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Amphetamine-Related Psychiatric Disorders
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Source: http://www.emedicine.com/med/topic3114.htmAuthor: Michael Larson, DO, Clinical Instructor, Department of Child and Adolescent Psychiatry, Harvard University
Michael Larson, DO, is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Child and Adolescent Psychiatry, American Medical Association, and Massachusetts Medical Society
Editor(s): Denis F Darko, MD, FACP, DFAPA, Executive Director, Clinical Research and Development, Neuroscience Global Licensing Medical Director, Clinical Neuroscience Therapy Area, CNS and Pain Control Research Area, AstraZeneca Pharmaceuticals LP; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eduardo Dunayevich, MD, Adjunct Assistant Professor, Department of Psychiatry, University of Cincinnati; Clinical Research Physician, Neuroscience, Lilly Research Laboratories; Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry, Assistant Professor, Department of Medicine, Froedtert Hospital, Medical College of Wisconsin; and Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
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INTRODUCTION Section 2 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
Background: The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) describes the following 10 amphetamine-related psychiatric disorders:
Amphetamine-induced anxiety disorder
Amphetamine-induced mood disorder
Amphetamine-induced psychotic disorder with delusions
Amphetamine-induced psychotic disorder with hallucinations
Amphetamine-induced sexual dysfunction
Amphetamine-induced sleep disorder
Amphetamine intoxication
Amphetamine intoxication delirium
Amphetamine withdrawal
Amphetamine-related disorder not otherwise specified
Either prescription or illegally manufactured amphetamines can induce these disorders. Prescription amphetamines are used frequently in children and adolescents to treat attention-deficit/hyperactivity disorder (ADHD), and they are the most commonly prescribed medications in children. The dose of Adderall(XR) (dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, amphetamine sulfate) needed to produce toxicity and psychiatric symptoms in a child is as low as 2 mg. A typical dose is 2.5-40 mg/d. In adults, narcolepsy, ADHD of the adult type, weight loss, and some depression can be treated with amphetamines. However, because of their addicting potential, these drugs are no longer used for weight loss. Although they are controlled substances, abuse is possible, especially in persons with alcoholism or substance abuse.
The substance 3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational stimulant commonly referred to as ecstasy, which was manufactured legally in the 1980s. MDMA has the desired effects of euphoria, high energy, and social disinhibition lasting 3-6 hours. The drug is often consumed in dance clubs, where users dance vigorously for long periods. The drug sometimes causes toxicity and dehydration, as well as severe hyperthermia. Several other amphetamine derivatives are para-methoxyamphetamine (PMA), 2,5-dimethoxy-4-bromo-amphetamine (DOB), methamphetamine (crystal methamphetamine, crystal meth, or "Tina"), and 3,4-methylenedioxyamphetamine (MDA). Crystal meth is the pure form of methamphetamine, and, because of its low melting point, it can be injected.
Khat (Catha edulis Forsk) is the only known organically derived amphetamine. It is produced from the leaves of the Qat tree located throughout East Africa and the Arabian Peninsula. The leaves of the tree are chewed, extracting the active ingredient, cathinone, and producing the desired effects of euphoria and, unlike other amphetamines, anesthesia.
In the midwestern United States, methcathinone, the synthetic form of cathinone, has been produced illegally since 1989, after a student at the University of Michigan stole research documents and began to illegally manufacture the drug. Methcathinone is relatively easy to produce and contains the same chemicals found in over-the-counter (OTC) asthma and cold medicines, paint solvents and thinners, and drain openers (eg, Drano). Its addiction potential is similar to that of crack cocaine.
Amphetamine-related psychiatric disorders are conditions resulting from intoxication or long-term use of amphetamines or amphetamine derivatives. The disorders are often self-limiting after cessation, though, in some patients, psychiatric symptoms may last several weeks after discontinuation. Some individuals experience paranoia during withdrawal as well as during sustained use. Amphetamine use may elicit or be associated with the recurrence of other psychiatric disorders. People addicted to amphetamines sometimes decrease their use after experiencing paranoia and auditory and visual hallucinations. Furthermore, amphetamines can be psychologically but not physically addictive.
The symptoms of amphetamine-induced psychiatric disorders can be differentiated from those of related primary psychiatric disorders by time. If symptoms do not resolve within 2 weeks after the amphetamines are discontinued, a primary psychiatric disorder should be suspected. Depending on the severity of symptoms, symptomatic treatment can be delayed to clarify the etiology.
