Management of Psychiatric Disorders in Patients with Cardiovascular Diseases

Abstract

INTRODUCTION Psychiatric illnesses and cardiovascular disorders (CVDs) are the leading causes of morbidity and mortality among the global population. CVDs are the leading cause of death according to the World Health Organization, representing 32% of all deaths globally.[1] About 970 million people are affected with mental illness (MI) throughout the world. Psychiatric disorders are one of the leading causes of morbidity across the globe.[2] The relationship between MI and CVD is a complex one, with no clear cause and effect. Both have many similarities. Like cardiovascular diseases, mental illnesses also run a chronic course. Both have higher rates of morbidity, mortality, and impaired quality of life when compared to the general population [Table 1].Table 1: Salient points about the relationship between coronary artery disease and psychiatric disorder[1 2 3]Cardiovascular disease has been found to be approximately 1.5–2 times higher in people having severe mental disorders like schizophrenia and bipolar disorder (BPAD).[3] Individuals with psychiatric disorders are also at risk for chronic obstructive airway diseases, tuberculosis, respiratory tract infections and other respiratory illnesses, obesity, diabetes and other lifestyle diseases compounded by psychoactive substance abuse, especially nicotine. Poor insight, poor access to healthcare services, lack of social support, stigma about psychiatric illness even amongst physicians often lead to insufficient screening for physical health in these patients. Commonly used psychiatric medications such as lithium, sodium valproate, olanzapine, clozapine, risperidone are known to cause weight gain and also increase the risk of metabolic syndrome and consequences thereof.[4] The cardiovascular risk factors (CVRF) are on rise in general population and poor control of these CVRF are responsible for poor health related quality of life. The self and perceived stigma is high among both mentally ill patients and their clinicians (both liaison physicians and psychiatrists). The integration of mental health care with other specialties and screening of cardiovascular risk factors starting from primary care level should be the call for the day. Many a time the treating doctor doesn’t pay due attention to their patients suffering from CVD as they are underdiagnosed which is a finding in literature. Pharmacoeconomics also contributes as a key factor for poorer management of cardiovascular risk factors among mentally ill persons.[4] From the cardiological point of view, it has been consistently found that the prevalence of psychiatric disorders in liaison psychiatry is very high ranging from 48% to 87% across cardiovascular, musculoskeletal and orthopedic patients.[5] Following adverse coronary events, many people do suffer from depression, anxiety, acute and posttraumatic stress disorders (PTSD) which can have a negative impact and further consequences leading to heart failure (HF), stroke and acute myocardial infarction (MI) thus increasing the cardiological morbidity and contributing to the mortality as added risk of psychiatric morbidity.[6] We will now look at individual psychiatric disorders and their relationship with CVDs. Management AND suggested guidelines will run along the lines of safety and efficacy profiles in this population of patients. It has been consistently shown that the chronic psychotic disorder Schizophrenia patients have higher risk of hypertension (HTN), coronary vascular disorders, MI and higher incidences of sudden unexplained death due to cardiac reasons when compared to the general population. The causes are attributable to multifactorial genetics, metabolic parameters prominently such as insulin resistance, obesity, less physical activity, and due to medication used in management of chronic psychotic disorders. In our clinical practice, we often see patients with physical disorders such as HTN or coronary artery disease (CAD). There might be some significant drug-drug interactions between the medications given for psychiatric illnesses and CVDs. For example when antihypertensives and antipsychotics are given together, there is a high chance of the individual having severe hypotension due to their synergistic effects. Many psychotropic medicines alter the cardiac conduction such as prolongation of PR, QRS and QTc intervals, ST segment depression, decreased T wave amplitude and large U waves in ECG. This effect can be potentiated by synergistic effects of antiarrhythmic drugs when given together. SSRIs can displace other protein bound drugs and may lead to toxicity. Hence patients with both cardiovascular and psychiatric morbidities need to be monitored as suggested by the guidelines for drug-drug interactions and pharmacokinetics. Prudent decisions should be made to give such medications which are both efficacious and with side effect profile and drug interactions not harmful to the patient. MOOD DISORDERS AND CARDIOVASCULAR DISORDERS Depressive disorders Depression and cardiovascular disease have a bidirectional relationship. Depression has been consistently linked to CVD as a risk factor.