Clinical features of patients with designer-drug-related disorder in Japan: A comparison with patients with methamphetamine- and hypnotic/anxiolytic-related disorders

Authors

  • Toshihiko Matsumoto MD, PhD,

    Corresponding author
    1. Department of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan
    • Correspondence: Toshihiko Matsumoto, MD, PhD, Department of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8553, Japan. Email: tmatsu@ncnp.go.jp

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  • Hisateru Tachimori PhD,

    1. Department of Mental Health Administration, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Yuko Tanibuchi MD, PhD,

    1. Department of Psychiatry, Chiba Hospital, Chiba, Japan
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  • Ayumi Takano MA,

    1. Department of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan
    2. Department of Psychiatric Nursing, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Kiyoshi Wada MD, PhD

    1. Department of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan
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Abstract

Aim

The aim of this study was to clarify the clinical features of designer-drug-abusing patients through comparisons with methamphetamine-abusing patients and hypnotics/anxiolytics-abusing patients.

Methods

Information on 126 designer-drug-abusing patients, 138 methamphetamine-abusing patients, and 87 hypnotics/anxiolytics-abusing patients was extracted from the 2012 database of ‘The Nationwide Mental Hospital Survey on Drug-related Psychiatric Disorders’ and the clinical variables of designer-drug-abusing patients compared with those of the other two groups.

Results

Multivariate analysis indicated the following significant differences between designer-drug-abusing patients and the other two types of patients: designer-drug-abusing patients were younger, included more men, had higher education and fewer relationships with antisocial groups, and included more patients meeting ICD-10 F1 sub-classification categories of ‘Harmful use’ and ‘Psychotic disorders’ than methamphetamine-abusing patients. Compared with hypnotics/anxiolytics-abusing patients, designer-drug-abusing patients were younger, included more men and more patients meeting criteria for ‘Psychotic disorders’, and more frequently cited ‘peer pressure’, ‘unable to refuse’, and ‘seeking stimulation’ as reasons for using the drug.

Conclusion

The advent of designer drugs has created a new class of drug abuse, and abuse of designer drugs may carry a strong psychosis-inducing risk, exceeding that of methamphetamine.

Recently, non-controlled, ‘designer’ drugs have become a social problem in Japan.[1] They are created by partial modifications to the chemical structure of existing illegal drugs, such as methamphetamine or synthetic narcotics, enabling them to avoid regulation under the law. Particularly notorious among these are drugs commonly known as ‘Dappou Herb’ (Dappou means evasion in Japanese), a product in which the aforementioned designer drugs are mixed with flakes of dried plant material. In addition to these ‘herbal’ products there are designer drugs known as ‘powder/liquid types’, which take the form of a powder or liquid, and are sold in shops, such as ‘adult shops’/‘head shops’ and via the Internet.

Herbal or powder/liquid-type designer drugs have been a serious social problem in the USA since around 2010, where 14.3% of college students are reported to have experienced herbal drug use;[2] the number of reports of adverse events at Texas addiction centers has risen sharply since 2010;[3] and a wide range of health damage has been identified,[4] from paranoia and aggressive behavior[5] to seizures and cardiac arrest. Furthermore, with respect to one of the powder-type drugs, called ‘Bath salts’, reports of cases presenting with schizophrenia-like symptoms have been reported,[6] and according to one source, they are ‘much more dangerous than methamphetamine and cocaine’.[7]

The escalation of designer drug abuse in Japan and the USA is occurring with very little time lag. According to a report from the Japan Poison Information Center,[8] accounts of adverse events related to designer drugs have increased sharply since 2010. According to the review by Wada et al.,[9] particularly since 2011, media attention has been attracted by car accidents and violence under the influence of designer drugs, neuropsychiatric symptoms, including impaired consciousness, and seizures, and cardiac arrest arising due to acute intoxication. This situation is also reflected in the field of psychiatric care. In the 2012 Nationwide Mental Hospital Survey on Drug-related Psychiatric Disorders (NMH Survey),[1] performed every 2 years, the new category of designer drugs overtook hypnotics/anxiolytics (which had previously been in second place in the 2010 survey) to become second only to methamphetamine.

