Elsevier

International Journal of Cardiology

Volume 219, 15 September 2016, Pages 367-372
International Journal of Cardiology

Review
Cardiovascular side effects of psychopharmacologic therapy

https://doi.org/10.1016/j.ijcard.2016.06.057Get rights and content

Highlights

  • Cardiovascular side effects of psychopharmacotherapy require broad attention.

  • Psychiatric disorders often occur in cardiac patients.

  • Creative approach to psychopharmacotherapy is recommended.

  • Psychopharmacotherapy of psychiatric disorders is complex.

  • When concomitant drug side effects significantly contribute to illness

Abstract

WHO defined in 1976 psychopharmaca as drugs affecting psychological functions, behaviour and self-perception. Psychopharmacology is the study of pharmacological agents that affect mental and emotional functions. Creative approach to psychopharmacotherapy reflects a transdisciplinary, integrative and person-centered psychiatry. Psychiatric disorders often occur in cardiac patients and can affect the clinical presentation and morbidity. Cardiovascular (CV) side effects (SE) caused by psychopharmaceutic agents require comprehensive attention. Therapeutic approach can increase placebo and decrease nocebo reactions. The main purpose of this review is to comprehend CV SE of psychotropic drugs (PD).

Critical overview of CV SE of PD will be presented in this review. Search was directed but not limited to CV effects of psychopharmacological substances, namely antipsychotics, anxiolytics, hypnotics, sedatives, antidepressants and stimulants. Literature review was performed and data identified by searches of Medline and PubMed for period from 2004 to 2015. Only full articles and abstracts published in English were included.

SE of PD are organized according to the following types of CV effects: cardiac and circulatory effects, abnormalities of cardiac repolarisation and arrhythmias and heart muscle disease. There is wide spectrum and various CV effects of PD. Results of this review are based on literature research. The reviewed data came largely from prevalence studies, case reports, and cross-sectional studies.

Psychopharmacotherapy of psychiatric disorders is complex and when concomitantly present with CV disease, presentation of drug SEs can significantly contribute to illness course. Further development of creative psychopharmacotherapy is required to deal with CV effects of PD.

Introduction

This paper discusses cardiovascular side effects of psychopharmacotherapy. In the first part of this article overview of classification, commonly used psychotropic drugs, cardiovascular side effects and general data of cardiovascular effects are given. The second part deals with the cardiovascular side effects of psychopharmacs divided in groups as follows cardiac and circulatory effects, abnormalities of cardiac repolarisation and arrhythmias and heart muscle disease are described. This paper underlines the importance of cardiovascular effects of psychopharmacologic therapy in order to prevent them.

Prescribing psychotropic drugs (PD) is frequent requirement in clinical practice. According to the definition of The World Health Organization (WHO) from 1976, psychopharmaca are drugs that affect psychological functions, behaviour and self-perception. This chemical compounds in defined dose affect psychological behaviour. Psychopharmaceutic or PD are medications for treatment of psychological disorders. According to The Anatomical Therapeutic Chemical (ATC) Classification System, nervous system drugs are sorted into several groups as shown in Table 1 [1], [2]. Medical group N includes anaesthetics, analgesics, hypnotics, anxiolytics, antidepressants, drugs against drug addiction and other drugs to treat diseases of nervous system [3]. PD have various cardiovascular (CV) side effects (SE). Furthermore, polypharmacy is the practice of administering or using multiple medications in the treatment of a single disease or several coexisting conditions. During the therapy it is important to contain pts' active participation. Thorough pt instruction has to be provided and they should be familiar with SE, their prevention, early detection and treatment.

Psychopharmacotherapy is considered as the primary treatment for all serious mental disorders including schizophrenias, bipolar disorders, depressions, anxiety disorders, obsessive–compulsive disorders, etc. [4]. The number of the effective medications significantly increased [5]. Positive therapeutic context may significantly increase placebo and decrease nocebo responses [4]. It is known that creative approach to psychopharmacotherapy reflects a synergism in the frame of transdisciplinary holistic, integrative and person-centered psychiatry [4]. Commonly used PD are antipsychotics and antidepressants, comprising of tricyclic anti-depressants (TCAs), selective serotonin and other neurotransmitter re-uptake inhibitors (SSRI and SNRI), mood stabilizers, anxiolytic agents and medications for opioid addiction treatment [6]. Psychiatric medications are associated with a variety of possible adverse effects (AE) [7]. The mechanisms of AE in psychotropic medications might not always be known [7]. Awareness of the mechanisms for adverse drug reactions (ADR) can help to direct prescription choice [7]. ADR can be augmented and bizarre. Augmented ADR are predictable, depending on dose and pharmacological characteristics of the drug. In this paper augmented ADR will be presented. It is important to note that the incidence of mortality is higher among psychiatric pts than in general population [8]. Sudden death (SD) associated with PD is an issue which is currently debated worldwide [9].

