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DESCRIPTION
- Methylphenidate (Ritalin, Ritalin S) is an amphetamine derivative used in the treatment of patients with attention deficit disorder (ADD) and narcolepsy.
- The phrase "T's and blues" refers to a combination of crushed pentazocine (Talwin) tablets and methyphenidate that is typically used illicitly by intravenous injection.
FORMS AND USES
- A typical dose for children with ADD is 5 mg orally twice a day initially, with a possible increase to maximum of 30 mg/day total.
- Adults with narcolepsy are treated with 30 to 40 mg orally per day.
TOXIC DOSE
Ingestion of 1 to 2 mg/kg may result in hyperactivity and mydriasis in children.
PATHOPHYSIOLOGY
Methylphenidate overdose produces a hyperadrenergic state similar to that induced by amphetamines.
EPIDEMIOLOGY
- Poisoning is uncommon.
- Toxic effects following exposure are typically mild to moderate.
- Death has occurred following intravenous abuse.
CAUSES
- Methylphenidate toxicity usually results from illicit use or therapeutic misadventures.
- Methylphenidate is commonly abused by adolescents without ADD for the sympathomimetic effects.
- Child abuse should be considered if the patient is under 1 year of age; attempted suicide if the patient is over 6 years of age.
DRUG AND DISEASE INTERACTIONS
- Use with monoamine oxidase (MAO) inhibitors may result in serotonin syndrome.
- Additive stimulant effects with other amphetamines are expected.
PREGNANCY AND LACTATION
- US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
- Intrauterine growth retardation and withdrawal symptoms may occur in infants chronically exposed to amphetamines in utero.
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DIFFERENTIAL DIAGNOSIS
- Toxic causes of agitation and seizure include amphetamine, methamphetamine, theophylline, cocaine, isoniazid, tricyclic antidepressants, MAO inhibitors, and phencyclidine (PCP).
- Nontoxic causes include alcohol withdrawal, meningitis, intracranial hemorrhage, hyperthyroidism, hypoxia from any cause, and manic behavior.
SIGNS AND SYMPTOMS
Acute intoxication is characterized by agitation, tachycardia, hypertension, and mydriasis.
Vital Signs
Tachycardia, hypertension, and hyperthermia occur with moderate to severe overdose.
HEENT
- Mydriasis and a dry mouth are common.
- Talc retinopathy may occur in methylphenidate abusers who crush tablets for intravenous use.
Dermatologic
Diaphoresis is common early in the course of moderate to severe overdose.
Pulmonary
- Precocious emphysema has rarely been reported in intravenous users of crushed tablets.
- Noncardiogenic pulmonary edema may occur.
Cardiovascular
- Tachycardia and hypertension are common.
- Ventricular dysrhythmias are rare but may occur with intravenous use.
- Cardiomyopathy may occur with chronic abuse.
Gastrointestinal
Nausea, vomiting, anorexia, and abdominal pain may occur.
Hepatic
Hepatitis occurs rarely.
Renal
Acute renal failure may result from dehydration, seizures, rhabdomyolysis, or hypotension.
Fluids and Electrolytes
Dehydration, hypokalemia, and lactic acidosis may occur.
Musculoskeletal
Agitation may lead to rhabdomyolysis.
Neurologic
- Agitation, hyperactivity, insomnia, euphoria, dizziness, and paranoid ideation can occur.
- Social withdrawal that resolves following discontinuation has been reported in children.
- Delirium, hallucinations, psychosis, and stereotypic behavior may occur.
- Psychosis may develop and persist beyond discontinuation.
- Tremors and seizures may occur with severe intoxication.
PROCEDURES AND LABORATORY TESTS
Essential Tests
No tests may be needed in asymptomatic patients.
Recommended Tests
- Serum electrolytes, BUN, creatinine, and glucose are recommended to evaluate other causes of seizure and altered mental status.
- Liver function, coagulation studies, and serum creatine kinase may be elevated in patients with hyperthermia or agitation.
- ECG, serum acetaminophen and aspirin levels are advised in an overdose setting to detect occult ingestion.
- Head CT, lumbar puncture, pulse oximetry, and toxicology studies may be needed to evaluate other causes of seizure and altered mental status.
- Chest radiographs may show infiltrates and signs of pulmonary hypertension in intravenous users of crushed tablets; precocious emphysema also has been reported.
- An abdominal radiograph may reveal radiopaque sustained-release preparations; however, their absence on a radiograph cannot exclude ingestion.
Not Recommended Tests
Serum methylphenidate levels are not clinically useful.
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- Treatment should focus on control of agitation, hyperthermia, seizures, and dysrhythmias, and on supporting hemodynamic function.
