Mind Matters (Issue 4) - Effective Management of Comorbid Depression and Hypertension: Role of Escitalopram

13 Feb, 17

Introduction

Depression significantly contributes to the global burden of diseases.¹ A recent World Mental Health Survey has reported that on an average about 1 in 20 people experience an episode of depression, and depression is reported to affect around 350 million people globally.² Hypertension affects around 20% to 50% of adults in most countries and is considered as the main cause of cardiovascular diseases and death globally. It is also reported to represent two-thirds of all strokes and one-half of all ischemic heart disease worldwide.^{3, 4} The worldwide prevalence of hypertension is projected to increase from 26 to 29% by the year 2025. Moreover, hypertensive patients are also prone to experience psychological distress that increases their risk of developing depression and anxiety.³

Various studies have revealed a high prevalence of depression in hypertensive patients, ranging from 29.8 to 66.7%.^1,5 Comorbid depression and hypertension increases the risk of stroke, reduces therapeutic compliance for anti-hypertensive therapy, increases the risk of suicide, may develop unipolar depression and may lead to higher use of limited health care resources.⁶

A high prevalence of depression ranging from 29.8 to 66.7% is observed in hypertensive patients.

Pathophysiological Link between Depression and Hypertension

The sympathetic nervous system is mainly involved in the physiological mechanisms underlying the relationship between depression or anxiety and blood pressure (BP).⁷ Both, hypertensive and depressive patients experience increased sympathetic tone and increased secretion of adrenocorticotropic hormone and cortisol. Moreover, BP may be increased or depression triggered due to lack of dopamine at key sites in the brain. Deficiency in monoamines such as serotonin, dopamine and norepinephrine in the central nervous system leads to development of depression. Furthermore, high BP causing the cerebrovascular and ischemic changes in the brain predisposes hypertensive patients to depression.⁸

Patients with comorbid hypertension and depression experience increased sympathetic tone, increased secretion of cortisol and deficiency of monoamines in the CNS. High BP causes changes in the brain which predisposes hypertensive patients to depression.

Comorbid Depression and Hypertension: Adverse Effect on Medication Adherence

Despite the high prevalence and impact of depression, it usually goes undiagnosed in primary care settings leading to inadequate treatment, which ultimately affects their quality of life of the patient and interferes with the treatment and prognosis of other chronic diseases.⁸Moreover, patients need to adhere to their anti-hypertensive therapy for effective management of hypertension, the process of which is adversely affected due to negative emotions that influence their adherence behaviour.³ Poor adherence to anti-hypertensive therapy leads to 50% of treatment failures and increases the risk of target organ damage in hypertensive patients. Researchers have suggested the problem of poor adherence to medications to be more than an ‘‘epidemiological finding”. Therefore, poor adherers to prescribed anti-hypertensive medications and with comorbid depression should be screened and treated for depression.⁹

Poor adherence to anti-hypertensive therapy could occur due to underlying and undiagnosed depression.

Anti-depressant Therapy in the Management of Comorbid Depression and Hypertension

Anti-depressants are reported to enhance the effects of the monoamine neurotransmitters, which are shown to have antihypertensive actions.⁸

Effect of SSRIs in BP Control¹⁰

The effect of selective serotonin reuptake inhibitors (SSRIs) on the BP is based on several pathways.

Since serotonergic neurons and receptors are reported to modulate vascular resistance, serotonin may play an important role in regulating vascular tone. SSRIs have inhibitory effect on the synthesis of nitric oxide as a vasodilator, thereby playing a role in vascular tone.
SSRIs are also shown to modulate peripheral serotonin and reduce platelet and whole blood serotonin concentrations.
They have been shown to affect circulating serotonin levels
Short-term use of SSRIs have also reported to reduce the sympathetic nervous system activation.¹⁰

Effective BP Control with SSRIs in Hypertensive Patients with Depression¹⁰

Researchers in a study evaluated the effect of SSRIs and alprazolam on the BP levels, and compared the BP levels between the group of users and nonusers. Patients with depression having a history of hypertension with antihypertensive treatment or an initial SBP >140 or diastolic BP (DBP) >90 mmHg and repeated high BP after a 5 min resting period were included. Patients were divided into four groups based on users of SSRIs, users of alprazolam, users of SSRIs and alprazolam, and users of SSRIs or alprazolam based on random digit number consecutively to four groups.

