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Methoxetamine toxicity reported to the National Poisons Information Service: clinical characteristics and patterns of enquiries (including the period of the introduction of the UK's first Temporary Class Drug Order)
  1. Simon L Hill1,5,
  2. Siân C D Harbon2,
  3. James Coulson2,
  4. Gillian A Cooper2,
  5. Gill Jackson3,
  6. David J Lupton3,
  7. J Allister Vale4,
  8. Simon H L Thomas1,5
  1. 1National Poisons Information Service, Newcastle, UK
  2. 2National Poisons Information Service, Cardiff, UK
  3. 3National Poisons Information Service, Edinburgh, UK
  4. 4National Poisons Information Service, Birmingham, UK
  5. 5Faculty of Medicine, Institute of Cellular Medicine, Newcastle University, Newcastle, UK
  1. Correspondence to Dr Simon L Hill, The Wolfson Unit of Clinical Pharmacology, Claremont Place, Newcastle University, Newcastle NE2 4HH, UK; simon.hill{at}ncl.ac.uk

Abstract

Objective To report the demographic and clinical characteristics of cases of methoxetamine toxicity reported to The National Poisons Information Service (NPIS) by healthcare professionals. To assess the pattern of enquiries from health professionals to the UK NPIS related to methoxetamine, including the period of the making of the UK first Temporary Class Drug Order (TCDO).

Methods All telephone enquiries to and user sessions for TOXBASE, the NPIS on-line information resource, related to methoxetamine (and synonyms ‘MXE’, ‘mket’ and ‘2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone’) were reviewed from 1 April 2010 to 1 August 2012. Data were compared for the 3 months before and after the TCDO.

Results There were 47 telephone enquiries and 298 TOXBASE sessions regarding methoxetamine during the period of study. Comparing the 3 months before and after the TCDO, TOXBASE sessions for methoxetamine fell by 79% (from 151 to 32) and telephone enquiries by 80% (from 15 to 3). Clinical features reported by enquirers were consistent with case reports of analytically confirmed methoxetamine toxicity and typical toxidromes were of stimulant (36%), reduced consciousness (17%), dissociative (11%) and cerebellar (6.4%) types, but also particularly featured acute disturbances in mental heath (43%).

Conclusions Structured NPIS data may reveal trends in drugs of abuse use and toxicity when interpreted within their limitations. Since April 2012, there have been fewer enquiries to NPIS from clinicians, indicating reduced presentations with suspected methoxetamine toxicity to healthcare services. It is unclear if this is related to the TCDO made on 5 April 2012.

  • drug abuse
  • mental health, drug abuse
  • toxicology
  • overdose
  • poisoning

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Introduction

The novel psychoactive substance, methoxetamine, 2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone, (3-MeO-2-Oxo-PCE) is an N-ethyl derivative of ketamine that was developed in the UK.1 As an analogue of ketamine, methoxetamine is thought to act as a non-competetive N-methyl-D-aspartate receptor antagonist, inhibit the dopamine reuptake transporter and, at high doses, demonstrate agonism at opioid κ and μ receptors.2

There has been increasing recent use of methoxetamine as a drug of misuse, with slang terms including ‘MXE’, ‘mexxy’, and ‘mket’. In an online survey of self-reported substance abuse, 4.2% of the 7700 respondents reported using methoxetamine in the previous 12 months.3 There are fewer than 10 published cases of methoxetamine toxicity, and these describe typical patterns of toxicity (toxidromes) consistent with activation of the sympathetic nervous system (stimulant), a ketamine-like dissociative state and cerebellar dysfunction.4–7

Although ketamine is a class C controlled drug under the UK Misuse of Drugs Act, 1971, methoxetamine was not controlled until recently. Following a review of available evidence, the UK's Advisory Council on the Misuse of Drugs concluded that methoxetamine is capable of producing significant harms while having no legitimate medical or industrial use.8 Following this advice, on 5 April 2012, the secretary of state in the UK made a Temporary Class Drug Order (TCDO) under the Misuse of Drugs Act, 1971, (SI2012/980) for methoxetamine and its simple derivatives, the first use of such a TCDO in the UK.9

The National Poisons Information Service (NPIS) provides information and advice to health professionals in the UK about the management of suspected poisoning, including that associated with drugs of misuse. Registered health professionals are able to access information on specific substances held on the NPIS website TOXBASE, and they can also make telephone enquiries about specific cases. The majority of these enquiries are thought to be related to actual clinical cases, but some may involve enquiries for information only.

Since October 2010, NPIS has received increasing numbers of enquiries related to methoxetamine. This paper describes the pattern of these enquiries and the clinical features as provided to NPIS by the healthcare professionals involved in the management of those presenting to them after reported methoxetamine use.

Methods

All TOXBASE user sessions and telephone enquiry data arising from UK health professionals relating to methoxetamine and synonyms ‘MXE’, ‘mket’ and ‘2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone’ were sought for the period 1 April 2010 to 1 August 2012. Ethical approval was not required for this study since it involved analysis of anonymised clinical information that is collected routinely for the NPIS clinical record.

A TOXBASE session is defined as a user logging onto TOXBASE and viewing the page on methoxetamine. Multiple views of the same page, screen refreshes or screen time-outs are included in the same user session. TOXBASE sessions from educational users or NPIS centres were excluded to avoid duplications.

