Depression is linked with negative cardiovascular health outcomes

Patients with cardiovascular disease (CVD) or other vulnerable patient populations (e.g. older or hospitalised patients) are at increased risk of depression [1]. For instance, the prevalence of depression in patients with coronary heart disease (CHD) is ≈ 3–4 times higher than in the general population. Depression is a major risk factor for negative health outcomes in these high-risk patients, contributing to increased cardiovascular (CV) morbidity and mortality [1, 2]. Depression, in the elderly in particular, is now a global public health concern, contributing to the burdens associated with an aging population due to its impact on comorbidities and quality of life [3].

Having second- and third-line antidepressant choices is necessary for proper management

Though psychotherapy has been proven to be very effective in managing depression, selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological option when treating depression [1]. Efficacy and safety have been established in numerous randomized controlled trials (RCTs) and observational trials [1]. In patients with depression and CHD, SSRIs did not increase the incidence of CV adverse effects or CV events [1], and a meta-analysis found SSRIs improved depressive symptoms and did not impact the rate of CHD hospitalisations or mortality compared with control [4].

SSRIs may not be appropriate for certain patients due to intolerance or lack of response, and alternative pharmacological treatments may be warranted [1]. There is concern that other antidepressant classes may also result in CV adverse effects, therefore determining the efficacy and CV safety of antidepressants is challenging but crucial for vulnerable groups, such as older patients, hospitalised patients and patients with CVD [1]. For example, evidence suggests tricyclic antidepressants are associated with a higher CV risk than SSRIs [5], and may increase the risk of acute heart disease [2].

With high-risk patient populations such as the elderly, the challenges around managing comorbidities and (usually life-long) medications are made more difficult by a lack of robust literature surrounding antidepressant choice and tolerability profiles [3]. With particular focus on older adults, the mechanisms of action, recommended dosages and CV adverse effects of non-SSRI antidepressants (serotonin and norepinephrine reuptake inhibitors and atypical monoaminergic antidepressants) are summarized in Tables 1 and 2, as reviewed by Behlke et al. [1]. Elucidating the findings in this patient group may prove relevant for other high-risk populations.

Table 1 Cardiovascular adverse effects of serotonin and norepinephrine reuptake inhibitors in older patients, as reviewed by Behlke et al. [1]
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Table 2 Cardiovascular adverse effects of atypical monoaminergic antidepressants in older adults, as reviewed by Behlke et al. [1]
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Take extra care when starting an antidepressant

Antidepressant medications should only be used in patients with or at risk of CVD when absolutely necessary, such as when the diagnosis is clear for depression (major and minor), suicidal ideation or specific anxiety disorders [1]. Depressive symptoms or episodes alone are inadequate to qualify for antidepressants in patients already at high risk of adverse effects [1].

Recommendations to reduce risk of CV adverse effects when initiating an antidepressant, include [1]:

  • Initiate at a low dose for 1–2 weeks and then up-titrate; take into consideration the potential for under dosing the patient.

  • Avoid drug-drug interactions (particularly in older patients or patients with polypharmacy); consider pharmacokinetics and risk of interactions before initiating.

  • Monitor blood pressure before and after initiating antidepressant treatment or when up-titrating; take particular care when administering drugs that can increase blood pressure (e.g. ketamine, esketamine) or cause orthostatic hypotension (e.g. venlafaxine, duloxetine).

  • ECG monitoring not necessary before and/or after initiating antidepressant.

Further investigation is required, but may be difficult

Although RCTs are optimal in assessing the CV adverse effects of antidepressants [1, 5], those with higher CVD risk such as elderly patients or patients with comorbidities may often not be eligible for RCTs [1]. This under representation can limit the usefulness of these trials in determining the longer term impact of such drugs, particularly as trial follow-up can be quite short (e.g. due to ethical concerns regarding the administration of placebo in patients with depression) and the inherent variability of smaller sample sizes [1, 5]. Additionally, due to the nature of depression, it may be difficult to determine whether efficacy and safety results from a study can be attributed to antidepressant use or the indication itself (or a combination of both) [1]. Thus, critical evaluation of available evidence and further clinical trial data are key to antidepressant choice in patients with high CVD risk [1, 5].

Take home messages

  • Treat depression in patients with or at high risk of CVD (e.g. older patients, hospitalised patients) to improve outcomes.

  • Start SSRIs; however, if unable, consider CV adverse effects when choosing second- and third-line options.

  • Serotonin and norepinephrine reuptake inhibitors and atypical monoaminergic antidepressants may be safe and effective alternatives in older patients; carefully monitor for adverse events and contraindications.

  • Further clinical trial data will be helpful in confirming the CV safety of non-SSRI antidepressants in high-risk patient groups.