Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Amphetamine-Related Psychiatric Disorders

  • Author: Amy Barnhorst, MD; Chief Editor: Eduardo Dunayevich, MD  more...
 
Updated: Dec 03, 2015
 

Background

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) describes the following 11 amphetamine-related psychiatric disorders:[1]

  1. Amphetamine-induced anxiety disorder
  2. Amphetamine-induced bipolar disorder
  3. Amphetamine-induced depressive disorder
  4. Amphetamine-induced psychotic disorder
  5. Amphetamine-induced sexual dysfunction
  6. Amphetamine-induced sleep disorder
  7. Amphetamine intoxication
  8. Amphetamine intoxication delirium
  9. Amphetamine withdrawal
  10. Amphetamine-induced obsessive-compulsive and related disorder
  11. Unspecified stimulant-related disorder

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, and some depression can be treated with amphetamines. 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.[2] 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.

In a web-based survey of 1,006 individuals who admitted mephedrone use, which is the largest survey to-date, results showed that users consider mephedro’e's effects to compare best with those of MDMA; the appeal of mephedrone for these individuals is in its availability, low price, and reliable purity.[3]

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. Such disorders can also be experienced during the withdrawal period from amphetamines. 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.

Unspecified stimulant-related disorder 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.

Case study

A 36-year-old white male who works as a real estate agent arrives at your office, depressed, disheveled, and slightly agitated. He is very guarded and reluctant to talk about his work history or relationships. After a period of time he describes how his coworkers are manipulating his clock to read 9:11, and the police drive by with their sirens on every day at 4:20. He refuses to open his mail, because he read secondary messages by rearranging letters. He admits to spending most of his time at home alone fixing his computer, sometimes all night long. His sleep cycle is reversed on the weekends, he is depressed most of the time, isolated, lost 25 lbs in the last 3 months, and has pale skin. Only when asked about the burn mark on his hand did he admit to "smoking some T." On further questioning he disclosed a 5-month period of crystal methamphetamine use.

Next

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 inhibition of the dopamine transporter in the striatum and nucleus accumbens. The longer the duration of use, the greater the magnitude of dopamine reduction. Methamphetamine has been suggested to induce psychosis through inhibiting the dopamine transporter, with a resultant increase in dopamine in the synaptic cleft.[4]

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.

Previous
Next

Epidemiology

Frequency

United States

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 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.

The rates for past month use of methamphetamine did not change from 2011 to 2013, remaining at approximately 0.2%. However, this does represent a nearly two-fold increase from the percentage of the population surveyed who had used in the last month in 2010 (0.1%). In 2013, an estimated 144,000 people became new users of methamphetamine, which is consistent with the new user initation rates of the preceding five years.[5]

Post-marketing studies of amphetamines prescribed to children and adolescents revealed a total of 865 unique case reports describing signs and/or symptoms of psychosis or mania, with nearly half reported in children 10 years or younger.[6]

International

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.[7] Khat dependency has been associated with people of Muslim religion and with people of low socioeconomic status.

Khat is also used to cope with the trauma of war in Somalia. One study showed that 36.4% of Somali combatants used khat 1 week prior to being interviewed.

Mortality/Morbidity

The Drug Abuse Warning Network (DAWN) Annual Medical Examiner Data for 2005 showed 10% of all drug-related hospital emergency department visits were stimulant-related. DAWN data indicated that 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, which 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.

Amphetamine withdrawal is consistent with a major depressive episode, though lasting less then 2 weeks and involving decreased energy, increased appetite, craving for sleep, and suicidal ideation.

Race-, sex-, and age-related demographics

Amphetamine-related psychiatric disorders most commonly occur in white individuals.

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.

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.

