Do antidepressants raise heart risk?

“Doctors have been warned about prescribing older style antidepressants after new research found they can increase the risk of heart disease,” reports the Daily Express.

The news report is based on a study in 14,784 people who were healthy when they were first recruited and whose health was then monitored for a number of years. At the start, participants were interviewed about their mental and physical health, and their use of antidepressants. Those who took tricyclic antidepressants were 35% more likely to have a cardiovascular event such as a heart attack or a stroke. People on tricyclic antidepressants were no more likely to die, however, and other antidepressants did not have this association.

This is a well-executed study, but it has several limitations and the association needs to be confirmed in further research. If there is an increase in risk, it is likely to be relatively small compared with that of other lifestyle factors. The researchers say:

“By giving up smoking, losing weight, and becoming more active people can reduce their risk of cardiovascular disease two to three-fold, which largely outweighs the risks of taking the medications.”

Importantly, people taking any medication should not stop taking it without consulting their doctor first.

Where did the story come from?

The study was carried out by researchers from University College London, the Medical Research Council Social and Public Health Sciences Unit in Glasgow, the University of Edinburgh and Vrije Universiteit in The Netherlands.

The research is based on data collected through the Scottish Health Survey, which is funded by the Scottish executive. The authors and their research groups were also funded by a number of organisations including the British Heart Foundation, the Wellcome Trust, the National Heart, Lung and Blood Institute, the National Institute on Aging, the National Institutes of Health, the Bupa Foundation and the Academy of Finland.

The study was published in the peer-reviewed European Heart Journal.

Newspaper coverage was mostly accurate, although the Daily Express may give the incorrect impression that formal recommendations have been made to medical professionals, which is not the case. The researchers’ advice not to stop taking medication without consulting a doctor could have been more prominent in all the newspaper reports. This also applies to the conclusion that the risk of cardiovascular disease from smoking or poor diet far outweighs any risk from medication.

What kind of research was this?

The aim of this study was to evaluate whether taking antidepressants affects the risk of cardiovascular disease (CVD), such as heart disease or stroke. There are different types or classifications of antidepressants, including tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), both of which were examined here. This was a cohort study in a large number of people who were healthy when they were first recruited and whose health was then monitored over a number of years.

Previous studies on the use of antidepressants and the risk of CVD in previously healthy people have had conflicting findings, possibly due to the different ways they were carried out or the different groups of people included in the studies. These researchers aimed to provide a more conclusive view of their effect by looking at a group of people they believed to be representative of the general population.

A cohort study is an appropriate type of study to use to examine this kind of question. However, a clinical trial in which participants took more closely monitored regulated doses of drugs would be likely to give a more accurate result.

What did the research involve?

The researchers identified 14,784 eligible participants aged 35 or older from the Scottish Health Survey. This survey, conducted by interview, takes place every 3-5 years in Scotland to get a nationally representative sample of the general population. The data used in this study were taken from the surveys in 1995, 1998 and 2003. Different people are invited to take part in each new survey. The survey collects data on people’s physical and mental health, lifestyle factors (such as smoking and alcohol intake) and their height, weight and blood pressure. The researchers combined data from a sample of people from these three surveys with data from hospital admissions and death certificates.

The survey assessed the participants’ mental health using the General Health Questionnaire (GHQ-12) for anxiety and depression symptoms in the past four weeks. Participants were also asked about any antidepressant medications they were taking, and hospital records were used to identify psychiatric admissions.

The researchers looked at both fatal and non-fatal “cardiovascular disease events”, including death from heart disease or stroke, non-fatal myocardial infarction (heart attack), coronary surgical procedures, stroke and heart failure. Data on these events were collected from hospital admissions and deaths in hospital up to 2007 recorded by the Information Service Division, Scotland. Participants were followed for eight years on average and there was a total of 1,434 CVD events recorded over the duration of the study.

The researchers took into account various factors linked with death from heart disease or stroke. These included age and sex, psychological distress and hospital stays for psychiatric conditions. In the final model, adjustments were also made for socioeconomic group, marital status, physical activity, smoking, alcohol, body mass index and for CVD medication and hypertension (diagnosed by a doctor as blood pressure higher than 140/90mmHg).

What were the basic results?

People who took TCAs had a 35% greater risk of all cardiovascular disease events compared with people who did not take any antidepressant medication. This analysis took into account age, sex, initial mental health symptoms, lifestyle and demographic factors, high blood pressure and use of CVD medication (hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.03 to 1.77).

People taking other types of antidepressant medication (e.g. SSRIs) did not have an increased risk of CVD events.

There was no increased risk of death from CVD, cancer or any cause from taking TCAs, SSRIs or other antidepressant medications in the adjusted analyses.

How did the researchers interpret the results?

The researchers state that they “found evidence that the use of TCAs, but not SSRIs, was associated with elevated risk of CVD, beyond that explained by the symptoms of psychiatric illness”.

They note that, although depression and psychological distress are also risk factors for CVD, the fact that the participants were assessed for some symptoms of mental illness at the beginning of the study, and that these were taken into account in the analysis, suggests that the effect of TCAs on CVD may be independent of people’s mental health.

Conclusion

This is a well-conducted cohort study, but there are several important limitations that should be considered:

As the authors point out, there was no assessment of how well people stuck to taking the antidepressants they had been prescribed, or any record of dosage or changes to prescription over time. This means that people classified as taking TCAs may be quite different to each other regarding the amount of exposure they had to their medication.
It is not possible to infer causation from this kind of study (i.e. although TCAs were associated with increased risk of CVD events, this does not mean that TCAs caused them). A large number of other CVD risk factors (such as smoking and drinking) were taken into account, but it is possible that there are other risk factors that were not measured by the researchers that could also explain some of this association between TCAs and CVD.
The factors adjusted for in the analysis (such as smoking, weight and medication use) were only measured once, when the participants were enrolled, so any changes to these factors over time could not be considered.
CVD can develop slowly over a period of years, and although people were excluded from the study if they had medically confirmed CVD at the time of recruitment, we do not know how ‘healthy’ people were in terms of the earlier, non-symptomatic stages of CVD, such as ‘furring of the arteries’. Similarly, people in the study may have developed CVD during the course of the study but not yet been diagnosed.
The researchers looked at a number of cardiovascular diseases together, so it is not possible to say whether the observed increased risk was associated with all forms of disease, or some more than others.

Overall, due to these limitations, this association needs to be confirmed in further studies, possibly examining whether the risk is affected by dosage or duration of use.

If this medication does increase the risk of cardiovascular events, it is likely to be a relatively small increase in risk compared with that caused by other avoidable risk factors. The researchers say that people who take antidepressants are also more likely to smoke, be overweight and do little physical activity.

“By giving up smoking, losing weight, and becoming more active they can reduce their risk of cardiovascular disease two to three-fold, which largely outweighs the risks of taking the medications. In addition, physical exercise and weight loss can improve symptoms of depression and anxiety.”