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Methylphenidate

Methylphenidate

Definition

Methylphenidate is a mild, central nervous system stimulant. In the United States, the drug is sold under the brand name Ritalin.

Purpose

Methylphenidate is used primarily in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults. It also may be used to treat the sleep disorder, narcolepsy . In rare cases, it is used to decrease sedation and lethargy from opioid pain medications and to help improve the mood of a terminally ill person suffering from depression.

Description

The mode of action for methylphenidate is not fully understood. It presumably activates the brain stem arousal system and cortex to produce a stimulant effect. The brain stem arousal system increases levels of electrical activity in the brain. The effect of methylphenidate is to produce increased alertness and, although children with ADHD are overactive and have decreased attention spans, in these children, methylphenidate actually decreases motor restlessness and increases attention span. Tablets are available in 5-, 10-, and 20-mg strengths, as well as in an extended release, 20-mg tablet.

Recommended dosage

The recommended dosage of methylphenidate is determined by trial and error based on individual responses. Methylphenidate is usually administered in two or three separate doses each day, preferably 45 minutes before a meal. For children suffering from ADHD, the initial recommended dosage is 5 mg twice daily before breakfast and lunch, increased by 510 mg per week to a maximum of 60 mg per day. The average total dosage is 2030 mg per day, although 1060 mg is not uncommon. For narcolepsy in adults, the recommended dose is 520 mg two to three times a day, 3045 minutes before meals.

The drug should be taken exactly as directed. Methylphenidate can become habit forming if taken in greater amounts or for longer periods than necessary. Individuals should take the last dose of the day before 6 P.M. to decrease sleep difficulties. The tablet should not be broken or crushed, as this changes the time for absorption. If the normal time of administration is missed, people should take the drug as soon as possible. However, two tablets should not be taken at the same time.

Precautions

Methylphenidate has a great potential to produce physical and mental dependence. Administration should not be stopped abruptly. Such action can cause withdrawal symptoms including depression, paranoid feelings, thoughts of suicide , anxiety, agitation, and sleep disturbances. Methylphenidate should not be given to people with extreme anxiety, tension, agitation, severe depression, mental or emotional instability, or a history of alcohol or drug abuse. It is not indicated for use by those with Tourette's syndrome, people with tic disorders , glaucoma, or certain mental health conditions. The drug should be used cautiously by those with high blood pressure, those with a history of seizures , and women who are breast-feeding. Methylphenidate is not typically ordered for women during their childbearing years, unless the physician determines that the benefits outweigh the risks.

Methylphenidate should not be ordered for children younger than six years of age as its safety has not been determined in this age group. People should not drive or operate machinery or appliances until they understand how this drug affects them. They should not drive if they become lightheaded or dizzy. Methylphenidate may cause irregularities in the composition of the blood and produce changes in liver function. People taking methylphenidate should receive regular blood tests.

Side effects

The most common side effects are nervousness, difficulties with sleep, tachycardia, and increased blood pressure. Reducing the dose or changing the time the drug is taken may reduce some side effects. Affected persons should discuss any adverse reactions with their health care professional. Individuals taking methylphenidate should receive regular blood pressure and pulse checks. Methylphenidate also may cause dizziness, irritability, vision changes, drowsiness, and a poor appetite. Less common side effects include chest pain, palpitations, joint pain, skin rash, and uncontrolled movements or speech. Side effects may also include a rapid or irregular heartbeat, stomach upset, nausea, headache, blood in the urine or stools, muscle cramps, red dots on the skin, or bruises. At higher dosages or with long-term use, people may experience weight loss or mental changes such as confusion, false beliefs, mood changes, hallucinations , or feelings that they or their environment are not real.

Interactions

Several drugs may interact adversely with methylphenidate, including anticoagulants and drugs to prevent seizures, combat depression, and treat high blood pressure. The dosages of these drugs may be reduced when taken simultaneously with methylphenidate.

Resources

BOOKS

Adams, Michael and Norman Holland. Core Concepts in Pharmacology. Philadelphia: Lippincott-Raven, 1998.

Breggin, Peter R. and Dick Scruggs. Talking Back to Ritalin: What Doctors Aren't Telling You About Stimulants and ADHD. Boulder, CO: Perseus Book Group, 2001.

Foreman, John C. and Torben Johansen. Textbook of Receptor Pharmacology. 2nd Ed. Boca Raton, FL: CRC Press,2002.

Markowitz, John S., and C. Lindsay DeVane. The Ritalin Handbook. Kearney, NJ: Morris Publishing, 2000.

Page, Clive P. and Michael Murphy. Integrated Pharmacology. St. Louis: Mosby-Year Book, 2002.

Von Boxtel, Chris, Budiono Santoso, and I. Ralph Edwards. Drug Benefits and Risks: International Textbook of Clinical Pharmacology. New York: John Wiley and Sons,2001.

PERIODICALS

Miller, A. R., C. E. Lalonde, K. M. McGrail, and R. W. Armstrong. "Prescription of methylphenidate to children and youth, 1990-1996." Canadian Medical Journal (2001) 165, no. 11: 1489-1494.

Perring C. "Medicating children: the case of Ritalin." Bioethics (1997) 11, no. 3-4: 228-240.

Sund, A. M., and P. Zeiner. "Does extended medication with amphetamine or methylphenidate reduce growth in hyperactive children?" Norwegian Journal of Psychiatry (2002) 56, no. 1: 53-57.

ORGANIZATIONS

American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. Telephone:(913) 906-6000. Web site: <http://www.aafp.org>.

American College of Physicians. 190 N Independence Mall West, Philadelphia, PA 19106-1572. Telephone: (800) 523-1546, x2600 or (215) 351-2600. Web site: <http://www.acponline.org>.