In a broad sense, the designer-drug problem in Japan has not just emerged recently. During the late 1990s, ‘magic mushrooms’, containing the psychedelic compound psilocybin, became a problem, and around 2005–2007, 5-methoxy-N, N-diisopropyltryptamine (5-MeO-DIPT), a tryptamine-derivative derived from a serotonin backbone,[10] and phenethylamine-based substances known as the 2C series, such as 2C-T-4 and 2C-T-7,[11] emerged. However, abuse of each of these drugs rapidly subsided because of laws and regulations.

However, it is difficult to apply the same measures as previously used in the recent epidemic of designer drugs. Initially, it was believed that herbal designer drugs contained a synthetic cannabinoid similar to the Δ9-THC (tetrahydrocannabinol) contained in cannabis and that powder or liquid types contained a cathinone derivative with a similar pharmacological action to methamphetamine (for example methylenedioxypyrovalerone [MDPV]). However, in actual fact, the structures of these materials are being changed continuously and they contain multiple components with unknown pharmacological actions. Furthermore, it is not uncommon for the components of powder and liquid types to be incorporated into herbal products.[12] Consequently, the same product may have a different component composition depending on the time it was purchased, making it extremely difficult to identify components that should be regulated, to predict clinical symptoms due to ingestion, and to reduce the drug supply by regulation.

Currently there is insufficient information regarding details of health damage caused by designer drugs and the clinical features of abusers, which is necessary to prevent abuse and re-abuse of the designer drugs. We previously compared abusers of designer herbs with abusers of methamphetamine,[13] historically and consistently Japan's most common drug of abuse.[14] We found that the former had higher educational backgrounds, less likelihood of a criminal record, and more had a history of psychiatric treatment prior to drug use, or were suspected of using drugs with the intention of self-medication.[15] However, a previous survey did not include powder/liquid-type users, and investigations were not made into whether the risk of induced psychosis was higher compared with methamphetamine.

Information regarding the differences and similarities between abusers of designer drugs and hypnotics/anxiolytics that are similarly classified as unregulated drugs is also necessary. We previously established that abusers of hypnotics/anxiolytics tend to include more women, fewer people with criminal records or relationships with antisocial groups, more among the dependence syndrome group and fewer among the psychotic disorders group compared with methamphetamine drug abuse patients. In addition, abusers of hypnotics/anxiolytics are more likely to use drugs with the intention of alleviating the unpleasant symptoms of insomnia and anxiety rather than because of a desire for stimulation or because of peer pressure, as is the case with stimulant abusers.[13] However, it is unclear whether the same features as these are recognized in abusers of the similarly unregulated designer drugs.

This study emerged from an awareness of the above problem and was conducted with the aim of clarifying the clinical features of patients with designer-drug-related disorder (DDRD), by comparing them with methamphetamine-related disorder (MARD), and hypnotics/anxiolytics-related disorder (HARD), using data from the 2012 NMH Survey. This is the first study to compare the clinical features of DDRD patients with MARD and HARD patients.

Methods

NMH Survey

Before describing the subjects of this study, an explanation will be given of the details of the subjects and method of the 2012 NMH Survey, the base material for this study.

Surveyed facilities

The 2012 survey included 1609 psychiatric facilities, all of psychiatric hospitals and general hospitals with a psychiatric ward in Japan, consisting of 46 National Hospital Organization hospitals, 136 municipal hospitals, 83 university hospitals and 1344 private psychiatric hospitals.

Subject inclusion criteria

Cases subject to investigation included all drug-related-disorder patients who were admitted to hospital or received outpatient consultations in the 2-month period from September to October 2012 (patients who were diagnosed as the ICD-10 ‘F1: Mental and behavioral disorders due to psychoactive substance use’ category by an attending psychiatrist of each survey facility, except those in which alcohol was the psychoactive substance that had the greatest impact on the clinical problem).

Method of collecting information

A guidance document was sent to all target facilities in advance of the survey. It was displayed in an appropriate location to make it known to patients, in principle, after which information was gathered through semi-structured interviews by the attending psychiatrist. Verbal consent was obtained when conducting interviews but no information was gathered on cases where patients were able to be interviewed but refused to cooperate with the survey, which were recorded as ‘refusal to cooperate with the survey’, and only a report on applicable numbers was requested. In cases where applicable subjects were minors (under 20 years), or interviews were problematic because of patients having been discharged from hospital, or being in an unstable medical condition, such as a severe psychotic state, the attending psychiatrist was asked to transcribe information applicable to the survey items from medical records, and in such cases, obtaining informed consent was unnecessary. Questionnaires filled out using the procedure described above were sent by post or fax and were gathered and analyzed under the guidance of the first author. The present study was conducted with the approval of the National Center of Neurology and Psychiatry Ethics Committee.

