Psychosis in acute methamphetamine intoxication is usually self‐limiting and can be managed in the emergency department: A retrospective series

There is little recent published data characterising acute psychosis associated with methamphetamine intoxication. We aim to describe the clinical features of psychosis, management of acute behavioural disturbance and disposition of patients with psychosis associated with acute methamphetamine intoxication.


Introduction
Methamphetamine use represents a major social and medical problem in Australia, accounting for 8.2% of all drug-related hospitalisations. 1 Australia's average consumption is high at 41 doses per 1000 people per day, when compared to 28 countries across Europe, Oceania and Asia. 2 Mortality in Australia is rising, with greater than a four-fold increase in amphetamine-related deaths noted in 2020 compared to 2000 (2.1 deaths compared with 0.5 deaths per 100 000 population, respectively). 1 Individuals intoxicated with methamphetamines often present to ED with acute behavioural disturbance and psychosis. 3,4Management of psychosis associated with methamphetamine intoxication can be difficult, resource-intensive, 5,6 and integral in ensuring staff and patient safety.Patients often require physical, mechanical and chemical restraint and spend long periods of time in emergency resuscitation bays. 3,7,8These

• In individuals presenting to
ED with acute methamphetamine intoxication, transient psychotic symptoms appear to occur commonly, but usually resolve with the resolution of intoxication.• Most patients in our series were managed within the ED shortstay unit and mental health admission was uncommon.
patients often have a dedicated mental health assessment once the intoxication has resolved. 3,6,9ethamphetamine use can produce a transient psychosis, lasting less than 24 h, typically manifesting in persecutory delusions and hallucinations. 10,11here is also a considerable association between methamphetamine use and primary psychotic disorders, such as schizophrenia. 12There is limited research that specifically distinguishes the acute, transient psychosis that occurs with methamphetamine intoxication, from the longer-lasting psychotic symptoms observed in persistent methamphetamine-associated psychosis and primary psychotic disorders. 13We aim to describe the clinical features of psychosis, management of acute behavioural disturbance, and disposition of patients with psychosis associated with acute methamphetamine intoxication.

Study design and setting
This is a retrospective observational study of patients presenting with suspected methamphetamine intoxication and evidence of psychosis to the ED at the Princess Alexandra Hospital (PAH) in Brisbane, Australia.The PAH is a tertiary adult (>15 years of age) hospital with an ED that has approximately 70 000 presentations each year.The PAH Clinical Toxicology Unit manages all patients presenting with poisoning, intoxication and envenomation.It admits approximately 2000 patients each year.All toxicological presentations are prospectively entered into a database that undergoes regular weekly audit.All identified acute methamphetamine-related presentations in ED are referred to the Clinical Toxicology Unit.The toxicology team conduct a bedside mental health assessment during review of each patient and refer to the mental health unit as required.A dedicated mental health unit operates in PAH ED and reviews patients in parallel with the Clinical Toxicology Unit.Mental health services document patients' clinical notes and diagnoses in the Consumer Integrated Mental Health and Addiction (CIMHA) application.
Management of acute behavioural disturbance in the PAH is standardised per a local area guideline (Fig. S1).The Sedation Assessment Tool (SAT) scoring system 14 is used to assess degree of patient agitation (Table 1).Patients with a SAT score of 1 are offered either oral diazepam 10-20 mg or olanzapine 10 mg.Those with a SAT score of 2 or 3 receive intramuscular droperidol 10 mg as first-line management, if unable to be verbally de-escalated.

Patient selection
All adult patients (>15 years) presenting to the PAH with suspected acute methamphetamine intoxication and psychotic symptoms on arrival, during a 4-month period from January to April 2020, were included in the present study.Acute methamphetamine exposure was defined as exposure within the 24 h preceding hospital presentation.Methamphetamine exposure was determined by patient self-report, or when this was not provided, through clinical examination findings consistent with sympathomimetic toxidrome and collateral history suggestive of methamphetamine use.Routine analytical testing was not performed to confirm the presence of methamphetamine.Psychotic symptoms were defined in accordance with the DSM-5 as presence of delusions, hallucinations or disorganised thinking/ speech (inferring a formal thought disorder). 15