American Medical Association. 515 N. State Street, Chicago, IL 60610. Telephone: (312) 464-5000. Web site: <http://www.ama-assn.org>.

American Psychiatric Association. 1400 K Street NW, Washington, DC 20005. Telephone: (888) 357-7924. Fax(202) 682-6850.

American Society for Clinical Pharmacology and Therapeutics; 528 North Washington Street, Alexandria, VA 22314; Phone: (703) 836-6981. Fax: (703) 836-5223.

American Society for Pharmacology and Experimental Therapeutics. 9650 Rockville Pike, Bethesda, MD 20814-3995. Telephone: (301) 530-7060.

National Institute on Drug Abuse: <http://www.nida.nih.gov/Infofax/ritalin.html>.

Nurse's PDR Resource Center. <http://www.nursespdr.com/members/database/>.

L. Fleming Fallon, Jr., M.D., Dr.P.H.

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Methylphenidate

Methylphenidate

Definition

The generic name for the drug Ritalin, the most commonly prescribed medication for treating children with attention-deficit hyperactivity disorder (ADHD).

Description

Methylphenidate is one of a group of drugs called central nervous system (CNS) stimulants. It is used to treat attention-deficit hyperactivity disorder, narcolepsy (uncontrollable desire for sleep or sudden attacks of deep sleep), and other conditions as determined by a physician or other healthcare provider.

Methylphenidate contributes to the treatment of ADHD by increasing attention and decreasing restlessness in children and adults who are overactive, cannot concentrate for very long, or are easily distracted, and are impulsive. Methylphenidate is intended to be used as part of a total treatment program that also includes social, educational, and psychological treatment.

A central nervous system stimulant, methylphenidate is also used to control narcolepsy, a condition characterized by an overpowering desire to sleep. Methylphenidate comes in short- and long-acting tablets. The latter should be swallowed whole, never broken into smaller pieces or chewed.

General use

Initially methylphenidate is prescribed in two daily doses of 2.5 mg each, taken at breakfast and lunch time. The dosage is gradually increased until the daily amount reaches 10.0 mg. The dosages should be strictly followed, and since anorexia is an important side effect, the dosages should always be accompanied by a meal or snack. The primary side effect of methylphenidate is growth suppression. Others include irritability, restlessness, agitation, nausea , and headaches. Occasionally it causes sleeplessness, in which case the last dosage of the day should be a short-action tablet. Physicians often recommend regular drug-free periods to combat these side effects. In many cases, a child only takes methylphenidate during the school year.

Precautions

Methylphenidate can be addictive and dosage should be tapered off gradually. Signs of physical dependency include the need to increase the dosage in order to achieve results, mental depression, unusual behavior, and unusual tiredness or weakness. Some medical professionals believe that methylphenidate is prescribed too often. They call for better diagnostic procedures conducted by trained personnel rather than relying primarily on subjective observations by parents and teachers.

The dosage of methylphenidate is different for different people. It is important to follow the prescribing physician's orders or the instructions that appear on the label of the container. Do not change dosages unless a physician approves such an alteration.

Side effects

Any serious reaction to the drug, such as shortness of breath, irregular heartbeat, or allergic reaction, should be reported to one's doctor. Less severe, more common side effects include blurred vision, insomnia, drowsiness, gastrointestinal distress (nausea or vomiting ), dizziness , headaches, and possible addiction .

Interactions

Persons taking methylphenidate should be aware of the possible adverse interactions with the following drugs: amphetamines, appetite suppressants, caffeine , chlophedianol, cocaine, asthma medication, cold, sinus and hay fever medications, nabilone, pemoline, monoamine oxidase inhibitors, and pimozide. Methylphenidate is also affected by epilepsy, Tourette's syndrome, glaucoma, high blood pressure, psychosis, severe anxiety , and tics .

Parental concerns

The use of methyphenidate has been subject to controversy over the last several years. Parents concerned about whether the drug is being properly prescribed for their children should seek out the opinion of the most suitable physician for the type of problems their child is having. If a parent is uncomfortable with a physician's response, they should not hesitate to get a second opinion.

KEY TERMS

Attention deficit hyperactivity disorder (ADHD) A condition in which a person (usually a child) has an unusually high activity level and a short attention span. People with the disorder may act impulsively and may have learning and behavioral problems.

Narcolepsy A life-long sleep disorder marked by four symptoms: sudden brief sleep attacks, cataplexy (a sudden loss of muscle tone usually lasting up to 30 minutes), temporary paralysis, and hallucinations. The hallucinations are associated with falling asleep or the transition from sleeping to waking.

Resources

BOOKS

Castro, E. A., and R. W. Hill. Getting Rid of Ritalin: How Neurofeedback Can Successfully Treat Attention Deficit Disorder without Drugs. Charlottesville, VA: Hampton Roads Publishing Company, 2002.

DeGrandpre, Richard J. Ritalin Nation: Rapid-Fire Culture and the Transformation of Human Consciousness. New York: Norton, 2000.

Ferreiro, Carmen. Ritalin and Other Methylphenidate-Containing Drugs. Langhorne, PA: Chelsea House Publishers, 2004.

Greenhill, Laurence L., and Bette B. Osman. Ritalin: Theory and Practice. Larchmont, NY: Mary Ann Liebert Incorporated, 2000.

PERIODICALS

Golan, N., et al. "Sleep disorders and daytime sleepiness in children with attention-deficit/hyperactive disorder." Sleep 27, no. 2 (2004): 2616.

Mott, T. F., and L. Leach. "Is methylphenidate useful for treating adolescents with ADHD?" Journal of Family Practice 53, no. 8 (2004): 65961.

ORGANIZATIONS

American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 662112672. Web site: <www.aafp.org/>.

American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 600071098. Web site: <www.aap.org/>.

