Effect and safety of escitalopram in the treatment of depressive disorder in patients with myocardial infarction: A prospective study

Sujata Sethi; Narender Rohilla; Kuldeep Lallar

doi:10.4103/0971-8990.182098

ORIGINAL ARTICLE

Year : 2016 | Volume : 21 | Issue : 1 | Page : 42-47

Effect and safety of escitalopram in the treatment of depressive disorder in patients with myocardial infarction: A prospective study

Sujata Sethi¹, Narender Rohilla², Kuldeep Lallar³
¹ Department of Psychiatry, Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
² Consultant Psychiatrist in Private Sector, India
³ Department of Cardiology, Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India

Date of Web Publication

10-May-2016

Correspondence Address:
Sujata Sethi
122/8, Shivaji Colony, Rohtak - 124 001, Haryana
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/0971-8990.182098

Abstract

Background: The top two contributors to the worldwide burden of disease are predicted to be ischemic heart disease (IHD) and major depression. Patients with established IHD are at risk to develop depression. Major depression is common among patients recovering from myocardial infarction (MI). As depression can worsen the prognosis of cardiac patients, it might be possible to improve the prognosis by treating the depression with antidepressants. Aim: The index study aimed to find the prevalence of depressive disorder in adult patients with MI admitted to the cardiology unit and to examine the outcome as regards to the effect and safety of escitalopram as per the treatment regime routinely followed for the treatment of depression in such patients. Methods: One hundred consecutive patients with an established diagnosis of MI admitted to the Department of Cardiology constituted the study sample. Patients who qualified for the major depressive disorder were then treated with escitalopram. Results: The overall prevalence of depression in patients with MI is 22%. The study highlights that depression in the post-MI period is common and responds well to antidepressant treatment. Escitalopram could be an effective and safe antidepressant for the treatment of depression in patients with MI. Conclusion: The study highlights that depression in post MI period is common and escitalopram seems to be an effective and safe antidepressant for the treatment of depression in MI patients.

Keywords: Depressive disorder, escitalopram, myocardial infarction

How to cite this article:
Sethi S, Rohilla N, Lallar K. Effect and safety of escitalopram in the treatment of depressive disorder in patients with myocardial infarction: A prospective study. J Mental Health Hum Behav 2016;21:42-7

How to cite this URL:
Sethi S, Rohilla N, Lallar K. Effect and safety of escitalopram in the treatment of depressive disorder in patients with myocardial infarction: A prospective study. J Mental Health Hum Behav [serial online] 2016 [cited 2023 Jun 3];21:42-7. Available from: https://www.jmhhb.org/text.asp?2016/21/1/42/182098

Introduction

By the year 2020, the top two contributors to the worldwide burden of disease are predicted to be ischemic heart disease (IHD) and major depression.^[1],[2] In long-term prospective studies, depression emerged as an independent risk factor for the development of IHD.^[3] On the other hand, patients with established IHD are at risk to develop depression.^[4]

Major depression is common among patients recovering from myocardial infarction (MI).^[5] In addition, clinically significant depressive symptoms not amounting to major depressive disorder are much more common in such patients.^[6] Persons with history of major depressive disorder are 4 times more likely to have MI than those with no history of depression.^[7] Increased mortality in persons who had MI and who manifest low level of depressive symptoms, states the importance of mental health to physical health outcome.^[6]

Although it is not unusual to have a depressed state of mind following MI, a persistent state of depression has been identified as a strong and independent risk factor for increased mortality, recurrent cardiac events, and lower functional status in patients with MI and unstable angina.^[8] Studies have shown that the patients with IHD are far less likely to recover from their illness if they have a history of depression or experience depression before, during, or after hospitalization than the patients without history of depression.^[9]