Amphetamine-induced psychosis (delusions and hallucinations) can be differentiated from psychotic disorders when symptoms resolve after amphetamines are discontinued. Absence of first-rank Schneiderian symptoms, including anhedonia, avolition, amotivation, and flat affect, further suggests amphetamine-induced psychosis. Symptoms of amphetamine use may be indistinguishable from those associated with the cocaine use. Amphetamines, unlike cocaine, do not cause local anesthesia and have a longer psychoactive duration.
Amphetamine-induced delirium follows a reversible course similar to other causes of delirium, and it is identified by its relationship to amphetamine intoxication. After the delirium subsides, little to no impairment is observed. Delirium is not a condition observed during amphetamine withdrawal.
Mood disorders similar to hypomania and mania can be elicited during intoxication with amphetamines. Depression can occur during withdrawal, and repeated use of amphetamines can produce antidepressant-resistant amphetamine-induced depression. Of interest, low-dose amphetamines can be used as an adjunct in the treatment of depression, especially in patients with medical compromise, lethargy, hypersomnia, low energy, or decreased attention.
Sleep disturbances appear in a fashion similar to mood disorders. During intoxication, sleep can be decreased markedly. In withdrawal, sleep often increases. A disrupted circadian rhythm can result from late or high doses of prescription amphetamines or from chronic or intermittent abuse of amphetamines. Individuals who use prescription amphetamines can easily correct their sleep disturbance by lowering the dose or taking their medication earlier in the day than they have been. Insomnia is the most common adverse effect of prescription amphetamines.
Amphetamine-related disorder not otherwise specified is a diagnosis assigned to those who have several psychiatric symptoms associated with amphetamine use but who do not meet the criteria for a specific amphetamine-related psychiatric disorder.
Pathophysiology: The pathophysiology of amphetamine-related psychiatric disorders is difficult to establish, because amphetamines influence multiple neural systems. In general, chronic amphetamine abuse may cause psychiatric symptoms due to dopamine depletion in 3 areas of the brain: the orbitofrontal cortex, the dorsolateral prefrontal cortex, and the amygdala.
Amphetamine-induced psychosis often results after increased or large use of amphetamines, as observed in binge use or after protracted use. Prescription amphetamines induce the release of dopamine in a dose-dependent manner; low doses of amphetamines deplete large storage vesicles, and high doses deplete small storage vesicles. This increase in dopaminergic activity may be causally related to psychotic symptoms because the use of D2-blocking agents (eg, haloperidol) often ameliorates these symptoms. Amphetamine-induced psychosis has been used as a model to support the dopamine hypothesis of schizophrenia, in which overactivity of dopamine in the limbic system and striatum is associated with psychosis. However, negative symptoms commonly observed in schizophrenia are relatively rare in amphetamine psychosis.
MDMA causes the acute release of serotonin and dopamine and inhibits the reuptake of serotonin into the neuron. MDMA has neurotoxic properties in animals and, potentially, in humans. Reports suggest that MDMA use is associated with cognitive, neurologic, and behavioral abnormalities, as well as hyperthermia, but these reports are confounded by the association with other factors (eg, heat, exertion, poor diet, other drug use). Serotonergic damage has been suggested to lead to cognitive impairment.
Delirium caused by amphetamines may be related to the anticholinergic activity, as observed in different classes of drugs, such as tricyclic antidepressants, benzodiazepines, sedatives, and dopamine-activating drugs. Rapid eye movement during the first phase is decreased during intoxication, and a rebound elevation of rapid eye movement occurs during withdrawal; this effect eventually alters the circadian rhythm and results in sleep disturbances.
Frequency:
In the US: Psychosis, delirium, mood symptoms, anxiety, insomnia, and sexual dysfunction are considered rare adverse effects of therapeutic doses of prescription amphetamines. Dextroamphetamine has a slightly increased rate of these adverse effects because of its increased CNS stimulation.
Data from the 1998 National Household Survey on Drug Abuse showed that 4.4% of people aged 12 years and older report use during their lifetime, 0.7% reported use in the year before the survey, and 0.3% reported use in the month before the survey.
Data about the frequency of amphetamine-related psychiatric disorders are unreliable because of comorbid primary psychiatric illnesses.
Intravenous (IV) use occurs more frequently in people of low socioeconomic status than in those of high socioeconomic status.