[7] Depression is seen in 15%–20% of patients with CAD. These rates are higher in patients with MI, with up to two-thirds of the patients having some form of depression either during hospitalization or in follow-up.[8] 15% of patients undergoing CABG have depression meeting diagnostic criteria. Women have a higher risk, almost two fold, when compared to men especially in those younger than 60 years.[9] It is also found in 20% of patients with congestive HF with higher rates in more severe patients and as well as peripheral artery disease.[81011] Around 30% of implanted cardioverter defibrillator recipients have been found to have anxiety.[12] DEPRESSION AND CARDIOVASCULAR DISORDERS Depression is often found to be persistent and recurrent in these patients [Table 2]. Studies have found that depression is often present before the incident cardiovascular disease presentation and is a major factor for poor outcome.[16] It was also seen that during follow-up following a cardiovascular episode, depression was found to be chronic or relapsing in almost half the patients diagnosed with major depression at the incident episode. 40% of the patients who had minor depressive symptoms progressed to have major depressive episodes within 1 year.[1718] At least 65% of patients with MI report depressive symptoms while 20% of them fulfill criteria for a major depressive episode.[192021]Table 2: Several biological mechanisms have been suggested to explain the underlying relation between depression and cardiological disorders[8 13 14 15]Co-morbid anxiety disorders have been found to co-exist with depressive disorders in at least 40% of the patients diagnosed with depression. Most common anxiety disorders include generalized anxiety disorder (GAD) and PTSD. These worsen the outcome of both depression and cardiac disease.[22] Screening for depression can be done using scales such as Public Health Questionnaire-9,[23] Beck Depression Inventory,[24] Hamilton Rating Scale for Depression.[25] Cardiac Depression Scale[26] has been developed for screening and measurement of severity of depression in cardiac patients specifically,[1927] hence practically whenever it is possible to use the rating scales is advisable. TREATMENT OF DEPRESSION IN COEXISTING CARDIOVASCULAR DISORDERS Many studies have been done which have looked at treatment of depression in cardiac patients. The prominent and significant among them are the following studies SADHART[28] and UPBEAT[29] studies that have looked at the efficacy of sertraline while MIND-IT[30] studied the effects of mirtazapine and citalopram. ENRICHD[31] and CREATE[32] studies looked at the efficacy of CBT and IPT along with pharmacological treatment. Most studies have found only a small to modest effect in cardiac outcomes in patients treated with proper antidepressants or psychological therapies. However, outcomes related to depression were significant, i.e., patients improved significantly following the interventions. Reduced morbidity and mortality in psychiatric patients has been documented to some extent in these studies [Table 3].Table 3: Summary of evidence of pharmacological management of depression[33 35 36]PSYCHOLOGICAL TREATMENT IN DEPRESSION WITH CARDIOVASCULAR PATIENTS Quality studies are by far less and in between. Stress management techniques, relaxation techniques, CBT have been found to be beneficial when compared to placebo in these patients though the sample size and methodology in these studies are not very rich and sound. They have been found to improve the quality of life. ENRICHD[31] and CREATE[32] studies looked at the efficacy of CBT and IPT along with pharmacological treatment. It is thus suggested that in patients with cardiovascular disorders, psychotherapies should be included in the guidelines.[37] BIPOLAR DISORDER AND CARDIOVASCULAR DISORDERS CVD is the leading cause of death in patients with BPAD, with 35%–40% of deaths accountable to it.[38] The rates of bipolar patients having CVD is 2–3 times more than compared to the general population.