Comparison of Psychiatric and Clinical Profiles Between People Who Use Synthetic Cathinones and Methamphetamine

Abstract

Background

Synthetic cathinones are the most used novel psychoactive substances in Taiwan because they exhibit psychoactive effects similar to those of methamphetamine, inducing acute psychosis, violence, and self-harm. However, the differences in the clinical characteristics of patients with synthetic cathinone and methamphetamine intoxication admitted to psychiatric emergency departments (EDs) remain unclear.

Methods

This study recruited patients with stimulant intoxication who were admitted to a psychiatric ED from April 2019 to May 2020. Sociodemographic, lifestyle, and psychopathological data were collected through face-to-face interviews and evaluated. Immunoassay tests and liquid chromatography–quadrupole time-of-flight mass spectrometry were performed to detect substances in urine specimens. The patients were matched by sex and age (in 5-year intervals). The associations between the 2 groups and physical complications were analyzed through logistic regression.

Results

Twenty-four patients with synthetic cathinone intoxication were identified and matched with 48 patients with methamphetamine intoxication. The 2 groups exhibited similar clinical severity of psychotic symptoms and high risks of violence and self-harm. Both groups were predominated by unmarried patients, unemployed patients, and habitual smokers and drinkers. However, family histories of substance use and criminal records were less prevalent among the patients with synthetic cathinone intoxication, but they had a higher rate of physical complications (odds ratio, 8.55; 95% confidence interval, 2.15–34.03), compared with patients with methamphetamine intoxication.

Conclusions

Compared with patients intoxicated with methamphetamine, those intoxicated with synthetic cathinones may have similar tendencies toward psychosis, violence, and self-harm but higher risks of physical complications, which are prioritized in psychiatric EDs.

Novel psychoactive substances (NPSs) have become the most used substances worldwide because many have psychoactive effects similar to those of traditional illicit substances but remain unregulated.¹ More than 500 types of NPS are known globally.² On the basis of their clinical psychoactive characteristics, NPSs can be classified as stimulants, sedatives, or hallucinogens.³ Synthetic cathinones, which constitute 1 of the most common types of NPS in Asia, can mimic the effects of methamphetamine, cocaine, or 3,4-methylenedioxymethamphetamine.⁴

In Taiwan, heroin, methamphetamine, and ketamine have been the most used illicit substances for decades,⁵ posing substantial threats to physical and mental health.⁶ According to police records and customs data, the amount of NPSs seized in 2020 was 40 times higher than it was in 2015,⁷ and this figure might be underestimated⁸ because people who use stimulants might unexpectedly consume substances mixed with NPSs.⁹ At present, synthetic cathinone mixtures¹⁰ are the most used NPSs in Taiwan,¹¹ often circulating, disguised as coffee packets, tea bags, or snacks. The Taiwanese legal schedules a substance only when that substance is determined by professionals or authorities to be addictive, commonly used, and harmful to society.¹¹ For years, 3,4-methylenedioxypyrovalerone and mephedrone have been regulated¹² in Taiwan; however, substance manufacturers can change an illicit substance into a legal one by modifying its chemical structures, thus evading the law.¹⁰ Many types of synthetic cathinone are unregulated in Taiwan, and their potential for harm may be underestimated.

People who use synthetic cathinones might visit emergency departments (EDs) for acute intoxication symptoms.¹³ When such patients exhibit agitation or attempt self-harm,¹¹ psychiatrists are consulted regarding related safety concerns and treatment suggestions. The psychiatric symptoms of synthetic cathinone intoxication are similar to those of stimulant intoxication or the acute exacerbation of psychosis,¹⁴ including agitation (82%), paranoia (36%), and hallucinations (40%).¹⁵

