Heart and Mind: (2) Psychotropic and Cardiovascular Therapeutics
Total Page：16
File Type：pdf, Size：1020Kb
33 Postgrad Med J: first published as 10.1136/pgmj.2003.015230 on 7 January 2005. Downloaded from REVIEW Heart and mind: (2) psychotropic and cardiovascular therapeutics S U Shah, Z Iqbal, A White, S White ............................................................................................................................... Postgrad Med J 2005;81:33–40. doi: 10.1136/pgmj.2003.015230 There is a plausible biological basis for the association review. In the following sections we will briefly discuss the pharmocological profiles, cardiac between psychiatric morbidity and cardiovascular disease. actions, and side effects of the major classes of Anxiety, panic disorder, and depression are common in psychotropic drugs. In addition, we will also patients with coronary heart disease and hypertension. review the neuropsychiatric effects of commonly used cardiovascular drugs. In the final sections, Despite this evidence there is poor recognition of anxiety we will highlight and summarise the recommen- disorders and depression in primary care and hospital dations for use of psychotropic medications in medical practice. Concern also surrounds the use of specific cardiovascular disorders. psychotropic drugs in patients with cardiovascular disease. EPIDEMIOLOGY In the first of the two articles on this subject, we highlighted Although there are no exclusive data on the the current evidence regarding the association between extent of cardiac effects and interaction of psy- cardiovascular and psychotropic conditions. In this second chotropic medication with drugs used in treating cardiovascular conditions, some inference can be article, we discuss the interaction of the drugs used in the derived from the epidemiological, observational, management of these two varied but commonly coexistent and anecdotal evidence available from various group of diseases as well as their relative effects on either sources. Medications range from the anxiolytics system. Finally, we summarise the data regarding the safe that, in general, are relatively safe with minimal cardiac effects, to antidepressants (tricyclic and use of these medications based on the recommendations monoamine oxidase inhibitors antidepressants from the currently available evidence. in particular) and antipsychotics that have been shown to have multiple cardiac effects including ........................................................................... increased incidence of cardiac arrhythmias and possibly sudden cardiac death. n the companion paper to this article, we Because many cardiac and psychotropic highlighted the association between neuro- agents lower blood pressure, additive hypoten- psychiatric illnesses and cardiovascular dis- sive effects are not uncommon, as for example http://pmj.bmj.com/ I 1 eases. Both conditions, in particular depression between the tricyclic antidepressants and anti- and ischaemic heart disease, are common in the hypertensives. Many psychotropic agents slow general population. Indeed, the Global Burden of conduction and prolong the PR, QRS, and QT Disease Study found that depression is second intervals, and synergistic effects can occur when only to ischaemic heart disease as a cause they are used in conjunction with antiarrhythmic of disability and early death in industrialised medications, resulting in heart block or the long countries.2 Although rates of depression are high QT syndrome. Selective serotonin reuptake inhi- in the general community, they are even higher bitors (SSRIs; for example, fluoxetine, sertra- on September 26, 2021 by guest. Protected copyright. in patients with cardiac illnesses. Other psychia- line, paroxetine, and fluvoxamine) are bound to tric conditions such as anxiety disorders and plasma proteins and can displace other protein- psychotic illnesses such as schizophrenia are also bound drugs, thereby increasing the level of not uncommon. Given the wide prevalence of active drug and resulting in possible toxicity. both sets of disease, it is quite likely that in a Antipsychotic (neuroleptic) drugs have gener- considerable number of patients these illnesses ally been regarded as a group of drugs with a will coexist. Drugs used to treat depressive and good margin of safety, but there have been psychotic conditions in particular have been regular case reports of sudden death associated See end of article for shown to have significant cardiac effects and with these agents since the 1960s.3–6 The part authors’ affiliations important pharmacological interactions with ....................... played by antipsychotic drugs is often uncertain, medications used to treat cardiovascular dis- but when sudden death occurs in previously Correspondence to: eases. Conversely, some