|Other names||Stimulant-induced psychotic disorder|
|Specialty||Psychiatry, addiction psychiatry|
Stimulant psychosis is a mental disorder characterized by psychotic symptoms (e.g., hallucinations, paranoid ideation, delusions, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs following an overdose or several day 'binge' on psychostimulants; however, it has also been reported to occur in approximately 0.1% of individuals, or 1 out of every 1,000 people, within the first several weeks after starting amphetamine or methylphenidate therapy. Methamphetamine psychosis, or long-term effects of stimulant use in the brain (at the molecular level), depend upon genetics and may persist for some time.
Signs and symptoms
The symptoms of stimulant psychosis vary depending on the drug ingested, but generally involve the symptoms of organic psychosis such as hallucinations, delusions, paranoia, and thought disorder. Other symptoms may include mania, erratic behavior, and aggression.
Drugs in the class of amphetamines, or substituted amphetamines, are known to induce "amphetamine psychosis" typically when chronically abused or used in high doses. In an Australian study of 309 active methamphetamine users, 18% had experienced a clinical level psychosis in the past year. Common amphetamines include methamphetamine, ephedrine, MDMA, as well as substituted cathinones like methcathinone, MDPV, and mephedrone, though a large number of other related compounds have been recently synthesized. Methylphenidate is sometimes incorrectly included in this class, although it is nonetheless still capable of producing stimulant psychosis.
The symptoms of amphetamine psychosis include auditory and visual hallucinations, grandiosity, delusions of persecution, and delusions of reference concurrent with both clear consciousness and prominent extreme agitation. A Japanese study of recovery from methamphetamine psychosis reported a 64% recovery rate within 10 days rising to an 82% recovery rate at 30 days after methamphetamine cessation. However it has been suggested that around 5–15% of users fail to make a complete recovery in the long term. Furthermore, even at a small dose, the psychosis can be quickly reestablished. Psychosocial stress has been found to be an independent risk factor for psychosis relapse even without further substituted amphetamine use in certain cases.
The symptoms of acute amphetamine psychosis are very similar to those of the acute phase of schizophrenia although in amphetamine psychosis visual hallucinations are more common and thought disorder is rare. Amphetamine psychosis may be purely related to high drug usage, or high drug usage may trigger an underlying vulnerability to schizophrenia. There is some evidence that vulnerability to amphetamine psychosis and schizophrenia may be genetically related. Relatives of methamphetamine users with a history of amphetamine psychosis are five times more likely to have been diagnosed with schizophrenia than relatives of methamphetamine users without a history of amphetamine psychosis. The disorders are often distinguished by a rapid resolution of symptoms in amphetamine psychosis, while schizophrenia is more likely to follow a chronic course.
Although rare and not formally recognized, a condition known as Amphetamine Withdrawal Psychosis (AWP) may occur upon cessation of substituted amphetamine use and, as the name implies, involves psychosis that appears on withdrawal from substituted amphetamines. However, unlike similar disorders, in AWP, substituted amphetamines reduce rather than increase symptoms, and the psychosis or mania resolves with resumption of the previous dosing schedule.
Cocaine has a similar potential to induce temporary psychosis with more than half of cocaine abusers reporting at least some psychotic symptoms at some point. Typical symptoms of sufferers include paranoid delusions that they are being followed and that their drug use is being watched, accompanied by hallucinations that support the delusional beliefs. Delusional parasitosis with formication ("cocaine bugs") is also a fairly common symptom.
Methylphenidate and its analogues (e.g., ethylphenidate, 4F-MPH, and isopropylphenidate) share similar pharmacological profiles as norepinephrine-dopamine reuptake inhibitors. Chronic abuse of methylphenidate has potential to lead to psychosis. Similar psychiatric side effects have been reported in a study of ethylphenidate. No studies regarding psychosis and 4F-MPH or isopropylphenidate have been conducted but given their high DAT binding and cellular uptake activity, the possibility of stimulant psychosis exists.