Because patients with stimulant use disorder often have comorbid psychiatric disorders that have not been adequately treated, they are prone to psychosocial dysfunction and physical illness,¹⁶ including criminality,¹⁷ high-risk sexual activity, cardiovascular complications, and infection.¹⁸ Compared with those who use traditional stimulants, people who use NPSs may unintentionally use additional substances, such as nonprescription sedatives, reducing their sympathomimetic toxidromes.¹⁹ However, limited by the cost and efficacy of clinical examinations for NPS use,¹⁰ specialists at EDs cannot efficiently distinguish synthetic cathinone intoxication from methamphetamine intoxication on the basis of psychiatric manifestations or initial chief complaints alone.²⁰ The risks of violence, vital organ failure, and even fatality from synthetic cathinone intoxication may be undervalued.^8,19,21 If patients with stimulant intoxication and physical or psychiatric complications can be rapidly identified as those who use synthetic cathinones, individualized treatment or addiction interventions may become more feasible. Therefore, we compared the clinical characteristics and severity of psychiatric symptoms among patients with synthetic cathinone and methamphetamine intoxication from a psychiatric ED.

MATERIALS AND METHODS

Patients

This retrospective study recruited patients who arrived at a psychiatric ED with 3350 ED visits annually in average from April 2019 to May 2020. Patients presenting with acute delirium, first-episode psychosis, or a history of NPS use were initially subjected to urine toxicology. Urine specimens were collected for immunoassay tests to detect morphine, methadone, cocaine, methamphetamine (limit of detection, 500 ng/mL urine), tetrahydrocannabinol, phencyclidine, barbiturates, and benzodiazepines. Liquid chromatography–quadrupole time-of-flight mass spectrometry was adopted to detect more than 100 NPSs (limits of detection, 50 ng/mL urine), including synthetic cathinones.²² In total, 120 patients with stimulant intoxication were recruited based on their urine examination reports, their clinical profiles, and the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) criteria for stimulant intoxication. The Research Ethics Committee of TYPC approved this study (institutional review board number B20190902).

Clinical Assessments

Psychopathological manifestations were evaluated on the basis of the Brief Psychiatric Rating Scale (BPRS), which has 18 items scored from 1 to 7 (range, 7–126)²³; and Clinical Global Impression—Severity (CGI-S; range, 1–7).²⁴ In face-to-face interviews, ED psychiatrists collected sociodemographic data, including sex, age, educational attainment, and occupational and marital status, as well as lifestyle and substance-related data, including smoking and alcohol use habits, family psychiatric history, personal history, and other substance use–related factors. We defined violent behaviors according to the following definition provided by the World Health Organization: “The intentional use of physical force or power, threatened or actual, against oneself, another person, or against a group or community, that either results in or has a high likelihood of resulting in injury, death, psychological harm, maldevelopment or deprivation.”²⁵ Substance-related crimes were excluded from criminal histories in our study because most synthetic cathinones were not designated as illicit in Taiwan. We would compare the rate of other crimes between the patients who use synthetic cathinones and those who use methamphetamine. In this study, physical complications were defined as those related to stimulant intoxication, including rhabdomyolysis, acute kidney failure, dystonia, and muscle weakness. Patients were considered to be transfer patients if they were transferred from the psychiatric ED to the general hospital as a result of unstable vital signs due to physical complications. Hospitalization in our study was defined as admission to an acute psychiatric ward for related treatment. On the basis of urine toxicology testing, synthetic cathinone intoxication was identified in 24 patients, who were recruited and matched by age (intervals of <5 years) and sex with 48 patients with only methamphetamine intoxication (control group). The patients' vital signs, serum parameters, length of ED stay, and length of hospitalization obtained from chart reviews.

Statistical Analysis

Fisher exact test and the independent-samples t test were respectively used for binary comparisons of categorical and continuous data between groups of patients (ie, those with synthetic cathinone or methamphetamine intoxication, requiring or not requiring hospitalization, and with or without physical complications). The laboratory data are expressed as medians with interquartile ranges, and the nonparametric Mann-Whitney U test was used for group comparisons. To evaluate the association between synthetic cathinone use and the risk of physical complications, we conducted logistic regression analysis with adjustment for CGI-S and BPRS scores. A 2-sided P value of <0.05 was considered statistically significant. Adjustments of the P values were not made out of consideration of the possible type II errors and interrelations that may occur among the characteristics of the two groups with a small effect size. All P values from the multiple comparisons would be demonstrated. All statistical analyses were conducted in IBM SPSS 26 (Chicago, IL).