[39] This decreases the life-span of patients by 10–15 years when compared to the general population. The elevated risk of CVD has been found even in the absence of poor lifestyle factors, substance use, and use of medication. The risk is higher in the younger subset of patients when compared to other age groups and the population. Meta-analytic studies showed a hazard risk ratio of 1.54 for CAD and 2.1 for CHF in bipolar patients when compared to control subjects.[4041] The medications used to treat BPAD include mood stabilizers such as lithium, divalproex, and antipsychotics, especially second generation antipsychotics, namely Olanzapine, Clozapine, Risperidone, etc., which have a propensity to cause weight gain, impaired glucose tolerance, hyperlipidemia, obesity and metabolic syndrome which are independent risk factors for CVD.[42] Behavioral factors such as poor nutrition, substance use, poor compliance to treatment, impaired sleep also play a role in elevating the risk for CVD. All these factors need to be taken into the picture while planning the management of CVD in bipolar patients. There are many biological theories existing to explain the basis of both cardiological disorders and depression. Some of the theories are found to have a commonality for both disorders [Table 4].[4344]Table 4: The suggested biological basis for cardiovascular and bipolar disorder[43 44]Commonly found comorbid psychiatric conditions in BPAD include substance use disorders (SUD), anxiety disorders, personality disorders, attention deficit hyperactivity disorders, conduct disorders and eating disorders. The comorbid conditions often make the treatment challenging and the course and prognosis of the illness is also affected.[45] BPAD is a chronic relapsing illness and often the treatment is lifelong. Scales such as Young Mania Rating Scale,[46] Bipolar Depression Rating Scale,[47] Bipolar Affective Disorder Dimension Scale[48] can be used to supplement and document the illness and management. TREATMENT OF BIPOLAR DISORDER AND CARDIOVASCULAR DISORDERS Pharmacological management is the mainstay of treatment.[4950] Baseline examination and investigations are a must and frequent monitoring is needed to assess if patients are at risk for CVD and other physical comorbidities. Common medications used are given in the Table 5.Table 5: The pharmacological and cardiovascular management in comorbid patientsThese guidelines recommend to optimize the management of bipolar mood disorders as detailed by Indian psychiatric clinical practice guidelines. The following guidelines are suggested to watch for the PHARMACOLOGICAL MANAGEMENT OF COMORBID issues of cardiovascular related side effects of the medications commonly used for mood disorders. PLEASE REFER to the guidelines suggested by Indian psychiatry for clinical practice guidelines for management of mood disorders. Following an acute episode MANAGEMENT, psychotherapies such as individual psychoeducation, CBT, IPSRT and family therapy have been found to be helpful in preventing relapses or worsening of mood episodes.[51] Hence recommended. SCHIZOPHRENIA Patients with schizophrenia often have poor physical health due to various factors including sedentary lifestyle, poor nutrition, poor access to healthcare services, smoking etc. Their life expectancy is reduced when compared to the general population. Cardiovascular disease has been found to be the leading cause of death in this population. It is reported to be 2–3 times more in patients with psychosis when compared to control population. The predicted risk ratio of CVD in these patients is 1.3–1.64 though this might be underestimated. MI has been found in at least 30% of the patients with schizophrenia. CAD has been found to be around 27% in these patients while metabolic syndrome ranges from 36% to 52%. The prevalence rates of arrhythmias, acute coronary syndromes, HTN, stroke and HF have been found to range from 1.43 to 2.17.[525354] Mechanisms underlying the common link between schizophrenia and CVD include behavioral factors, effects of antipsychotics, biological factors such as inflammation, autonomic dysfunction, deficiency of long chain fatty acids, shared genetic loci between the two illnesses that have an effect on cholesterol levels, systolic blood pressure, and BMI.[5556] Schizophrenia can be diagnosed using standard diagnostic criteria and its course can be objectively documented using scales such as positive and negative syndrome scale[57] and brief psychiatric rating scale.