There is limited evidence that caffeine, in high doses or when chronically abused, may induce psychosis in normal individuals and worsen pre-existing psychosis in those diagnosed with schizophrenia.
Though less common than stimulant psychosis, stimulants such as cocaine and amphetamines as well as the dissociative drug phencyclidine (PCP, angel dust) may also cause a theorized severe and life-threatening condition known as excited delirium. This condition manifests as a combination of delirium, psychomotor agitation, anxiety, delusions, hallucinations, speech disturbances, disorientation, violent and bizarre behavior, insensitivity to pain, elevated body temperature, and hysterical strength. Despite some superficial similarities in presentation excited delirium is a distinct (and more serious) condition than stimulant psychosis. The existence of excited delirium is currently debated.
Transition to schizophrenia
A 2019 systematic review and meta-analysis by Murrie et al found that the pooled proportion of transition from amphetamine-induced psychosis to schizophrenia was 22% (5 studies, CI 14%–34%). This was lower than cannabis (34%) and hallucinogens (26%), but higher than opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were slightly lower in older cohorts but were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up.
Treatment consists of supportive care during the acute intoxication phase: maintaining hydration, body temperature, blood pressure, and heart rate at acceptable levels until the drug is sufficiently metabolized to allow vital signs to return to baseline. Typical and atypical antipsychotics have been shown to be helpful in the early stages of treatment. In the instance of persistent psychosis after repeated use of stimulants, there are cases in which electroconvulsive therapy has been beneficial. This is followed by abstinence from psychostimulants supported with counseling or medication designed to assist the individual preventing a relapse and the resumption of a psychotic state.
- World Health Organization (2018). "ICD-11 for Mortality and Morbidity Statistics: 6C46.6 Stimulant-induced psychotic disorder including amphetamines, methamphetamine or methcathinone". Retrieved 7 April 2019.
- "Adderall XR Prescribing Information" (PDF). United States Food and Drug Administration. Shire US Inc. December 2013. Retrieved 30 December 2013.
Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without prior history of psychotic illness or mania can be caused by stimulants at usual doses. ... In a pooled analysis of multiple short-term, placebo controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.
- Shoptaw, Steven J; Kao, Uyen; Ling, Walter (21 January 2009). "Treatment for amphetamine psychosis". Cochrane Database of Systematic Reviews (1): CD003026. doi:10.1002/14651858.CD003026.pub3. PMC 7004251. PMID 19160215.
- Mosholder AD, Gelperin K, Hammad TA, Phelan K, Johann-Liang R (February 2009). "Hallucinations and other psychotic symptoms associated with the use of attention-deficit/hyperactivity disorder drugs in children". Pediatrics. 123 (2): 611–616. doi:10.1542/peds.2008-0185. PMID 19171629. S2CID 22391693.
- Greening, David W.; Notaras, Michael; Chen, Maoshan; Xu, Rong; Smith, Joel D.; Cheng, Lesley; Simpson, Richard J.; Hill, Andrew F.; van den Buuse, Maarten (10 December 2019). "Chronic methamphetamine interacts with BDNF Val66Met to remodel psychosis pathways in the mesocorticolimbic proteome". Molecular Psychiatry. doi:10.1038/s41380-019-0617-8. PMID 31822818. S2CID 209169489.
- Shoptaw SJ, Kao U, Ling W (2009). "Treatment for amphetamine psychosis (Review)". Cochrane Database of Systematic Reviews. 2009 (1): 1. doi:10.1002/14651858.cd003026.pub3. PMC 7004251. PMID 19160215.
- McKetin R, McLaren J, Lubman DI, Hides L. The prevalence of psychotic symptoms among methamphetamine users. Addiction 2006;101(10):1473–8.
- Dore G, Sweeting M (2006). "Drug-induced psychosis associated with crystalline methamphetamine". Australasian Psychiatry. 14 (1): 86–9. doi:10.1080/j.1440-1665.2006.02252.x. PMID 16630206. S2CID 196398062.
