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Pramipexole Overdose Associated with Visual Hallucinations, Agitation and Myoclonus

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Abstract

Introduction

Pramipexole is a dopamine D2 receptor agonist used to treat idiopathic Parkinson’s disease and primary restless legs syndrome. There is limited information on pramipexole overdose.

Case Report

A 59-year-old male ingested 3 mg pramipexole, 2250 mg venlafaxine, 360 mg mirtazapine, with suicidal intent. He presented alert, had normal vital observations and normal pupillary reflexes. He was mildly agitated, reported visual hallucinations and was given 5 mg diazepam. He had a mildly elevated lactate of 1.7 mmol/L, but otherwise normal laboratory investigations. Overnight, he remained agitated with visual hallucinations and developed myoclonus while awake. He had increasing difficulty passing urine on a background of mild chronic urinary retention. On review, 14 h post-ingestion, he was hypervigilant, jittery and mildly agitated. He had pressured speech and difficulty focusing on questioning. He had a heart rate of 110 bpm, but had an otherwise normal examination, with no clonus or extrapyramidal effects. He was unable to mobilize due to dizziness and ataxia. Over the next few hours, he improved, the visual hallucinations and agitation resolved and he mobilized independently. Pramipexole was measured with liquid chromatography mass spectrometry. The initial plasma pramipexole concentration was 34.2 ng/mL (therapeutic range 0.2 to 7 ng/mL), 9 h post-overdose. Concentration time data fitted a one-compartment model with an estimated elimination half-life of 18 h.

Discussion

Pramipexole overdose with hallucination, agitation, and myoclonus is consistent with adverse effects reported with therapeutic toxicity, but mirtazapine and venlafaxine may have contributed. Pramipexole concentrations exceeded the therapeutic range for over 24 h. With the increasing use of pramipexole in restless legs syndrome, adult overdoses may become more common.

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References

  1. Ishibashi K, Ishii K, Oda K, Mizusawa H, Ishiwata K. Binding of pramipexole to extrastriatal dopamine D2/D3 receptors in the human brain: a positron emission tomography study using 11C-FLB 457. PLoS One. 2011;6(3):e17723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. de Biase S, Valente M, Gigli GL. Intractable restless legs syndrome: role of prolonged-release oxycodone-naloxone. Neuropsychiatr Dis Treat. 2016;12:417–25.

    PubMed  PubMed Central  Google Scholar 

  3. Frampton JE. Pramipexole extended-release: a review of its use in patients with Parkinson’s disease. Drugs. 2014;74(18):2175–90.

    Article  CAS  PubMed  Google Scholar 

  4. Winkelman JW, Sethi KD, Kushida CA, Becker PM, Koester J, Cappola JJ, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006;67(6):1034–9.

    Article  CAS  PubMed  Google Scholar 

  5. Parkinson Study G. Pramipexole in levodopa-treated Parkinson disease patients of African, Asian, and Hispanic heritage. Clin Neuropharmacol. 2007;30(2):72–85.

    Article  Google Scholar 

  6. Constantinescu R. Update on the use of pramipexole in the treatment of Parkinson’s disease. Neuropsychiatr Dis Treat. 2008;4(2):337–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635–42.

    Article  CAS  PubMed  Google Scholar 

  8. Chunduri RHB, Dannana GS, Chodae SB, Koppula KC, Deta SI, Konduru B. UPLC-MS/MS method for simultaneous quantification of pramipexole, ropinirole and rasagiline in human plasma and its application to a pharmacokinetic study. Am J PharmTech Res. 2013;3(3).

  9. Mohamed S, Riva R, Contin M. Validated UHPLC-MS/MS method for the simultaneous determination of pramipexole and ropinirole in plasma of patients with Parkinson’s disease. J Chromatogr B Anal Technol Biomed Life Sci. 2016;1017-1018:114–9.

    Article  CAS  Google Scholar 

  10. Dresen S, Ferreiros N, Gnann H, Zimmermann R, Weinmann W. Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching. Anal Bioanal Chem. 2010;396(7):2425–34.