RESULTS

Clinical Characteristics of Patients

Table 1 presents the clinical characteristics of the patients with synthetic cathinone or methamphetamine intoxication. Among the 72 patients, 24 had synthetic cathinone intoxication, and 48 had methamphetamine intoxication. The mean age was 31.1 years (SD, 6 years; range, 19–44 years). Men were predominant (87.5%) in the study population. Delusions (cathinone, 79.2%; methamphetamine, 66.7%) and hallucinations (cathinone, 58.3%; methamphetamine, 47.9%) were common psychotic symptoms in both groups. Violent behaviors were also common (>50%) in both groups. Moreover, 3 (12.5%) and 11 patients (22.9%) in the synthetic cathinone and methamphetamine groups, respectively, attempted suicide.

TABLE 1.

Clinical Characteristics of Patients With Synthetic Cathinone or Methamphetamine Intoxication

Characteristics	Synthetic Cathinone (n = 24)	Methamphetamine (n = 48)	P
Age, y	30.4 ± 6.5	31.5 ± 5.7	0.480
Male	21 (87.5)	42 (87.5)	1.000
Married	3 (12.5)	5 (10.4)	1.000
Educational year	8.8 ± 4.6	10.4 ± 4.1	0.136
Job	15 (62.5)	21 (43.8)	0.211
Family history
Psychotic disorder	2 (8.3)	3 (6.3)	1.000
Mood disorder	3 (12.5)	10 (20.8)	0.522
Substance use	0 (0.0)	9 (18.8)	0.025
Personal history			0.358
Psychotic disorder	5 (20.8)	11 (22.9)
Depressive disorder	5 (20.8)	4 (8.3)
Bipolar disorder	2 (8.3)	2 (4.2)
Smoking	21 (87.5)	36 (75.0)	0.356
Alcohol	12 (50.0)	31 (64.6)	0.309
No. illicit substance use	2.6 ± 1.3	1.9 ± 1.1	0.028*
Criminal history	5 (20.8)	25 (52.1)	0.013*
Psychotic symptoms
Delusions	19 (79.2)	32 (66.7)	0.410
Hallucinations	14 (58.3)	23 (47.9)	0.460
Thought disorder	5 (20.8)	14 (29.2)	0.575
Self-harm	3 (12.5)	11 (22.9)	0.359
Violence	13 (54.2)	27 (56.3)	1.000
CGI	6.21 ± 0.98	5.98 ± 1.02	0.366
BPRS	71.7 ± 13.8	67.3 ± 11.6	0.157
Physical complications	11 (45.8)	4 (8.3)	<0.001†
No. detected illicit substance	3.0 ± 1.3	1.0 ± 0.0	<0.001†
Temperature, °C	37.0 ± 0.9	36.6 ± 0.6	0.022
Respiratory rate, breaths/min	20.2 ± 2.4	18.8 ± 1.1	0.001†
SBP, mm Hg	132.3 ± 25.0	129.7 ± 21.0	0.638
Heart rate, beats/min	108.5 ± 23.3	103.0 ± 21.1	0.324
Length of stay at ED, h	25.8 ± 19.1	30.3 ± 27.9	0.476
Transfer	3 (12.5)	2 (4.2)	0.325
Hospitalization	9 (37.5)	15 (31.3)	0.607

Data are presented as frequency (percentage) or mean ± SD.

*P < 0.05.

^†P < 0.01.

SBP indicates systolic blood pressure.