Survey items

The items were the same as in the previous survey, including population demographics data (sex, age), educational background, employment status, current marital status, antisocial ties or criminal background, lifetime experience of usage of various drugs, status of use within the last year, the current type of ‘principal drug’, motivation for use, route of acquisition, ICD-10 F1 sub-classification of drug use, and ICD-10 classification of comorbid mental disorders. For each item the attending psychiatrist would make a judgment and answer the questions using information obtained through interviews and previous medical records.

The principal drug was defined as the drug of abuse that was considered to have the greatest impact on the clinical problem, such as a psychosis or dependence, by the attending psychiatrist. The following categories were established: methamphetamine; organic solvents; cannabis; cocaine; heroin; 3,4-methylenedioxy-N-methylamphetamine (MDMA); psychedelic agents other than MDMA; designer drugs; hypnotics/anxiolytics; analgesics; antitussives; Ritalin; other; and multi-agent. The multi-agent category was selected if multiple drugs were exerting comparable influences on the clinical problem being treated.

Drug-related disorder cases collected in the NMH Survey

Replies were obtained from 1136 of the 1609 target facilities (70.6%) in 2012. The number of cases of drug-related disorder consultations or hospitalizations reported during the survey implementation period was 1161, and information was collected from 877 cases from which consent to cooperate with the interview study was obtained. However, information relating to sex, age or principal drug was missing in 29 cases, and the remaining 848 cases (602 men, 246 women: average age [SD], 38.3 [12.2] years) became the drug-related disorder cases for the NMH Survey.

Subject of the present study

For the present study, 138 cases in which a designer drug was the principal drug (DDRD), 356 cases in which methamphetamine was the principal drug (MARD), and 128 cases in which a hypnotics/anxiolytics was the principal drug (HARD) were extracted from among the drug-related disorder cases in the 2012 NMH Survey described above. Patients reporting use of the principal drug within the last year (in the case of hypnotics/anxiolytics, abuse or improper use) were selected from among these three drug-related-disorder groups. This was done to reduce the recall bias regarding survey items as much as possible, in order to reflect the reality of drug abuse in recent years. The resulting 137 DDRD cases, 158 MARD cases, and 115 HARD cases were selected as target candidates. Cases in which no data were missing relating to all of the variables used in the analysis, which will be described later, were 126 DDRD cases (91.9%), 138 MARD cases (87.3%) and 86 HARD cases (74.8%). These cases formed the three study groups and were the object of the final analysis.

Variables used for analysis

Variables identified in a prior study as being effective in distinguishing between DDRD patients and MARD patients,[12] and HARD patients and MARD patients,[13] were used from the information gathered in the NMH Survey for this study.

Demographic variables

Demographic variables included the age and sex of subjects.

Lifestyle-related variables

Lifestyle-related variables included educational background (high school dropout or below, high school graduate or above), and existence of ties to antisocial groups.

Reason for drug use

Information was collected in the NMH Survey regarding the reason for using the principal drug, using 11 categories, with multiple answers allowed. The categories were: (i) ‘peer pressure/unable to refuse’; (ii) ‘seeking stimulation or out of curiosity’; (iii) ‘out of desperation’; (iv) ‘seeking arousal’; (v) ‘alleviation of fatigue’; (vi) ‘seeking sexual effects’; (vii) ‘stress relief’; (viii) ‘alleviation of depression’; (ix) ‘alleviation of anxiety’; (x) ‘alleviation of insomnia’; and (xi) ‘to lose weight’. For this study, we used information relating to four categories that were found to differ significantly between HARD patients and MARD patients in a previous study:[13] ‘peer pressure/unable to refuse’, ‘seeking stimulation or out of curiosity’, ‘alleviation of anxiety’ and ‘alleviation of insomnia’.

ICD-10 F1 diagnosis sub-classification

Of the F1 sub-classification categories (F1x.0 Acute intoxication through F1x.8 Other mental and behavioral disorders), the four categories that are considered to be the most commonly encountered drug-related disorders clinically (‘F1x.0 Acute intoxication’, ‘F1x.1 Harmful use’, ‘F1x.2 Dependence syndrome’, and ‘F1x.5 Psychotic disorder’) were used for each case collected in the NMH Survey, as an index to reflect the major clinical condition of cases.