- Srisurapanont M, Ali R, Marsden J, Sunga A, Wada K, Monteiro M (2003). "Psychotic symptoms in methamphetamine psychotic in-patients". International Journal of Neuropsychopharmacology. 6 (4): 347–52. doi:10.1017/s1461145703003675. PMID 14604449.
- Sato M, Numachi Y, Hamamura T (1992). "Relapse of paranoid psychotic state in methamphetamine model of schizophrenia". Schizophrenia Bulletin. 18 (1): 115–22. doi:10.1093/schbul/18.1.115. PMID 1553491.
- Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329.
- Yui K, Ikemoto S, Goto K (2002). "Factors for susceptibility to episode recurrence in spontaneous recurrence of methamphetamine psychosis". Annals of the New York Academy of Sciences. 965 (1): 292–304. Bibcode:2002NYASA.965..292Y. doi:10.1111/j.1749-6632.2002.tb04171.x. PMID 12105105. S2CID 25830663.
- Alan F. Schatzberg; Charles B. Nemeroff (2009). The American Psychiatric Publishing Textbook of Psychopharmacology. The American Psychiatric Publishing. pp. 847–48. ISBN 978-1-58562-309-9.
- Chen CK, Lin SK, Pak CS, Ball D, Loh EW, Murray RM (2005). "Morbid risk for psychiatric disorder among the relatives of methamphetamine users with and without psychosis". American Journal of Medical Genetics Part B. 136 (1): 87–91. doi:10.1002/ajmg.b.30187. PMID 15892150. S2CID 25135637.
- McIver C, McGregor C, Baigent M, Spain D, Newcombe D, Ali R. Guidelines for the medical management of patients with methamphetamine-induced psychosis. Drug and Alcohol Services: South Australia 2006.
- Sarampote CS, Efron LA, Robb AS, Pearl PL, Stein MA (2002). "Can stimulant rebound mimic pediatric bipolar disorder?". J Child Adolesc Psychopharmacol. 12 (1): 63–7. doi:10.1089/10445460252943588. PMID 12014597.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000.
- Hegerl U, Sander C, Olbrich S, Schoenknecht P (August 2006). "Are psychostimulants a treatment option in mania?". Prog Neuropsychopharmacol Biol Psychiatry. 30 (6): 1097–102. doi:10.1016/j.pnpbp.2006.04.016. PMID 16740350. S2CID 13239942.
- Brady KT, Lydiard RB, Malcolm R, Ballenger JC (1991). "Cocaine-induced psychosis". J Clin Psychiatry. 52 (12): 509–512. PMID 1752853.
- Thirthalli J.; Vivek B. (2006). "Psychosis Among Substance Users". Curr Opin Psychiatry. 19 (3): 239–245. doi:10.1097/01.yco.0000218593.08313.fd. PMID 16612208. S2CID 13350537.
- Elliott A.; Mahmood T.; Smalligan R. D. (2012). "Cocaine Bugs: A Case Report of Cocaine-Induced Delusions of Parasitosis". The American Journal on Addictions. 21 (2): 180–181. doi:10.1111/j.1521-0391.2011.00208.x. PMID 22332864.
- DiSCLAFANI; et al. (1981). "Drug-induced psychosis: Emergency diagnosis and management". Psychosomatics. 22 (10): 845–855. doi:10.1016/s0033-3182(81)73092-5. PMID 7313045.
- Robins, Meridith T.; Blaine, Arryn T.; Ha, Jiwon E.; Brewster, Amy L.; Van Rijn, Richard M. (2019). "Repeated Use of the Psychoactive Substance Ethylphenidate Impacts Neurochemistry and Reward Learning in Adolescent Male and Female Mice". Frontiers in Neuroscience. 13: 124. doi:10.3389/fnins.2019.00124. PMC 6389692. PMID 30837836.
- McLaughlin, G.; Morris, N.; Kavanagh, P. V.; Power, J. D.; Dowling, G.; Twamley, B.; O'Brien, J.; Hessman, G.; Murphy, B.; Walther, D.; Partilla, J. S.; Baumann, M. H.; Brandt, S. D. (2017). "Analytical characterization and pharmacological evaluation of the new psychoactive substance 4-fluoromethylphenidate (4F-MPH) and differentiation between the (±)-threo- and (±)-erythro- diastereomers". Drug Testing and Analysis. 9 (3): 347–357. doi:10.1002/dta.2167. PMC 5378611. PMID 28103426.
