Mixed depression describes a state of depression accompanied by a few symptoms typically associated with mania. At the 2015 meeting of the International Society for Bipolar Disorders, researcher Roger McIntyre shared some findings about mixed depression.
People with mixed depression have higher levels of MHPG, which is produced as the neurotransmitter norepinephrine breaks down. They also have higher levels of the stress hormone cortisol and their depressions are more difficult to treat. Those with unipolar mixed depression may respond poorly to traditional antidepressants.
There are also medical risks associated with mixed depression. People with mixed depression are more susceptible to cardiovascular disease than are people with depressive symptoms alone.
The drugs lurasidone, olanzepine, and ziprasidone have each shown efficacy in mixed depression.
Severe mental illness is one of the leading causes of death worldwide. Recently researchers led by E.R. Walker performed a meta-analysis of all cohort studies comparing people with mental illness to non-ill populations. They used five databases to find 203 eligible studies from 29 countries. Their findings, published in the journal JAMA Psychiatry in 2015, show that people with mental illness have a mortality rate 2.22 times higher than people without mental illness. People with mental illness lose a potential 10 years of life compared to those without severe mental disorders. The researchers estimated that 14.3% of deaths worldwide are attributable to mental illness.
Editor’s Note: Comorbid cardiovascular illness accounts for a large part of the disparity in life expectancy between people with and without mental illness. Those at risk for serious mental illness should pay close attention to their cardiovascular as well as psychiatric risk factors.
People with major mental disorders such as schizophrenia and bipolar disorder are at increased risk for medical symptoms including overweight, obesity, high cholesterol or triglycerides, diabetes, and the metabolic syndrome, all of which increase risk of cardiovascular disease (heart attack), cerebrovascular disease (or strokes), and other medical difficulties. In a 2013 review article in the journal Bipolar Disorders, researcher Chittaranjan Andrade discussed the use of statins to prevent cardiovascular events in people with major mental disorders.
Statins decrease lipids, and have significant benefits in decreasing cardiac events, but their use is low among psychiatric populations. Psychiatric patients often receive less cardiac care. It may be up to their psychiatrists to push for aggressive prevention of cardiac illnesses.
The most significant side effect of statins is the possibility that they can increase risk of diabetes. In a meta-analysis by Preiss et al., intensive dosing with statins increased the risk of diabetes but also lowered the risk of cardiovascular events. In a year, 1,000 patients would get two extra cases of diabetes but 6.5 fewer cases of cardiovascular events. For patients at high risk for heart attack or stroke, a cardiovascular event is more dangerous than diabetes, so it makes sense to treat these patients with statins. In patients at lower risk, there is some evidence that diabetes risk was a problem mostly in patients with other risk factors for diabetes, including metabolic syndrome, impaired fasting glucose levels, a body mass index of 30 kg/m2 or higher, or glycated haemoglobin A (1c) above 6%.
Most studies of statins are conducted on patients in middle age, but there is a rationale for treating even younger patients with statins. Patients with bipolar disorder develop cardiovascular disease more than a decade earlier than controls. There is some evidence that cholesterol deposits in arteries begin even before age 20, and are cumulative. The risk-benefit ratio for statin use improves with years of use, so starting it earlier may lead to better prevention. Long-term use may reduce the risk of Alzheimer’s disease and Parkinson’s disease and some cancers in addition to reducing heart attacks and strokes.
Despite the risk of diabetes, it is important to consider statin use in psychiatric patients, especially those who receive antipsychotic medications. Read more
In a study of over 60,000 women, Swedish researcher Karl Michaëlsson et al. found that those women with the highest intakes of calcium (>1400mg/day) were at higher risk of mortality, particularly from cardiovascular causes such as cardiovascular disease and heart disease (but not stroke), than women with calcium intakes of between 600 and 1000mg/day. The research was published in the journal BMJ in 2013.
While calcium dietary supplements were not associated with elevated risk per se, those women with the highest calcium intake levels who also took supplements had a risk of mortality from all causes that was more than 2.5 times that of women with similar total calcium intake who did not take supplements.
Calcium levels in blood are tightly controlled by the body, but very low or very high calcium intake levels can override this control, causing imbalances.
The efficacy of calcium supplements for conditions such as osteoporosis or chronic kidney disease has not been established, and a healthy balanced diet and avoidance of water filters that remove calcium from drinking water may be best.