Previous
 
 
Contributor Information and Disclosures
Author

Amy Barnhorst, MD Assistant Clinical Professor, Department of Psychiatry and Behavioral Sciences, University of California, Davis, Medical Center; Medical Director of Crisis Services, County of Sacramento

Amy Barnhorst, MD is a member of the following medical societies: Association for Academic Psychiatry, California Medical Association, Sierra Sacramento Valley Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Glen L Xiong, MD Associate Clinical Professor, Department of Psychiatry and Behavioral Sciences, Department of Internal Medicine, University of California, Davis, School of Medicine; Medical Director, Sacramento County Mental Health Treatment Center

Glen L Xiong, MD is a member of the following medical societies: AMDA - The Society for Post-Acute and Long-Term Care Medicine, American College of Physicians, American Psychiatric Association, Central California Psychiatric Society

Disclosure: Received royalty from Lippincott Williams & Wilkins for book editor; Received grant/research funds from National Alliance for Research in Schizophrenia and Depression for independent contractor; Received consulting fee from Blue Cross Blue Shield Association for consulting. for: Received book royalty from American Psychiatric Publishing Inc.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Eduardo Dunayevich, MD Executive Director, Clinical Development, Amgen

Eduardo Dunayevich, MD is a member of the following medical societies: Schizophrenia International Research Society

Disclosure: Received salary from Amgen for employment; Received stock from Amgen for employment.

Additional Contributors

Michael F Larson, DO Clinical Instructor, Department of Child and Adolescent Psychiatry, Harvard Medical School; Psychiatrist, Harvard Vanguard Medical Associates and Private Practice

Michael F Larson, DO is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Child and Adolescent Psychiatry, American Society of Addiction Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Michael F Larson, DO Clinical Instructor, Department of Child and Adolescent Psychiatry, Harvard Medical School; Psychiatrist, Harvard Vanguard Medical Associates and Private Practice

Michael F Larson, DO is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Child and Adolescent Psychiatry, and American Society of Addiction Medicine

Disclosure: Nothing to disclose.

References
  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Washington, DC: American Psychiatric Association; 2013.

  2. Pardo-Lozano R, Farré M, Yubero-Lahoz S, O'Mathúna B, Torrens M, Mustata C, et al. Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"): the influence of gender and genetics (CYP2D6, COMT, 5-HTT). PLoS One. 2012. 7(10):e47599. [Medline]. [Full Text].

  3. Carhart-Harris RL, King LA, Nutt DJ. A web-based survey on mephedrone. Drug Alcohol Depend. 2011 Oct 1. 118(1):19-22. [Medline].

  4. Thirthalli J, Benegal V. Psychosis among substance users. Curr Opin Psychiatry. 2006 May. 19(3):239-45. [Medline].

  5. Substance Abuse and Mental Health Services Administration. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. 2014. Available at http://www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.pdf.

  6. Mosholder AD, Gelperin K, Hammad TA, Phelan K, Johann-Liang R. Hallucinations and other psychotic symptoms associated with the use of attention-deficit/hyperactivity disorder drugs in children. Pediatrics. 2009 Feb. 123(2):611-6. [Medline].

  7. Alem A, Kebede D, Kullgren G. The prevalence and socio-demographic correlates of khat chewing in Butajira, Ethiopia. Acta Psychiatr Scand Suppl. 1999. 397:84-91. [Medline].

  8. Shen W, Liu Y, Li L, Zhang Y, Zhou W. Negative moods correlate with craving in female methamphetamine users enrolled in compulsory detoxification. Subst Abuse Treat Prev Policy. 2012 Oct 30. 7:44. [Medline]. [Full Text].

  9. Bramness JG, Gundersen ØH, Guterstam J, Rognli EB, Konstenius M, Løberg EM, et al. Amphetamine-induced psychosis--a separate diagnostic entity or primary psychosis triggered in the vulnerable?. BMC Psychiatry. 2012 Dec 5. 12:221. [Medline]. [Full Text].

  10. McKetin R, Lubman DI, Baker AL, Dawe S, Ali RL. Dose-related psychotic symptoms in chronic methamphetamine users: evidence from a prospective longitudinal study. JAMA Psychiatry. 2013 Mar. 70(3):319-24. [Medline].

  11. Jayaram-Lindström N, Hammarberg A, Beck O, Franck J. Naltrexone for the treatment of amphetamine dependence: a randomized, placebo-controlled trial. Am J Psychiatry. 2008 Nov. 165(11):1442-8. [Medline].

  12. Gawin FH, Kleber HD. Cocaine abuse treatment. Open pilot trial with desipramine and lithium carbonate. Arch Gen Psychiatry. 1984 Sep. 41 (9):903-9. [Medline].

