eMedicine Specialties > Neurology > Pediatric Neurology

Mental Retardation: Treatment & Medication

Author: Karen H Harum, MD, Clinical Assistant Professor, Department of Pediatrics, Eastern Carolina School of Medicine; Neurodevelopmental Pediatrician, Chief Executive Officer, Clinic for Special Children, Inc
Contributor Information and Disclosures

Updated: Apr 17, 2006

Treatment

Medical Care

  • The mainstay of treatment of MR is developing a comprehensive management plan for the condition. The complex habilitation plan for the individual requires input from care providers from multiple disciplines, including special educators, language therapists, behavioral therapists, occupational therapists, and community services that provide social support and respite care for families affected by MR.
  • No treatments are available specifically for cognitive deficiency. Although the pharmacologic enhancement of cognition is an area of interest, research on such nootropic (ie, knowledge-enhancing) compounds is limited. Such drugs have not become part of the routine or even experimental clinical management of this population.

Consultations

  • Ophthalmology
  • Genetic evaluation, testing, and counseling

Diet

Nutritional supplements are of no proven benefit.

Medication

No specific pharmacologic treatment is available for cognitive impairment in the developing child or adult with MR. Medications, when prescribed, are targeted to specific comorbid psychiatric disease or behavioral disturbances.

Development of nootropic drugs that may alter cognitive processes positively has been of interest to researchers. Medications currently prescribed for dementia, such as acetylcholinesterase inhibitors, are not accepted treatments for MR, although clinical trials have not been conducted in children. Phosphodiesterase inhibitors enhance cortical plasticity in an animal model of fetal alcohol syndrome.

Although vitamin and mineral therapies have gained popularity, their efficacy has not been established in clinical trials. The use of antioxidant supplements in patients with Down syndrome is of theoretical benefit but has not yet been tested vigorously.

CNS stimulants

The most common class of drugs prescribed in this population is the psychostimulants because of the coexistence of attention deficit with or without hyperactivity disorder (ADHD/ADD) in as many as 50%. The most widely used psychostimulants are methylphenidate and dextroamphetamine, which appear to enhance dopamine and norepinephrine activity in the CNS.


Methylphenidate hydrochloride (Ritalin, Metadate ER)

Stimulates cerebral cortex and subcortical structures.

Adult

Pediatric

Dosages vary widely with no optimal dose schedule established
Recommended: 5 mg PO qd to start, titrate to tid or sustained release preparation; no known benefit of doses >60-70 mg/d

Reduces effects of guanethidine and bretylium; may increase toxicity of phenytoin, TCAs, warfarin, primidone, and phenobarbital; MAOIs increase toxicity

Documented hypersensitivity; marked anxiety and agitation; glaucoma; motor tics
Because of mild sympathomimetic cardiac effects, should be used with caution in children with congenital cardiac disease or hypertension

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Most common adverse effects are insomnia and anorexia; other adverse effects include headaches, stomachache, irritability, anxiety; "overly quiet" periods may limit titration to higher doses


Dextroamphetamine sulfate (Dexedrine) and racemic amphetamine (Adderall)

Increase amount of circulating dopamine and norepinephrine in cerebral cortex by blocking reuptake of norepinephrine or dopamine from synapse.

Adult

Pediatric

5 mg/d PO initially and titrate to tid; no benefit to doses >30-40 mg/d; required doses may actually be less in child with MR

MAOIs may precipitate hypertensive crisis and, with anesthetics, may precipitate arrhythmias; may increase toxicity of phenobarbital, propoxyphene, meperidine, TCAs, phenytoin, and norepinephrine

Documented hypersensitivity; hypertension; MAOIs; advanced arteriosclerosis; hyperthyroidism; glaucoma

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in angina, glaucoma, cardiovascular disease, and psychopathic personalities

Antidepressants

These agents may be used when ADHD is comorbid with depression.


Bupropion (Wellbutrin, Zyban)

Aminoketone that primarily blocks neuronal dopamine uptake and is modestly effective for ADHD symptoms.

Adult

Pediatric

Not established; 75 mg PO qd to start and titrate up to 300 mg/d divided tid; long-acting preparations are available

Carbamazepine, cimetidine, phenytoin, and phenobarbital may decrease effects; levodopa and MAOIs increase toxicity

Documented hypersensitivity; seizure disorder; anorexia nervosa; concurrent MAOIs

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Slightly increased rate of seizures (0.4%); few adverse cardiovascular effects; adverse effects include agitation, insomnia, psychosis, and anorexia; efficacy may not be apparent before 4 wk of therapy

Alpha-adrenergic agonists

These agents are used commonly to modulate hyperactivity, aggression, tics, and dyssomnias.