Analysis
Descriptive statistics were used, with continuous variables reported as medians, interquartile ranges and ranges.To compare proportions a two-tailed z test was used, with a P-value of <0.05 considered significant.All analysis was performed in GraphPad Prism 9 for Mac OS (GraphPad Software, San Diego, CA, USA).Of the 205 presentations with evidence of psychosis, the commonest features were delusional thinking (72%), disorganised thinking/speech (55%) and auditory hallucinations (34%) (Table 3).There were 28 (14%) presentations with all three features.
Sedation was given in 194 (95%) exposures and constituted the mainstay of managing acute behavioural disturbance, in addition to supportive care.Oral sedation was given in 51 (25%) presentations, parenteral sedation (droperidol) was given in 76 (37%) presentations and a combination was given in 67 (33%) presentations (Table 4).There were 10 (5%) presentations where rescue chemical sedation was given to individuals with acute behavioural disturbance refractory to droperidol.All 10 presentations received parenteral lorazepam, two also received ketamine.There were no significant complications due to sedation.
Complete resolution of psychosis occurred in 170 exposures (83%).Complete resolution occurred less frequently when comparing those with pre-existing psychotic disorders to those without a previous diagnosis (51/70, 73% vs 119/135, 88%; P = 0.006).Clinical features of patients with transient (resolved within 24 h) and persisting psychosis are compared in Table 3; persecutory (P = 0.0002) and grandiose (P = 0.0001) delusions and oral route of exposure (P = 0.001) were more common in those with a persisting psychosis.A dedicated mental health assessment occurred in 55 (27%) presentations and 9 (4%) resulted in a mental health admission (Table 3).Of the nine mental health admissions, eight were for management of psychosis (three diagnosed with drug-induced psychosis, five for relapse of their primary psychotic disorder) and one was for suicidal ideation.The remaining 27 (13%) presentations with ongoing psychosis were reviewed by the mental health unit and discharged with persisting psychosis for community management.Almost all (200/205, 98%) patients were managed within the ED (primarily the short-stay unit, 163 [80%]) with a median length of stay of 15 h (IQR 11-20 h).