American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 191061572. Web site: <www.acponline.org/>

American Medical Association. 515 N. State Street, Chicago, IL 60610. Web site: <www.ama-assn.org/>.

American Osteopathic Association. 142 East Ontario Street, Chicago, IL 60611. Web site: <www.osteopathic.org/>.

American Psychiatric Association. 1400 K Street NW, Washington, DC 20005. Web site: <www.psych.org/>. National Institute of Mental Health. 6001 Executive Boulevard, Rm. 8184, MSC 9663, Bethesda, MD 208929663. Web site: <www.nimh.nih.gov/home.cfm>.

OTHER

"ADHD Medicines." Kid's Health. Available online at <http://kidshealth.org/kid/feel_better/things/ritalin.html> (accessed November 11, 2004).

"Methylphenidate (Ritalin)." National Institute of Drug Abuse. Available online at <www.nida.nih.gov/Infofax/ritalin.html> (accessed November 11, 2004).

"Methylphenidate." Internet Mental Health. Available online at <www.mentalhealth.com/drug/p30-r03.html> (accessed November 11, 2004).

"Ritalin: Miracle Drug or Cop-Out?" Public Broadcasting System. Available online at <www.pbs.org/wgbh/pages/frontline/shows/medicating/readings/publicinterest.html> (accessed November 11, 2004).

L. Fleming Fallon, Jr., MD, DrPH

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Methylphenidate

Methylphenidate


Methylphenidate is a mild stimulant prescribed to individuals (usually for children, and sometimes controversially) who have behavioral problems characterized by hyperactivity and short attention span. The National Institute of Mental Health estimates that approximately 35 percent of the general population has attention-deficit disorder (ADD) or attention-deficit hyperactivity disorder (ADHD). The administration of methylphenidate to children diagnosed with hyperactivity and/or attention-deficit disorder can have a calming effect on the children and can enable them to focus on schoolwork. Methylphenidate is also used to treat narcolepsy, a sleep disorder characterized by a permanent and overwhelming feeling of sleepiness and fatigue.

Methylphenidate is similar to amphetamine and, like amphetamine, stimulates the central nervous system (CNS), which consists of the brain and spinal cord. Stimulant drugs affect mood and alertness, and depress food appetite by increasing levels of several neurotransmitters in the brain. Although the exact therapeutic mode of action of methylphenidate is not known, the drug has been shown to elevate levels of some of these neurotransmitters, primarily dopamine and norepinephrine (noradrenaline).

Dopamine and norepinephrine are excitatory neurotransmitters. When nerve cells in the brain are stimulated, neurotransmitters stored in vesicles in nerve cell endings are released to extracellular spaces (synapses). The liberated chemical messengers can then interact with receptors on an adjacent nerve cell and can generate a new nerve signal (a nerve impulse). When levels of dopamine or norepinephrine are depressed, regions of the brain that rely on the two substances to regulate nerve impulse conduction are unable to function properly. Research has shown that children with ADD or ADHD have lower levels of dopamine in the CNS. It is believed that drugs acting as CNS stimulants, such as amphetamine, cocaine, and methylphenidate, compensate for lowered levels of excitatory neurotransmitters (i.e., dopamine and norepinephrine) in the brain. Indeed, administration of methylphenidate to healthy adult men has been found to increase dopamine levels.

Different theories have been proposed to explain how methylphenidate increases levels of dopamine in the brain. One such theory propounds that methylphenidate causes dopamine to remain longer in extracellular spaces. Once a neurotransmitter has transmitted its message, it dissociates from the receptor to which it was bound and is taken up by the nerve cell from which it was originally released. Researchers at Brookhaven National Laboratory have demonstrated that methylphenidate inhibits this "reuptake" of dopamine by nerve cells. As a result, extracellular dopamine levels are increased, and the neurotransmitter continues to be available to initiate nerve impulses.

Ritalin is the brand name of a formulation of methylphenidate that is available in tablet form. Ritalin tablets are most often prescribed to children, aged 7 to 18, who have been diagnosed with ADHD. However, individuals who suffer from anxiety or panic disorders are warned not to take the drug, as Ritalin may aggravate symptoms of agitation and/or anxiety. Nervousness and insomnia are the most common side effects associated with Ritalin. There have also been reports of the onset of Tourette's syndrome, a neurological disorder characterized by repeated and involuntary body movements (tics), or at least of symptoms resembling those of Tourette's, in patients taking Ritalin, and therefore patients with this disorder are advised not to take Ritalin. In April 2002 the National Institutes of Health reported that a combination of Ritalin and Clonidine, a drug often used to treat hypertension , is more effective in the treatment of ADHD than either drug alone. Furthermore, Clonidine is reported to have a tic-suppressing effect, and it is believed that the drug may counteract the apparent tic-accentuating effect of methylphenidate.

During the early 1990s, reports of abuse of methylphenidate began to appear. Nonmedical use of the drug for its stimulant effects impelled the U.S. Drug Enforcement Administration (DEA) to regulate the manufacture, distribution, and prescription of methylphenidate. Because methylphenidate is related to amphetamine, it can be addictive and result in physical and psychological dependence.

see also Neurochemistry; Neurotransmitters; Pharmaceutical Chemistry.

Nanette M. Wachter

Bibliography

Goldman, Larry S., et al. (1998) "Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents." Journal of the American Medical Association 279(14):11001107.

Internet Resources

National Institute of Drug Abuse. National Institutes of Health. Available from <http://www.nida.nih.gov/>.

National Institute of Neurological Disorders and Stroke. Available from <http://www.ninds.nih.gov/>.

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Methylphenidate

Methylphenidate

Definition

Methylphenidate is a mild central nervous system stimulant. This drug is sold under the brand name Ritalin in the United States.