Internationally: The first amphetamine epidemic occurred after World War II in Japan, when leftover supplies intended to counteract fatigue in pilots were made available to the general public. This even resulted in many cases of amphetamine psychosis. Of interest, both German and American troops used these preparations during World War II, as did Japanese kamikaze pilots.
Khat, which is primarily used in Ethiopia for cultural and religious purposes, has been well studied. A house-to-house survey of 10,468 adults showed a lifetime prevalence of khat use of 55.7%. Daily use occurred among 17.4%, and 80% indicated they used khat to increase concentration during prayer. Khat dependency has been associated with people of Muslim religion and with people of low socioeconomic status.
Mortality/Morbidity: The Drug Abuse Warning Network (DAWN) Annual Medical Examiner Data for 1998 showed 5% of all drug-related deaths were due to methamphetamines. DAWN data indicated 26% of all drug-related deaths in Oklahoma City were due to methamphetamine, making it the city's most frequent drug-related cause of death in 1998.
In high doses, prescription amphetamines can produce cardiovascular collapse, myocardial infarction, stroke, seizures, renal failure, ischemic colitis, and hepatotoxicity. Death related to MDMA can occur from malignant hyperthermia that leads to kidney failure and cardiovascular collapse. Heart attacks, seizures, subarachnoid and intracranial hemorrhage, and strokes may also result in death. The rate of suicide and accidents can increase during periods of toxicity and withdrawal.
In high doses, prescription amphetamines and amphetamine derivatives increase sexual arousal and disinhibition, increasing the risk of exposure to sexually transmitted diseases.
Memory impairment can result after long-term use of high doses of amphetamines because of damage to serotonin-releasing neurons. In the emergency department patients with amphetamine-related disorders are one third more likely than patients with cocaine-related disorders to be transferred to an inpatient psychiatric ward. This difference may partly be because amphetamine withdrawal lasts longer then cocaine withdrawal, and amphetamines are more psychogenic than cocaine.
Race: Amphetamine-related psychiatric disorders most commonly occur in white individuals.
Sex:
With IV use, amphetamine-related psychiatric disorders most commonly occur in men, with a male-to-female ratio of 3-4:1.
With non-IV use, amphetamine-related psychiatric disorders occur equally in men and women.
Age:
Amphetamine-related psychiatric disorders most frequently occur in people aged 20-39 years who are inclined to abuse amphetamine derivatives at rave parties and dance clubs.
Adolescents have developed a method for abusing prescription amphetamines in which prescription tablets are crushed into a powder and inhaled nasally.
CLINICAL Section 3 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
History: Amphetamine-related psychiatric disorders can be confused with psychiatric disorders caused by organic, medical, neurologic, and/or psychological etiologies. The causes of amphetamine-related psychiatric disorders usually can be determined by assessing the patient's history and the family's genealogy.
The DSM-IV-TR provides criteria helpful for determining if the patient is in a state of intoxication or withdrawal. The criteria helps clinicians distinguish disorders occurring during intoxication (eg, psychosis, delirium, mania, anxiety, insomnia) from those occurring during withdrawal (eg, depression, hypersomnia).
Developmental history: The developmental history provides information about the patient's in utero exposure to medications, illicit drugs, alcohol, pathogens, and trauma.
As children, patients may have had prodromal symptoms of psychiatric disorders, such as social isolation, deteriorating school performance, mood liability, amotivation, avolition, anhedonia, sleep disturbances, sexual paraphilias, poor interest, psychomotor retardation, demoralization, social isolation, and suicidal thoughts and behaviors.
Delinquency, truancy, educational failure, early use of drugs and alcohol, oppositional behavior associated with conduct disorder, and participation in the rave party scene are developmental behaviors that suggest an amphetamine-related psychiatric disorder.
Psychiatric history: Two issues are emphasized:
Determine whether a psychiatric disorder or symptoms ever occurred when the patient was not exposed to amphetamines.
Determine whether the patient ever had a psychiatric disorder or symptoms similar to the present symptoms in relation to any other drug or medication.
Recent history: The patient's history of amphetamine abuse is the most important factor and is determined by asking the following questions:
When did the patient's amphetamine use start?
How often does the patient use amphetamines?
How much does he or she use?
Is the patient currently intoxicated or in withdrawal from amphetamines?
Does the patient frequently attend rave parties?
Has the patient recently increased his or her amphetamine use or started to binge?