Statistical analysis

Bivariate and multivariate analysis were performed by multinomial logistic regression analysis using the three categories of DDRD group, MARD group, and HARD group as dependent variables, and the demographic variables, lifestyle-related variables, reason for use, and ICD-10 F1 sub-classifications diagnosed by the attending psychiatrist of each survey facilities as independent variables. spss 17.0 (IBM, Chicago, IL, USA) for Windows was used for statistical analysis and a level of less than 5% in the two-sided test in the analysis of either was considered significant.

Results

Before presenting results of bivariate and multivariate analyses, the average ages and sex ratios, and the proportions of the lifestyle-related and psychiatric variables of the DDRD, MARD and HARD groups are shown in Table 1.

Table 1. Average ages and sex ratios, and the proportions of the lifestyle-related and psychiatric variables in the DDRD, MARD and HARD groups
 Group according to primary drug
DDRDMARDHARD
n = 126n = 138n = 86
  1. DDRD, designer-drug-related disorder; HARD, hypnotics/anxiolytics-related disorder; MARD, methamphetamine-related disorder.
Demographic variablesAgeAverage27.939.337.6
SD7.910.614.1
Sex (male)Frequency1149836
%90.5%71.0%41.9%
Lifestyle-related variablesEducation (High school dropout or below)Frequency408718
%31.7%63.0%20.9%
Relationship with antisocial groupFrequency9696
%7.1%50.0%7.0%
Reason for drug usePeer pressure/unable to refuseFrequency24321
%19.0%23.2%1.2%
Seeking stimulation or out of curiosityFrequency63563
%50.0%40.6%3.5%
Alleviation of anxietyFrequency211755
%16.7%12.3%64.0%
Alleviation of insomniaFrequency9348
%7.1%2.2%55.8%
ICD-10 F1diagnosis sub-classificationF1x. 0 Acute intoxicationFrequency2177
%16.7%5.1%8.1%
F1x. 1 Harmful useFrequency21422
%16.7%2.9%25.6%
F1x. 2 Dependence syndromeFrequency748562
%58.7%61.6%72.1%
F1x. 5 Psychotic disorderFrequency57473
%45.2%34.1%3.5%

Table 2 shows the results of bivariate and multivariate analysis by multinomial logistic regression analysis. This table, in which the DDRD group was set as the reference category, shows the adjusted odds ratio of independent variables and 95% confidence interval to clarify differences with MARD and HARD groups.