cardiac drugs have also healthy young individuals a common conjecture Dr Saeed Ullah Shah, been implied in causing psychiatric symptoms. It is that medication was responsible. This concern Department of Cardiology, is therefore important to understand the actions, Ysbyty Gwynedd, Bangor, follows several reports of unexpected deaths in North Wales, UK; side effects, and interactions of the drugs used in young people, usually males, where the con- saeedshah@miranshah. treatment of these two varied groups of diseases. current prescription of antipsychotic drugs has freeserve.co.uk A comprehensive discussion of these effects and interactions is beyond the scope of this Submitted 19 September 2003 review, which is mainly addressed to cardiolo- Abbreviations: CSM, Committee on Safety of Medicines; Accepted 7 August 2004 gists and other medical physicians. Readers GABA, gamma amino butyric acid; SSRI, selective ....................... should refer to other texts for a more in-depth serotonin reuptake inhibitor www.postgradmedj.com 34 Shah, Iqbal, White, et al Postgrad Med J: first published as 10.1136/pgmj.2003.015230 on 7 January 2005. Downloaded from been implicated.78 There are insufficient data to prove that tricyclic or related antidepressants may have relatively safe sudden death is more likely among people being treated with toxicity, but this is uncertain. antipsychotic medication than it is among the general population. However, there are no data that prove that there USE OF PSYCHOTROPIC DRUGS IN is no causal relationship between the use of this group of CARDIOVASCULAR CONDITIONS (TABLE 1) drugs and sudden death. Further, the Committee on Safety Anxiolytics/hypnotics of Medicines (CSM) has received reports of 31 cases of Of the anxiolytics and hypnotic agents used to treat anxiety unexplained sudden death and 63 reports of fatal cardiac and sleep disorders, benzodiazepines and the newer hypno- arrest/arrhythmias in association with people treated with tics are now the most widely used group. Approximately 20 various antipsychotic drugs, covering the period that each 9 benzodiazepines derivatives are currently available. They bind drug was introduced up to May 1996. to specific, high affinity sites on the cell membrane parallel to Abnormalities seen on electrocardiography are relatively the receptors for gamma amino butyric acid (GABA). The common in people receiving neuroleptics, occurring in binding of benzodiazepines increases the affinity of GABA 10 11 around 25% of patients receiving this class of medications. receptors for this neurotransmitter causing hyperpolarisation There are numerous reports of ventricular arrhythmias asso- and inhibition of neural firing. Benzodiazepines are used in ciated with repolarisation disturbances such as prolonged QT treating the anxiety that accompanies some form of depres- intervals, widening of QRS complexes, depression of ST seg- sion and schizophrenia. They are very useful in treating panic ments, and most commonly abnormal T morphology or large disorders and are also used as sedatives, anticonvulsants, and 11–19 U waves. They are observed more often in patients with muscle relaxants. 20 pre-existing heart disease. In another study, QTc (QT inter- Anxiety disorders, especially panic and generalised anxiety val corrected for heart rate) prolongation (.420 ms) was disorder and disturbed sleep pattern, are prevalent in patients found to be significantly more common (23%) in a sample of with cardiac disease. Hospitalised cardiac patients are acutely 111 chronic inpatients with schizophrenia receiving antipsy- anxious, and because anxiety itself can threaten cardiac chotic medication than in 42 age matched, drug-free controls status, benzodiazepines have been widely used in coronary 21 (2%). Thioridazine and, less frequently, chlorpromazine care units. They are considered as one of the safest groups of have been particularly implicated in the development of ven- drugs in cardiovascular diseases. They are generally shown to 22 tricular tachycardia, primarily in patients taking overdoses. be free of cardiac side effects and can be used safely in Thioridazine in particular was found to be significantly more seriously ill cardiac patients, even in the period immediately likely to cause tachycardia, a prolonged QT interval, pro- after myocardial infarction.32 They can, however, decrease longed QTc (.450 ms), a widened QRS (.100 ms), and respiratory drive in patients with chronic obstructive pul- arrhythmias.23 24 Electrocardiographic abnormalities have monary disease and chronic hypercapnia. No significant work also been found in 10% of patients treated with pimozide.25 has been done to assess the effects of using benzodiazepines Indeed, from 1971 to 1995, the CSM received 40 reports (16 on cardiac mortality or morbidity.