Substance abuse history: Potentially abused substances include the following:
Alcohol
Marijuana
Cocaine
Lysergic acid diethylamide (LSD)
OTC sympathomimetics
Steroids
Family history: A family history of a psychiatric disorder may suggest a primary psychiatric disorder. A diagnosis of amphetamine-related psychiatric disorder might still be possible if the patient has no family history of psychiatric disorder.
The DSM-IV-TR criteria for amphetamine intoxication are as follows:
The patient has recently used an amphetamine or related substance, such as methylphenidate.
Clinically significant maladaptive behavioral or psychological changes developed during or shortly after the patient used amphetamines or a related substance. Such changes include the following:
Euphoria or affective blunting
Changes in sociability
Hypervigilance
Interpersonal sensitivity
Anxiety, tension, or anger
Stereotyped behaviors
Impaired judgment
Impaired social or occupational functioning
Two or more of the following conditions develop during or shortly after the patient used amphetamines or a related substance:
Tachycardia or bradycardia
Pupillary dilatation
Elevated or lowered blood pressure
Perspiration or chills
Nausea or vomiting
Evidence of weight loss
Psychomotor agitation or retardation
Muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias
Disorientation and memory loss, seizures, dyskinesias, dystonias, or coma
The symptoms are not due to a general medical condition, and another mental disorder does not account for them better than amphetamine intoxication does.
The DSM-IV-TR criteria for amphetamine withdrawal are as follows:
The patient has recently ceased or reduced heavy or prolonged use of amphetamines or related substances.
A dysphoric mood and 2 or more of the following physiologic changes develop within a few hours to several days after the patient ceases or reduces his or her use:
Fatigue
Vivid, unpleasant dreams
Insomnia or hypersomnia
Increased appetite
Psychomotor retardation or agitation
A complete mental-status examination must be preformed, with an emphasis on hallucinations, delusions, suicide and/or homicide, orientation, memory, and judgment.
The aforementioned symptoms cause clinically significant distress or impairment in terms of social, occupational, or other important areas of functioning.
The symptoms are not due to a general medical condition, and another mental disorder does not account for them better than amphetamine withdrawal does.
Physical: Full physical and neurologic examination should be performed. Initially assess patients for medical stability and then for level of danger.
During physical examination, assess the patient for medical complications of amphetamine abuse, including hyperthermia, dehydration, renal failure, and cardiac complications.
During neurologic examination, assess the patient for neurologic complications of amphetamine abuse, including subarachnoid and intracranial hemorrhage, delirium, and seizures.
Mental-status examination should emphasize delusions, hallucinations, suicide, homicide, orientation, insight and judgment, and affect.
Causes:
Amphetamine intoxication, binge pattern use, and long-term exposure
Comorbid psychiatric disorders
Abuse of other substances such as alcohol, OTC sympathomimetics, and illicit drugs
Dehydration
Fluoxetine (Prozac) - Increases CNS concentrations of amphetamine and potentiates its effects
Increased risk for HIV infection and acquiring other sexually transmitted diseases
In large metropolitan areas, gay men are at increased risk of HIV infection because of their use of crystal methamphetamine, also called Tina.
Crystal methamphetamine is commonly used in conjunction with gamma-hydroxybutyrate (GHB) and/or prescription drugs to treat erectile dysfunction medications, which helps to reverse the impotence crystal methamphetamines cause.
During euphoria, unsafe sexual activity is common, and individuals have little awareness or concern about the risks of sexual encounters.
DIFFERENTIALS Section 4 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
Cannabis Compound Abuse
Cocaine-Related Psychiatric Disorders
Delirium
Depression
Hallucinogens
Hyperthyroidism
Hypothyroidism
Inhalant-Related Psychiatric Disorders
Insomnia
Opioid Abuse
Phencyclidine (PCP)-Related Psychiatric Disorders
Schizophrenia
Toxicity, Heroin
Toxicity, Mushroom
Wernicke-Korsakoff Syndrome
Other Problems to be Considered:
AIDS-related complex
Thyrotoxicosis
Syphilis
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WORKUP Section 5 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
Lab Studies:
The purpose of the workup is to exclude complications of amphetamine abuse and other causes of psychosis and altered mental status.
Laboratory evaluation should include the following tests:
Finger-stick blood glucose test
CBC determination
Determination of electrolyte levels, including magnesium, amylase, albumin, total protein, uric acid, BUN, alkaline phosphatase, and bilirubin levels
Urinalysis
Stat urine or serum toxicology screening to exclude acetaminophen, tricyclic antidepressants, aspirin, and other potential toxins: Individuals who abuse drugs may ingest a substance called Urine Luck, or pyridinium chlorochromate (PCC), to produce invalid results on urine drug screens. PCC alters the results for cannabis and opiates but elevates levels of amphetamines.