Clinical Characteristics of Patients With Synthetic Cathinone or Methamphetamine Intoxication

Compared with the methamphetamine group, the synthetic cathinone group tended to use more substances (2.6 ± 1.3 vs 1.9 ± 1.1, P = 0.028) and have more illicit substances detected (3.0 ± 1.3 vs 1.0 ± 0.0, P < 0.001) and experienced more physical complications (45.8% vs 8.3%, P < 0.001). Three of the 11 patients in the synthetic cathinone group with physical complications were referred to general hospitals for treatment of progressive rhabdomyolysis, persistent dystonia, and muscle weakness with paresthesia, and 2 of the 4 patients in the methamphetamine group with physical complications were transferred for treatment of rhabdomyolysis and acute kidney injury. By contrast, the synthetic cathinone group was less likely to have a family history of substance use (0% vs 18.8%, P = 0.025) or a criminal history (20.8% vs 52.1%, P = 0.013). Despite the exclusion of substance-related crimes including trafficking and dealing, and those on deferred prosecution, the methamphetamine group had more criminal offenses, such as jeopardizing public safety, assaults, and theft. Notably, the CGI and BPRS scores were not significantly different between the 2 groups (Table 1). An additional comparison of the groups' laboratory data is provided in Supplementary Table 1, http://links.lww.com/JCP/A838.

Detection of Synthetic Cathinones and Illicit Substances

Figure 1 illustrates the distribution of detected synthetic cathinones. The most common synthetic cathinone was methcathinone (n = 16 [66.7%]), followed by eutylone, mephedrone (both n = 6 [25%]), and ephylone (n = 3 [12.5%]). The other less common (<10%) synthetic cathinones were acetyl-3,4-MDMC, methylone, dibutylone, and 4-chloromethcathinone. Figure 2 presents the distribution of other substances detected in the urine of patients with synthetic cathinone intoxication. In addition to synthetic cathinones, benzodiazepines (62.5%), methamphetamine (37.5%), caffeine (33.3%), antihistamines (25%), antitussives (25%), and acetaminophen (16.7%) were detected. All toxicity analyses for the methamphetamine group detected methamphetamine only.

FIGURE 1.

Specific synthetic cathinones detected in 24 patients with synthetic cathinone intoxication.

FIGURE 2.

A, Substances detected in 24 patients with synthetic cathinone intoxication. B, Substances detected in 48 patients with methamphetamine intoxication only.

Clinical Characteristics of Hospitalized and Nonhospitalized Patients

Table 2 displays the clinical characteristics of patients who were hospitalized (n = 24) or not (n = 48) after presentation at the ED. The hospitalized group had more psychotic disorders (37.5% vs 14.6%), used more illicit substances (2.5 ± 1.3 vs 1.9 ± 1.1, P = 0.048), and had a longer average ED stay (47.5 ± 30.3 hours vs 19.4 ± 15.8 hours, P < 0.001). However, the CGI-S and BPRS scores were not significantly different between the 2 groups. An additional comparison of these groups' laboratory data is provided in Supplementary Table 2, http://links.lww.com/JCP/A838.

TABLE 2.

Clinical Characteristics of Patients Who Required or Did Not Require Hospitalization