Purpose

Methylphenidate can be used to decrease sedation and lethargy from opioid pain medications. In addition, methylphenidate may improve the mood of a cancer patient suffering from feelings of depression , often raises a patient's energy level, and may improve his or her appetite. This drug is also used to treat attention deficit disorder in children and the sleep disorder narcolepsy.

Description

Exactly how methylphenidate acts in the brain is not clear. It is believed to trigger arousal systems or increase the release of brain chemicals. It produces added alertness.

Recommended dosage

How the patient responds to treatment will determine the recommended dose. The usual dose for adults when methylphenidate is ordered with opiate pain medication is 2.5 mg. to 15 mg., daily or twice per day. This drug should be taken exactly as directed. It can become habit-forming if taken in greater amounts or for longer periods than is necessary. Patients should take the last dose of the day before 6 P. M. to decrease sleep difficulties. Patients should not crush or break this medication. If a dose is missed, the patient should take it as soon as possible. Patients should not take two pills at the same time.

Precautions

Methylphenidate can produce physical and mental dependence. Patients should not suddenly stop taking it. A sudden discontinuation of the drug can cause withdrawal symptoms, including depression, paranoid feelings, thoughts of suicide, anxiety, agitation, and sleep disturbances.

Methylphenidate should not be given to patients with extreme anxiety, tension, agitation, severe depression, instability, or a history of alcohol or drug abuse. It is not indicated for use in those with Tourette's syndrome, people with tics, glaucoma, or some mental-health conditions. This drug should be used cautiously in patients with high blood pressure, those with a history of seizures, and women who are breastfeeding. Methylphenidate is not typically ordered for women during their childbearing years, unless the doctor determines that the benefits outweigh the risks. Methylphenidate should not be ordered for patients less than six years of age. Its safety has not been determined in this age group.

Side effects

The most common side effects are nervousness, sleep difficulties, a rapid heartbeat, and increased blood pressure. Reducing the dose or changing the time the drug is taken may reduce some side effects. Patients should discuss any adverse reactions with their doctor. Patients should receive regular blood pressure and pulse checks while on this drug. Methylphenidate also may cause dizziness, irritability, vision changes, drowsiness, and a poor appetite. Patients may experience chest pain, palpitations, joint pain, skin rash, and uncontrolled movements or speech. Patients may develop a rapid or irregular heartbeat, stomach upset, nausea, headache, blood in the urine or stools, muscle cramps, red dots on the skin, or bruises. Patients should not drive or operate machinery or appliances until they understand how this drug affects them. Patients should not drive if they become lightheaded or dizzy. Methylphenidate may cause irregularities in the makeup of the blood and produce changes in liver function. Patients should receive regular blood work.

At higher doses or with long-term use, patients may experience confusion, false beliefs, mood changes, hallucinations, feelings that they or their environment are not real, and weight loss .

Interactions

Several drugs may interfere with methylphenidate, including anticoagulants (blood thinners), and drugs to prevent seizures, combat depression and treat high blood pressure.

Debra Wood, R.N.

KEY TERMS

Narcolepsy

Disorder that causes people to suddenly fall asleep

Opiate

Remedy containing or derived from opium, or any drug that induces sleep

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methylphenidate

methylphenidate (mee-thyl-fen-id-ayt) n. a drug that stimulates the central nervous system. It is administered by mouth to treat attention-deficit/hyperactivity disorder in children. Trade names: Concerta, Equasym XL, Ritalin.

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Methylphenidate

Methylphenidate

Definition

Purpose

Description

Recommended dosage

Precautions

Side effects

Interactions

Resources

Definition

Methylphenidate is a mild, central nervous system stimulant. In the United States, the drug is sold under the brand name Ritalin.

Purpose

Methylphenidate is used primarily in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults. It also may be used to treat the sleep disorder, narcolepsy . In rare cases, it is used to decrease sedation and lethargy from opioid pain

medications and to help improve the mood of a terminally ill person suffering from depression .

Description

The mode of action for methylphenidate is not fully understood. It presumably activates the brain stem arousal system and cortex to produce a stimulant effect. The brain stem arousal system increases levels of electrical activity in the brain. The effect of methyl-phenidate is to produce increased alertness and, although children with ADHD are overactive and have decreased attention spans, in these children, methylphenidate actually decreases motor restlessness and increases attention span. Tablets are available in 5-, 10-, and 20-mg strengths, as well as in an extended release, 20-mg tablet.

Recommended dosage

The recommended dosage of methylphenidate is determined by trial and error based on individual responses. Methylphenidate is usually administered in two or three separate doses each day, preferably 45 minutes before a meal. For children suffering from ADHD, the initial recommended dosage is 5 mg twice daily before breakfast and lunch, increased by 5–10 mg per week to a maximum of 60 mg per day. The average total dosage is 20–30 mg per day, although 10–60 mg is not uncommon. For narcolepsy in adults, the recommended dose is 5–20 mg two to three times a day, 30–45 minutes before meals.

The drug should be taken exactly as directed. Methylphenidate can become habit forming if taken in greater amounts or for longer periods than necessary. Individuals should take the last dose of the day before 6 P.M. to decrease sleep difficulties. The tablet should not be broken or crushed, as this changes the time for absorption. If the normal time of administration is missed, persons should take the drug as soon as possible. However, two tablets should not be taken at the same time.

Precautions

Methylphenidate has a great potential to produce physical and mental dependence. Administration should not be stopped abruptly. Such action can cause withdrawal symptoms including depression, paranoid feelings, thoughts of suicide , anxiety , agitation, and sleep disturbances. Methylphenidate should not be given to persons with extreme anxiety, tension, agitation, severe depression, mental or emotional instability, or a history of alcohol or drug abuse . It is not indicated for use by those with Tourette’s syndrome, people with tic disorders , glaucoma, or certain mental-health conditions. The drug should be used cautiously in persons with high blood pressure, those with a history of seizures , and women who are breastfeeding. Methylphenidate is not typically ordered for women during their childbearing years, unless the physician determines that the benefits outweigh the risks.