Blood test for an alcohol level if the patient appears intoxicated
HIV and rapid plasma reagin (RPR) tests
Imaging Studies:
In the presence of neurologic impairments, CT or MRI helps in evaluating for subarachnoid and intracranial hemorrhage.
Other Tests:
Perform ECG to evaluate for cardiac involvement.
Perform EEG if a seizure disorder is considered possible.
Use of the brief psychotic rating scale (BPRS), Beck Depression Scale, violence and suicide assessment, and other measures may be helpful.
If persistent psychiatric conditions are noted, neuropsychological testing can be beneficial to assess levels of psychosocial and neurologic function to guide treatment and to assess the need for placement.
Results of projective testing, such as the Rorschach test and the Thematic Apperception Test, can help in clarifying thought disorders.
During amphetamine intoxication, the Mini-Mental State Examination (MMSE) can be helpful in measuring cognitive change.
Histologic Findings: Repeated exposure to amphetamines is theorized to alter the morphology of dendrites in the prefrontal cortex and in the nucleus accumbens. Amphetamines may increase the length of dendrites for longer than 1 month. These alterations may help explain the behavioral cravings and psychosis that long-term abuse of amphetamines produces.
TREATMENT Section 6 of 10
Author Information Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Bibliography
Medical Care: Initial treatment should include medically stabilizing the patient's condition by assessing his or her respiratory, circulatory, and neurologic systems. The offending substance may be eliminated by means of gastric lavage and acidification of the urine. Psychotropic medication can be used to stabilize an agitated patient with psychosis. Because most cases of amphetamine-related psychiatric disorders are self-limiting, removal of the amphetamines should suffice.
Induced emesis, lavage, or charcoal may be helpful in the event of overdose.
The excretion of amphetamines can be accelerated by the use of ammonium chloride, given either IV or orally (PO).
Amphetamine intoxication can be treated with ammonium chloride, often found in OTC expectorants, such as ammonium chloride (Quelidrine), baby cough syrup, Romilar, and P-V-Tussin.
The recommended dose to acidify the urine is ammonium chloride 500 mg every 2-3 hours.
The ingredients in OTC cough syrups vary, and the clinician should become familiar with 1 or 2 stock items for use in the emergency department.
Ammonium chloride (Quelidrine), an OTC expectorant, can be used in the absence of liver or kidney failure.
Administer IV fluids to provide adequate hydration.
If the patient is psychotic or if he or she is in danger of harming him or herself or others, a high-potency antipsychotic, such as haloperidol (Haldol), can be used. Exercise caution because of the potential for extrapyramidal symptoms, such as acute dystonic reactions, and neuroleptic malignant syndrome.
Agitation also can be treated cautiously with benzodiazepines PO, IV, or intramuscularly (IM). Lorazepam (Ativan) and chlordiazepoxide (Librium) are commonly used.
Administer naloxone (Narcan) in the event of concurrent opiate toxicity. Use caution to avoid precipitation of acute opioid withdrawal in a patient who has used high doses of opioid on a long-term basis.
Beta-blockers, such as propranolol (Inderal), can be used in the event of elevated blood pressure and pulse. They also may be helpful with anxiety or panic.
Consultations:
Neurologist
Internal medicine specialist
Psychiatrist: Consult for inpatient substance abuse treatment or further psychiatric stabilization.
Social services: Social services coordinate outpatient services, such as Alcoholics Anonymous and Narcotics Anonymous meetings and sober houses, and provide appointments. Some large metropolitan areas have groups that specifically focus on crystal methamphetamine abuse in the gay population.
Activity: Patients intoxicated with amphetamines are dangerous, and their activity should be limited (eg, no driving) until their symptoms have resolved.
MEDICATION Section 7 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
Several psychiatric conditions can be associated with amphetamine intoxication and withdrawal, all of which may require different management strategies. However, amphetamine-related psychiatric disorders are typically self-limited and usually remit on their own.
Amphetamine-related psychiatric disorders occur most often during intoxication; therefore, treatment should focus on controlling medical and psychiatric symptoms while eliminating the offending substance. Medical therapy involves stabilizing agitation and minimizing psychosis. Gastric lavage directly removes the amphetamines before they have an opportunity to be absorbed. Medication and charcoal eliminate amphetamines from the gastrointestinal and circulatory systems.