Characteristics	Hospitalized (n = 24)	Nonhospitalized (n = 48)	P
Age, y	31.8 ± 5.4	30.8 ± 6.3	0.480
Male	20 (83.3)	43 (89.6)	0.469
Married	1 (4.2)	7 (14.6)	0.255
Educational year	11.0 ± 3.9	9.4 ± 4.4	0.126
Job	9 (37.5)	27 (56.3)	0.211
Family history
Psychotic disorder	3 (12.5)	2 (4.2)	0.325
Mood disorder	8 (33.3)	5 (10.4)	0.025*
Substance use	4 (16.7)	5 (10.4)	0.469
Personal history			0.006†
Psychotic disorder	9 (37.5)	7 (14.6)
Depressive disorder	4 (16.7)	5 (10.4)
Bipolar disorder	3 (12.5)	1 (2.1)
Smoking	21 (87.5)	36 (75.0)	0.356
Alcohol	15 (62.5)	28 (58.3)	0.803
No. previous illicit substance use	2.5 ± 1.3	1.9 ± 1.1	0.048
Criminal history	9 (37.5)	21 (43.8)	0.800
Psychotic symptoms
Delusions	19 (79.2)	32 (66.7)	0.410
Hallucinations	11 (45.8)	26 (54.2)	0.619
Thought disorder	7 (29.2)	12 (25.0)	0.779
Self-harm	5 (20.8)	9 (18.8)	1.000
Violence	15 (62.5)	25 (52.1)	0.458
CGI	6.21 ± 1.02	5.98 ± 1.00	0.366
BPRS	69.0 ± 11.0	68.6 ± 13.2	0.895
Physical complications	5 (20.8)	10 (20.8)	1.000
No. detected illicit substance	1.8 ± 1.2	1.6 ± 1.3	0.735
Temperature, °C	36.6 ± 0.5	36.8 ± 0.8	0.225
Respiratory rate, breaths/min	19.4 ± 1.5	19.3 ± 1.9	0.776
SBP, mm Hg	131.3 ± 25.9	130.2 ± 20.6	0.848
Heart rate, beats/min	102.8 ± 19.2	105.9 ± 23.1	0.575
Length of stay at ED, h	47.5 ± 30.3	19.4 ± 15.8	<0.001†
Transfer	1 (4.2)	4 (8.3)	0.659
Inpatient days	29.1 ± 19.9	NA	NA
Synthetic cathinone users	9 (37.5)	15 (31.3)	0.607

Data are presented as frequency (percentage) or mean ± SD.

*P < 0.05.

^†P < 0.01.

SBP indicates systolic blood pressure; NA, not applicable.

Association Between Synthetic Cathinone Use and Risk of Physical Complications

Table 3 illustrates the clinical characteristics of the patients with (n = 15) and without physical complications (n = 57). Compared with the group without complications, the group with physical complications had a greater proportion of patients with synthetic cathinone intoxication (73.3% vs 22.8%, P < 0.001), a higher average temperature (37.4 ± 1.0°C vs 36.6 ± 0.6°C, P < 0.001), greater average CGI (6.6 ± 0.6 vs 5.9 ± 1.0, P = 0.017) and BPRS scores (77.2 ± 11.4 vs 66.5 ± 11.8, P = 0.003), and a greater proportion of patients transferred to the hospital (33.3% vs 0%, P < 0.001). An additional comparison of the laboratory data of patients with and without physical complications is provided in Supplementary Table 3, http://links.lww.com/JCP/A838. The results of multivariable logistic regression controlled for CGI and BPRS scores revealed that synthetic cathinone intoxication was significantly associated with an increased risk of physical complications (odds ratio, 8.55; 95% confidence interval, 2.15–34.03; Table 4).

TABLE 3.

Clinical Characteristics of Patients With or Without Physical Complications Related to Stimulant Intoxication