The WHO has defined an ADR as a response to a drug that is noxious and unintended and occurs at average dose in pts for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function. Drug-related SE and ADR result from the intended use of pharmaceuticals. SE may vary individually, by age, weight, gender, ethnicity, diseases and general health. Further, SE can happen during initiation, decreasing or increasing dosages, or ending a medication treatment. When severe SE occur, medication may be discontinued, the dosage adjusted or a second medication prescribed. Drugs may cause various CV SE, from abnormal heart rate (HR) to heart attack or sudden death. CV disease (CVD) is an extensive class of disorders that involve the heart and the blood vessels [10]. CVDs include following conditions such as angina, atherosclerosis, cerebrovascular disease, coronary artery disease, heart attack, myocarditis, peripheral vascular disease and stroke [10]. CV SEs of antipsychotics and antidepressants are prolonged baseline QTc, myo(peri)carditis, cardiomyopathy, coronary disease and hypertension. The known CV complications of PD and the significant consequences of depression treatment in pts with previous cardiac history was already discussed in literature [10]. In cardiac pts PDs should be restricted because of SE they have on the CV system. They include orthostatic hypotension, tachycardia, reduction in HR variability and slowing of intraventricular conduction [10]. Psychopharmaca which have various CV effects may also harmfully affect clinical outcome of cardiac pts. The published data indicates that pts with severe mental illness should be considered as a ‘high risk’ population with concern to CV morbidity and mortality [11]. In addition, psychiatric pts are predisposed to abnormalities in cardiac rate, and SD. There is evidence that mortality rate is high in psychiatric pts versus general population [12]. There is an emergent evidence that people affected by psychiatric disorders are more likely to suffer from CV disease [11], [13] [14], [15], [16]. Among modifiable factors that attribute to CV RFs are psychosocial factors [11]. The relative contributions to cardiac risk of specific antipsychotic agents rests to be clarified [14]. Pts must be closely monitored for the CV risks related to psychopharmaceutic agents. A comprehensive risk assessment needs to be applied before initiation of PD treatment to reduce the risk of serious CV SE. The evaluation must include a medical history of HD, present and previous CV symptoms, used medications, assessment of potential drug interactions, and an electrocardiogram (ECG) for assessment of HD signs, conduction disorders, or prolonged QT interval. ECG monitoring includes measure QTc in all pts prescribed antipsychotics. It should be repeated as clinically indicated. Integrated care approach can optimize health outcomes [17]. Special precaution is needed with drugs that may have effects, SEs or interactions [18]. Furthermore, drug consumption is high and many are used chronically [19]. Due to the risk of AE and drug–drug interactions, the prescribing and dosage of should be carefully re-evaluated [19]. Critical judgement and careful drug prescription is compulsory. Regular follow-up and re-evaluation should be performed according to the recommendations. Collaboration with patients may significantly improve treatment outcome [4]. Similarly, a significant increase in dose of these drugs requires re-evaluating symptoms and a new ECG. Drug discontinuation should be performed if necessary. If the psychiatric disease is life threatening, a higher CV risk may be accepted, but it demands close follow-up.

According to the drug consumption in Croatia from 2007 to 2012, drugs that affect the nervous system, N group, are the second highest in total consumption, amounting to 815.6 million kunas in 2012 [3]. The same, second place in consumption and in financial terms, these drugs hold through the entire period from 2007 to 2012 [3]. Total consumption of drugs that act on the nervous system is 794,628,399 [20]. According to the report on the SE of drugs in 2014, by the Agency for Medicinal Products and Medical Devices (HALMED) on monitoring adverse reactions occurring in the Republic of Croatia during the 2014 received a total of 3112 reports of suspected adverse reactions in the Republic of Croatia [21]. Those include augmented and bizarre ADR. The number of reports SE of drugs was 2658 (85%) [21]. The total number of drugs for which in 2014 reported suspected adverse reaction is 3807, and according to the ATC classification N group number of drugs is 451 [21]. The SE are listed [21]. According to the Medical Dictionary for regulatory Activities (MedDRA) classification of organ systems in 2014 there was 139 (1.7%) cardiac disorders and 191 (2.3%) circulatory disorders [21].