Methylphenidate should not be ordered for children younger than six years of age as its safety has not been determined in this age group. People should not drive or operate machinery or appliances until they understand how this drug affects them. They should not drive if they become lightheaded or dizzy. Methylphenidate may cause irregularities in the composition of the blood and produce changes in liver function. People taking methylphenidate should receive regular blood tests.

Side effects

The most common side effects are nervousness, difficulties with sleep, tachycardia, and increased blood pressure. Reducing the dose or changing the time the drug is taken may reduce some side effects. Affected persons should discuss any adverse reactions with their health care professional. Individuals taking methylphenidate should receive regular blood pressure and pulse checks. Methylphenidate also may cause dizziness, irritability, vision changes, drowsiness, and a poor appetite. Less common side effects include chest pain, palpitations, joint pain, skin rash, and uncontrolled movements or speech. Side effects may also include a rapid or irregular heartbeat, stomach upset, nausea, headache, blood in the urine

or stools, muscle cramps, red dots on the skin, or bruises. At higher dosages or with long-term use, people may experience weight loss or mental changes such as confusion, false beliefs, mood changes, hallucinations , or feelings that they or their environment are not real.

Interactions

Several drugs may interact adversely with methyl-phenidate, including anticoagulants and drugs to prevent seizures, combat depression, and treat high blood pressure. The dosages of these drugs may be reduced when taken simultaneously with methylphenidate.

Resources

BOOKS

Adams, Michael and Norman Holland. Core Concepts in Pharmacology. Philadelphia: Lippincott-Raven, 1998.

Breggin, Peter R. and Dick Scruggs. Talking Back to Ritalin: What Doctors Aren’t Telling You About Stimulants and ADHD. Boulder, CO: Perseus Book Group, 2001.

Foreman, John C. and Torben Johansen. Textbook of Receptor Pharmacology. 2nd Ed. Boca Raton, FL: CRC Press, 2002.

Markowitz, John S., and C. Lindsay De Vane. The Ritalin Handbook. Kearney, NJ: Morris Publishing, 2000.

Page, Clive P. and Michael Murphy.Integrated Pharmacology. St. Louis: Mosby-Year Book, 2002.

Von Boxtel, Chris, Budiono Santoso, and I. Ralph Edwards. Drug Benefits and Risks: International Textbook of Clinical Pharmacology. New York: John Wiley and Sons, 2001.

PERIODICALS

Miller, A. R., C. E. Lalonde, K. M. McGrail, and R. W. Armstrong. “Prescription of methylphenidate to chil-

KEY TERMS

Anticoagulant —A medication (such as Warfarin, Coumadin, or Heparin) that decreases the blood’s clotting ability preventing the formation of new clots. Although anticoagulants will not dissolve existing clots, they can stop them from getting larger. These drugs are commonly called blood thinners.

Glaucoma —A group of eye diseases characterized by increased pressure within the eye significant enough to damage eye tissue and structures. If untreated, glaucoma results in blindness. Opiate—A drug derived from opium.

Tachycardia —A pulse rate above 100 beats per minute.

Tourette’s syndrome —Neurological disorder characterized by multiple involuntary movements and uncontrollable vocalizations called tics that come and go over years, usually beginning in childhood and becoming chronic. Sometimes the tics include inappropriate language.

dren and youth, 1990-1996.” Canadian Medical Journal(2001)165, no. 11: 1489-1494.

Perring C. “Medicating children: the case of Ritalin.” Bioethics (1997) 11, no. 3-4: 228-240.

Sund, A. M., and P. Zeiner. “Does extended medication with amphetamine or methylphenidate reduce growth in hyperactive children?” Norwegian Journal of Psychiatry(2002)56, no. 1: 53-57.

ORGANIZATIONS

American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. Telephone: (913) 906-6000. Web site: http://www.aafp.org

American College of Physicians. 190 N Independence Mall West, Philadelphia, PA 19106-1572. Telephone: (800) 523-1546, x2600 or (215) 351-2600. Web site: http://www.acponline.org

American Medical Association. 515 N. State Street, Chicago, IL 60610. Telephone: (312) 464-5000. Web site: http://www.ama-assn.org

American Psychiatric Association. 1400 K Street NW, Washington, DC 20005. Telephone: (888) 357-7924. Fax (202) 682-6850.

American Society for Clinical Pharmacology and Therapeutics; 528 North Washington Street, Alexandria, VA 22314; Phone: (703) 836-6981. Fax: (703) 836-5223.

American Society for Pharmacology and Experimental Therapeutics. 9650 Rockville Pike, Bethesda, MD 20814-3995. Telephone: (301) 530-7060.

National Institute on Drug Abuse: http://www.nida.nih.gov/Infofax/ritalin.html

Nurse’s PDR Resource Center. http://www.nursespdr.com/members/database/

L. Fleming Fallon, Jr., M.D., Dr.P.H.

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Methylphenidate

METHYLPHENIDATE

OFFICIAL NAMES: Methylphenidate, Ritalin, Methylin, Metadate, Concerta

STREET NAMES: Vitamin R, West Coast

DRUG CLASSIFICATIONS: Schedule II, stimulant


OVERVIEW

Methylphenidate (MPH), one of the most commonly prescribed psychoactive drugs in the United States, is the drug of choice for the treatment of attention deficit hyperactivity disorder (ADHD) in children, adolescents, and adults. It is also a drug of choice for thieves: MPH is on the U.S. Department of Justice's Drug Enforcement Administration's (DEA) list of the top 10 prescription drugs most often stolen.

According to The Christian Science Monitor, legal use of MPH in the 1990s increased by about 700% between 1990 and 2000. However, as the legal usage of MPH increased, so did its abuse. That abuse is well documented among high school and college students who use it to overcome fatigue and to enhance memory, without realizing the drug's dangers.