[58] Mainstay of treatment is the use of antipsychotics. The efficacy and the safety profile of the same in CVD have already been discussed [Table 5]. Regular monitoring of the physical attributes such as weight, HTN, glucose levels, lipid levels, renal and liver function, and cardiac profile is absolutely needed in these patients [Table 6]. Psychological therapies also play a role in the prognosis of the illness.Table 6: Suggested cardiovascular considerations for prescribing psychotropic medicinesThe life expectancy of persons with Schizophrenia and other severe mental disorders is reduced by 10 years due to adverse coronary outcomes when compared to general population. Psychotropic drugs can cause cardiological adverse effects either by themselves or if given in conjunction with other medication. Thioridazine, Chlorpromazine, Pimozide can prolong QT and QTc intervals (>450 ms) and Pimozide can also lead to ultrastructural changes in cardiac muscles resulting in toxic cardiomyopathy. Clozapine can also cause cardiomyopathy and sudden cardiac death which is rare but is TO BE KEPT IN MIND. ANXIETY DISORDERS AS COMORBIDITY WITH CARDIOVASCULAR DISORDERS Anxiety disorders are common in patients with CVD and often affect the outcome of the cardiac illness. Many symptoms overlap between anxiety disorders and CVD such as chest pain, heaviness of etc. This overlap of symptoms often Hence more often than patients with anxiety disorder present to and for cardiac of patients of anxiety following an acute coronary episode, the of which chronic in at least half of the patients. rates are seen in patients to CABG of patients with HF have been found to have anxiety disorder while of patients with cardioverter defibrillator have elevated anxiety the relationship between of anxiety and CVD was it was found that patients suffering from had a hazard ratio of for of is in patients with CAD and in patients with of in CVD patients ranges from to while patients suffering from are found to CVD symptoms more than of disorder from to in patients with CVD though some studies higher especially chronic has been found to affect the mortality of patients in with poorer quality of life when compared to patients with CVD with no mechanisms underlying anxiety disorder and CVD include autonomic such as decreased heart dysfunction, impaired and inflammation, genetic factors such as Scales such as Hamilton Anxiety Rating and Anxiety and Depression can be used to assess the severity of anxiety TREATMENT OF ANXIETY DISORDERS AND CARDIOVASCULAR DISORDERS SSRIs and are the common of drugs used to treat anxiety disorders. are often used for for of anxiety Studies have shown to have beneficial effects in patients with CVD with no anxiety symptoms as like and and like and are long of to drug-drug interactions and effects of other used in CVD. significant cardiac adverse effects have been like and can be second medications as they have some efficacy in anxiety disorders. techniques, CBT, therapies and other and other psychotherapies including therapies and family therapies are recommended. a long in the patients. They are commonly used as psychological for various of anxiety The evidence though is not but recommended. DISORDERS AND CARDIOVASCULAR DISORDERS to treatment is very common in patients who are suffering from mental The of metabolic syndrome by obesity, ratio and insulin has the persons with MI at an added risk of suffering from cardiovascular than 15% of patients having depression in coronary artery diseases are DISORDERS with are at a risk for both acute and chronic effects of the on the cardiovascular This is very but common risk factors are often For drug use might lead to and various illnesses such as and which also to poor vascular CVD is one of the leading causes of mortality in this We will be on the commonly used and their effects on the cardiovascular is one of the common psychoactive used There were studies which reported that of is but is that there are many harmful physical effects of though it is not has been shown to have an effect on levels, inflammation, function, and use of standard has been shown to either be or to not have a significant effect on the cardiac use of of comorbid disorders, and of use have been shown to increase the morbidity and mortality related to HTN is very among and the relationship is on the of ratio of HTN in of has been found to range from to HTN an individual to stroke and to a in incident risk of MI from to that of was and that of HF was The relation between and peripheral vascular disease was found to be not very use especially in the form of smoking has been consistently linked with CVD with other in the have been found to be and and also to increase the of increase cholesterol and insulin The in the also to of has been found to cause HTN, and diabetes which are risk factors for CVD. due to CVD is 60 higher in those who use as compared to The showed that smoking the risk of MI is with a increase in There is a of risk for in use can be as a cause of peripheral vascular disease by almost of heart disease is almost higher in of when compared to also have