- Markowitz, J. S.; Zhu, H. J.; Patrick, K. S. (2013). "Isopropylphenidate: An ester homolog of methylphenidate with sustained and selective dopaminergic activity and reduced drug interaction liability". Journal of Child and Adolescent Psychopharmacology. 23 (10): 648–54. doi:10.1089/cap.2013.0074. hdl:2027.42/140321. PMID 24261661.
- Morton WA, Stockton GG (2000). "Methylphenidate abuse and psychiatric side effects". Prim Care Companion J Clin Psychiatry. 2 (5): 159–64. doi:10.4088/pcc.v02n0502. PMC 181133. PMID 15014637.
- Spensley J, Rockwell D (April 1972). "Psychosis during methylphenidate Abuse". New England Journal of Medicine. 286 (16): 880–1. doi:10.1056/NEJM197204202861607. PMID 5061074.
- Robertson, Roy (2017). "Prolonged mental health effects of ethylphenidate beyond cessation of use". Addiction. 112 (1): 183–184. doi:10.1111/add.13630. PMID 27936504.
- McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V.; Power, John D.; Dowling, Geraldine; Twamley, Brendan; O'Brien, John; Hessman, Gary; Murphy, Brian; Walther, Donna; Partilla, John S.; Baumann, Michael H.; Brandt, Simon D. (March 2017). "Analytical characterization and pharmacological evaluation of the new psychoactive substance 4‐fluoromethylphenidate (4F‐MPH) and differentiation between the (±)‐threo and (±)‐erythro diastereomers". Drug Testing and Analysis. 9 (3): 347–357. doi:10.1002/dta.2167. PMC 5378611. PMID 28103426.
- Markowitz, John S.; Zhu, Hao-Jie; Patrick, Kennerly S. (December 2013). "Isopropylphenidate: An Ester Homolog of Methylphenidate with Sustained and Selective Dopaminergic Activity and Reduced Drug Interaction Liability". Journal of Child and Adolescent Psychopharmacology. 23 (10): 648–654. doi:10.1089/cap.2013.0074. hdl:2027.42/140321. PMID 24261661.
- Hedges, D. W.; F. L. Woon; S. P. Hoopes (September 2009). "Caffeine-induced psychosis". CNS Spectrums. 14 (3): 127–9. doi:10.1017/S1092852900020101. PMID 19407709. S2CID 32188625.
- Cerimele, Joseph M.; Stern, Adam P.; Jutras-Aswad, Didier (March 2010). "Psychosis Following Excessive Ingestion of Energy Drinks in a Patient With Schizophrenia". American Journal of Psychiatry. 167 (3): 353. doi:10.1176/appi.ajp.2009.09101456. PMID 20194494. S2CID 5832823.
- Broderick, P.; Benjamin, A. B. (2004). "Caffeine and psychiatric symptoms: A review". The Journal of the Oklahoma State Medical Association. 97 (12): 538–542. PMID 15732884.
- "White Paper Report on Excited Delirium Syndrome", ACEP Excited Delirium Task Force, American College of Emergency Physicians, 10 September 2009
- Murrie, Benjamin; Lappin, Julia; Large, Matthew; Sara, Grant (16 October 2019). "Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis". Schizophrenia Bulletin. 46 (3): 505–516. doi:10.1093/schbul/sbz102. PMC 7147575. PMID 31618428.
- Penders, T. M.; Lang, M. C.; Pagano, J. J.; Gooding, Z. S. (2013). "Electroconvulsive therapy improves persistent psychosis after repeated use of methylenedioxypyrovalerone ("bath salts")". The Journal of ECT. 29 (4): e59-60. doi:10.1097/YCT.0b013e3182887bc2. PMID 23609518. S2CID 45842375.