Section snippets

Aim

This review sought to present insights in CV SE of psychopharmacologic treatment. One of the main goals for this paper is promoting creative psychopharmacotherapy comprehensive, integrative and transdisciplinary approach in understanding and treatment of mental disorders and CVD. There is evident association between PD and CV AE. However, it is major area of interest due to lack of comprehensive investigation to determine multiple CV effects. Wide spectrum and various effects of PD have to be

Literature search

This paper is based on a systematic evidence review evaluating published literature. The literature search was made to identify relevant systematic reviews, randomized controlled trials, meta-analysis and other from 2004 through 2015. Data for this review were identified by searches of Medline, PubMed, and references from relevant articles. The search was limited to only studies in the English language. Totally approximately 200 scientific texts were reviewed. Only to full articles or abstract

Results

In this review CV effects of psychopharmacological substances namely antipsychotics, anxiolytics, hypnotics, sedatives, antidepressants and stimulants will be presented [2]. SE of psychopharmaceutic drugs are organized into groups according to the following types of CV effects: cardiac and circulatory effects, abnormalities of cardiac repolarisation and arrhythmias and heart muscle disease.

Cardiac and circulatory effects

Researchers found a link between PD usage and sudden cardiac death (SCD). Epidemiological studies provide evidence that antipsychotics increase the risk of SCD. Published reports, show that when taking PD SCD is more likely to occur [12]. Additionally, PD have been shown to cause less severe cardiac problems, such as irregular heartbeat and high blood pressure (BP) that occur in pts with no cardiac risk prior to consumption of the drug [10]. Importantly, PD may cause hypertension as well as

Abnormalities of cardiac repolarisation and arrhythmias

Many psychotropic medications are linked with ECG deviations. QT prolongation can cause Torsades de Pointes (TdP), ventricular fibrillation (VF) and SD. Arrhythmias in pts with conduction and abnormalities of heart structures or coronary disease might be intensified by use of psychotropic or antidepressant drugs. The most common cardiac SE are a mild bradycardia, orthostatic hypotension, QRS lengthening or prolonged QT interval [10]. Serious conduction alterations are revealed in ECG as

Heart muscle disease

Psychopharmaca use may also be associated with myocarditis, pericarditis and cardiomyopathy. Myocarditis and cardiomyopathy, are potentially reversible complications. However, pts with pre-existing CVD should be carefully evaluated before they begin any antipsychotic treatment [10]. Presentation of myo(peri)carditis can range from non-specific symptoms to severe left ventricular impairment, pulmonary oedema, cardiogenic shock and death. They usually occur within weeks of introduction of drug.

Discussion

Resulting from population growth, the aging populations, and epidemiologic changes global deaths from CVD are increasing [62]. Health care system is developing to the reduction of CVD. However it is important to note that an evidence suggests a possible increase in CV events in pts treated with PD. From a worldwide perspective CHD and depression are two of the most important diseases [37]. Anxiety and depressive disorders are common in the general population and are particularly prevalent in

Conclusion

Various PD have shown to have CV effects that can be therapeutically beneficial or harmful to pts. A variety of drugs for the treatment of the central nervous system diseases are associated with cardiac SE. Some of them are linked to reports of arrhythmia and SD [71]. The CV effects of PD depends on the potency of the drug. The correct CVD diagnosis can be beneficial in exposing a pt to the appropriate pharmacologic therapy. In pts with higher risk of CVD, the choice of PD has to be performed

Conflict of interest

The enclosed manuscript has been read and approved by all the authors. The manuscript, or part of it, has neither been published nor is currently under consideration for publication by any other journal. The authors declare that they have no financial or any other conflict of interest. The authors declare no external financial support for making this article. The copyright shall be transferred to the journal after accepting this article for publication.

Acknowledgments

None.

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