- The dose and time of exposure should be determined for all substances involved.
DIRECTING PATIENT COURSE
The health-care provider should call a poison control center when:
- Seizure, shock, hyperthermia, or other severe effects develop.
- Toxic effects are not consistent with methylphenidate poisoning.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
The patient should be referred to a health-care facility when:
- Attempted suicide or homicide is possible.
- Patients or caregivers seem unreliable.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
Admission Considerations
Inpatient treatment is warranted when patients present with refractory agitation, seizure, hyperthermia, persistent tachycardia, or other end-organ injury.
DECONTAMINATION
Out of Hospital
Induction of emesis is not recommended due to seizure potential.
In Hospital
- Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
- One dose of activated charcoal (1-2 g/kg) should be administered if the patient has ingested a substantial amount within the previous few hours.
- Whole-bowel irrigation with polyethylene glycol has been recommended in patients who have ingested sustained-release preparations.
ANTIDOTES
There are no specific antidotes for methylphenidate poisoning.
ADJUNCTIVE TREATMENT
Agitation
- While closely monitoring the patient's airway, a benzodiazepine should be administered.
- For diazepam, the adult dose is 5 to 10 mg intravenously, and the pediatric dose is 0.2 to 0.5 mg/kg intravenously, with doses repeated at 10-minute intervals, titrating to effect.
- For lorazepam, the adult dose is 1 to 2 mg intravenously; the pediatric dose is 0.05 mg/kg, with doses repeated at 10-minute intervals, titrating to effect.
Seizures
- After the patient's airway has been assured, a benzodiazepine should be administered in the same dose as described above for initial control of agitation.
- If seizures persist or recur, another anticonvulsant should be added, such as phenobarbital.
Hypertension
If hypertension persists after treatment of agitation with benzodiazepine or end-organ damage develops (e.g., aortic dissection, central nervous system bleed, myocardial infarction), a short-acting titratable agent such as nitroprusside should be administered.
Hypotension
- Hypotension should be treated with isotonic fluid infusion, Trendelenburg positioning, and a vasopressor if needed (preferably dopamine).
- Norepinephrine is recommended for refractory hypotension.
Ventricular Dysrhythmia
See SECTION II, Ventricular Dysrhythmias chapter.
Rhabdomyolysis
Adequate hydration and urine output (1-2 ml/kg/h) should be ensured. Urinary alkalinization may be beneficial, but definitive data are not available.
Not Recommended Therapies
beta-blocker therapy for tachycardias or hypertension may result in unopposed alpha-adrenergic receptor stimulation and worsening of hypertension.
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PATIENT MONITORING
ECG, respiratory and hemodynamic function, and core temperature should be monitored.
EXPECTED COURSE AND PROGNOSIS
- Toxic effects occur soon after ingestion.
- Recovery is usually complete with no sequelae.
- Complications are more common in patients with massive or chronic intravenous abuse.
- Pulmonary granulomatosis may occur following chronic intravenous use of crushed tablets.
- End-organ injury may occur from hypertension or seizures.
- Acute renal failure can result from severe rhabdomyolysis or hypotension.
DISCHARGE CRITERIA/INSTRUCTIONS
- From the emergency department
- Asymptomatic patients who have ingested non-sustained-release formulations may be discharged after observation for 6 hours, gastrointestinal decontamination, and psychiatric evaluation, if needed.
- Symptomatic patients should be discharged after resolution of effects and referral for psychiatric evaluation, if needed.
- From the hospital
- Patients should be discharged after resolution of symptoms, normalization of laboratory values, and psychiatric evaluation, if needed.
- Patients should be referred for substance abuse treatment, if needed.
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DIAGNOSIS
- It is important to evaluate other causes of mental status change, such as hypoglycemia; hypoxia; CNS bleed, infection, or infarct; and infection.
- Methylphenidate may be detected as amphetamine by some urine toxicology screens.
TREATMENT
Intravenous abusers are at risk for the complications of intravenous drug use.
Section Outline:
ICD-9-CM 969.7Poisoning by psychotropic agents: psychostimulants.
See Also: SECTION II, Hypotension, Seizures, and Ventricular Dysrhythmias chapters; and SECTION III, Nitroprusside and Whole-Bowel Irrigation chapters.
RECOMMENDED READING
Sherman CB, Hudson LD, Pierson DJ. Severe precocious emphysema in intravenous methylphenidate (Ritalin) abusers. Chest 1987;92:1085-1087.
Stecyk O, Loludice TA, Demeter S, et al. Multiple organ failure resulting from intravenous abuse of methylphenidate hydrochloride. Ann Emerg Med 1985;14:597-599.
Authors: Lada Kokan and Steven A. Seifert
Reviewer: Luke Yip