Lifetime Heart Disease Risk Increases Dramatically When One or More Risk Factors Are Present in Middle Age
A meta-analysis of 18 studies that was published by Donald Lloyd-Jones in the New England Journal of Medicine in 2012 shows that increasing cardiovascular risk factors during middle age can dramatically increase a person’s risk of experiencing fatal cardiovascular disease, fatal coronary heart disease, nonfatal heart attack, or stroke later in life.
Data were analyzed from 257,384 patients, who included black and white men and women spanning a 50-year range of birth cohorts. The studies examined cardiovascular risk factors such as smoking, cholesterol levels, diabetes, and blood pressure at ages 45, 55, 65, and 75.
Having even one risk factor at age 55 dramatically increased the lifetime risk of cardiovascular disease compared to having no risk factors, and having more risk factors during middle age increased risk even further. Among people with no risk factors at age 55 (meaning cholesterol under 180mg/dL, blood pressure under 120 mm Hg systolic and 80 mm HG diastolic, nonsmoking and nondiabetic), men had 4.7% risk of death from cardiovascular disease by age 80 (compared to 29.6% for those with 2 or more risk factors). Women had a 6.4% risk of death from cardiovascular disease by age 80 (compared to 20.5% among those with 2 or more risk factors).
Lifetime risk of death from cardiovascular disease and coronary heart disease and risk of nonfatal heart attack were about twice as high in men, while risk of stroke was similar for men and women.
Across race, trends were similar, but this finding can be misleading. While African-Americans have more cardiovascular risk factors than whites, they are also more likely to die at younger ages from other causes before developing serious cardiovascular illnesses. Large studies with Latino and Asian American participants were begun too recently to provide robust data about long-term risk, but this research is expected to become available soon.
Editor’s Note: Watch your risk factors for heart disease, including high blood pressure, cholesterol, weight, and blood sugar. The more risk factors one has, the greater the increased risk of fatal cardiovascular illness.
Depression is also a risk factor for coronary artery disease, and should be treated just as aggressively and persistently as the other risk factors. Exercise is one element of a healthy lifestyle that can positively affect all of these risk factors. Implementing a healthy diet and exercise regimen by middle age will have long-term positive effects in reducing risks in older ages.
Physical activity and light to moderate drinking (as is often associated with the Mediterranean diet) are recommended as ways to reduce risk for heart disease and type 2 diabetes. New research shows that among healthy people, symptoms of depression can counteract the anti-inflammatory benefits of both exercise and light to moderate alcohol consumption.
C-reactive protein (CRP) is a cardiometabolic risk marker. High measures of CRP are a sign of inflammation. Leisure-time physical activity and light to moderate alcohol intake (defined as about half a drink per day for women and one drink per day for men) are associated with lower levels of CRP. Depression is associated with higher levels.
A study by Edward C. Suarez et al. published recently in the journal Brain, Behavior, and Immunity examined 222 nonsmoking men and women aged 18-65 years. These participants were physically healthy and had no history or diagnosis of psychiatric conditions. Participants recorded the amount of alcohol they consumed and the amount of physical activity in which they participated. CRP levels in their fasting blood samples were measured, and they also completed an inventory of depressive symptoms.
Those people who were physically active had lower levels of CRP, but the 4.5% of participants with depressive symptoms did not see any anti-inflammatory benefits from physical activity. Similarly, light to moderate drinking was associated with lower levels of CRP only in men who were not depressed.
Depression did not seem to affect other markers of physical health in this study, such as levels of triglycerides or cholesterol.
Editor’s Note: This study suggests that treating depressive symptoms should be a part of any plan to reduce cardiovascular risk. It seems that depression has effects that go beyond psychological distress and may prevent patients from reaping the benefits of their healthy behaviors. The effect of depression in preventing heart healthy changes in CRP could be one of many factors mediating the high levels of cardiovascular risk in depression. People with depression are twice as likely to have a heart attack than those without depression.
Adults with bipolar disorder have higher rates of cardiovascular disease and premature death from cardiovascular illness than the general population. At the 2012 meeting of the American Academy of Child and Adolescent Psychiatry, Benjamin Goldstein presented a poster in which he showed that youth with bipolar disorder may also have abnormal cardiovascular function.
