risk of out-of-hospital cardiac (OHCA) arrest in antidepressant users

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NICE have previously given guidance as to the treatment of depression in the context of heart disease (1)

  • when initiating treatment in a patient with a recent myocardial infarction or unstable angina, sertraline is the treatment of choice as it has the most evidence for safe use in this situation
  • take account of the increased risks associated with tricyclic antidepressants in patients with cardiovascular disease
    • an ECG should be carried out and blood pressure measurement taken before prescribing a tricyclic antidepressant for a depressed patient at significant risk of cardiovascular disease
  • venlafaxine and tricyclic antidepressants (with the exception of lofepramine) should not be prescribed for patients with a:
    • high risk of serious cardiac arrhythmias
    • recent myocardial infarction

  • however, in the updated version of the NICE depression guideline (CG90 guideline) then the guidance regarding which antidepressant to use in coronary heart disease (CHD) was not included

In updated NHS guidance (2):

  • SSRIs are the preferred antidepressants in CHD
    • sertraline, fluoxetine, or paroxetine are the SSRIs of choice

    • citalopram and escitalopram are less preferred options and should generally be avoided. In particular do not use citalopram in people with known QT interval prolongation, congenital long QT syndrome or in people taking other medicines that prolong the QT interval

  • mirtazapine is also a preferred antidepressant in CHD

  • tricyclic antidepressants (TCAs)
    • tricyclic antidepressants are less preferred options and should generally be avoided
    • of the TCAs: doxepin, lofepramine and mianserin may be considered lower risk, but should still be used with caution
    • if TCAs are the only feasible option consider ECG monitoring (at baseline and a week after dose increases), particularly in those who may be vulnerable to arrhythmias

  • monoamine oxidase inhibitors (MAOIs)
    • MAOIs should almost always be avoided
    • where they are used, they will usually be initiated by mental health specialists after careful consideration. There will be a reason why preferred antidepressants cannot be used
    • it is important to seek advice from the specialist who knows the person before considering any changes to an MAOI regimen
    • of the MAOIs:
      • Moclobemide is considered a lower risk option.
      • If MAOIs are used in people with a risk of arrhythmias, discuss the risks with the mental health specialist and consider if ECG monitoring would be beneficial

  • other antidepressants
    • antidepressants other than SSRIs, TCAs, or MAOIs may vary with respect to their risks and monitoring requirements
    • agomelatine and vortioxetine
      • may be considered third line options
    • duloxetine, reboxetine, and venlafaxine
      • should be avoided if possible

  • managing patients currently on a less preferred antidepressant
    • managing patients with a new diagnosis of CHD currently on an antidepressant requires care. You should:
      • seek advice from a mental health specialist (ideally one who knows the person) before switching.
      • take into account the extent and severity of CHD and other medical history
      • consider the person's preferences and past experience with antidepressant use if any
      • check cautions, contraindications relating to the cardiovascular system and any drug interactions (e.g. in electronic medicines compendium)

  • risk of out-of-hospital cardiac (OHCA) arrest in antidepressant users
    • a Danish nested case-control study (10,978 cases; 109,869 controls) found when compared to sertraline, high-dose citalopram (>20mg) and escitalopram (>10mg) associated with increased rate of out-of-hospital cardiac arrest (OHCA) (HR 1.46; 95% CI1.27-1.69 and 1.43; 1.16-1.75, respectively)
    • compared to the reference drug amitriptyline, none of the tricyclic antidepressants were associated with an increased rate of OHCA
    • risk of OHCA for high-dose mirtazapine (>30) (HR:1.59[95%-CI:1.18-2.14]) is increased among the serotonin-norepinephrine reuptake inhibitors or noradrenergic and specific serotonergic antidepressants (reference drug duloxetine)
    • based on their findings, the authors suggest that careful titration should be considered when citalopram, escitalopram and mirtazapine are prescribed

Notes:

  • mirtazapine has a unique pharmacological profile, including potent antagonism of central alpha 2-adrenergic autoreceptors and heteroreceptors and antagonism of both serotonin 5-hydroxytryptamine-2 (5-HT2) and 5-HT3 receptors (3)
    • is classified as a NaSSA (noradrenergic and specific serotonergic antidepressant)
    • antagonism of alpha 2-adrenergic receptors leads to blockade of presynaptic autoreceptors and thus enhances norepinephrine release, while blockade of heteroreceptors on serotonergic neurons increases serotonin release

Reference:

  1. NICE (April 2007). Management of depression in primary and secondary care.
  2. NHS Specialist Pharmacy Service (July 2nd 2021) Choosing a suitable antidepressant for people with coronary heart disease (CHD)
  3. Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2011;(12):CD006528. Published 2011 Dec 7. doi:10.1002/14651858.CD006528.pub2
  4. Eroglu TE et al. Risk of out-of-hospital cardiac arrest in antidepressant drug users. British Journal of Pharmacology January 2022.

Last edited 01/2022 and last reviewed 01/2022

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