QJM Advance Access originally published online on November 12, 2008
QJM 2009 102(1):51-56; doi:10.1093/qjmed/hcn148
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Patterns of antiepileptic drug overdose differ between men and women: admissions to the Edinburgh Poisons Unit, 2000–2007
From the 1Scottish Poisons Information Bureau, The Royal Infirmary of Edinburgh, Edinburgh, UK and 2Medicines Management Team, NHS Lothian, Edinburgh, UK
Address correspondence to Dr W. Stephen Waring, Scottish Poisons Information Bureau, The Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK. email: s.waring{at}ed.ac.uk
Received 23 July 2008 and in revised form 13 October 2008
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Background and Aims: Antiepileptic drugs are increasingly used in patients with psychiatric disorders who are at increased risk of self-harm. This might increase the likelihood that these agents are used as a means of overdose. This study was designed to examine the rate of occurrence of antiepileptic drug overdose between 2000 and 2007.
Methods: A retrospective observational study examined patterns of antiepileptic drug overdose in patients admitted to the Edinburgh Poisons Unit, and compared prescription data for the corresponding region. Data were compared using chi-square trend tests.
Results: There were 18 010 admissions to the Toxicology Unit, and 613 patients ingested at least one antiepileptic drug (3.4%). The most frequently implicated were carbamazepine, sodium valproate, phenytoin and lamotrigine, which corresponded with those most commonly prescribed. Women were more likely to ingest lamotrigine than men (P < 0.0001), and less likely to ingest sodium valproate (P = 0.0234). Patients that ingested antiepileptic drugs were more likely to be admitted to hospital for >1 day (22% vs. 8%, P < 0.0001) and need transfer to a psychiatric facility (14% vs. 7%, P < 0.0001).
Conclusions: Patients that ingested antiepileptic drugs required more intensive medical and psychiatric intervention compared to ingestion of other agents. Significant gender differences were noted in the specific antiepileptic drug ingested. Further work is required to establish whether this discrepancy may be explained by gender-based prescribing practices.
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Introduction |
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Around 0.5–1% of the adult population in the United Kingdom have epilepsy, and the prevalence is rising.1–3 There has been an expansion in the choice of therapies available, and the overall volume of antiepileptic drug prescribing has increased in recent years.4,5 Antiepileptic drugs are being used across a wider number of indications, including bipolar affective disorder and other psychiatric diseases.6–8 Furthermore, epilepsy often coexists with psychiatric illness, including depression.9,10 Carbamazepine, valproate and lamotrigine have efficacy in acute mania, and are capable of preventing relapse in patients with bipolar disorder, as sole therapy and when combined with lithium.11–13 In view of all these factors, there has been more widespread use of antiepileptic drugs in patients with underlying psychiatric disorders, often as an unlicensed indication. This patient group is at substantially increased risk of self-poisoning.14–16
The choice of agent ingested in the setting of deliberate drug overdose is predominantly determined by the most readily accessible medications, including prescribed drugs.17,18 Greater availability of antiepileptic drugs in patients at risk of self-harm may increase the likelihood that these agents are used as a means of overdose. For example, in the United States, there has been a 25% increase in the rate of occurrence of antiepileptic drug overdose between 2000 and 2006.19,20 However, the extent to which these data corresponded to changes in local prescribing practices is unknown. Few data are available regarding the rate of antiepileptic drug overdose in other regions. Therefore, the present study sought to examine patterns of admissions due to antiepileptic overdose at a regional Toxicology Unit between 2000 and 2007, and to compare local prescribing patterns.
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Methods |
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A retrospective observational study examined admissions to the Toxicology Unit of the Royal Infirmary of Edinburgh between 2000 and 2007. Around 2500 adults are admitted to this Unit annually, and clinical details of each admission episode are held in a local database. The Emergency Department receives all patients aged >13 years with suspected poisoning from a catchment population of around 600 thousand, whereas patients
13 years are directed to a local paediatric institution.
Data collection
The following data were collected: agent ingested, whether admitted to a critical care area, duration of admission and destination after discharge from hospital. Data from 2004 and onward also included details of patient age and gender. For the purposes of this study, antiepileptic drugs included all of the following agents: carbamazepine, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, primidone, phenytoin, pregabalin, topiramate, valproate and vigabatrin. Each ingestion was considered as a separate entry; for example, a patient that co-ingested carbamazepine and phenytoin was recorded as a single admission, and counted as an entry for carbamazepine and an entry for phenytoin. Therefore, the number of drug entries is greater than the number of overdose admissions episodes.
Prescribing data
Prescription data for NHS Lothian were obtained from the Information Services Division (ISD) of NHS Scotland from 2004 to 2007. This data contain the overall number of prescriptions items dispensed in Lothian, a region with a population of around 42 0000.
Data analyses
Data are presented as median and interquartile range. Admissions involving antiepileptic drugs were presented as a proportion of all overdose admissions to minimize the effect that changes in clinical practice might have an absolute admission numbers.
Chi-square trend tests were used to study admissions due to antiepileptic drug overdose across the study period. Comparison was made between groups using Yate's corrected chi-square trend tests, and P < 0.05 were considered statistically significant (Software version 9.5, MedCalc, Mariakerke, Belgium).