When a tourniquet is applied, blood vessels normally expand to make up for the period of oxygen deprivation. This does not happen as readily in patients with mood disorders. This lack of flexibility and compensatory response could be one of the reasons for increased cardiovascular difficulties in those with mood disorders.
In Goldstein’s study, noninvasive ultrasound imaging was used to measure the thickness of the walls of the carotid artery and flow mediated dilation of the artery in adolescents with bipolar disorder and those without the illness. The data was collected by a certified ultrasound technologist who remained blind to the patients’ diagnostic and symptom status.
Goldstein found highly abnormal results in 14 adolescents aged 14 to 19 with bipolar disorder compared to controls. He concluded that reducing cardiovascular risk in bipolar disorder is a pressing clinical and public health challenge and that treating these patients while they are adolescents may offer considerable advantages both for prevention and for understanding the progression of cardiovascular problems in patients with bipolar disorder.
Patients with Bipolar Depression Have a Higher Mortality Rate, Especially if They Also Have Cardiovascular Disease
In a large longitudinal study of depressed patients in Taiwan that was published in the Journal of Psychiatric Research this year, Chang et al. found that after 10 years, patients with bipolar depression (N=1,542) had significantly higher mortality rate than those with other types of depression (N=17,480). Patients with bipolar depression were twice as likely to have died from suicide or accidental death than were patients who had other types of depression. When cardiovascular disease was also present in both groups, patients with bipolar disorder were also four times more likely to have died from suicide or accidental death than those with other types of depression.
Editor’s Note: These data again emphasize the critical importance of patients with bipolar disorder carefully looking after their medical and cardiovascular health both early on and throughout the entire course of their illness.
Much of the excess medical mortality in bipolar disorder is attributed to cardiovascular disease, and now those with cardiovascular disease also appear more prone to suicide. This should be a call to action to improve the long-term treatment of both bipolar disorder and its common comorbidity, cardiovascular disease.
Get your medical illness treated!
It will improve your health and longevity. Especially treat these signs of the metabolic syndrome, a major risk factor for cardiovascular disease:
- Cholesterol–Increase “good” cholesterol (high-density lipoproteins or HDLs) and lower “bad” cholesterol (low-density lipoproteins or LDLs)
- High Triglycerides–Triglycerides should be below 150 mg/dL
- Blood Pressure–Aim for 130/85 mmHg or lower
- Blood Sugar–Fasting blood sugar (glucose) should stay below 100 mg/dL
- Overweight & Obesity–Keep waist circumference under 40” for men or 35” for women
Exercise is good for all of these!
According to Heartwire, an article in the New England Journal of Medicine indicates that having any of these risk factors increases the likelihood of cardiovascular disease later in life. The more risk factors one has, the greater the increase in risk.
Across the whole meta-analysis, participants with no risk factors at age 55 (total cholesterol level: <180 mg/dL;
blood pressure: <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking; nondiabetic) had drastically better odds
of avoiding death from cardiovascular disease through the age of 80 than participants with two or more major risk
factors (4.7% vs 29.6% among men and 6.4% vs 20.5% among women).
People with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal MI (Editor’s Note: myocardial infarction, or heart attack) (3.6% vs 37.5% among men, <1% vs 18.3% among women) and fatal or nonfatal stroke (2.3% vs 8.3% among men,
5.3% vs 10.7% among women), compared with those with two or more risk factors.
What this article does not mention is that depression is a risk factor for coronary artery disease, and should be treated just as aggressively and persistently as the other cardiovascular risk factors.
Also as we’ve written before in the BNN, exercise is one element of a healthy life style that can positively affect all of these risk factors. Starting a healthy diet and exercise regimen in middle age will have long-term positive effects and reduce risks later in life.
Research from 2010 shows that tricyclic antidepressants (TCAs) are linked to 35% greater risk for cardiovascular disease, while selective serotonin reuptake inhibitors (SSRIs) were not shown to confer any extra cardiovascular risks.
Editor’s Note: This is another one of many reasons to use second generation antidepressants such as the SSRIs and bupropion instead of the first generation tricyclics. The TCAs have more side effects, are more dangerous in overdose, are not indicated for children or adolescents, and are more likely to cause switches into mania in individuals with bipolar disorder than the newer ADs.