Antidepressants in cardiology practice

Depression and cardiovascular diseases are closely interrelated. In recent years, evidence has emerged that depression is an independent risk factor for coronary heart disease (CHD). At the same time, in some patients with coronary artery disease, depression may develop a second time, as a person’s reaction to a severe somatic disease. According to domestic and foreign studies, the prevalence of depression among IHD patients is approximately 20%.

In patients with IHD, depression not only aggravates the clinical condition and makes rehabilitation difficult, but also shortens the life expectancy. The results of recent studies suggest that depression increases the risk of coronary accidents and coronary death in patients with coronary artery disease. The mortality rate in patients who have had myocardial infarction and are suffering from depression is 3-6 times higher than in patients who have had myocardial infarction and who do not have signs of depression.

Despite the prevalence, depression in cardiac patients in most cases is not recognized and cannot be treated. This entails repeated visits to a cardiologist, more and more new examinations, and both the patient and his attending physician are not satisfied with the results of treatment. This situation is primarily due to the fact that patients, as a rule, do not present depressive complaints, such as depressed mood and loss of interests. The clinical picture is dominated by chronic pain syndrome (cardialgia), various sleep disorders, increased fatigue, decreased activity, loss of appetite, weight change, decreased performance, problems with concentration, decreased sexual desire, panic attacks, or permanent autonomic disorders. The described symptoms are characteristic of the so-called somatized or hidden, masked depression.

A certain role in the hypo diagnosis of depression in cardiac patients is played by the fact that cardiologists do not fully master the technique of examining depressed patients. The identification of depressive disorders is greatly facilitated by the use of psychometric scales and tests, including subjective ones (the patient himself answers the questions).

Among the subjective psychometric scales for screening for depression, the Hospital Anxiety and Depression Scale is the most well-known (A. Zigmond, 1983) and the Beck Depression Questionnaire (A. Beck , 1961). Repeated use of psychometric scales allows studying the dynamics of the patients’ condition during treatment. Given the negative impact of depression on the prognosis, screening in order to identify depression is advisable to conduct among the most vulnerable categories of patients with coronary artery disease – patients with unstable angina, those who have experienced acute coronary syndromes, including myocardial infarction, as well as patients undergoing CABG surgery.

According to the concept adopted today, mild to moderate depression in cardiac patients can be treated by a cardiologist or general practitioner. This has become possible due to the emergence in recent years of a number of new highly effective antidepressants that, unlike classical tricyclic antidepressants (amitriptyline, etc.), do not have pronounced behavioral toxicity and negative side effects on the cardiovascular system.

The use of tricyclic antidepressants in cardiac patients is highly undesirable because of the somatotropic effects of these drugs, including due to their effect on the cardiac conduction system. The administration of these drugs in therapeutic doses is accompanied by a prolongation of the PQ, QRS and QT intervals, especially in patients with baseline conduction disorders. It has been shown that tricyclic antidepressants that block fast sodium channels exhibit the properties of guanethidine – like antiarrhythmic agents of cancer cells, which, according to several studies, including Cardiac Arrhythmia Suppression Trial (1992), increase the mortality rate in patients with coronary artery disease.

Among the side effects characteristic of tricyclic antidepressants and significantly limiting their use in cardiology are reflex tachycardia. The results of a well-known Framingham study suggest that patients with established coronary artery disease should avoid prescribing drugs that increase heart rate (HR), since an increase in heart rate correlates with an increase in mortality in this category of patients. Obviously, tricyclic antidepressants should also not be prescribed to patients who have a high risk of developing coronary artery disease.

Another adverse side effect of tricyclic antidepressants is orthostatic hypotension, most pronounced in the first two weeks of therapy and especially characteristic of elderly patients. Negative behavioral effects arising during treatment with tricyclic antidepressants, such as drowsiness, decreased attention, memory impairment, difficulty in intellectual activity, and poor coordination of movements, cannot be ignored either.

In an effort to minimize the side effects described above, doctors often prescribe tricyclic antidepressants in very small doses (for example, 1 / 4-1 / 2 amitriptyline tablets per day), which are not enough to produce an antidepressant effect (the minimum therapeutic dose of amitriptyline is 2-3 tablets per day ).

