Heart disease and depression
Depression is common in people with CHD. It is associated with higher risk of death due to cardiovascular causes and so it is important that it is well-managed.
This article assumes the decision to prescribe an antidepressant in someone with CHD has already been made. Refer to NICE Clinical Knowledge Summary for management of depression in general.
Making a suitable choice needs to include consideration of both the characteristics of the medicines available and those of the patient.
These options are preferred by a range of mental health resources including Bazire’s Psychotropic Drug Directory, Maudsley Prescribing Guidelines in Psychiatry and published papers. Preferred antidepressants have data to demonstrate safe use in people with CHD and have minimal or no effects on the cardiovascular system.
The recommendations on choices assume use of antidepressants at standard doses.
Selective Serotonin Re-uptake Inhibitors (SSRIs) and Mirtazapine
SSRIs are the preferred antidepressants in CHD. Sertraline, fluoxetine, or paroxetine are the SSRIs of choice. Mirtazapine is also a preferred antidepressant in CHD.
The NICE Guideline on Depression in adults with a chronic physical health problem [CG91] advises that SSRIs increase the risk of gastrointestinal (GI) bleeding, particularly in older people and in those who take aspirin and SSRIs. Consider if gastroprotection is needed in these scenarios.
Less preferred antidepressants
You should always explore first whether preferred antidepressants can be used; however, there may be a good reason why they can’t.
The options below are less preferred by a range of mental health resources including Bazire’s Psychotropic Drug Directory, Maudsley Prescribing Guidelines in Psychiatry, published papers and manufacturer’s recommendations. There are fewer data to demonstrate safe use in people with CHD and/or they have demonstrated effects on the cardiovascular system.
Citalopram and escitalopram
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.
Safety and monitoring
If citalopram and escitalopram are the only feasible antidepressant options:
- The MHRA advises that both citalopram and escitalopram be subject to additional monitoring in patients with CHD.
- Use citalopram with extreme caution in people with CHD, particularly in those with recent MI, bradyarrhythmias / bradycardia, hypokalaemia or hypomagnesaemia or decompensated heart failure.
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.
Antidepressants other than SSRIs, TCAs, or MAOIs may vary with respect to their risks and monitoring requirements.
Agomelatine and vortioxetine
These may be considered third line options
Duloxetine, reboxetine, and venlafaxine
These should be avoided if possible
Patient characteristics and considerations
When making an initial choice to prescribe, or deciding how to manage people who are currently on an antidepressant, you should consider the persons individual needs as well as their CHD.
Making a choice when starting an antidepressant
Individualise choice using the options above. Consider:
- Persons circumstances, history, preferences and past experience with antidepressants and indication for use
- Extent and severity of CHD (including any complications) and other medical history
Initiate with a low dose first and titrate up
Initiate the chosen antidepressant at a low dose and increase gradually until a standard therapeutic dose is achieved. Review regularly thereafter as recommended by NICE Clinical Knowledge Summary for management of depression.
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).
Switching from less to more preferred options
Switching patients with CHD from their current antidepressant to another antidepressant may sometimes be necessary. Our advice on antidepressant switching may be helpful.
With thanks to Makhan Chohan, Deputy Chief Pharmacist at the Essex Partnership University NHS Foundation Trust for his contribution.
The advice above was generated using a range of literature. We’ve provided the summary below to support our review together with a full bibliography:
Published trials investigating the safety (and efficacy) of antidepressants in CHD are small RCTs or observational studies with short duration and narrow scope in various different populations, making comparison difficult.
Antidepressant choice is based on the known safety profile in CHD which varies between classes and individual antidepressants.
- SSRIs are preferred according to NICE [CG91] and the European Society of Cardiology (ESC). Several randomised trials show SSRIs are safe in CHD and may even have a protective effect. Except for citalopram (and perhaps escitalopram), SSRIs have little effect on heart rhythm and blood pressure.