If the induced disorders persist and interfere with the patient's social and occupational functioning, treatment should be related to the remaining psychiatric symptoms. Antidepressants, such as sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa), can be used to treat depression. Antimanic agents, such as valproic acid (Depakote), carbamazepine (Tegretol), and lithium carbonate, can be used to treat mania. Anxiety can be treated with nonbenzodiazepine drugs, such as beta-blockers and antimanic agents.
Data from recent studies suggest typical antipsychotics (haloperidol thioridazine, Thorazine, etc) may increase amphetamine and cocaine cravings in patients with dual diagnoses of amphetamine and cocaine abuse. Typical antipsychotics should be used for acute stabilization with the intention of switching to an atypical antipsychotic drug (eg, risperidone, quetiapine, olanzapine, aripiprazole, and ziprasidone) for long-term use.
For the purposes of this discussion, specific treatment of amphetamine toxicity is reviewed. For further information, please refer to the articles on Depression, Substance-Induced Mood Disorder, Depressed Type, Bipolar Affective Disorder, Schizophrenia, Anxiety Disorders, and Sleeping Disorders.
Drug Category: Antipsychotics -- Clinicians should select a high-potency antipsychotic that is available in tablet, liquid, and IM forms for administration in emergency situations. Antipsychotics help control psychotic symptoms and provide rapid tranquilization of the agitated and psychotic patient.Drug Name Haloperidol (Haldol) -- Provides rapid sedation of agitated anxious patient; available PO and IM, allowing for flexible, emergency administration.
Adult Dose 2-5 mg PO/IV/IM
Pediatric Dose 0.5-2 mg PO/IV/IM
Contraindications Documented hypersensitivity; narrow-angle glaucoma; bone-marrow suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage
Interactions May increase TCA serum concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects; coadministration with anticholinergics may increase intraocular pressure; encephalopathy-like syndrome associated with concurrent administration of lithium
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in severe cardiovascular disease and in patients receiving anticonvulsants, anticoagulants, or rifampin; may increase prolactin levels; may cause extrapyramidal symptoms of muscle rigidity, inability to walk or talk, akathisia, and dystonia (opisthotonos and oculogyric crisis); extrapyramidal symptoms readily treated with benztropine mesylate (Cogentin), diphenhydramine (Benadryl) PO/IV/IM, or trihexyphenidyl (Artane)
Drug Name Thiothixene (Navane) -- Blocks postsynaptic blockade of CNS dopamine receptors, inhibiting dopamine-mediated effects. PO and IM forms allow for rapid tranquilization.
Adult Dose 5-20 mg PO/IM single dose or divided throughout day
Pediatric Dose 2.5-10 mg PO/IM single dose or divided throughout day
Contraindications Documented hypersensitivity; lactation; circulatory collapse; comatose; CNS depression by any cause; blood dyscrasias
Interactions Decreases effects of guanethidine; increases toxicity of CNS depressants, anticholinergics, and alcohol
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Increases prolactin levels; increases photosensitivity; caution in cardiovascular disease and history of convulsions or state of alcohol withdrawal (may precipitate seizures); may cause extrapyramidal symptoms of muscle rigidity, inability to walk or talk, akathisia, and dystonia (opisthotonos and oculogyric crisis); extrapyramidal symptoms readily treated with benztropine mesylate (Cogentin), diphenhydramine (Benadryl) PO/IV/IM, or trihexyphenidyl (Artane)
Drug Category: Benzodiazepines -- These drugs are primarily used to sedate agitated patients. Availability in PO, IV, and IM forms allowing the drug to be used in emergency situations. Caution must be used in the violent, aggressive patient because benzodiazepines may cause disinhibition.Drug Name Lorazepam (Ativan) -- Provides rapid onset and efficacy in sedating aggressive patient; flexible administration in emergency situation.
Adult Dose 5-10 mg PO/IV/IM single dose or divided over 24 h
Pediatric Dose 1-5 mg PO/IV/IM single dose or divided throughout day
Contraindications Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Interactions Toxicity of benzodiazepines in CNS increases with concurrent alcohol, phenothiazines, barbiturates, or MAOIs
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Because of concern of sedation in elderly and debilitated patients, initial doses should be 2 mg; caution in renal or liver failure; paradoxical excitement can occur, resulting in rage behavior; should be used with caution in patients who are depressed and at risk of suicide
Drug Name Chlordiazepoxide (Librium, Libritabs, Mitran) -- Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing activity of gamma-aminobutyric acid (GABA) activity, major inhibitory neurotransmitter.