Patients on SSRIs therapy demonstrated significant improvement in DBP (p<0.05 and mean BP (p<0.05), whereas significant improvement was seen only in DBP (p<0.05) in nonusers of SSRIs (Table 1).
When users and nonusers of alprazolam were compared, no significant association was found between using alprazolam and all of the variables. However, significant improvement in DBP (p<0.05) and mean BP (p<0.05) was observed in the nonusers of alprazolam.
Therefore, patients administered SSRIs alone showed significant improvement in DBP and mean BP.¹⁰

Table 1: Comparison of the changes within group and between groups¹⁰

Another study by Diminic-Lisica et al showed that antidepressant therapy with SSRIs for 24-weeks in patients with comorbid hypertension and depression led to better BP control in addition to improvement of depressive symptoms. Patients who had administered antidepressants together with antihypertensives had significantly lower levels of both systolic and diastolic blood pressure (Z=7.42; p<0.001; and Z=7.36; p<0.001).¹¹

SSRIs lead to significant improvement of DBP and mean BP in patients with hypertension and depression.

Escitalopram is Effective in Treating Depression and Reducing BP in Patients with Comorbid Depression and Hypertension

Researchers evaluated the influence of escitalopram treatment on the regularization of BP and heart rate of individuals with hypertension and depression. Escitalopram (10 - 20 mg) was administered to 15 patients, while the other 15 were given placebo for 8 weeks. Results observed were as follows:¹²

The heart rate (HR) at 2 months (time 4) was found to be lower in the escitalopram group compared with that in the placebo group (66.88±9.62 vs. 74.19±9.55; p=0.04; Figure 1). Since HR is an important marker of the activity of the sympathetic nervous system, the decrease in HR by escitalopram supports the theory that the sympathetic nervous system is an important mediator between hypertension and depression.

Figure 1: Heart rate average variation in placebo and escitalopram groups. ¹²

A higher proportion of remission was observed in the escitalopram group than in the placebo group. (58% vs. 42% respectively).
Of those who had regularized sleep independent of escitalopram or placebo treatment, 86% showed remission of depression and only 14% showed no improvement. Finally, of the 15 individuals who used escitalopram, 54% achieved regularized sleep while 46% remained sleepless.
Of the patients who had regularized sleep, a significant decrease in the average SBP was observed during treatment, whereas SBP decrease was not seen in the insomniac group (−20.07 ± 13.45 vs. −9.43 ± 14.87 mmHg; p = 0.04; Figure 2).
The average scores on the HAM-D scale were significantly lower in the normal sleep group vs. insomniac group; 4.5 ± 3.52 vs. 11.4 ± 4.81, p ≤ 0.001.
Greater sleep regularization occurred with depression remission (71% of the 17 individuals remitting) compared with individuals who remained depressed (only 15% had regular sleep of the 13 non-remitting individuals) (chi-square = 9.020 Pearson, p=0.003).

Figure 2: Change in average SBP normal sleep and sleepless groups.

Therefore, escitalopram significantly reduces the HR of individuals with hypertension and depression which is independent of depression remission. Thus, escitalopram treatment in hypertensive patients with depression decreased heart their rate, improved their sleep quality, and decreased their blood pressure.¹²

Escitalopram decreases heart rate, improves sleep quality, and decreases blood pressure in hypertensive patients with depression. Therefore, it is a preferred choice for treatment of comorbid depression and hypertension.

Summary

A high prevalence of depression is observed in hypertensive patients. Comorbid depression and hypertension lead to several hindrances such as increased risk of cardiovascular complications, increased severity of depression and may lead to poor medication adherence further worsening the comorbid condition.
The pathophysiological link of hypertension and depression involves increased sympathetic tone and increased secretion of adrenocorticotropic hormone and cortisol. Deficiency in monoamines such as serotonin, dopamine and norepinephrine is also responsible for increasing BP and triggering depression. Moreover, high BP causing the cerebrovascular and ischemic changes in the brain predisposes hypertensive patients to depression.
Adherence to antihypertensive therapy is necessary for effective management of hypertension, which can be adversely affected due to depression. Therefore, it is essential to treat depression in these patients.
Antidepressants enhance the effects of the monoamine neurotransmitters. SSRIs have shown to significantly improve BP compared with those hypertensive patients with depression not using SSRIs in. SSRIs also lead to better BP control in addition to improvement of depressive symptoms.
Escitalopram has shown to reduce heart rate, has higher proportion of remission and regularised sleep in higher number of hypertensive patients, which ultimately reduced BP in hypertensive patients with depression.

References

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