    Article  CAS  PubMed  Google Scholar 

  11. Schulz M, Schmoldt A. Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie. 2003;58(7):447–74.

    CAS  PubMed  Google Scholar 

  12. Kataoka H, Ueno S. Auditory musical hallucinations associated with extended-release pramipexole in an elderly patient with Parkinson’s disease. Medicine (Baltimore). 2014;93(27):e251.

    Article  Google Scholar 

  13. Signorelli MS, Battaglia E, Costanzo MC, Cannavo D. Pramipexole induced psychosis in a patient with restless legs syndrome. BMJ Case Rep. 2013;2013.

  14. Berling I, Isbister GK. Mirtazapine overdose is unlikely to cause major toxicity. Clin Toxicol (Phila). 2014;52(1):20–4.

    Article  CAS  Google Scholar 

  15. Waring WS, Good AM, Bateman DN. Lack of significant toxicity after mirtazapine overdose: a five-year review of cases admitted to a regional toxicology unit. Clin Toxicol (Phila). 2007;45(1):45–50.

    Article  CAS  Google Scholar 

  16. Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM. 2003;96(5):369–74.

    Article  CAS  PubMed  Google Scholar 

  17. Hack JB, Powell G, Nelson LS, Hoffman RS, Howland MA. Acute pediatric exposure to pramipexole dihydrochloride (Mirapex (R) ). J Toxicol Clin Toxicol. 1999;37(7):891–2.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang W, Wang Y, Cong SY, Nao JF, Feng J, Bi GR. Efficacy and tolerability of pramipexole for the treatment of primary restless leg syndrome: a meta-analysis of randomized placebo-controlled trials. Neuropsychiatr Dis Treat. 2013;9:1035–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Antonini A, Calandrella D. Pharmacokinetic evaluation of pramipexole. Expert Opin Drug Metab Toxicol. 2011;7(10):1307–14.

    Article  CAS  PubMed  Google Scholar 

  20. Wright CE, Sisson TL, Ichhpurani AK, Peters GR. Steady-state pharmacokinetic properties of pramipexole in healthy volunteers. J Clin Pharmacol. 1997;37(6):520–5.

    Article  CAS  PubMed  Google Scholar 

  21. Dutra LA, Pedroso JL, Felix EP, Barsottini OG. Venlafaxine induced-myoclonus in a patient with mixed dementia. Arq Neuropsiquiatr. 2008;66(4):894–5.

    Article  PubMed  Google Scholar 

  22. Anghelescu I, Klawe C, Himmerich H, Szegedi A. Topiramate in venlafaxine-induced visual hallucinations in an obese patient with a posterior cerebral artery infarction. J Clin Psychopharmacol. 2001;21(4):462–4.

    Article  CAS  PubMed  Google Scholar 

  23. Padala KP, Padala PR, Malloy T, Burke WJ. New onset multimodal hallucinations associated with mirtazapine: a case report. Int Psychogeriatr. 2010;22(5):837–9.

    Article  PubMed  Google Scholar 

  24. Hoque R, Chesson AL Jr. Pharmacologically induced/exacerbated restless legs syndrome, periodic limb movements of sleep, and REM behavior disorder/REM sleep without atonia: literature review, qualitative scoring, and comparative analysis. J Clin Sleep Med. 2010;6(1):79–83.

    PubMed  PubMed Central  Google Scholar 

  25. Fulda S, Kloiber S, Dose T, Lucae S, Holsboer F, Schaaf L, et al. Mirtazapine provokes periodic leg movements during sleep in young healthy men. Sleep. 2013;36(5):661–9.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

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Corresponding author

Correspondence to Geoffrey K. Isbister.

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Consent for publication of this case was obtained and provided to the journal in accordance with JMT policy.

Funding

The study was supported by an NHMRC Program Grant (1055176). GKI is supported by an NHMRC Senior Research Fellowship ID1061041 and MR is supported by an NHMRC Senior Principal Research Fellowship ID1002611.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Cardon-Dunbar, A., Robertson, T., Roberts, M.S. et al. Pramipexole Overdose Associated with Visual Hallucinations, Agitation and Myoclonus. J. Med. Toxicol. 13, 343–346 (2017). https://doi.org/10.1007/s13181-017-0615-7

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  • DOI: https://doi.org/10.1007/s13181-017-0615-7

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