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162 PSYCHIATRIKI 23 (2), 2012

Case report
Ενδιαφέρουσα περίπτωση

A case of pregabalin intoxication
C.D. Miljevic,1 C. Crnobaric,1 S. Nikolic,1 D. Lecic-Tosevski1,2
1
Institute of Mental Health, Belgrade,
2
School of Medicine, University of Belgrade, Belgrade, Serbia

Psychiatriki 2012, 23:162–165

P
regabalin, or S-(+)-3-isobutylgaba, is a lipophilic analogue of GABA. Although pregabalin is
structurally related to GABA, it is inactive at GABA receptors and does not appear to mimic
GABA physiologically. Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-
gated calcium channels in the central nervous system. It is currently being licensed for epilepsy,
neuropathic pain, and generalized anxiety disorder. There are few case reports that have demonstrated
safety of pregabalin in case of intoxication. We report here a case of pregabalin toxicity with a moderate
pregabalin concentration that was successfully managed with conservative treatment only. The case
report describes a 54-year-old man who was treated with pregabalin for generalized anxiety disorder.
After having experienced a significant stress on a job the patient ingested huge amount of pregabalin
(4,2 r) together with bromazepam (21 mg) and chlorimipramine (125 mg). On presentation he was con-
scious and alert with a stable condition of cardiovascular and respiratory systems. The serum pregabalin
concentration was 20.8 mg/L but the patient did not have any signs of toxicity. Thanks to his good and
stable somatic condition the patient was managed with supportive treatment only. Although anecdotal,
our case report points toward safety of pregabalin following deliberate self-poisoning. Our observation
is in accordance with the recent international literature underlining that pregabalin was listed as the
drug injested in only 1% of fatalities, usually in combination with other drugs.
Key words: Pregabalin, intoxication, psychopharmacology, anxiety.

Introduction to mimic GABA physiologically.1,2 Pregabalin is a
potent ligand for the alpha-2-delta subunit of volt-
Pregabalin, or S-(+)-3-isobutylgaba, is a lipophilic age-gated calcium channels in the central nervous
analogue of GABA substituted at the 3-position to system. The alpha-2-delta site is an auxiliary pro-
facilitate diffusion across the blood-brain barrier. tein associated with voltage-gated calcium chan-
Although pregabalin is structurally related to GABA, nels. The binding of pregabalin and its structural
it is inactive at GABA receptors and does not appear analogues at the alpha-2-delta site has been shown

We report here a case of isolated pregabalin tox. with a temperature patient who ingested 11. 8 tory.12 . On presentation he was conscious and pregabalin and required supportive management alert with a Glasgow Coma Score (GCS) of 30. the third pa- gas chromatography mass-spectrometry detected tient had "initial" pregabalin plasma concentration only chlorimipramine and bromazepam which he of about 65 mg/L and had developed coma after 3 had also ingested. none of these cases were isolated pre- consciousness.12 In terms of pre- day. plasma pregabalin con- A 54-year-old male. For example.9 The "initial" pregabalin plasma previously described method.7 moderate compared to those previously reported.8 mg/L. apeutic serum/plasma concentrations of pregabalin. with a consequential reduction one day and his psychiatric treatment continued. After having There are three previous reported cases of pre- experienced a significant stress on a job the patient gabalin toxicity following deliberate self-poison- ingested 4. to 2006.9–14. mazepam and chorimipramine.9–11 One patient presented with mild drowsi- bromazepam and 125 mg of chlorimipramine in or. in the release of several excitatory neurotransmit- ters. The serum prega- neuropathic pain. It is currently being licensed for epilepsy. except observed for signs of clinical deterioration for one when it was involved in a fatality. the American two hours after ingestion and as he was clinically Association of Poison Control Centers annual re- stable he was not administered any drug and was ports do not include data on pregabalin. car. As the patient had no ongoing fea. bro- nisms. The patient was admitted more then gabalin self-poisoning. including glutamate. Pregabalin with 32 g of lamotrigine. but the tration at the time of admission was 20. pregabalin was ing spontaneous recovery.5 g of pregabalin. noradrenalin. he had neither an electrocardiogram Apart from these case reports.11 presentation. However. and it was decided that the patient should be man. and generalized anxiety disor- balin concentration in this patient of 20.8 mg/L is der. together of 36.6. concentration was approximately 60 mg/L. pregabalin was not mentioned in any fatalities prior aged with general supportive care only.10 The other case was a blood pressure of 110/70 mmHg. 2012 a case of pregabalin intoxication 163 to reduce depolarization-induced calcium influx tures of pregabalin toxicity he was discharged after at nerve terminals. abnormal facial and generalised body movements ple that had been obtained on admission using a and drowsiness. Between 2006 and 2008. with no signs of deterioration of his of fatalities. one report states that in samples collect- Case report ed at random times relative to dose from patients maintained on 600 mg/day. and calcitonin gene-related peptide (CGRP). who initially developed concentrations were measured in the plasma sam.2 mg/L. substance Discussion P. only. gabalin cases. trations to date that was successfully managed with Very little information is available regarding ther- conservative treatment only. The clinical toxicology review was undertaken gabalin-associated fatalities in these annual reports.PSYCHIATRIKI 23 (2). has been treated with 450 mg of pregabalin daily for generalized anxiety disorder. there is limited (ECG) nor arterial blood gases or renal function information available about the frequency of pre- performed. ment only.8 °C and respiratory rate of 18/min. Finally. 3–5 We have described here a case of severe toxic- Pregabalin has no effects on GABA-ergic mecha- ity following self-poisoning. As he was clinically stable on hours. He remained cardiovas. but we managed the patient with supportive treat- icity with the highest recorded pregabalin concen. with pregabalin. ness following ingestion of an unknown amount of der to relax. 2 Pregabalin concen.2 g of pregabalin together with 21 mg of ing. A sample also contained lamotrigine at a concentra- comprehensive toxicological screening of urine by tion of approximately 45 mg/L. that patient had pregabalin concentration of diovascularly stable with a heart rate of 84 bpm and 29 mg/L 9 h post-ingestion. with no relevant medical his- centrations ranged from 0. anticipat. listed as a drug used/ingested in approximately 1% cularly stable.