Characteristics	With Physical Complication (n = 15)	Without Physical Complication (n = 57)	P
Age, y	32.3 ± 6.4	30.8 ± 5.9	0.382
Male	13 (86.7)	50 (87.7)	1.000
Married	1 (6.7)	7 (12.3)	1.000
Educational year	9.93 ± 3.88	9.89 ± 4.43	0.976
Job	7 (46.7)	29 (50.9)	1.000
Family history
Psychotic disorder	1 (6.7)	4 (7.0)	1.000
Mood disorder	2 (13.3)	11 (19.3)	0.723
Substance use	0 (0.0)	9 (15.8)	0.189
Personal history			0.716
Psychotic disorder	3 (20.0)	13 (22.8)
Depressive disorder	3 (20.0)	6 (10.5)
Bipolar disorder	1 (6.7)	3 (5.3)
Smoking	13 (86.7)	44 (77.2)	0.721
Alcohol	8 (53.3)	35 (61.4)	0.571
No. previous illicit substance use	2.3 ± 1.3	2.1 ± 1.2	0.653
Criminal history	3 (20.0)	27 (47.4)	0.078
Psychotic symptoms
Delusions	12 (80.0)	39 (68.4)	0.528
Hallucinations	10 (66.7)	27 (47.4)	0.249
Thought disorder	2 (13.3)	17 (29.8)	0.324
Self-harm	5 (33.3)	9 (15.8)	0.150
Violence	8 (53.3)	32 (56.1)	1.000
CGI	6.6 ± 0.6	5.9 ± 1.0	0.017*
BPRS	77.2 ± 11.4	66.5 ± 11.8	0.003†
No. detected illicit substance	2.8 ± 1.6	1.4 ± 0.9	<0.001†
Temperature, °C	37.4 ± 1.0	36.6 ± 0.6	<0.001†
Respiratory rate, breaths/min	19.4 ± 2.4	19.3 ± 1.5	0.789
SBP, mm Hg	132.6 ± 25.2	130.0 ± 21.7	0.695
Heart rate, beats/min	108.2 ± 25.5	104.0 ± 20.9	0.507
Length of stay at ED, h	30.3 ± 22.2	28.4 ± 26.2	0.791
Transfer	5 (33.3)	0 (0.0)	<0.001†
Hospitalization	5 (33.3)	19 (33.3)	1.000
Synthetic cathinone user	11 (73.3)	13 (22.8)	<0.001†

Data are presented as frequency (percentage) or mean ± SD.

*P < 0.05.

^†P < 0.01.

SBP indicates systolic blood pressure.

TABLE 4.

Association Between Synthetic Cathinone Intoxication and Risk of Physical Complications Related to Stimulant Intoxication

Variables	Univariate Analysis		Multivariable Analysis
	OR (95% CI)	P	OR (95% CI)	P
CGI	2.49 (1.12–5.53)	0.025*	1.14 (0.22–5.96)	0.875
BPRS	1.08 (1.02–1.15)	0.006†	1.07 (0.95–1.20)	0.293
Study group
Methamphetamine	Reference		Reference
Synthetic cathinone	9.31 (2.53–34.18)	<0.001†	8.55 (2.15–34.03)	0.002†

*P < 0.05.

^†P < 0.01.

OR indicates odds ratio; CI, confidence interval.

DISCUSSION

This study compared the clinical characteristics of patients with synthetic cathinone or methamphetamine intoxication who presented to a psychiatric ED. When the patients were matched by sex and age, patients with synthetic cathinone intoxication or methamphetamine were similar in their clinical severity of psychotic symptoms, and some exhibited violent behavior or attempted suicide. Both groups remained in the psychiatric ED for a long period, and some patients were eventually hospitalized for even longer ED stays than those who were not hospitalized. Most patients were unmarried and unemployed and were habitual smokers or drinkers. Compared with that among patients with methamphetamine intoxication, the prevalence of family substance use history and criminal records was lower among patients with synthetic cathinone intoxication; however, the rate of hospital transfer for treatment was higher, and more types of substances were detected in the urine specimen. To the best of our knowledge, this is the first matched case-control study comparing the psychiatric features of synthetic cathinone or methamphetamine intoxicated patients admitted to a psychiatric ED with evaluation scales.