Adult Dose 25-50 mg PO and repeat in 2-4 h if necessary
Pediatric Dose Not established
Contraindications Documented hypersensitivity; narrow-angle glaucoma
Interactions Coadministration with alcohols, phenothiazines, barbiturates, and MAOIs increases CNS toxicity; cisapride can significantly increase levels
Pregnancy D - Unsafe in pregnancy
Precautions Caution in patients receiving other CNS depressants or with low albumin levels or hepatic failure
Drug Category: Opiate antagonists -- These drugs inhibit the action of opiates.Drug Name Naloxone (Narcan) -- Used to treat concurrent opiate toxicity. Consider in patients with altered mental status due to opiate overdose. Poorly absorbed PO route and should be administered IM or IV. Available in IV, IM, and SC forms. Use caution to avoid precipitating acute opioid withdrawal in patient using opioids long term.
Adult Dose 0.4-2 mg IV/IM/SC/ET
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Interactions Decreases analgesic effects of narcotics
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in cardiovascular disease; naloxone may precipitate withdrawal symptoms in patients addicted to opiates
Drug Category: Beta-blockers -- Propranolol (Inderal) is useful in patients who are agitated, anxious, and hyperarousable because of amphetamines. They are temporarily used until the amphetamine is eliminated from the patient's system. For some patients, anxiety can be prolonged, and nonaddictive beta-blockers may be helpful.Drug Name Propranolol (Inderal) -- Antihypertensive agent useful in psychiatry to treat anxiety and impulse control. Often well tolerated with minimal effect on hemodynamics of blood pressure and pulse.
Adult Dose Immediate control of anxiety: 40 mg PO 1 dose
Persistent anxiety: 10 mg PO hs to 40 mg bid as initial dose, reaching maintenance dose not to exceed 120-240 mg qd
Pediatric Dose Acute anxiety: 0.5 mg/kg PO 1 dose
Persistent anxiety: 1 mg/kg PO per dosage schedule (0.5 mg/kg bid)
Contraindications Toxicity of benzodiazepines in CNS increases with concurrent alcohol, phenothiazines, barbiturates, or MAOIs; cardiogenic shock; sinus bradycardia; bronchial asthma; heart failure
Interactions Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; may increase toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Not indicated for hypertensive emergencies; use with caution in impaired renal or liver function; may reduce intraocular pressure and should be used with caution in glaucoma because withdrawal can cause rebound increase in intraocular pressure
Drug Category: Expectorants -- Expectorants are used to acidify the urine and increase amphetamine excretion when intoxication from amphetamines has resulted in psychiatric and medical complications. These agents are available in PO form, and the patient must be able to swallow or receive a nasogastric tube.Drug Name Ammonium chloride (Quelidrine) -- Commonly used as OTC expectorant; acidifies urine at high doses. Safe and easy to use.
Adult Dose Acidification of urine: 500 mg PO/IV q2-4h
As expectorant: 300 mg PO/IV q2-4h
Pediatric Dose Not established
Contraindications Documented hypersensitivity; severe hepatic and renal dysfunction; primary respiratory acidosis
Interactions May reduce aspirin, chlorpropamide, ephedrine, methadone, pseudoephedrine, spirolactone, and para aminosalicylic acid
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Caution in hepatic and renal impairment
Drug Category: Adsorbents -- These agents, given through a nasogastric tube into the stomach, absorb intentionally and accidentally ingested substances to prevent their further absorption into the systemic circulation.Drug Name Activated charcoal suspension (Actidose-aqua, Inst-Aqua, Liquid-Char) -- Bottles and tubes. Use long after amphetamine ingestion can reduce systemic levels by adsorbing amphetamines recirculating through gastric mucosa.
Adult Dose Bottle: 25-50 mg PO; dose depends on size of patient
Tube: 15-50 mg PO; dose depends on size of patient
Pediatric Dose Bottle: 25-50 mg PO; dose depends on size of patient; should begin with 15 mg in children and increase to 50 mg in adolescents; safe and well tolerated
Tube: 15-50 mg; dose depends on size of patient; should begin with 15 mg in children and increase to 50 mg in adolescents; safe and well tolerated
Contraindications Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies
Interactions May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases adsorptive properties)
Pregnancy A - Safe in pregnancy
Precautions Not effective in ethanol, methanol, or iron-salt poisoning; induce emesis before administration; after emesis with ipecac syrup, patient may not tolerate for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns black
FOLLOW-UP Section 8 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
Further Inpatient Care:
Admit the patient for observation in the event of mania, severe depression, psychosis, or delirium.