- Sertraline is the most widely studied SSRI in CHD and the preferred option according to the ESC and specialist mental health resources. It has few known cardiac adverse effects and no interactions with cardiac medicines.
- Fluvoxamine, fluoxetine and paroxetine are considered lower risk antidepressants with minimal effects on the cardiovascular system. Fluoxetine is contraindicated with metoprolol and paroxetine may increase cholesterol levels.
- Citalopram causes dose dependent QT interval prolongation and is generally avoided in CHD. Escitalopram is structurally related to citalopram and there are similar, mostly theoretical, concerns with its use. The MHRA provide guidance for monitoring in patients with CHD who are taking these.
- Mirtazapine is also considered a lower risk antidepressant with minimal effects on the cardiovascular system.
- TCAs are largely avoided in CHD. Several studies demonstrate that they lead to worse outcomes than SSRIs in CHD. TCAs increase heart rate and rhythm, prolong the PR and the QT intervals and can cause postural hypotension (risking MI). They are highly cardiotoxic in overdose, dosulepin in particular which is on NHS England’s Low Value Medicines list.
- Different TCAs are associated with variation in risks with lofepramine, mianserin and possible doxepin carrying lower risk in CHD.
- MAOIs are avoided where possible in CHD because they can cause hypotension and serious drug-drug and drug-food interactions. MAOI overdoses can be dangerous.
- Different MAOIs are associated with variation in risks with moclobemide carrying a lower risk in people with CHD compared to other MAOIs.
- There are limited published data on alternative antidepressants in CHD.
- Venlafaxine and duloxetine are SNRIs. Their use has not been evaluated in people with a recent history of MI or unstable CHD. Over a 10 year historical cohort study (n= 1,694) there was no increased risk of major adverse cardiovascular events (MACE) with use of SNRI’s. However, they can cause dose related increases in blood pressure, postural hypotension and arrhythmias.
- Vortioxetine and agomelatine have not been linked to QT prolongation or other adverse effects but as newer agents, less is known about these.
- Reboxetine can cause tachycardia, palpitations and dose-related postural hypotension. Blood pressure monitoring is recommended with its use.
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Baumeister H, Hutter N, Bengel J. Psychological and pharmacological interventions for depression in patients with coronary artery disease. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD008012.
Bazire S. Chapter 2.1.2 Selecting drugs, doses and preps (antidepressants) and 3.2 psychotrophics in problem areas (antidepressants and cardiovascular disease). Psychotropic Drug Directory 2020/21. Lloyd-Reinhold Publications.
Beach, S.R. Celano, C. M. Sugrue, A.M et al QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A Five Year Update, Psychosomatics 2018; 59(2):105-122.
Douros, A. Dell’Aniello, S. Dehghan, G et al. Degree of serotonin reuptake inhibition of antidepressants and ischemic risk. Neurology 2019; 93 (10): e1010-e1020
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Medicines and Healthcare products Regulatory Agency (MHRA). Citalopram and escitalopram: QT interval prolongation, December 2014. Available at: https://www.gov.uk/drug-safety-update/citalopram-and-escitalopram-qt-interval-prolongation
NICE Clinical Knowledge Summary for depression. Updated March 2021.
Ostuzzia, G. Turrinia, G. Gastaldona, C. Efficacy and acceptability of antidepressants in patients with ischemic heart disease: systematic review and meta-analysis. International Clinical Psychopharmacology 2019, 34:65–75
Taylor D, Barnes TRE, Young AH. Chapter 10: Drug treatment of psychiatric symptoms occurring in the context of other disorders. The Maudsley Prescribing Guidelines in Psychiatry. 13th Edition. Oxford: Wiley-Blackwell.
Tofler, G.H. Psychosocial factors in acute coronary syndrome. UpToDate.com (subscribed resource). Last updated: January 12, 2021.
Vaccarino,V. Badimon,L. Bremner,J.D et al. Depression and coronary heart disease: 2018 position paper of the ESC working group on coronary pathophysiology and microcirculation. European Heart Journal 2020; 41: 1687–1696