Both groups of patients exhibited severe psychosis, aggression, and suicidal attempts, but the patients with synthetic cathinone intoxication had a higher rate of physical complications. Similar to methamphetamine, synthetic cathinones are classified as psychostimulants²⁶; they promote the release of catecholamines, including dopamine, serotonin, and noradrenaline, in the central nervous system and restrict their reuptake. However, the ketone groups of some synthetic cathinones give them greater polarity and hydrophilicity than those of methamphetamine,²⁷ thus inhibiting such synthetic cathinones from penetrating the blood-brain barrier²⁸ and lowering their potency.²⁹ To achieve similar effects to those of methamphetamine, which include euphoria, sensory enhancement, and hypersexuality,^26,30 people who use synthetic cathinones often rapidly consume considerable amounts of the substance,^31,32 which may cause intoxication symptoms, including anxiety, confusion, agitation, psychosis, violence, and suicide attempts.³³ Synthetic cathinone–induced psychotic symptoms are sometimes similar to the positive symptoms of schizophrenia²⁶ and therefore influence the differential diagnosis when patients are in acute psychotic states.³⁴

Synthetic cathinones and methamphetamine can increase the risks of sympathetic nerve activity,³⁵ serotonin syndrome,³⁶ and physical complications, including myocarditis,³⁷ seizure, dystonia, myoclonus,¹⁴ paresthesia, and fever.³⁸ Hyperthermia resulting from synthetic cathinone intoxication can indicate rhabdomyolysis, acute kidney failure, metabolic acidosis, and disseminated intravascular coagulation.³⁹ In addition, renal hypoperfusion⁴⁰ or hepatic mitochondrial injury secondary to synthetic cathinone intoxication may respectively result in tubular necrosis⁴⁰ or hepatic encephalopathy⁴¹ and elevate the glutamate concentration in the central nervous system, increasing neurotoxicity and the risks of delirium and multiple organ failure.⁴²

We used liquid chromatography–quadrupole time-of-flight mass spectrometry to detect synthetic cathinones. If stimulant intoxication was suspected and synthetic cathinones were detected in a patient's urine, the patient was recruited for our study. Although patients were enrolled when they met the DSM-5 criteria for stimulant intoxication, many patients also met the DSM-5 criteria for substance-induced psychotic disorder and substance withdrawal. Synthetic cathinones may induce several weeks of psychosis or worsen a preexisting psychotic disorder.²⁶ The prevalence of primary psychotic disorder in this study was higher than that among the general population of Taiwan,⁴³ suggesting a vulnerability among patients sent to the psychiatric ED with synthetic cathinone or methamphetamine intoxication. Although synthetic cathinones can be administered through a muscular or vascular injection or as an anal suppository, our group of patients intoxicated with synthetic cathinones tended to favor nasal or oral administration.⁴⁴ People who use NPSs may use more than 1 type of substance and do so in various places and at different times.^45–48 Thus, they may not remember all of the details of their substance consumption.⁴⁹

As phenylalkylamine derivatives,⁵⁰ synthetic cathinones can be classified as N-alkylated cathinone derivatives, 3,4-methylenedioxy-N-alkylated cathinone derivatives, N-pyrrolidine cathinone derivatives, or 3,4-methylenedioxy-N-pyrrolidine cathinone derivatives⁵¹ on the basis of their chemical structures. We checked for methcathinone, mephedrone, eutylone, ephylone, acetyl-3,4-MDMC, methylone, ethylone, dibutylone, N-acetyl-3,4-DMMC, and 4-chloromethcathinone, all of which belonged are N-alkylated or 3,4-methylenedioxy-N-alkylated cathinone derivatives, in the urine of patients with synthetic cathinone intoxication. Similar to methamphetamine, N-alkylated cathinone derivatives act as dopamine and norepinephrine reuptake inhibitors and dopamine releasers with high inhibitory potency for dopamine transporters but low inhibitory potency for serotonin transporters. Similar to cocaine, 3,4-methylenedioxy-N-pyrrolidine cathinone derivatives function as monoamine reuptake inhibitors and have a relatively low affinity ratio of dopamine to serotonin transporters.^3,52 Because knowledge of these NPSs is limited,³ their metabolism, distribution, dose-effect relationships, and withdrawal timelines are unclear. By modifying the structure of synthetic cathinones by adding aromatic rings, alkyl side chains, or amino groups, manufacturers can render their substances undetectable in typical urine examinations.⁵¹ Clinicians can therefore be misled if an intoxicated patient denies NPS use.⁸