Clonidine hydrochloride (Catapres)

Agonist at presynaptic alpha2-adrenergic receptors within brain stem. Clonidine reduces norepinephrine release at these sites, reducing sympathetic outflow and enhancing parasympathetic outflow. May reduce aggression by increasing release of GABA in frontal cortex and other brain regions.

Adult

Pediatric

ADHD and Tourette disorder: 3-6 mcg/kg/d PO qhs or divided qid; initial dose typically 0.05 mg PO qhs; transdermal patches are available, although contact dermatitis reported in as many as 40%

Sedating drugs may cause untoward CNS depression; carbamazepine, cimetidine, phenytoin, and phenobarbital may decrease effects; levodopa and MAOIs may increase toxicity

Documented hypersensitivity; conduction disturbances; chronic renal failure; seizure disorder; anorexia nervosa; concurrent MAOIs

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Adverse effects include sedation, dry mouth, constipation, dizziness, fatigue, syncope, and dysrhythmias; must be tapered to discontinue over several days and never stopped abruptly


Guanfacine (Tenex)

Presynaptic alpha2-adrenergic receptor agonist that stimulates alpha2-adrenergic receptors in brain stem, activating an inhibitory neuron, which in turn decreases vasomotor tone and heart rate. Similar reduction in potentially negative impact on academic performance and cognitive function.

Adult

Pediatric

Not established; usually prescribed as 0.5-1 mg PO qhs and titrated to bid/tid

Increases effect of other hypotensive agents; TCAs may decrease hypotensive effects

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Caution in hepatic impairment, severe coronary insufficiency, recent myocardial infarction

Neuroleptic drugs (antipsychotics)

The neuroleptic drugs are the most frequently prescribed agents for aggression, self-injury, and hyperactivity in people with MR. Increasingly, they are more likely to be reserved for the older child or adult in whom intensive behavioral intervention has failed. Likewise, the prevalence of comorbid psychiatric disorders in MR increases with age. Neuroleptics interact with receptors for a variety of brain neurotransmitters, including dopamine, serotonin, acetylcholine, histamine, and norepinephrine. Their ability to antagonize dopamine receptors appears to correlate well with the efficacy of these drugs and imparts their antipsychotic properties. Likewise, antidopaminergic activity evokes extrapyramidal symptoms. Rarely, neuroleptic malignant syndrome may occur.


Risperidone (Risperdal)

Atypical antipsychotic with fewer adverse neurologic effects and less propensity for extrapyramidal movements (eg, pseudoparkinsonism, akathisia, acute dystonias, tardive dyskinesia).

Adult

Pediatric

Not well established; titrate from initial dose of 0.5 mg PO bid

Carbamazepine may decrease effects; may inhibit effects of levodopa; clozapine may increase levels

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Adverse effects include sedation, orthostatic hypotension, dysphagia, hyperprolactinemia, hyperkinesia, nausea, impaired learning, extrapyramidal movements; upon discontinuation, "withdrawal" disorder may occur and is not always prevented by slow taper


Haloperidol (Haldol)

DOC for acute psychosis when no contraindications. Haloperidol and droperidol are of butyrophenone class and are noted for high potency and low potential for causing orthostasis. Downside is high potential for EPS/dystonia.

Adult

Pediatric

0.5-6 mg/d total; titration can begin as 0.5 mg PO qd; increase by 0.5 mg PO q5-7d; not to exceed 0.15 mg/kg/d or 6 mg/d PO divided bid/tid

May increase TCA serum concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects; anticholinergics may increase intraocular pressure; lithium may cause encephalopathy-like syndrome

Documented hypersensitivity; narrow-angle glaucoma; bone marrow suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Severe neurotoxicity manifesting as rigidity or inability to walk or talk may occur in patients with thyrotoxicosis also receiving antipsychotics; if IV/IM, watch for hypotension; caution in diagnosed CNS depression or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue drug if it occurs)


Aripiprazole (Abilify)

A newer atypical antipsychotic, aripiprazole is indicated in acute bipolar mania and schizophrenia.