As depression can worsen the prognosis of cardiac patients, it might be possible to improve the prognosis by treating the depression with antidepressants. Tricyclic antidepressants have been used with caution in patients with MI due to the risk of serious adverse cardiac events. In contrast, selective serotonin reuptake inhibitors (SSRIs) are safe and effective drugs in the cardiac population. Various controlled trials including enhancing recovery in coronary heart disease,^[10] sertraline antidepressant heart attack randomized trial (SADHART),^[11] cardiac randomized evaluation of antidepressant and psychotherapy efficacy,^[12] and depression in coronary artery disease ^[13] used the SSRIs such as fluoxetine, sertraline for treatment of post-MI depression and established the efficacy and safety of these drugs in these patients. Despite the fact that escitalopram is an effective antidepressant drug with proven efficacy and lesser side effects,^[13] the drug is not commonly used due to apprehension in the minds of physicians about drug interactions or many other reasons.

Based on the above mentioned facts and to generate supportive evidence regarding the use of escitalopram, we planned to study the prevalence of depressive disorder in adult patients with MI admitted to the cardiology unit and to examine the outcome as regards to the effect and safety of escitalopram as per the treatment regime routinely followed for treatment of depressive disorder.

Methods

This study was a prospective quasi-experimental and open-label study conducted in the Departments of Cardiology and Psychiatry at Pt. B. D. Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India. The study was approved by the Local Research and Ethical Committee.

Eligibility criteria

Inclusion criteria

Admission to Cardiology Department
Age >18 years
Screened within a period of more than 2 weeks to 3-months post-MI
Signed informed consent.

Exclusion criteria

Cardiovascular exclusions

Uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg)
Cardiac surgery anticipated during the next 6 months
Index MI or unstable angina developed <3 months after coronary artery bypass graft procedure
Resting heart rate of <40/min.

Other medical exclusions

Chronic medical illness including significant renal dysfunction, hepatic dysfunction, or other significant noncardiac disease
Pregnant women.

Concomitant treatment exclusions

Current use of Class I antiarrhythmic medications
Initiation of psychotherapy in the 3 months before study entry.

Psychiatric exclusions

Alcohol or substance abuse or dependence in past 6 months
Psychotic symptoms, history of psychosis, bipolar disorder, organic brain syndrome, dementia (or a mini-mental status examination score <23)
Significant suicide risk.

Study sample

One hundred consecutive patients with an established diagnosis of MI admitted to the Department of Cardiology and meeting the eligibility criteria constituted the study sample. All cases that consented to participate in the study were subjected to a detailed history, clinical examination, mental status examination, and baseline investigations including echocardiography (ECG).

Tools

The following assessment tools were used:

Proforma for sociodemographic variables

A special proforma was used to gather information from the patients about their age, gender, locality, family structure, educational level, profession, and income. Details regarding past medical history including past history of MI and subsequent hospitalization; past history of psychiatric illness as well as relevant family history of medical and psychiatric illness were gathered.

Primary care evaluation of mental disorders scale

Primary care evaluation of mental disorders (PRIME-MD)^[14] has two components. First, the patient questionnaire (PQ) consists of nine questions. Second, component of PRIME-MD is clinical evaluation guide that the clinician uses to gather additional information in diagnostic areas to which patient responded positively on the PQ.

The mood module begins with questions regarding nine characteristic symptoms of major depressive disorder. A score of 5 or more is suggestive of depressive disorder.

Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for major depressive disorder

This was used for establishing the diagnosis of major depressive disorder in the patients with MI.^[15]

Hamilton Depression Scale Version-17

It is designed to quantify the severity of depression in the patients already diagnosed as suffering from the depressive disorder. Hamilton Depression Scale (HAM-D)^[16] is an interviewer-rated scale based on 17 variables graded on a scale of 0–4 where 0 means the absence of problem and a score of 4 means severe problem.

Udvalg for Kliniske Undersøgelser side effect rating scale

This scale ^[17] was used to record the side effects of escitalopram.

Psychiatric assessment

After demographic data collection during the baseline visit, PRIME-MD scale was administered. Based on PRIME-MD scores, the study sample was divided into two groups. Group I, henceforth termed as “case” group, comprised the patients who scored 5 or more on PRIME-MD as well as fulfilled the criteria for major depressive disorder as per the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria. HAM-D rating was used to quantify the symptoms of major depressive disorder.