Methamphetamine, an illicit substance, has circulated extensively in Taiwan for decades.⁵ People who use methamphetamine are mostly middle-aged men.^5,53 We initially enrolled 106 patients with methamphetamine intoxication. Before matching, their average age was 35.59 years, and more than 80% of them were men, numbers that approximate official statistical data. Some individuals who use methapmhetamine may focus on the substance's effect of allowing them to stay awake for work, rather than its effects of euphoria and sensory enhancement.⁵⁴ In addition, patients with methamphetamine intoxication and concurrent methamphetamine-induced psychotic disorder may develop primary psychosis⁵⁵ or criminal tendencies.^56–58 Compared with methamphetamine, synthetic cathinones are less expensive⁵¹ and more accessible¹⁵; they can also be disguised as everyday goods, accounting partially for the lower crime rate among people who use synthetic cathinones.

According to the DSM-5, physical complications related to stimulant intoxication include tachycardia, bradycardia, blood pressure changes, perspiration, nausea, vomiting, respiratory depression, chest pain, and arrhythmia, which might be inefficiently treated in psychiatric EDs⁵⁹ because patients may be physically restrained or chemically sedated when agitated or violent, potentially exacerbating intoxication symptoms.⁶⁰ People who use synthetic cathinones may also use alcohol⁶¹ or other types of NPS,⁴⁹ which may interact and lead to unexpected clinical consequences.⁶²

As an alternative to traditional stimulants, synthetic cathinones are often unregulated and thus commonly available on college campuses or at clubs. People who use synthetic cathinones are less frequently embroiled with the legal system or referred to addiction clinics for treatment than those who use methamphetamine are. However, similar to methamphetamine, synthetic cathinones can affect the reward system and result in tolerance, dependence, cravings, and withdrawal, with risk of dependence.^32,44,46 Our results suggest that patients presenting to psychiatric EDs with stimulant intoxication may be biologically prone to primary psychotic disorders, severe psychosis, and violent or suicidal behavior. Clinically, NPS-induced psychosis must be considered among young patients with first-episode psychosis, confusion, or high potential for violence or suicide. Future treatment plans may emphasize the potential harm of psychotic relapse caused by NPSs.

Limitations

Our study has several limitations. First, this was a cross-sectional study; thus, causal relationships could not be inferred. Second, all the patients were recruited from a single psychiatric ED; thus, our sample population may differ from those of general hospitals and from those of people who use substances who do not have prominent psychiatric comorbidities. The prevalence of psychosis or mood disorders was higher among our recruited patients than it is among the general population of Taiwan.⁴³ Furthermore, unlike rural areas, Northern Taiwan has a large concentration of manufacturing and commercial industry; thus, the generalizability of our results may be limited by the unique sociodemographic characteristics of individuals in the study location. Third, we did not account for some confounding factors, such as multiple substance use and concurrent psychotropic medication use. Patients might have used several substance (or even synthetic cathinones and methamphetamine) simultaneously within unspecified periods of time before their arrival at the ED. However, this cannot be completely distinguished through current toxicology analysis methods. All the recruited patients intoxicated with synthetic cathinones claimed to have consumed their substance orally, whereas all patients in the control group claimed to have smoked methamphetamine only. To avoid statistical collinearity and confounding by indication, we included prevalent severe mental illnesses as variables to exclude some confounding effects of psychiatric illness and treatments.

CONCLUSIONS

Substance use is closely related to mental health; therefore, reducing substance exposure is imperative. Although not all types of synthetic cathinone are regulated, their extensive circulation and use may actually pose health threats, such as physical complications and subsequent psychiatric disorders, similar to those posed by methamphetamine. Larger comparative studies and longer follow-ups are required to explore the psychopathology of patients with synthetic cathinone or other stimulant intoxication and primary psychosis to establish individualized treatment strategies for reducing disability.