Adult

10-15 mg PO qd; if needed, may increase dose gradually q2wk, not to exceed 30 mg/d

Pediatric

Not established

CYP450 3A4 and 2D6 isoenzyme substrate, thus, inhibitors (ie, ketoconazole, quinidine, fluoxetine, paroxetine) or inducers (ie, carbamazepine) may increase or decrease serum levels, respectively

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Common adverse effects include headache, anxiety, somnolence, or insomnia; rare reports of tardive dyskinesia and neuroleptic malignant syndrome; may cause orthostatic hypotension, seizure, dysphagia, or suicidal ideation; hyperglycemia may occur and in some cases be extreme, resulting in ketoacidosis, hyperosmolar coma, or death

More on Mental Retardation

Overview: Mental Retardation
Differential Diagnoses & Workup: Mental Retardation
Treatment & Medication: Mental Retardation
Follow-up: Mental Retardation
References

References

  1. Ahn KJ, Jeong HK, Choi HS. DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis. Jan 30 2006;[Medline].

  2. Amir RE, Van den Veyver IB, Wan M. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- CpG-binding protein 2. Nat Genet. Oct 1999;23(2):185-8. [Medline].

  3. Autti-Ramo I, Fagerlund A, Ervalahti N. Fetal alcohol spectrum disorders in Finland: Clinical delineation of 77 older children and adolescents. Am J Med Genet A. Jan 15 2006;140(2):137-43. [Medline].

  4. Capute AJ, Accardo PJ. Developmental Disabilities in Infancy and Childhood. Vol 1 and 2. Baltimore: Paul H Brookes;1996: 1-619 and 1-521.

  5. Doheny KF, McDermid HE, Harum K. Cryptic terminal rearrangement of chromosome 22q13.32 detected by FISH in two unrelated patients. J Med Genet. Aug 1997;34(8):640-4. [Medline].

  6. Flint J, Wilkie AO, Buckle VJ. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. Feb 1995;9(2):132-40. [Medline].

  7. Greenberg F, Lewis RA, Potocki L. Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2). Am J Med Genet. Mar 29 1996;62(3):247-54. [Medline].

  8. Gripp KW, Lin AE, Stabley DL. HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. Am J Med Genet A. Jan 1 2006;140(1):1-7. [Medline].

  9. Kaufmann WE, Abrams MT, Chen W. Genotype, molecular phenotype, and cognitive phenotype: correlations in fragile X syndrome. Am J Med Genet. Apr 2 1999;83(4):286-95. [Medline].

  10. Kirchhoff M, Gerdes T, Brunebjerg S. Investigation of patients with mental retardation and dysmorphic features using comparative genomic hybridization and subtelomeric multiplex ligation dependent probe amplification. Am J Med Genet A. Dec 15 2005;139(3):231-3. [Medline].

  11. Mao R, Wang X, Spitznagel EL. Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart. Genome Biol. 2005;6(13):R107. [Medline][Full Text].

  12. Medina AE, Krahe TE, Ramoa AS. Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a model of fetal alcohol exposure. J Neurosci. Jan 18 2006;26(3):1057-60. [Medline].

  13. Miyake N, Shimokawa O, Harada N. BAC array CGH reveals genomic aberrations in idiopathic mental retardation. Am J Med Genet A. Feb 1 2006;140(3):205-11. [Medline].

  14. Reiss S, Aman MG. Psychotropic Medications and Developmental Disabilities: The International Consensus Handbook. The Ohio State University Nisonger Center. 1998;1-355.

  15. Richardson SA, Koller H. Twenty-Two Years. Cambridge, MA: Harvard University Press. 1996;1-328.

  16. Tassabehji M, Metcalfe K, Fergusson WD. LIM-kinase deleted in Williams syndrome [letter]. Nat Genet. Jul 1996;13(3):272-3. [Medline].

  17. Volkmar FR, Lewis M. Mental Retardation: Child and Adolescent Psychiatric Clinics of North America. Philadelphia: WB Saunders Company. 1996;5:769-993.

Further Reading

Keywords

cognitive impairment, intelligence quotient, IQ less than 70, learning disability, Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Smith-Magenis syndrome, CATCH 22 (22q11 deletion) syndrome, DiGeorge syndrome, velocardiofacial syndrome, Williams syndrome, Wolf-Hirschhorn syndrome, Langer-Giedion syndrome, Miller-Dieker syndrome, tuberous sclerosis, Rubinstein-Taybi syndrome, Coffin-Lowry syndrome, Rett syndrome, Smith-Lemli-Opitz syndrome, fetal alcohol syndrome, fetal alcohol effects, cretinism, congenital hypothyroidism, congenital cytomegalovirus, congenital rubella, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, traumatic brain injury, shaken baby syndrome, meningitis

Contributor Information and Disclosures

Author

Karen H Harum, MD, Clinical Assistant Professor, Department of Pediatrics, Eastern Carolina School of Medicine; Neurodevelopmental Pediatrician, Chief Executive Officer, Clinic for Special Children, Inc
Karen H Harum, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Association on Mental Retardation, and Child Neurology Society
Disclosure: Nothing to disclose.

Medical Editor

Beth A Pletcher, MD, Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey
Beth A Pletcher, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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