negative health to is the used drug It is known as the drug and its use is more common in the younger population. in the cardiovascular may have a role in and vascular has been known to cause and studies and have shown that can be linked to and sudden The risk of MI is found to be in of may be a risk factor for of peripheral vascular cardiomyopathy due to use has been more studies are needed to the chronic effects of on the cardiovascular have also been found to cause acute changes in and use has been increasing in the Indian It can include both use and has been consistently linked to use of However, other cardiac adverse effects have been studied less have been in the cardiac but the biological link between and CVD has been There are studies that report the effects of use while other studies about the harmful effects. have been used in cardiac patients and for cardiovascular more in this can a on the relation between use and such as and have been with QT and can to and ratio of CAD in use ranges from to It is possible that lifestyle factors and substance use might play a TREATMENT management of symptoms and use of to and [Table Cardiac safety of of and substance therapies include psychoeducation, CBT, and family therapies. is a chronic and relapsing hence long management is Many people already have some form of physical disorder or the other when they present to a The following guidelines can in the treatment. therapy is one of the in psychiatric there are no for one of the include or MI and the drugs used in it cause both and changes leading to changes in cardiac blood pressure, and heart include arrhythmias, and In patients with cardiac these changes may the cardiovascular health in is needed when is given in Following are recommended. risk should be taken from the patients and their for and cardiac are needed to assess the of the is more than a should be to the stress on the should be monitoring should in the care or a high MANAGEMENT OF PATIENTS CARDIOVASCULAR It is well known that psychiatric to psychotropic use or factors, have an risk for of cardiovascular Regular screening for physical illnesses is However, the of the patients do not have proper due to various and when they the following are recommended. In of chronic cardiovascular the care should with the and on pharmacological management into the and present of the psychiatric severity of the need to the psychotropic and an efficacious drug which also has a safety profile in cardiac patients with interactions with the cardiac In of acute cardiac illnesses such as MI or cardiac should be on an basis the of the drug the acute illness is The drug should be at the as MI or cardiac as of psychiatric illness is often which have a safety profile and least drug-drug interactions should be with up [Table of drugs in TO IN OF QT AS AS should we QTc is or need to QTc is more than or but the of the drug to a risk drug a other causes of QTc QTc is more than the drug to a risk drug with a at the monitoring if is symptoms such as other causes of QTc [Table Table and their risk of QT cardiac disease in their to adverse cardiac side effects due to use of in QT prolongation and is needed when prescribing drugs in these Baseline and investigations including physical examination should be done before therapy in monitoring of adverse effects should be done as long as the is on these In of using such as in with studies have shown an risk of and MI though risk is should be done especially in the of the treatment as risk is high during these The should be in and frequent with the to In with heart is population are the than the in this often in of and the drug interactions often lead to significant adverse effects in the starting of all the physical of the medications in use and physical examination are with drug interactions should be at treatment is to treatment as of the drug may cause side effects. of antipsychotics has been shown to cause sudden deaths in especially in those with to be are often used in this population. It has been shown that the used drugs of this such as and do not have significant adverse cardiac effects in the patients and hence can be used IN The guidelines suggested are the evidence at this point of with the clinical practice guidelines of Indian psychiatry it is to and the cardiovascular issues in of psychiatric illness. It is also to do a up with an in the to It is also to do investigations and to be in liaison with a for CVD in psychiatric patients. The suggested guidelines as detailed in this have to be for ill patient. These guidelines further the need to care of both cardiovascular disorders and psychiatric illnesses and of There are no of

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