Discussion
Psychosis appears to be a common clinical feature of acute methamphetamine intoxication and can occur in the absence of features of a sympathomimetic toxidrome.In the present study, we observed that psychosis was usually transient, resolving  within 24 h as the acute intoxication passes.Persisting psychosis appeared to be less common, occurring in 17% of presentations in this series with 4% of patients admitted to the mental health unit.
Methamphetamine use places significant burden on the healthcare system.In 2013, the annual healthcare cost of methamphetamine use in Australia was estimated to be $270.8million. 5Nationally, methamphetamine use was estimated to have resulted in 29 700-151 800 additional ED presentations and 28 400-80 900 additional psychiatric admissions to hospitals in 2013. 16More recent, statebased data suggests the burden has only worsened; in 2021, Victoria recorded 2319 ambulance attendances for methamphetamine, of which 1906 (82%) were transported to hospital and 1150 required police co-attendance.This is in comparison to 1536 attendances in 2013. 17ethamphetamine use places particular strain on acute mental health services with the most common indication for admission to hospital being for mental health disorders.In a prospective study of 138 amphetamine users, between 2005 and 2009 there were 309 separations for 'mental disorders', with a total combined length of stay of 3671 days.In contrast, 'injury and poisoning', the second most common indication, had 114 separations with a combined length of stay of 211 days. 18SW Health data for 2017-2018 indicate that individuals presenting to ED with an amphetamine-related diagnosis are about 22 times more likely than the general population to receive inpatient psychiatric care (50.9% vs 2.3%, respectively). 6otably, our cohort recorded a significantly lower rate of mental health admission (4% of presentations), likely reflecting a site-specific difference in how patients with transient methamphetamine-induced psychosis are managed at our site with mental health referral occurring only after the intoxication has resolved.
Inpatient psychiatric care is also burdensome, with high rates of absconding 19 and aggression towards staff and patients. 6,19Individuals who use methamphetamines are also four times more likely to be readmitted to hospital within 28 days of their last admission. 19Clinical opinions may differ as to whether management of ABD and psychotic symptoms should occur in an ED versus mental health unit.When psychiatric review is 'mandated' for patients with these symptoms, this places further pressure on the acute mental health system. 6t appears that the transient psychosis related to acute methamphetamine intoxication may be a separate clinical entity to the persistent methamphetamine-associated psychosis that likely reflects a primary psychotic disorder in vulnerable patients. 13The most common manifestation of psychosis associated with methamphetamine intoxication in the present study was paranoid delusions, followed by visual and auditory hallucinations.This is similar to a longitudinal, prospective cohort study examining the lifetime experience of psychotic symptoms in methamphetamine-dependent individuals.Individuals reporting persistent methamphetamine-related psychoses had similar symptoms to primary psychotic disorders: delusions of reference, thought interference and complex auditory hallucinations. 13In comparison, transient psychosis associated with acute intoxication was typically paranoid delusional, with similar rates of visual and auditory hallucinations.
This theory is supported by other researchers when comparing transient methamphetamine-related psychotic symptoms with those that are more persistent. 20chneiderian first-rank symptoms (FRS) appear to be specific to persistent methamphetamine psychosis and primary psychosis. 13,20These symptoms include delusional perceptions; auditory hallucinations experienced as voices speaking one's thoughts, voices commenting on one's actions and voices arguing; and seven types of delusions: thought withdrawal, thought broadcasting, thought insertion, somatic passivity, belief that one's emotions are not one's own, and belief that impulses and/or actions are controlled by an outside force. 21,22Schneiderian FRS may be an important clinical marker for identifying individuals at risk of experiencing persistent psychosis, who would benefit from early intervention to prevent persistent psychoses or development of a chronic psychotic disorder. 13In our series, grandiosity and persecutory delusions appeared to occur more commonly in patients with persisting (>24 h) methamphetamine psychosis.
Our series suggests that those with acute methamphetamine intoxication and psychosis can be managed supportively through their period of intoxication in the ED short-stay environment.We propose that if psychotic symptoms resolve, the focus of treatment can be on addressing the underlying methamphetamine use disorder.Diverting these patients away from routine mental health Median length of stay (IQR), hour 15 (11-20)    †Admission to ward under subspecialty: one patient under general medicine for alcohol withdrawal, one patient under general surgery for trauma, two patients under orthopaedics for osteomyelitis/wound washout, one patient under infectious diseases for sepsis.IQR, interquartile range.review would not only rationalise important psychiatric resources, but may re-centre the clinical focus on Alcohol & Other Drug involvement, consistent with recommendations from the 2020 NSW special commission into methamphetamines. 6he present study provides evidence that while paranoid-delusional psychotic features are common in methamphetamine intoxication, they are typically transient, may occur in the absence of sympathomimetic features, and usually do not require mental health admission or dedicated mental health review.The median length of stay was 15 h.We suggest that most presentations can be managed with sedation in the short-stay environment.Specific short-stay behavioural units located in the ED, resourced to provide a multidisciplinary approach towards drug use and intoxication, may reduce burden on already busy EDs.
The prevalence of mental health disorders in our study was expectedly higher than the general population, where lifetime morbid risk of schizophrenia has been estimated to be 7.2 per 1000. 23In our series 71% of all presentations of methamphetamine intoxication had psychosis.The prevalence of psychotic symptoms in the present study (205 presentations with psychotic features, from a total of 287 presentations) was also higher than the prevalence of 36.5% reported in a 2018 meta-analysis of methamphetamine users.The meta-analysis was limited by significant inter-study heterogeneity and acknowledged uncertainties in distinction between methamphetamine-induced psychotic symptoms versus disorder, as well as methamphetamine use versus methamphetamine use disorder. 24The increased prevalence of both methamphetamine-induced psychosis and psychiatric illness in our study may be explained by several factors.Our study selected for individuals presenting to ED with acute methamphetamine intoxication often associated with acute behavioural disturbance prompting intervention, whereas the meta-analysis and cross-sectional study included individuals in the community with lower acuity.Methamphetamine users and individuals with psychosis are potentially less likely to seek healthcare in the community, 16,25,26 selecting for more severe presentations in higher-risk, more comorbid individuals presenting to ED.Additionally, one quarter (28%) of patients in the present study reported homelessness, which is correlated with an increased prevalence (21%) of psychotic disorders. 27While complete resolution of psychosis occurred in the majority (83%) of presentations, individuals with pre-existing diagnosis of a primary psychotic disorder were more likely to have persisting psychotic symptoms.This may suggest an association between methamphetamine use and relapse of the primary psychotic disorder.
The present study is limited by its retrospective design and potential inaccuracies in the documented risk assessment.It is possible clinical features of psychosis were under-reported.The clinical toxicology unit prospectively enters all exposures into its clinical database, which includes information on the most important clinical effects and management, minimising some of the limitations of the retrospective design.Accuracy was also improved by access to patients' electronic medical records, which include detailed progress notes.Another limitation of the study was that formal mental health evaluation occurred in only 27% of presentations, raising the possibility of diagnostic error; however, this effect should be limited as the abstractor did not rely on clinician diagnosis of psychosis but rather the presence of psychotic symptoms throughout the entire presentation.
Furthermore, co-exposures like cannabis may have contributed to psychosis, albeit this only occurred in 4% of presentations so is unlikely to have a large effect.Methamphetamine exposure was not confirmed by analytical testing, rather relying on the patient's history and clinical examination.Previous literature has supported the reliability of patient report when presenting with deliberate exposure to a single drug. 28

Conclusions
Acute psychosis was common in this series of patients presenting to ED with acute methamphetamine intoxication, and occurred in some that did not have a sympathomimetic toxidrome.Psychosis was transient in 83% and resolved with the resolution of intoxication.Most patients were successfully managed within a short-stay environment with sedation and supportive care.

TABLE 1 .
14dation Assessment Tool14 median age 36 years, range 16-57 years) had features of psychosis and were included in the study.Baseline characteristics of the presentations are presented in Table2.Preexisting mental health diagnoses and injecting drug use were common.

TABLE 2 .
Baseline characteristics of 205 presentations of acute methamphetamine intoxication with features of psychosis, from January to April 2020

TABLE 3 .
Clinical features of psychosis in methamphetamine intoxication, in presentations with transient (resolved <24 h) psychosis compared with presentations where psychosis did not resolve within 24 h

TABLE 4 .
Management of behavioural disturbance and disposition of 205 presentations with methamphetamine intoxication and psychosis