Children with ADHD are inattentive, impulsive, and hyperactive. The areas of their brains that control attention and restraint do not function properly. Stimulant drugs, specifically amphetamines, have been used in the United States to treat children with inattention and hyperactivity disorders since the 1930s. MPH was also discovered to have a calming effect on hyperactive children and a "focusing" effect on those with attention deficit disorder (ADD). However, it was not until the 1960s that the U.S. Food and Drug Administration (FDA) approved methylphenidate for the treatment of ADHD. At the turn of the twenty-first century, approximately 90% of all methylphenidate was prescribed for ADHD children. Most of the rest was prescribed to treat adults with a sleeping sickness known as narcolepsy.

Estimates suggest that 6–7% of all American school-age children were being prescribed MPH for behavior problems in 2002. Although the exact amount of MPH abuse is unknown, experts agree its prevalence is low compared to cocaine abuse, but warn that the number of new cases of methylphenidate abuse is growing. In 2001, Terrace Woodworth, DEA deputy director, told the U.S. Congress that the problem of MPH abuse is primarily a U.S. problem. The United States is the primary consumer of methylphenidate, producing and consuming about 85% of the entire world's supply.

Unlike other amphetamine stimulants, MPH has not been clandestinely manufactured in homemade laboratories. According to the DEA, legally manufactured MPH has been diverted for illegal, non-prescription use. Police authorities report rising rates of illegal sales, prescription forgery, scams involving doctor shopping, and outright thefts of the drug. In a one-year period from 1996 to 1997, the DEA reports that 700,000 pills were stolen.

CHEMICAL/ORGANIC COMPOSITION

Methylphenidate, a derivative of piperidine, a synthetic chemical that is used in the manufacture of rubber, is structurally similar to amphetamine and cocaine. These three drugs are all central nervous system stimulants that act on a chemical within the human body known as dopamine, one of the substances within the human body that controls feelings of pleasure.

Unlike cocaine and amphetamine, however, MPH does not cause feelings of pleasure in the brains of individuals with ADHD. However, when healthy people unaffected by ADHD take methylphenidate illicitly, they get, at least initially, a sharp signal reception that the brain interprets as pleasure. Unfortunately, people without ADHD soon develop a tolerance to the drug and need increasing amounts of the drug to achieve the same effect, often leading to methylphenidate abuse.

INGESTION METHODS

MPH is most often taken in pill form. It is available in prescribed quantities of 5-, 10-, and 20-mg tablets. A sustained or delayed release 20-mg tablet is also available. In 2001, the FDA approved Concerta, a longer acting MPH tablet that is taken once a day. Besides its long lasting action, Concerta has another benefit: Abusers sometimes grind MPH tablets into a powder and snort it up their noses, but Concerta is formulated so that it cannot be ground into a powder. According to the DEA, methylphenidate abusers also dissolve the immediate-release MPH tablets in water and then inject the mixture.

THERAPEUTIC USE

Besides attention deficit hyperactivity disorder (ADHD), methylphenidate is used to treat narcolepsy, a sleeping disorder. Occasionally, MPH has also been used to treat behavioral symptoms that result from traumatic brain injury (TBI), stroke, depression, and the pain experienced by people with cancer. Combined with pain relievers, MPH tends to produce significant reductions in pain intensity and sedation in cancer patients.

Individuals with narcolepsy suffer sudden onsets of deep sleep. Regular use of MPH on a twice-a-day dosage schedule (or a once-a-day schedule if the newer sustained release forms of MPH are used) allows those individuals to live relatively normal lives.

Individuals with TBI, which usually is caused by a blow to the head, a fall, or a car accident, often exhibit ADHD-like symptoms. MPH is sometimes used to treat those symptoms. Before the development of modern antidepressants, MPH was sometimes used for the treatment of depression. Any benefits seen in TBI treatment appear to be related to an improvement in symptoms of depression.

However, by far the largest group of users of methylphenidate are people who have ADHD. Children with ADHD often exhibit symptoms such as inattention, distractibility, impulsiveness, and hyperactivity. These symptoms interfere with the patient's ability to learn. MPH is used to modify brain chemistry and allows the individuals to better focus on tasks such as homework.

One unpredictable benefit of MPH treatment, according to a 1999 research paper, is that children with ADHD who receive MPH treatment may be less likely to develop substance abuse disorders.

USAGE TRENDS

While the prevalence of MPH abuse is low, at least compared to other forms of drug abuse, officials worry that the rate of MPH abuse is increasing, especially among high school and college students.

Scope and severity

In 1999, methylphenidate was the most widely dispensed stimulant medication used for treating ADHD. More of it was used than amphetamine, the next most frequently used stimulant that is used to treat ADHD.

Yearly, an estimated four to six million children in the United States take MPH on a daily basis as a treatment for ADHD. In comparison, only about 25,000 school-age youths were on the medication in England and Wales during 2000. Definitive statistics are not available for the drug's illegal use, and so the exact extent to which it is being abused in any country is unknown. However, it is known that abuse rates increase along with the number of legal prescriptions written. In a study of MPH abusers over a four-year period of 1992–1996, researchers found a significant increase in methylphenidate misuse, especially in white adolescents.

According to a 2001 published survey of cases reported to poison control centers, there was a sevenfold increase in the number of cases in which MPH was involved during the five-year period that ended in 1999. However, the total number of cases making up the sevenfold increase totaled only 530.

In 1990, there were 271 emergency room mentions for MPH in reports to the Drug Abuse Warning Network (DAWN). In 1999, that figure had grown to 1,478 mentions, but the good news is that the 1999 figure represented a slight decrease from 1998's all-time high of 1,728 mentions. To put those figures into context, in 1998 there were 168,763 cocaine-related visits to hospital emergency rooms.