Numerous somatotropic and behavioral effects of tricyclic antidepressants are associated with their non – selectivity – the effect on several groups of CNS receptors (α 1 -adrenoreceptors, serotonin, muscarinic and histamine H1-receptors).

Unlike drugs of the first generation, modern antidepressants have selectivity and, in this connection, lack many of the side properties characteristic of tricyclic antidepressants.

New antidepressants include:

  • selective serotonin reuptake inhibitors:citalopram (cipramil), paroxetine (paxil), fluoxetine (prozac), fluvoxamine (fevarin), sertraline (zoloft);
  • selective serotonin reuptake stimulants:tianeptine (Сoaxil);
  • tetracyclic antidepressants:mianserin (lerivon);
  • selective serotonin and norepinephrine reuptake inhibitors:milnacipran (ixel).

Selective antidepressants have a sufficiently high antidepressant activity. In terms of the severity of the antidepressant effect, they are somewhat inferior to the classic tricyclic antidepressants, but they are superior when it comes to tolerability and safety of use. In this regard, selective antidepressants can be considered as first-line drugs in patients with cardiovascular diseases, as well as in elderly patients.

Most widely used today are selective serotonin reuptake inhibitors (SSRIs). Preparations of this group inhibit serotonin reuptake from the synaptic cleft into the presynaptic neuron and do not have a significant effect on other neurotransmitters.

The SSRIs got their name because of their greater selectivity for blocking serotonin reuptake than noradrenaline reuptake (at least 10 times). In addition, SSRIs have an insignificant affinity for α 1 -adrenoreceptors, m- cholinergic receptors, histamine H1 receptors, which ensures their good tolerability. SSRIs, unlike tricyclic antidepressants, do not have the ability to block slow sodium channels, and therefore they are safer in overdose.

The drugs of the SSRI group have a favorable cardiac profile. So, in a study by S. Roose and colleagues who studied the safety of SSRIs in patients with coronary artery disease with concomitant depression, it was shown that 7-week therapy with fluoxetine at a dose of 60 mg / day did not cause any cardiac complications, did not affect blood pressure (BP), conductivity and ventricular ectopic activity and was accompanied by a statistically significant decrease in heart rate by 5 beats / min. It should be noted that 47% of patients included in the study had previously suffered ischemia.

In patients with cardiovascular diseases, the benefits of SSRIs are particularly pronounced in comparison with tricyclic antidepressants. Prospective A randomized, controlled 6-week comparative study of paroxetine (in a daily dose of up to 40 mg) and nortriptyline in patients with coronary artery disease with depression who had had myocardial infarction no earlier than 3 months before being included in the study clearly demonstrated the advantages of the SSRIs. Paroxetine therapy was not accompanied by statistically significant changes in blood pressure, heart rate, cardiac rhythm and conduction disturbances.

Due to cardiac complications, only one patient from the paroxetine group and 7 patients from the nortriptyline group left the study early (a total of 81 patients participated in the study). Against the background of nortriptyline, an increase in the average heart rate by 11% (from 75 to 83 beats / min) was observed, there was also a statistically significant increase in the cases of orthostatic hypotension and myocardial repolarization disorders, according to the ECG. At the same time, the drugs were equally effective in relieving depressive disorders in IHD patients.

In 1999, Sertraline research data was published. Antidepressant Heart Attack Trial, the purpose of which was to study the efficacy and safety of one of the drugs of the SSRI group – sertraline – and its effect on the cardiac profile in patients with clinically severe depression that developed after MI. The study included patients who had myocardial infarction (5-30 days after a heart attack) with an ejection fraction of 35% or more. 16 week therapy sertraline at a dose of 50-200 mg / day did not have a significant effect on the level of blood pressure, heart rate, myocardial conductivity and left ventricular ejection fraction.

