Propranolol overdose following prescription for anxiety

Case

A 20-year-old female was brought in by ambulance to the emergency department 2.5 hours after an intentional ingestion of 2 g propranolol (200 tablets of 10 mg) and 20 g hydroxychloroquine (100 tablets of 200 mg). The patient reported stockpiling propranolol tablets over many months, including by obtaining a prescription from her regular general practitioner and using her mother’s prescription. The hydroxychloroquine was accessed from her mother.

The patient had a background of 2 previous propranolol overdoses and 3 overdoses related to other substances, and had a significant mental health history including borderline personality disorder, anorexia nervosa, generalised anxiety disorder, chronic suicidality, and methamphetamine and gamma-hydroxybutyrate use disorder. The patient had previously received psychotherapy, including dialectical behaviour therapy. She was prescribed propranolol 10 to 40 mg daily as required to manage sympathetic symptoms (e.g. tremor, palpitations, sweating) associated with anxiety. No specific mitigation strategies were in place to reduce the risk of overdose.

Three hours post ingestion, the patient had a blood pressure of 58/38 mmHg, a heart rate of 72 beats per minute and a decreased level of consciousness (Glasgow Coma Scale score of 5). Her electrocardiogram demonstrated PR prolongation of 200 ms, and a sodium channel blockade with a widened QRS interval of 140 ms and, on review of aVR, a terminal R wave of more than 3 mm and an R/S ratio of more than 0.7. She had an undetectable paracetamol concentration.

The patient was diagnosed with acute propranolol toxicity compounded by co-ingestion with hydroxychloroquine. She was admitted to the intensive care unit with input from the clinical toxicology team. She required intubation to protect the airway because of her decreased conscious state. Gastrointestinal decontamination with activated charcoal (administered via a nasogastric tube) was used to reduce systemic absorption of propranolol in the upper gastrointestinal tract. The patient also received inotropic and vasopressor support with metaraminol, noradrenaline, adrenaline and high-dose insulin euglycaemic therapy (HIET),^1-3 and infusions of sodium bicarbonate and calcium gluconate for management of QRS widening. She developed a severe hypokalaemia of 2.6 mmol/L in the context of hydroxychloroquine ingestion and HIET, and potassium was replaced.

Her physiology normalised over the next 24 hours and she was deemed sufficiently stable for transfer to the psychiatry ward for ongoing management. She was discharged with a plan for follow-up by the psychiatric and addiction medicine teams.

 

Comment

Propranolol is a nonselective beta blocker with sodium channel–blocking properties. It is more toxic than other beta blockers because of its co-inhibition of sodium channels and high lipophilicity, which increases penetration of the blood–brain barrier and therefore the risk of central nervous system manifestations.⁴ In overdose, particularly ingestions greater than 2 g, propranolol can cause bradycardia, heart block, QRS widening, haemodynamic instability, coma and seizures.^2,5

Propranolol is indicated in the management of a number of conditions, including migraine prophylaxis, thyrotoxicosis and essential tremor.⁶ It is also commonly prescribed for various anxiety disorders, particularly panic disorder or performance (situational) anxiety disorder, which is a subtype of social anxiety disorder. Propranolol and atenolol, another beta blocker used for anxiety, do not have an anxiolytic effect, but are used to reduce sympathetic symptoms associated with anxiety, such as tremor and palpitations. However, their role in managing anxiety is controversial, with insufficient evidence to support routine use. Studies have not demonstrated superiority of these drugs over placebo in social anxiety disorder.^7,8 A small double-blind pilot study (n=60) found self-reported speech distress and questionnaire measures of public-speaking anxiety were reduced with 40 mg of propranolol, but it did not reliably outperform placebo.⁹ Psychosocial interventions, including cognitive behavioural therapy with an exposure component, remain first-line therapy for panic disorder and performance anxiety disorder.¹⁰

Propranolol is available in strengths of either 10 mg or 40 mg in packs of 100 tablets and is often prescribed as a full pack. Limiting the amount prescribed to a smaller quantity than the full pack size can reduce the risk of misuse. With any drug that is potentially toxic in overdose or that may be misused, staged supply can be considered. This involves the prescriber directing the patient’s pharmacy to provide the drug in instalments. All patients prescribed propranolol should be made aware of its potential toxicity in overdose and advised to ensure access to tablets and prescriptions is restricted.

In this case, the co-ingestion of hydroxychloroquine increased the complexity of this beta-blocker overdose, given the additive effect of conduction abnormalities, negative inotropy, hypotension and electrolyte derangements.

 

Conclusion and recommendations

Any prescribing decision is a consideration of potential harms and benefits. Patients with anxiety, particularly those who have had previous overdoses, are at increased risk of impulsivity and self-harm. History of previous overdose should be sought before prescribing propranolol for anxiety. Propranolol (or an alternative beta blocker) should be used with extreme caution in these patients given the lack of evidence of benefit and potential for significant harm in overdose. If the use of propranolol is considered necessary, limited or staged supply may reduce the potential for harm. Additionally, all patients prescribed propranolol should be counselled to keep medicines and prescriptions secure to prevent diversion.

Patient consent for publication of this case study was obtained by the authors.

Conflicts of interest: Evan Browne was the Clinical Pharmacology Trainee participant on the Australian Prescriber Editorial Advisory Committee at the time of writing. He was excluded from editorial decision-making related to the acceptance and publication of this case study. Bridin Murnion and Jacqueline Huber have no conflicts of interest to declare.

This article is peer reviewed.

 

References

1. Hamzic J, Raos D, Radulovic B. High-Dose Insulin Euglycemic Therapy. Acta Clin Croat 2022;61:73-7.
2. Beta-blocker poisoning. In: Therapeutic Guidelines. Melbourne: Therapeutic Guidelines Limited; 2020. [cited 2024 Jun 13]
3. Rotella JA, Greene SL, Koutsogiannis Z, Graudins A, Hung Leang Y, Kuan K, et al. Treatment for beta-blocker poisoning: a systematic review. Clin Toxicol (Phila) 2020;58:943-83.
4. Sharifpour A, Sadeghi M, Zakariae Z, Soleymani M. Seizures and Irreversible Cardiogenic Shock Following Propranolol Poisoning: Report of 2 Cases and Literature Review. Clin Med Insights Case Rep 2022;15:11795476221126981.
5. Lauterbach M. Clinical toxicology of beta-blocker overdose in adults. Basic Clin Pharmacol Toxicol 2019;125:178-86.
6. Therapeutic Guidelines. Melbourne: Therapeutic Guidelines Limited; [cited 2024 Dec 12]
7. Steenen SA, van Wijk AJ, van der Heijden GJ, van Westrhenen R, de Lange J, de Jongh A. Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. J Psychopharmacol 2016;30:128-39.
8. Andrews G, Bell C, Boyce P, Gale C, Lampe L, Marwat O, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of panic disorder, social anxiety disorder and generalised anxiety disorder. Australian & New Zealand Journal of Psychiatry 2018;52:1109-72.
9. Elsey JWB, Filmer AI, Galvin HR, Kurath JD, Vossoughi L, Thomander LS, et al. Reconsolidation-based treatment for fear of public speaking: a systematic pilot study using propranolol. Transl Psychiatry 2020;10:179.
10. Psychotropic. In: Therapeutic Guidelines. Melbourne: Therapeutic Guidelines Limited; 2021. [cited 2024 Dec 12]