Age, ethnic, and gender trends

According to the Woodworth congressional testimony, "Boys are four times more likely to receive a diagnosis of ADHD and be prescribed stimulant medication." Critics are also disturbed about a trend of prescribing the drug to ever-younger children. For instance, in 1998 a national auditing firm estimated that 4,000 MPH prescriptions were written for children two years of age or less. Some experts, disturbed by this disquieting statistic, point out that MPH has not been approved for use in children under six years of age because safety and effectiveness in that age range has not been established.

MENTAL EFFECTS

Methylphenidate is considered a mild central nervous system stimulant that affects the brain and nerves, relieving fatigue, and inducing clearer thoughts for relatively short periods. According to the DEA, possible effects experienced by those who do not have ADHD or narcolepsy include increased alertness, excitation, and euphoria. Increased energy and increased mental clarity may be experienced for a short period.

PHYSIOLOGICAL EFFECTS

Physiological effects include increased pulse rate and blood pressure, which contribute to the feelings of increased energy and stamina.

Harmful side effects

Common harmful side effects include insomnia, nervousness, and loss of appetite. Other adverse reactions include skin rash, fever, anorexia, nausea, dizziness, headache, abdominal pain, irregular heartbeat and breathing, and generalized anxiety. The irregular breathing may come from an allergic reaction to the drug. The allergic reaction can also cause swelling of the lips, tongue, face, or throat.

Individuals who ingest methylphenidate by dissolving the tablets in water and injecting the mixture risk complications due to the insoluble fillers used in the tablets. When injected, these materials block small blood vessels and can cause serious damage to the lungs and retina of the eye.

Snorting the drug can also be dangerous. The delicate tissues that line the nasal cavities and air passages can be damaged by direct contact with MPH because the tablets contain hydrocholoride salt of methylphenidate, which yields dilute hydrochloric acid when it comes into contact with moisture within the nose. While this is not a problem in the stomach (because hydrochloric acid is one of the stomach acids used to digest foods), the acid can burn the delicate epithelial nasal tissues. This can result in open sores, nose bleeds, and with chronic use can lead to deterioration of the nasal cartilage.

"Shooting up," street parlance for dissolving the drug in water and using a syringe to inject it, can cause harmful side effects. Not only can dust, dirt, and other contaminants fall into the liquid mixture, but bacteria, talc, lint, and other particles are also injected with the drug. The inert ingredients that manufacturers include to increase the bulk of the tablets can create serious health problems when injected directly into veins or body tissues. Complications from injections include overdose, blood clots, infections such as blood poisoning, abscesses, hepatitis, AIDS from sharing needles, scars, and circulatory and pulmonary problems. The effects of overdose include agitation, increased body temperature, hallucinations, paranoia, convulsions, and possibly even death.

The FDA classifies methylphenidate as being in pregnancy category C, which means it is not known whether it would harm an unborn baby. Medical authorities advise pregnant women not to take MPH without consulting a doctor.

Other side effects of MPH include allergic reactions, extensive bruising, and abnormally low red and white blood cells counts. Individuals who abuse the drug suffer from loss of appetite so severe that they develop anorexia. They can also suffer abdominal pain, extreme weight loss, and skin rashes.

Long-term health effects

Chronic abuse of MPH can lead to marked tolerance and psychological dependence. According to the DEA, chronic MPH intoxication is identical to the paranoid psychosis of amphetamine intoxication. Studies indicate that 5–15% of the amphetamine users who become psychotic fail to make a complete recovery.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Because of the dangerous adverse reactions (including the risk of death), individuals should not take methylphenidate if they have taken a class of drugs known as monamine oxidase (MAO) inhibitors within 14 days. Most MAO inhibitors are antidepressants, but some anti-tuberculosis drugs such as Ethambutol also have MAO effects. Since drug users are prone to many infectious diseases, it is not unheard of for drug abusers to come down with tuberculosis (TB).

TREATMENT AND REHABILITATION

Withdrawal from methylphenidate abuse can be both difficult and dangerous. Medical reference books warn that MPH withdrawal should be undertaken with careful supervision by slowly reducing dosages over time.

Individuals who go through MPH withdrawal experience intense cravings for the drug. Other expected unpleasant withdrawal side effects include agitation, anxiety, decreased energy, fatigue, increased appetite, lethargy, increased need for sleep, and vivid or unpleasant dreams. During withdrawal, individuals may also experience abdominal pain, fever, infection, loss of appetite, diarrhea, shortness of breath, nausea, vomiting, dizziness, emotional upset, insomnia, nervousness, and weight loss. MPH withdrawal can also cause depression and suicidal feelings. Psychosis and paranoia, though rare, can also be precipitated.

A review of the medical literature reveals no specific treatments or rehabilitation regimes for MPH withdrawal. However, drug rehabilitation organizations can help individuals go through MPH withdrawal.

PERSONAL AND SOCIAL CONSEQUENCES

Like its chemical cousins cocaine and amphetamine, MPH abuse can lead to tolerance and psychic dependence. Tolerance develops when the drug is used chronically and higher and higher dosages are needed to get the same effects. Frequent episodes of binge use can be followed by severe depression and an overpowering desire to continue using the drug despite the onset of serious negative medical and social consequences, including psychotic episodes, paranoid delusions, hallucinations, hospitalization, or incarceration.

LEGAL CONSEQUENCES

In the United States, the legal consequence of possession, illegal sale, or even giving away of MPH drugs can be severe under terms of the Controlled Substance Act (CSA), which is part of the Comprehensive Drug Abuse Prevention and Control Act of 1970, the legal foundation of the federal government's fight against the abuse of drugs and other substances. Because of the abuse potential of MPH, the DEA has placed stringent Schedule II controls and licensing requirements on the manufacture, distribution, and prescription of the sub-stance. Breaking those rules can result in fines and imprisonment.