Intervention

Patients who qualified for the major depressive disorder were then treated with escitalopram. The initial daily dose of escitalopram was 10 mg. The dose of escitalopram was increased to 15 mg if patients score 13 or more on HAM-D after 2 weeks of initiation of treatment. The maximum dose prescribed during the study period was 20 mg depending on the improvement. Patients were regularly followed up fortnightly for the next 6 months. HAM-D rating was administered at the time periods of 0, 2, 4, 6, and 12 weeks and then monthly till the study period of 6 months was over to evaluate their response to treatment.

In addition, at each visit, blood pressure, pulse rate, and ECG were done to evaluate any adverse effect of the drug.

Tolerability of study treatment and possible side effects were recorded using the Udvalg for Kliniske Undersøgelser side effect rating scale.

For the purpose of analysis, Group II, henceforth known as “comparison” group, included the patients who had shown depressive symptoms on initial screening with PRIME-MD but did not fulfill the criteria for major depressive disorder as per the DSM-IV criteria as well as the patients who did not even qualify the initial PRIME-MD screening test for depressive symptoms. These patients were also followed up on fortnightly basis to see if they develop and fulfill the criteria for major depressive disorder. Patients who did so were included in the treatment group, and the same protocol was followed for them as for the patients in Group I.

Statistical analysis

The data collected was subjected to appropriate descriptive and inferential statistics, i.e., Chi-square test, ANOVA for repeated measures and post hoc tests with Bonferroni adjustment for multiple pair-wise comparisons.

Results

[Table 1] and [Table 2] describe various sociodemographic and clinical variables, respectively. A maximum number of patients in case group were between the ages 36 and 45 years (9%) while the maximum number of patients in comparison group were between the ages 46 and 55 years (25%). Majority of patients in case group (18%) as well as in comparison group (71%) were males. Ten percent of patients in case group and 45% of patients in comparison group had an educational level between 5^th to 10^th standard. Majority of patients in both groups (11% vs. 48%) hailed from rural background. The two groups did not differ statistically on the measures of age, gender, education, locality, profession, and income. However, there was a significant difference between the two groups in terms of family type (P < 0.028).

Table 1: Sociodemographic characteristics of the study sample

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Table 2: Clinical variables

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When compared on various clinical variables, the two groups did not differ statistically in terms of past history of medical illness and family history of medical and psychiatric illness. However, there was a significant difference between the case and the comparison group in terms of past history of psychiatric illness (P < 0.002).

[Table 3] shows comparison of HAM-D score versus visits, to test the significant decrease in HAM-D score at each visit.

Table 3: Multiple pairwise comparisons of the Hamilton Depression Scale scores of study subjects at various visits

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As the variances of the differences between various levels of the variable HAM-D scores were significantly different as indicated by Mauchly's test results (P < 0.05), Greenhouse–Geisser estimates of sphericity (ε = 0.289) were used to correct degrees of freedom. The results showed that there was a significant effect of the treatment on the HAM-D score of the patients, F (1.73, 27.06) = 144.5, P < 0.001. As the main effect was significant, we applied post hoc tests for multiple pairwise comparisons using the Bonferroni adjustments. The differences between mean HAM-D scores at various visits were found to be highly statistically significant as shown in [Table 3].

[Figure 1] shows the comparison of HAM-D score with respect to dose in the same visit. Unpaired t-test was applied for the purpose. There was a significant mean difference (P = 0.006) at visit 3 when we compare the patients with dose 10 mg and 15 mg; patients on 15 mg of escitalopram did better than the ones on 10 mg dose. The mean HAM-D at other visits with respect to dose showed no significant difference.

Figure 1: Comparison of Hamilton Depression Scale scores versus dose

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[Table 4] shows the number of patients who had side effects. Thirteen patients on 10 mg, six patients on 15 mg, and three patients on 20 mg of escitalopram had one or more side effects. Indigestion was the most common side effect seen with all the three doses of escitalopram. It is evident that appearance of side effects is dose-dependent, i.e., doses higher than 10 mg/day are associated with more side effects.