Table 2. Results of multinomial logistic regression analysis on the characteristics of DDRD, MARD and HARD groups
Primary drugIndependent variableBivariateMultivariate
BWaldPAdjusted OR95%CIBWaldPAdjusted OR95%CI
Lower limitUpper limitLower limitUpper limit
  1. Bold characters indicate a significance probability of less than 0.05.
  2. Reference category is DDRD (n = 126). Reference category is female. §Reference category is high school graduate or above. Reference category is not applicable.
  3. CI, confidence interval; DDRD, designer-drug-related disorder; HARD, hypnotics/anxiolytics-related disorder; MARD, methamphetamine-related disorder; OR, odds ratio.
MARDIntercept−3.0211.460.001
n = 138Age0.1364.07<0.0011.131.101.170.1539.62<0.0011.171.111.22
Sex (male)1.4016.90<0.0010.250.130.482.5123.11<0.0010.080.030.23
Education (High school dropout or below)§1.3226.70<0.0013.742.276.171.3011.200.0013.661.717.83
Relationship with antisocial group2.5046.64<0.00112.185.9424.962.3322.09<0.00110.223.8826.95
Reason for drug use/Peer pressure, unable to refuse0.220.570.4501.250.702.200.340.400.5251.410.494.07
Reason for drug use/Seeking stimulation or out of curiosity0.473.900.0480.620.391.00−0.703.040.0810.500.221.09
Reason for drug use/Alleviation of anxiety−0.381.210.2710.680.341.35−0.390.570.4510.680.241.88
Reason for drug use/Alleviation of insomnia−1.273.520.0610.280.071.06−1.462.430.1190.230.041.46
F1x. 0 Acute intoxication1.409.580.0020.250.100.60−0.520.810.3670.590.191.85
F1x. 1 Harmful use2.0313.35<0.0010.130.040.392.268.510.0040.110.020.48
F1x. 2 Dependence syndrome0.010.000.9561.010.641.62−0.140.120.7320.870.381.97
F1x. 5 Psychotic disorder0.494.100.0430.610.380.980.824.050.0440.440.200.98
HARDIntercept−3.226.770.009
n = 86Age0.1256.97<0.0011.131.091.170.1422.344<0.0011.151.081.22
Sex (male)2.6658.41<0.0010.070.040.142.9423.32<0.0010.050.020.17
Education (High school dropout or below)§0.643.910.0480.530.281.000.200.120.7271.220.403.73
Relationship with antisocial groups−0.360.440.5050.700.251.99−0.370.180.6690.690.133.73
Reason for drug use/Peer pressure, unable to refuse3.2810.220.0010.040.000.283.284.050.0440.040.000.92
Reason for drug use/Seeking stimulation or out of curiosity3.5834.43<0.0010.030.010.092.6010.160.0010.070.020.37
Reason for drug use/Alleviation of anxiety2.2252.99<0.0019.255.0816.841.356.110.0133.861.3211.28
Reason for drug use/Alleviation of insomnia2.9957.73<0.00119.859.1842.912.4210.140.00111.202.5349.58
F1x. 0 Acute intoxication0.934.590.0320.390.170.92−0.310.170.6780.730.173.17
F1x. 1 Harmful use0.837.380.0072.291.264.160.760.740.3902.150.3812.22
F1x. 2 Dependence syndrome0.351.800.1791.430.852.390.821.290.2552.270.559.30
F1x. 5 Psychotic disorder3.3630.38<0.0010.030.010.113.0211.910.0010.050.010.27

First, the following independent variables that affect the distinction between DDRD and MARD groups significantly were extracted in the bivariate analysis: age (P < 0.001: adjusted odds ratio [95% confidence interval], 1.13 [1.10–1.17]); sex (P < 0.001: 0.25 [0.13–0.48]); educational background (P < 0.001: 3.74 [2.27–6.17]); relationships with antisocial groups (P < 0.001: 12.18 [5.94–24.96]); reason for drug use/‘seeking stimulation or out of curiosity’ (P = 0.048: 0.62 [0.39–1.00]); F1x.0 Acute intoxication (P = 0.002: 0.25 [0.10–0.60]); F1x.1 Harmful use (P < 0.001: 0.13 [0.04–0.39]); and F1x.5 Psychotic disorder (P = 0.043: 0.61 [0.38–0.98]).

Independent variables that affected the distinction between the HARD and DDRD groups were: age (P < 0.001: 1.13 [1.09–1.17]); sex (P < 0.001: 0.07 [0.04–0.14]); educational background (P = 0.048: 0.053 [0.28–1.00]); reason for drug use/‘peer pressure, unable to refuse’ (P = 0.001: 0.04 [0.00–0.28]); reason for drug use/‘seeking stimulation or out of curiosity’ (P < 0.001: 0.03 [0.01–0.09]); reason for drug use/‘alleviation of anxiety’ (P < 0.001: 9.25 [5.08–16.84]); reason for drug use/‘alleviation of insomnia’ (P < 0.001: 19.85 [9.18–42.91]); F1x.0 Acute intoxication (P = 0.032: 0.39 [0.17–0.92]); F1x.1 Harmful use (P = 0.007: 2.29 [1.26–4.16]); and F1x.5 Psychotic disorder (P < 0.001: 0.03 [0.01–0.11]).

In multivariate analysis, independent variables that affected the distinction between the MARD and DDRD groups were: age (P < 0.001: 1.17 [1.11–1.22]); sex (P < 0.001: 0.08 [0.03–0.23]); educational background (P = 0.001: 3.66 [1.71–7.85]); relationships with antisocial groups (P < 0.001: 10.22 [3.88–26.95]); F1x.1 Harmful use (P = 0.004: 0.11 [0.02–0.48]); and F1x.5 Psychotic disorder (P = 0.044: 0.44 [0.20–0.98]). These results show that, compared with the DDRD group, the MARD group has a significantly higher age, has more women, lower educational background, more subjects with ties to antisocial groups and fewer who apply to the F1 diagnosis sub-classifications Harmful use and Psychotic disorder.

