunted subjective effects of methylphenidate. , 1998, Experimental and clinical psychopharmacology.

[38]  D. Hill.  Comprehensive Textbook of Psychiatry , 1968 .

[39]  F. Frankel.  Hypnosis as a Treatment Method in Psychosomatic Medicine , 1975, International journal of psychiatry in medicine.

[40]  J. Biederman,et al.  A Randomized, Placebo-Controlled Trial of OROS Methylphenidate in Adults with Attention-Deficit/Hyperactivity Disorder , 2006, Biological Psychiatry.

[41]  François Chollet,et al.  Methylphenidate modulates cerebral post-stroke reorganization , 2006, NeuroImage.

[42]  Jeffrey M. Hausdorff,et al.  Gait variability and fall risk in community-living older adults: a 1-year prospective study. , 2001, Archives of physical medicine and rehabilitation.

[43]  L. Pollak,et al.  Low dose methylphenidate improves freezing in advanced Parkinson's disease during off-state. , 2007, Journal of neural transmission. Supplementum.

[44]  S. Sharfstein,et al.  ADHD drugs and cardiovascular risk. , 2006, The New England journal of medicine.

[45]  J. Rapoport,et al.  Motor/vocal tics and compulsive behaviors on stimulant drugs: Is there a common vulnerability? , 1990, Psychiatry Research.

[46]  Jeffrey M. Hausdorff,et al.  Gait in attention deficit hyperactivity disorder , 2007, Journal of Neurology.

[47]  J. Buitelaar,et al.  Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder. A randomized placebo-controlled double-blind cross-over trial , 2004, Psychological Medicine.

[48]  Karl Herholz,et al.  Predominant ventromedial frontopolar metabolic impairment in frontotemporal dementia , 2003, NeuroImage.

[49]  Jean Logan,et al.  Imaging endogenous dopamine competition with [11C]raclopride in the human brain , 1994, Synapse.

[50]  S. Blinder,et al.  Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: Positron emission tomographic studies , 2006, Movement disorders : official journal of the Movement Disorder Society.

[51]  R. Pary,et al.  Attention Deficit Disorder in Adults , 2002, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[52]  L. Defebvre,et al.  Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson’s disease , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[53]  J M Swanson,et al.  Effects of Stimulant Medication on Learning in Children with ADHD , 1991, Journal of learning disabilities.

[54]  J. Nutt,et al.  Effects of methylphenidate on response to oral levodopa: a double-blind clinical trial. , 2007, Archives of neurology.

[55]  R. Z. Fisch.  Methylphenidate for Medical In-Patients , 1986, International journal of psychiatry in medicine.

[56]  B. Pfefferbaum,et al.  The use of methylphenidate in a depressed adolescent with AIDS. , 1990, Journal of developmental and behavioral pediatrics : JDBP.

[57]  Jeffrey M. Hausdorff,et al.  Effects of Methylphenidate on Cognitive Function and Gait in Patients With Parkinson's Disease: A Pilot Study , 2006, Clinical neuropharmacology.

[58]  R. Kurlan.  Tourette’s syndrome: Are stimulants safe? , 2003, Current neurology and neuroscience reports.

[59]  J. Christensen,et al.  Methylphenidate as a treatment for depression in acquired immunodeficiency syndrome: an n-of-1 trial. , 1992, The Journal of clinical psychiatry.

[60]  G. Salmon,et al.  Attention deficit hyperactivity disorder. , 2018, British journal of hospital medicine.

[61]  Jeffrey M. Hausdorff,et al.  The role of executive function and attention in gait , 2008, Movement disorders : official journal of the Movement Disorder Society.

[62]  B. Leonard,et al.  Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects , 2004, Human psychopharmacology.

[63]  A. Chatterjee,et al.  Methylphenidate treats apathy in Parkinson's disease. , 2002, The Journal of neuropsychiatry and clinical neurosciences.

[64]  J. Biederman,et al.  Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder. , 2004, The international journal of neuropsychopharmacology.

[65]  W. Pelham,et al.  Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. , 2001, Pediatrics.