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Results |
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During 2000–07, 18 010 patients were admitted to the Toxicology Unit, including 613 patients that ingested at least one antiepileptic drug (3.4%). This corresponded with 652 entries for individual antiepileptic drug ingestion. Carbamazepine was the most commonly ingested antiepileptic drug (Table 1). The annual rate of occurrence of phenytoin overdose fell between 2000 and 2007, whereas the overall rate of antiepileptic drug overdose remained constant (Table 2). Ethanol was co-ingested by 94 patients (15.3%). Additional drugs were co-ingested by 401 patients (65.4%), including antidepressants (23.8%), benzodiazepines (22.8%), paracetamol (17.3%), antipsychotics (16.5%), opioids (10.8%) and non-steroidal anti-inflammatory drugs (5.5%). All patients had taken a deliberate overdose, rather than an accidental or inadvertent ingestion.
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There were 7797 patients admitted during 2004–07 excepting antiepileptic drug overdose. This included 4480 women (57.5%) and the median (interquartile range) age was 34 years (23–44 years). There were 274 patients that ingested antiepileptic drugs during the same period, including 152 women (55.5%, P = 0.5512), and age was 38 years (28–45 years) in this group (P < 0.0001). The age distribution of patients admitted to hospital after antiepileptic drug overdose is shown in Figure 1. Women were more likely to ingest lamotrigine than men (P < 0.0001), but less likely to ingest sodium valproate (P = 0.0234), as shown in Figure 2. The annual number of prescription items issued in Lothian region between 2004 and 2007 is shown in Table 3.
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The duration of hospital stay was longer in patients admitted after overdose involving antiepileptic drugs vs. other drugs; only 156 (25.4%) patients were discharged home on the same day as presentation after antiepileptic overdose, compared to 7127 (39.6%) after other overdoses (P < 0.0001), and a higher proportion of patients required >1 overnight hospital stay (22.0% vs. 8.2%, P < 0.0001). After the acute episode, a higher proportion of antiepileptic drug overdose patients required transfer to a psychiatric institution (14.0% vs. 7.6%, P < 0.0001), whereas similar proportions were discharged home (78.3% vs. 81.1%, P = 0.0996), required treatment for ongoing medical problems (1.8% vs. 2.8%, P = 0.1814) and died (0.2% vs. 0.1%, P = 0.9288).
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Discussion |
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Antiepileptic drug overdose accounted for only a small proportion of all overdose admissions, as reported by other institutions.20,21 The most commonly encountered agents were carbamazepine, valproate, phenytoin and lamotrigine, which generally corresponded with community prescribing patterns. Prescription items for phenytoin were declining, and there was discernible fall in the proportion of admissions involving phenytoin overdose, which extends a similar pattern reported the 1990s.4 Duration of hospital stay was longer after ingestion of antiepileptic drugs than other agents. Elsewhere, carbamazepine and phenytoin overdose have given rise to longer hospital stay than ingestion of valproate due to excess sedation.22 A higher than expected proportion of patients had co-ingested an antipsychotic agent, and an unexpectedly high proportion of patients required transfer to a psychiatric facility.23,24 These findings are subject to bias due to the use of antiepileptic drugs in patients with underlying psychiatric illness, and severity may be greater given that these agents are normally reserved for second-line therapy.
Women were more likely than men to present with self-poisoning by antiepileptic drugs and other agents, as reported previously.17,25–27 Substantial differences were noted between the agents ingested by men and women. This might be due to greater use of lamotrigine in young women, which is less likely to interact with the combined oral contraceptive pill than other antiepileptic drugs.28 Patients that ingested antiepileptic drugs were older than patients that ingested other agents. This may be due to more widespread use of antiepileptic drugs in older rather than younger adults, and might also be influenced by avoidance of antiepileptic drugs in women of childbearing potential in view of possible teratogenic effects.29,30 These data support the view that altered prescribing practices can have a major impact on patterns of drug overdose, as reported for antipsychotics, antidepressants and analgesics.31–33
The number of antiepileptic drugs dispensed in this region had increased by >10% during the study period, in line with prescribing trends reported elsewhere.1 Despite this, the proportion of overdose admissions arising from antiepileptic drug ingestion has remained constant between 2000 and 2007. Reassuringly, the increased prescription of antiepileptic drugs in the community has not been associated with a similar rise in hospital admissions due to overdose. This is in contrast to other regions that have witnessed a recent increase in the number of poisoning cases involving antiepileptic drugs.20 These data underpin the importance of judicious prescribing, so that antiepileptic drugs are not easily accessible to patients at highest risk of self-harm behaviour.
A limitation is that the indication for antiepileptic drug treatment is not known and, for example, direct comparison cannot be made between patients with epilepsy and other indications. A further limitation is that prescribing data are available only between 2004 and 2007, and do not allow discrimination between prescriptions issued to men and women. Additional work is required to examine gender-related differences in antiepileptic drug prescribing, to so that the patterns of overdose may be interpreted more clearly. Most patients were thought to have ingested their own medications, but the number of patients that ingested drugs belonging to someone else is unknown.
In conclusion, the proportion of poisoning admissions due to antiepileptic drugs has remained constant despite a recent increase in community prescribing. The pattern of agent ingested varies significantly between women and men. Further work is required to explore whether prescribing practices might have a direct influence on the choice of antiepileptic drug ingested.
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Acknowledgements |
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There were no specific sources of funding associated with this research. The authors gratefully acknowledge the staff of the Poisons Unit and Emergency Department for their contribution to the care of these patients and for their support.
Conflict of interest: None declared.
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