Telephone enquiries to the NPIS from across the UK are handled by information scientists from the four NPIS units in Birmingham, Cardiff, Edinburgh and Newcastle. Clinical details provided by the caller are stored on the UK Poisons Information Database that is held on a central server allowing rapid access to information collected UK-wide. Data on demographic characteristics, (eg, age, sex, coingested substances), clinical features of poisoning and Poisoning Severity Score (PSS) were extracted from the database. Toxidromes were defined from terms included in the clinical records as listed in table 1. The PSS (originally jointly developed by the World Health Organisation International Programme on Chemical Safety and the Swedish Poisons Information Service) is an internationally agreed standard used in triage and for data comparison in cases of poisoning, which scores stated clinical features, subdivided by organ groups, as none (0), minor (1) (mild, transient and spontaneously resolving clinical symptoms and signs), moderate (2) (pronounced or prolonged symptoms or signs), severe (3) (severe or life threatening) or fatal (4).10

Table 1

Clinical features reported in telephone enquiries related to suspected methoxetamine exposure

Results

There were 47 telephone enquiries and 298 TOXBASE sessions regarding methoxetamine during the period of study (figure 1). The first NPIS telephone enquiry was received in October 2010, while the TOXBASE entry for methoxetamine was first made available on TOXBASE in May 2011. Numbers of contacts with NPIS, particularly via TOXBASE increased in late 2011 and early 2012, but reduced from April 2012 (figure 1). There were 151 TOXBASE sessions related to methoxetamine in the 3 months before the TCDO compared with 32 TOXBASE sessions in the 3 months after the TCDO introduction, a reduction of 79%. Similarly, telephone enquiry numbers fell by 80% from 15 to 3 comparing these same time periods.

Figure 1

Number of telephone enquiries (above) and TOXBASE accesses (below) to National Poisons Information Service by month regarding patients with reported methoxetamine toxicity. Note the arrow indicates the date of the introduction of the temporary class drug order on 5 April 2012.

The majority (n=35, 74%) of the 47 telephone enquiries to NPIS related to male patients, and the age range reported was from 16 to 49 years (median=24 years). Coingested substances were reported in nine of the cases (19%) and were ibuprofen, alcohol, dextromethorphan, ‘NRG-3’, etizolam, 5-IAI, co-codamol, cannabinoids and drug of abuse (unknown).

Clinical features of methoxetamine toxicity reported to NPIS during telephone enquiries and classified by toxidrome are shown in table 1. Each reported clinical feature was classified into one of the categories (toxidromes) listed. Patients could exhibit clinical features in more than one group, but each reported feature could only be classified into a single toxidrome. One patient had multiple seizures, but no patients were reported to have died. PSSs for the 47 telephone enquiries were: none in 6 cases, minor in 20, moderate in 15, severe in 2 and not recorded in 4 cases.

Conclusions

Data collected by the NPIS in this way are subject to a number of limitations that should be considered in their interpretation. NPIS data do not measure directly the numbers of people presenting to medical services with methoxetamine toxicity. Information from NPIS, especially telephone advice, is most likely to be sought for more serious cases, or when clinicians are unfamiliar with the agent involved. Consequently, more subtle, yet common, clinical features may not be identified by this methodology. Although multiple telephone enquiries about the same patient can be accounted for, several sessions on TOXBASE may be made by different health professionals in managing the same case. The clinical data relies upon healthcare professionals reporting accurate information on the agents involved, which in turn, depends on accurate reporting by drug users. This is a particular limitation for drugs of abuse, where similar drug names and slang terms may be used to describe different products, and where users may not know or say what they have used. Analytical confirmation is not part of routine clinical practice, and is therefore rarely available. Clinical features captured are those that have occurred up to the time of enquiry to NPIS, and although follow-up is attempted, this is difficult and information may be incomplete particularly for clinical features that develop after the enquiry. Coingestants, which may or may not have been reported by users, may account for some of the clinical features described.

Allowing for these limitations however, structured data collected by NPIS are of use in the identification of trends encountered by health professionals relating to suspected poisoning, and for the identification and confirmation of clinical toxidromes associated with new drugs of misuse.11 The clinical features reported here (table 1) are biologically plausible from anticipated mechanisms of action of methoxetamine, and are in keeping with the published case reports and case series of analytically confirmed methoxetamine toxicity.4–7

There was a substantial reduction in the numbers of both TOXBASE sessions and telephone enquiries immediately following the introduction of the TCDO in April 2012. While this may indicate that the TCDO has resulted in fewer episodes of toxicity, other explanations are possible. The reduction in NPIS encounters post-April 2012 may reflect clinicians becoming more experienced or familiar with methoxetamine toxicity, therefore, feeling less inclined to seek NPIS guidance. Conversely, increasing TOXBASE sessions in advance of the TCDO may have resulted from health professionals seeking background information on the drug as a result of increased media publicity. This would not increase telephone enquiries, however, as these are related to clinical cases. It is also possible that patients did not wish to present to medical services or report taking methoxetamine following the change in legal status due to concerns over prosecution. Presentation to hospital with toxicity following controlled drug use is common, however, and this explanation would, therefore, seem unlikely. Another plausible explanation, particularly in such a dynamic area of Emergency Medicine and legislative controls, is that the suppliers and users may simply have moved on to another substance.

In conclusion, structured NPIS data provides useful information about trends in toxicity associated with drugs of misuse, but the limitations of these data need to be taken into account in interpretation. The data presented here describe typical clinical features associated with exposure. It is unclear if the reduction in enquiry frequency from April 2012 is related to the introduction of the TCDO for methoxetamine introduced in the UK on 5 April 2012.

References

Footnotes

  • Collaborators On behalf of the National Poisons information Service.

  • Contributors SLH analysed the data, wrote the initial manuscript and subsequent drafts and is guarantor. GJ, GC and DL extracted the data for relevant databases. SH also extracted data and reviewed/revised the manuscript draft. JC and AV reviewed/revised the manuscript draft. ST reviewed the data, analysed and revised the draft.

  • Competing interests None.

  • Ethics approval Data were collected as part of the routine clinical record and are fully anonymised.

  • Provenance and peer review Not commissioned; externally peer reviewed.