Under Section 844 of the CSA, simple possession of a controlled substance (including methylphenidate) without a doctor's prescription can result in imprisonment for one year for a first offense and a fine of $1,000 or both. A second offense can result in imprisonment for up to two years and a fine of $2,500. A third offense can result in up to three years of prison time and a fine of $5,000.

Distribution, which includes selling or even giving any mixture or substance containing a detectable amount of methylphenidate is illegal under CSA Section841. For a first offense, it is punishable by a prison term of not more than 20 years and fines up to $1 million for an individual or $5 million if not an individual. If death or serious bodily injury results, imprisonment terms not less than 20 years or more than life. A second offense is punishable by a prison term of not more than 30 years, and a fine of up to $2 million for an individual or up to $10 million if not an individual. If death or serious injury results, life imprisonment is the punishment. A person convicted of selling MPH to someone younger than 21 years of age is subject to "twice the maximum punishment authorized."

Legal history

The FDA approved Ritalin, the original brand name of methylphenidate, in 1961 as a Schedule II drug. When the U.S. Congress passed the CSA in 1970, MPH, as a controlled Schedule II substance, came under the regulation of that law.

In 2001, plaintiffs representing children treated with Ritalin filed a federal lawsuit against Novartis Pharmaceuticals Corp. (the manufacturers of Ritalin), the American Psychiatric Association (APA), and the Children and Adults with Attention Deficit Hyperactivity Disorder organization (CHADD). The lawsuit charged that the trio of organizations had conspired to increase the sales of MPH by broadening the definition of ADHD in the APA's Diagnostic and Statistical Manual of Mental Disorders (DSM). The plaintiffs also criticized CHADD for accepting grant money from Novartis.

However, senior U.S. District Judge Rudi Brewster ruled that the plaintiffs did not have enough evidence to support their claims. He gave them additional time to produce new evidence, but when they failed to do so he ultimately dismissed the case with prejudice, meaning the plaintiffs cannot re-file it.

In 2002, several states, including Connecticut and Minnesota, passed laws that ban teachers from recommending psychotropic drugs, especially Ritalin, to parents. The legislators were concerned that educators were pressuring parents to put their children on MPH so that it would be easier for teachers to deal with ADHD kids in classrooms. Legislators believe it should be up to parents and their doctors to decide whether their children should be put on the drug.

Federal guidelines, regulations, and penalties

Since methylphenidate is a Schedule II controlled substance, it is tightly regulated from manufacture to delivery to the doctor or pharmacy. Schedule II drugs require strict manufacturing quotas, careful inventory controls that require special order forms, and separate record-keeping requirements. Prescriptions may not be refilled—a new prescription is required for every new supply. Unlike less stringently regulated drugs, the methylphenidate prescriptions cannot be phoned in to the pharmacy; the prescriptions must be written. Some states such as California and Indiana require special numbered and triplicate prescription forms for tracking purposes. Breaking those regulations can result in jail time of up to one year and a fine of $25,000, according to CSA Section 842: Prohibited Acts B.

See also Amphetamines

RESOURCES

Books

Breggin, P. R. Talking Back to Ritalin: What Doctors Aren't Telling You About Stimulants for Children. Monroe, ME: Common Courage Press, 1998.

DeGrandpre, R. Ritalin Nation: Rapid Fire Culture and the Transformation of Human Consciousness. New York: W.W. Norton & Company, 1999.

Diller, L. H. Running on Ritalin: A Physician Reflects on Children, Society and Performance in a Pill. New York: Bantam Books, 1998.

Hallowell, E. M., and Ratey, J. J. Driven to Distraction: Recognizing and Coping with Attention Deficit Disorder from Childhood to Adulthood. New York: Pantheon Books, 1994.

Periodicals

"Abusing Ritalin: Dangers of Prescription Drug Abuse." Scholastic Choices v. 17 (September 2001).

"Frequently Asked Question About Ritalin." Ritalin on College Campuses.<http://pubweb.acns.nwu.edu/~cam717/faq.html>.

Marks, A. "Schoolyard Hustlers' New Drug: Ritalin." The Christian Science Monitor's Electronic Edition (October 31, 2000): pp. 4.

"Ritalin (Methylphenidate)." Alberta Alcohol and Drug Abuse Commission (AADAC).<http://corp.aadac.com/drugs/factsheets/Ritalin.asp>.

Other

Ciampa, L. Ritalin Abuse Scoring High on College Illegal Drug Circuit. CNN.Com (January 8, 2001). <http://www.cnn.com/2001HEALTH/children/01/08/college.ritalin/>.

Organizations

Attention Deficit Information Network, 475 Hillside Ave., Needham, MA, USA, 02194, (617) 455-9895.

Children and Adults with Attention Deficit Disorders, 499 N.W. 70th Ave., Suite 101, Planation, FL, USA, 33317, (800) 233-4050, <http://www.chadd.org>.

Health Services Administration (SAMHSA), U.S. Dept. of Health and Human Services, 5600 Fishers Lane, Rockville, MD, USA, 20857, (301) 443-0001, (301) 443-1563, 1-800-622-Help, [email protected], <http://www.samhsa.gov/centers/cmhs/cmhs.html>.

National Attention Deficit Disorder Association, 1788 Second Street, Suite 200, Highland Park, IL, USA, 60035, (847) 432-3223, (847) 432-5874, [email protected], <http://www.add.org>.

University of Kentucky Center for Prevention Research, 1151 Red Mile Rd. Ste. 1-A, Lexington, KY, USA, 40507, (606) 257-5588, <http://www.uky.edu/RGS/PreventionResearch/welcome.html>.

Maury M. Breecher, PhD, MPH

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