Table 4: Distribution of dosage of drug given to cases and their side-effects

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Discussion

A negative impact of depression on the outcome of coronary artery disease is well documented, and timely recognition and treatment of associated depression can prevent an adverse outcome in the patients with MI,^[18] but depression in such patients remains unrecognized and untreated.

This study was designed primarily to screen the patients with MI for the presence of depressive disorder and to study the safety and efficacy of escitalopram in the treatment of depressive disorder in patients with MI. Data from a total of 100 consecutive patients with an established diagnosis of MI admitted to the Department of Cardiology was analyzed. The overall prevalence of depression in patients with MI in our study was 22% which is quite comparable to the other studies. Carney et al. reported that 26% of post-MI patients met criteria for major depression.^[19] Forrester et al. reported that 19% of the patients had major depressive disorder within 10 days of MI.^[20] Similar results were reported by other studies.^{[4], 5, [21],[22],[23]} A higher incidence reported by many studies is due to the inclusion of both minor and major depressive syndromes.^{[19], 21, [24],[25],[26]}

Sociodemographic characteristics were used to identify any specific variables associated with depression in post-MI period. Most of the patients in “case” group were older (49.09 ± 10.4 years) as compared to those in comparison group (47.53 ± 8.98 years) although this difference was statistically insignificant.

Males outnumbered females in both the groups (18% in case group and 71% in comparison group). Although not significant statistically, this finding is in keeping with other studies such as SADHART.^[11] However, this is in contrast to the finding by Dickens et al.^[23] and Naqvi et al.^[26] To the best of our knowledge, there is no study from India and other Asian countries to compare the results. Preponderance of males in case group could be a reflection of total sample wherein males outnumbered females. Different lifestyle habits such as smoking, alcoholism, and consumption of more animal fat and meat by Indian males could contribute to higher rates of MI in males.

Further, the two study groups showed no significant difference when compared on variables such as family type, income, history of medical illness, and family history of medical and psychiatric illness. However, the two groups did differ on the variable of positive history of psychiatric illness. No patient in the comparison group had a history of psychiatric illness (depressive disorder) as compared to 18% of patients in case group. Past psychiatric history has been found as a risk factor for developing depression in post-MI period by various studies.^{[23],[25],[26],[27]} History of MI in the past has also been reported as a risk factor for post-MI depression, but it was not supported by the findings of index study.

Efficacy of antidepressant treatment in post-MI depression is evident from the finding that HAM-D score decreased steadily at each visit. This decrease in HAM-D score was statistically significant at visit 3, i.e., at 6 weeks, the time when the antidepressant action of escitalopram would be at its peak and becomes evident. This finding is in keeping with the findings of other studies.^{[11],[27],[28]} Most patients (60%) showed remarkable improvement with 10 mg of escitalopram per day, which is the usually recommended daily dose for the drugs.^[29] As compared to 10 mg dose of escitalopram higher dosage schedules (15 mg and 20 mg) were associated with more side effects as reported in the literature,^[29] but this finding was statistically not confirmed. No adverse change in blood pressure, pulse rate, and ECG was noticed in any of the patients receiving escitalopram (all dosage groups included) as has been reported earlier.^[30] Further, the side effects noticed were seen early in the treatment and were not very troublesome, suggesting that escitalopram is a well-tolerated drug.

One of the limitations of this study is that many of the patients who were too sick were excluded, so the findings cannot be generalized to all post-MI patients. Furthermore, our study was an open-label study; the therapists were not blind to the treatment provided.

Conclusions

The study highlights that depression in post-MI period is common, i.e., 22% and responds well to antidepressant treatment. Escitalopram treatment regime is an effective and safe antidepressant for the treatment of depression in MI patients. Side effects with escitalopram were seen in the initial period of treatment and were not that disabling. The side effects were more with higher doses and also gradually disappeared with time. Further research would be required to establish the precise efficacy of escitalopram in patients with MI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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