with peak plasma concentrations with. University of Belgrade. Nikolic. nolence. Υπάρχουν ελάχιστες αναφορές περιπτώσεων που καταδεικνύουν την ασφάλεια της πρεγκαμπαλίνης σε περιπτώσεις υπερδοσολογίας. the use of extra-corporeal methods such as haemo- ity. Republic of Serbia Pregabalin has a low volume of distribution (ap- proximately 0. 2 School of Medicine.13 It is also not subject to treatment only and did not have any signs of tox- hepatic metabolism and does not induce or inhibit icity. som. Belgrade.3 g) σε συνδυασμό με βρωμαζεπάμη (21 mL) και χλωριμιπρα- μίνη (125 mg).14. including dizziness. weight gain. Our case report de- in humans (<2% metabolism) and is excreted virtu. 2012 Pregabalin is rapidly absorbed following oral ad. στον νευροπαθητικό πόνο και στη διαταραχή γενικευμένου άγχους. MILJEVIC et al PSYCHIATRIKI 23 (2). have been reported during therapeutic use of pre- This work was supported by the grant No 175013 of The gabalin at doses of 50–600 mg/day. Miljevic. These pharmacokinetic features make it likely that ministration. Παρουσιάζεται περίπτωση τοξικότητας πρεγκαμπαλίνης με μέτρια συγκέντρωση πρεγκαμπαλίνης στον ορό σε σύγ­ κριση με τις προαναφερθείσες περιπτώσεις και που αντιμετωπίστηκε επιτυχώς μόνο με συντηρη- τική αγωγή. psychosis and myoclonus. 23:162–165 Η πρεγκαμπαλίνη ή S(+)-ισοβουτυλο-γ-αμινοβουτυρικό οξύ είναι λιπόφιλο ανάλογο του GABA (γ-αμινοβουτυρικού οξέος). Η περίπτωση αφορά σε 54χρονο που ελάμβανε πρεγκαμπαλίνη για διαταραχή γενι- κευμένου άγχους.1 D. Lecic-Tosevski1. scribes a patient with a moderate serum pregabalin ally unchanged by the kidneys. Η περίπτωση αυτή. toward safety of pregabalin following deliberate Unwanted clinical effects. Although anecdotal.D. Pregabalin does not concentration who was managed with supportive bind to plasma proteins. . Λέξεις ευρετηρίου: Πρεγκαμπαλίνη. συνήθως συγχορηγούμενη με άλλα φάρμακα. Author disclosure informaton: All authors declare no proximately 159 Da) and is not protein bound.15 Ministry of Science and Education.9 Pregabalin undergoes negligible metabolism dialysis and/or haemofiltration. elimination of pregabalin would be enhanced by in an hour of dosing and up to 90% oral bioavailabil.1 S. our case report points liver enzymes such as the cytochrome P450 system. ο ασθενής αντιμετωπίσθη- κε με υποστηρικτική αγωγή μόνο.5 L/kg). Belgrade. Η πρεγκαμπαλίνη δεσμεύεται ισχυρά στην άλφα-2-δέλτα (α2δ) υπομονάδα των τασεοεξαρτώμενων διαύλων ασβεστί- ου στο Κεντρικό Νευρικό Σύστημα. self-poisoning.D. Αν και η πρεγκαμπαλίνη σχετίζεται δομικά με το GABA είναι ανενεργή στους υποδοχείς του GABA και δεν φαίνεται να μιμείται τη φυσιολογία του GABA. Crnobaric. Χάρη στη σταθερά καλή σωματική του κατάσταση. Έχει λάβει άδεια χρήσης στην επιληψία.8 mg/L αλλά ο ασθενής δεν είχε σημεία τοξικότητας. αν και μεμονωμένη.2 1 Institute of Mental Health.164 C. Περίπτωση τοξίκωσης από πρεγκαμπαλίνη C. Μετά την εμφάνιση ιδιαίτερα έντονου στρες στην εργασία του. παρέχει ενδείξεις υπέρ της ασφάλειας της πρεγκαμπαλίνης μετά από λήψη υπερβολικής δόσης. ο ασθενής έλαβε μεγάλη ποσότητα πρεγκαμπαλίνης (4. ψυχοφαρμακολογία. τοξίκωση. Η συγκέντρωση πρεγκαμπαλίνης στον ορό ήταν 20. H παρατήρησή μας έρχεται σε συμφωνία με την πρόσφατη διεθνή βιβλιογραφία όπου επισημαίνεται το γεγονός ότι η πρεγκα- μπαλίνη έχει εκτιμηθεί ότι συμβάλλει μόνο κατά 1% στη θνησιμότητα από δηλητηριάσεις. άγχος.1 C. low molecular weight (ap.16 conflicts of interest. Serbia Ψυχιατρική 2012.

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