On the other hand, the independent variables that significantly affected the distinction between HARD and DDRD groups were: age (P < 0.001: 1.15 [1.08–1.22]); sex (P < 0.001: 0.05 [0.02–0.17]); reason for drug use/‘peer pressure, unable to refuse’ (P = 0.044: 0.04 [0.00–0.92]); reason for drug use/‘seeking stimulation’ (P = 0.001: 0.07 [0.02–0.37]); reason for drug use/‘alleviation of anxiety’ (P = 0.013: 3.86 [1.32–11.28]); reason for drug use/‘alleviation of insomnia’ (P = 0.001: 11.20 [2.53–49.58]); and F1x.5 Psychotic disorder (P = 0.001: 0.05 [0.01–0.27]). These results show that, compared with the DDRD group, the HARD group had a significantly higher age, more women, fewer who cited the reason for drug use as ‘peer pressure, unable to refuse’ or ‘seeking stimulation’, more who cited the reason for drug use as ‘alleviation of anxiety’ or ‘alleviation of insomnia’, and fewer who applied to the F1 diagnosis sub-classification of Psychotic disorder.

Discussion

In this study we investigated the clinical features of DDRD patients through comparisons with MARD patients, who are historically and consistently the largest group of drug abusers in Japan, and HARD patients, who, like DDRD patients, fall outside the scope of the law. Results of multivariate analysis demonstrated that DDRD patients have characteristics that differ in several respects from MARD and HARD patients.

At first, DDRD patients were younger than both MARD and HARD patients and the proportion of men was higher. This study has also confirmed our previous report[13] that the proportion of men was overwhelmingly higher among MARD than HARD patients. However, the proportion of men was even higher among the DDRD patients than the MARD patients. This study also confirmed that the educational background of DDRD patients was higher and the relationships with antisocial groups lower than MARD patients and, as such, this type of lifestyle background has more in common with HARD patients. These findings are consistent with our previous study.[13] The above suggests the possibility that designer-drug abuse has spread from the center of a class with a relatively general lifestyle background of young men who are also not antisocial. This may mean that the advent of designer drugs has created a new class of drug abuse.

This study also confirmed that DDRD patients use drugs not with the intent to self-medicate to ‘alleviate the unpleasant symptoms of anxiety or insomnia’ but for the purpose of ‘seeking stimulation or pleasure’ or because of ‘peer pressure’. This shows that even among similarly unregulated drugs, designer-drug abusers and abusers of essentially therapeutic hypnotics/anxiolytic agents differ in their motive or reason for drug use. Although we may be required to consider that DDRD patients use drugs for the same reasons as MARD patients, this is inconsistent with our supposition in the previous study.[12] Our previous study demonstrated that the high number of Dappou-Herb-related disorder patients had a history of psychiatric treatment prior to the start of drug use, compared with the MARD patients, and from this finding, we speculated that the motive for drug use might be a type of ‘self-medication’[15] intent for the symptoms of the antecedent mental disorder.[12] It is inferred that this inconsistency is due to the differences in the objects of investigation in the two studies. In our previous study, the subjects were outpatients, most of whom received consultations voluntarily. In contrast, the subjects of the present study were drug-related disorder patients who consulted as outpatients or were hospitalized at psychiatric care units nationwide, and included patients who received hospital treatment for psychotic disorders involuntarily. In that sense, findings from the previous study were targeted at a particular group among drug-related disorder patients and it is possible that the results of this study better reflect the general trend of DDRD patients.

The present study also confirmed the characteristics that more DDRD patients fall under the category of psychotic disorders than either MARD or HARD patients. These results would appear to include important implications concerning the psychosis-inducing risk of designer drugs. The existence of more DDRD patients in the psychotic disorders category compared with HARD patients has been regarded as natural considering the pharmacological effects of hypnotics/anxiolytics, but unexpectedly, more DDRD patients fall within the psychotic disorders category than MARD patients, who conventionally use substances that possess strong psychosis-inducing effects. The following two possibilities can be considered as an explanation for this.