Although all SSRIs have a similar mechanism of action, nevertheless , individual drugs of this group differ in chemical structure, as well as in the degree of binding to the non-serotonin receptors of the CNS, that is, in the degree of selectivity. Citalopram has the highest selectivity in the SSRI group. High selectivity of the drug ensures its good tolerability and safety in the most vulnerable groups of patients (elderly patients with cardiovascular diseases, organic lesions of the central nervous system). According to our data, the use of citalopram at a therapeutic dose of 20 mg / day in patients with coronary artery disease who have had myocardial infarction is not accompanied by cardiotoxic effects – fluctuations in blood pressure, heart rate, cardiac rhythm and conduction disturbances, including according to daily ECG monitoring. A meta-analysis of several studies in which more than 1,400 patients who received citalopram (30% were in old age) participated showed that citalopram does not have a significant effect on the duration of the PQ, QRS, QT intervals and myocardial repolarization processes. Citalopram has a minimal risk of inter-drug interactionscompared to other antidepressants and is therefore well combined with drugs that are regularly taken by patients with cardiovascular diseases (β-blockers, nitrates, calcium antagonists, angiotensin – converting enzyme inhibitors , diuretics).

For the treatment of mild to moderate depression in cardiac patients, the following doses of SSRIs are recommended: Citalopram (Cipramil) – 20 mg / day , Paroxetine ( Paxil ) – 20 mg / day , Sertraline (Zoloft) – 50 mg / day , Fluoxetine ( Prozac ) – 20 mg / day , fluvoxamine (fevarin) – 50 mg / day . These doses are initial and at the same time can be considered as optimal therapeutic in case of depression of mild and moderate severity. Thus, in most cases, a cardiologist or general practitioner, when prescribing an SSRI, is not required to dose titration. It is important to consider some Delay in the clinical effect of most antidepressants: the pronounced anti-depressant effect of SSRIs is noted by the end of the first two weeks of therapy. It is advisable to inform the patient about this so that he does not expect an immediate positive effect from taking the antidepressant. In case of insufficient efficacy, the above doses may be increased.

The drugs of the SSRI group have not only antidepressive, but also anti-anxiety (anxiolytic) effects, and therefore they are effective when patients have concomitant anxiety symptoms, with panic attacks, phobic syndromes. Some representatives of SSRIs also have a mild activating effect (for example, citalopram, fluoxetine).

The side effects of SSRIs are minimal, especially when prescribing drugs at recommended doses. When using SSRIs, there were side effects from the gastrointestinal tract (dry mouth, nausea, diarrhea), as well as drowsiness, headaches, dizziness, tremor, and sweating. These side effects are rare, usually in the first two weeks of treatment, and are reduced on their own. In most cases, drug withdrawal is not required.

Milnacipran (Ixel), a selective serotonin reuptake inhibitor and norepinephrine reuptake inhibitor, is close in clinical efficacy to SSRIs. Along with the anti-depressive effect, this drug has a moderate activating effect. Sedation is not pronounced. Therapeutic doses of milnacipran for the treatment of mild to moderate depression – 50-100 mg / day.

Tetracyclic antidepressant mianserin (lerivon) is considered a “mild” antidepressant. Its mechanism of action is to blockade the presynaptic adrenoreceptors, the drug also blocks serotonin and histamine H1 receptors. Mianserin has a mild antidepressant, as well as pronounced sedative effects. It is prescribed at bedtime at a dose of 15-60 mg. At therapeutic doses, the anticholinergic side effects of mianserin are less pronounced than in tricyclic antidepressants.

In recent years, in addition to SSRIs, Tianeptine (coaxil) has been widely used in cardiac practice . According to the chemical structure, the drug belongs to atypical tricyclic antidepressants, and according to the mechanism of action it is a selective stimulator of serotonin reuptake. Tianeptine antidepressant, anti-anxiety and activating effects, it is safe in treating depression in the elderly and patients with cardiovascular disease. The drug does not cause clinically significant orthostatic hypotension, does not affect the level of blood pressure, heart rate, blood sugar levels and other hematological parameters. Tianeptine is recommended at a dose of 37.5 mg / day (1 tablet 3 times a day), if necessary, the dose can be increased to 50 mg / day.

Treatment of comorbid depression in cardiac patients, especially in patients undergoing acute coronary incidents and cardiac surgery, not only leads to an improvement in the mental state, but is also accompanied by a positive dynamic of the clinical and functional status of patients, improves the quality of life, reduces the period of rehabilitation and the return of patients to labor activity. It should also be assumed that the treatment of depression in IHD patients has a positive effect on the prognosis. Currently, two large studies are underway – SADHART and ENRICH, apparently in a few years it will be possible to more definitely answer the question, does the treatment of depression after myocardial infarction reduce mortality in IHD patients?

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