  13. Tiihonen J, Kuoppasalmi K, Föhr J, Tuomola P, Kuikanmäki O, Vorma H, et al. A comparison of aripiprazole, methylphenidate, and placebo for amphetamine dependence. Am J Psychiatry. 2007 Jan. 164 (1):160-2. [Medline].

  14. Elkashef AM, Rawson RA, Anderson AL, Li SH, Holmes T, Smith EV, et al. Bupropion for the treatment of methamphetamine dependence. Neuropsychopharmacology. 2008 Apr. 33 (5):1162-70. [Medline].

  15. Jayaram-Lindström N, Hammarberg A, Beck O, Franck J. Naltrexone for the treatment of amphetamine dependence: a randomized, placebo-controlled trial. Am J Psychiatry. 2008 Nov. 165 (11):1442-8. [Medline].

  16. Miles SW, Sheridan J, Russell B, Kydd R, Wheeler A, Walters C, et al. Extended-release methylphenidate for treatment of amphetamine/methamphetamine dependence: a randomized, double-blind, placebo-controlled trial. Addiction. 2013 Jul. 108 (7):1279-86. [Medline].

  17. Payer DE, Lieberman MD, London ED. Neural correlates of affect processing and aggression in methamphetamine dependence. Arch Gen Psychiatry. 2011 Mar. 68(3):271-82. [Medline].

  18. Anderson BB, Chen G, Gutman DA, Ewing AG. Dopamine levels of two classes of vesicles are differentially depleted by amphetamine. Brain Res. 1998 Mar 30. 788(1-2):294-301. [Medline].

  19. Brown ES, Nejtek VA, Perantie DC, et al. Cocaine and amphetamine use in patients with psychiatric illness: a randomized trial of typical antipsychotic continuation or discontinuation. J Clin Psychopharmacol. 2003 Aug. 23(4):384-8. [Medline].

  20. Cooper N. Inappropriate prescription of methylphenidate. N Z Med J. 2003 Oct 10. 116(1183):U636. [Medline].

  21. Drug Enforcement Agency. Drug Enforcement Agency: Khat. [Drug Enforcement Administration Web site]. [Full Text].

  22. Farber NB, Hanslick J, Kirby C, et al. Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity. Neuropsychopharmacology. 1998 Jan. 18(1):57-62. [Medline].

  23. Galanter M, Kleber DH, eds. American Psychiatric Press Textbook of Substance Abuse Treatment. 2nd ed. Arlington, VA: American Psychiatric Press; 1999.

  24. Guze BH, Ferng HK, Szuba MP, Richeimer SH. The Psychiatric Drug Handbook. St Louis, Mo: Mosby-Year; 1995. 184-260.

  25. Kaplan HI, Sadock BJ. Comprehensive Textbook of Psychiatry. Baltimore, Md: Lippincott Williams & Wilkins; 1995. 792-798.

  26. Kaplan HI, Sadock BJ. Pocket Handbook of Emergency Psychiatric Medicine. Baltimore, Md: Lippincott Williams & Wilkins; 1993. 108-110.

  27. Leamon MH, Gibson DR, Canning RD, Benjamin L. Hospitalization of patients with cocaine and amphetamine use disorders from a psychiatric emergency service. Psychiatr Serv. 2002 Nov. 53(11):1461-6. [Medline].

  28. Methamphetamine abuse and addiction. National Institute of Health, National Institue on Drug Abuse. January, 2002. Available at http://www.nida.nih.gov/ResearchReports/Methamph/Methamph.html.

  29. Sekine Y, Minabe Y, Ouchi Y, et al. Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms. Am J Psychiatry. 2003 Sep. 160(9):1699-701. [Medline].

  30. Sills TL, Greenshaw AJ, Baker GB, Fletcher PJ. Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction. Psychopharmacology (Berl). 1999 Feb. 141(4):421-7. [Medline].

  31. Srisurapanont M, Jarusuraisin N, Jittiwutikan J. Amphetamine withdrawal: II. A placebo-controlled, randomised, double-blind study of amineptine treatment. Aust N Z J Psychiatry. 1999 Feb. 33(1):94-8. [Medline].

  32. Thirthalli J, Benegal V. Psychosis among substance users. Curr Opin Psychiatry. 2006 May. 19(3):239-45. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.