One explanation is the possibility that designer drugs have a strong psychosis-inducing risk surpassing that of methamphetamine. An indication that designer drugs are more dangerous than methamphetamine and cocaine in the USA[8] can be considered as supporting evidence, as was mentioned above. Another possibility is that the DDRD group is prone to include more patients who fall within the psychotic disorders category because, in the case of designer drugs, unlike the illegal drug methamphetamine, simply using the drug is not easily recognized but when obvious psychiatric symptoms occur, it is recognized. At this point, it is difficult to judge which of these possibilities is more valid. This study was based on a survey of abusers who accessed psychiatric care. Furthermore, components of designer drugs differ in various ways depending on the product, and there is insufficient knowledge regarding the substances that are responsible for causing psychiatric symptoms. There is therefore insufficient supplementary information to draw conclusions.

This study also found that the ratio of DDRD patients falling within the dependence syndrome category did not differ from MARD or HARD patients. This result showed that designer drugs, like methamphetamine and hypnotics/anxiolytics, carry a risk of only causing dependence syndrome. In addition, a higher ratio of DDRD patients fell within the harmful use category than MARD patients. If the concept of ‘harmful use’ in the ICD-10 is, in principle, considered to be a mutually exclusive diagnosis category to dependence syndrome, this result may suggest that even in the case of a mode of use that does not reach the level of dependence syndrome, it has the potential to cause such health damage as psychotic disorders.

In recent years, there has been much in the news relating to accidents caused by reckless driving, violence or self-harm and suicide under the influence of designer drugs. One can observe from simply watching these reports that designer drugs have a serious impact on the behavior and mental state of a drug user, and this study has significance in that it proves scientifically one part of this. The Ministry of Health, Labor, and Welfare is already implementing comprehensive regulations and other strengthening crackdown measures to deal with this type of situation but from the clinical experience of the authors, which shows that large numbers of DDRD patients continue to consult at specialist outpatient drug dependence centers, it is difficult to say that there is any visible effect, at least at this point. It can be said that in addition to a review of regulatory methods, the provision of a treatment system is a pressing issue.

There are several limitations to this study but the major ones are the following four. First, the subjects of this study were drug-related-disorder patients who consulted as outpatients or were hospitalized at psychiatric units, and do not reflect the characteristics of all the drug abusers in the community. Therefore, caution is required in generalizing the results of the present study. Second, the information used in the analysis was collected by the psychiatrist in charge of treatment of drug-related disorder patients in each survey facility. Therefore, there is a possibility of variation in judgment criteria among individual psychiatrists. We also cannot exclude the possibilities that patient reporting bias is also present at the treatment site, and that only limited information was collected in case of patients’ refusing to cooperate in this survey. Third, in this study all three types of herbal-, powder-, and liquid-based drugs were treated together as designer drugs, but because of the various differences in the component contents, there is a problem with the validity of grouping them together in this way. Finally, to create an appropriate multivariate analysis model, we narrowed down to a minimum the variables of interest for analysis, and as a result, analysis of relations to the variables, such as those relating to alcohol-related disorder and other comorbid disorders, family background, and employment status were not carried out.

Despite the limitations described above, this study has important clinical and social significance. It is the first study to compare the clinical features of abusers of designer drugs, which have become a problem in recent years in Japan, with abusers of methamphetamine, historically and consistently a problematic drug of abuse in Japan, and with abusers of hypnotic/anxiolytics drugs, which share a common feature with designer drugs, that of being unregulated under the law.

Conclusion

The 2012 NMH Survey database was used to investigate the clinical features of DDRD patients through comparisons with MARD and HARD patients for this study. The DDRD group tended to be younger and included more men than the MARD and HARD groups. Furthermore, while DDRD patients had more in common with HARD patients with respect tolifestyle background, they had more in common with MARD patients with respect to the reason for drug use.

In addition, more DDRD patients than MARD patients fell within the ICD-10 F1 diagnosis code for psychotic disorders and harmful use, and it is speculated that designer drugs pose a strong risk of induced psychosis. In conclusion, designer drugs may have created a new young drug abuse subculture in Japan. It is feared that these drugs may also carry a strong psychosis-inducing risk, exceeding that of methamphetamine. We believe that emergency measures aimed at preventing the abuse or the re-abuse of designer drugs are necessary.

Acknowledgments

This study has been supported by the Health Labour Research Grant by the Ministry of Health and Welfare, Research on Pharmaceutical and Medical Regulatory Science (Principal Investigator, K. Wada). We declare that we have no conflicts of interest in relation to this study.

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