A patient who is in a state of delirium should be placed in a quiet, cool (not cold), dimly lit (not dark) room and, if uncontrollable, placed in restraints.
Further Outpatient Care:
The patient should be monitored closely for recurring psychosis, depression, mania, anxiety, sleep disturbances, and relapse of amphetamine abuse.
Psychiatric follow-up care should occur within, at most, 2 weeks of the initial evaluation to ensure compliance.
Depending on the complications of amphetamine abuse in the specific patient, consider a follow-up examination with a neurologist and an internal medicine specialist.
In/Out Patient Meds:
If psychosis persists after the offending substance is eliminated, use of an atypical antipsychotic (risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone) may be considered. No single atypical antipsychotic has been proven to be more beneficial than the others in managing prolonged amphetamine-induced psychosis.
Antimanic agents may be continued if mania persists longer than 2 weeks.
Antidepressants can be useful if depression persists for 2 weeks after withdrawal. Antidepressants alone may not be as effective as other options in amphetamine-induced depression due to neuronal damage. Medication regimens for treatment-resistant organic mood disorders are the applicable approach.
If anxiety persists longer than 2 weeks, consider the use of nonbenzodiazepine drugs. Medications such as beta-blockers, valproic acid, carbamazepine, or gabapentin have shown promise in patients with substance abuse who also have anxiety.
Sleep medication may help patients adjust their circadian rhythm and can be used for approximately 1-2 weeks. If sleep medication is required for long periods, a referral to a sleep clinic is recommended.
Transfer:
If psychiatric conditions persist, causing social and occupational impairment, inpatient treatment may be required.
Medical or neurologic complications require treatment in an inpatient medical or neurologic unit.
Deterrence/Prevention:
Abstinence prevents disorders and is the primary treatment.
Relapse prevention occurs though patient education, individual psychotherapy, appropriate medical treatment of continuing psychiatric illness (eg, major depression, panic disorder), and attendance at substance abuse meetings.
Mandatory weekly urine drug screens help prevent relapse or expose relapse early so that aggressive treatment intervention can be pursued.
If psychiatric conditions arise during prescription amphetamine use for ADHD, lower doses may be tried and/or nonamphetamine treatments can be pursued, such as bupropion (Wellbutrin), desipramine, venlafaxine (Effexor), or clonidine. Please refer to the Attention-Deficit/Hyperactivity Disorder article for a full discussion of treatment options.
Complications:
Complications include an increased risk of the following:
Psychosis
Depression
Anxiety disorder
Sleep disturbance
Memory impairment
Medical complications
Neurologic complications
Abuse of another or several substances
Psychosocial impairment
If amphetamine abuse and amphetamine-related psychiatric disorders occur in the context of 1 or more personality disorders, the amphetamine-related disorder is more difficult to successfully treat than it is in other contexts.
Prognosis:
The patient's prognosis depends on the severity of psychiatric impairment and on the medical complications.
Overall, the prognosis is good if the patient abstains from drug use after the initial psychiatric impairment occurs.
The prognosis worsens if personality disorders are present.
Patient Education:
Encourage the patient to abstain from the use of alcohol and illicit drugs, especially because dual diagnosis is a real issue. The only effective treatment is abstinence.
Patients should be in a support group.
The family must be educated about the patient's addiction and its dangers.
Refer the patient for psychosocial counseling.
Hospitalize the patient if he or she is suicidal or homicidal.
Refer the patient for substance abuse counseling.
For excellent patient education resources, visit eMedicine's Substance Abuse Center. Also, see eMedicine's patient education articles Drug Dependence and Abuse and Substance Abuse.
MISCELLANEOUS Section 9 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
Medical/Legal Pitfalls:
Failure to identify and treat medical and neurologic complications of amphetamine intoxication and withdrawal
Failure to evaluate for other potentially dangerous illicit drugs and medication
Failure to evaluate the patient for suicidal or homicidal tendencies
Failure to caution against driving when in an impaired mental state and failure to document this caution in the chart and/or medical record
BIBLIOGRAPHY Section 10 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
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NOTE:
Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER
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