How Does Lithium Augmentation Affect Heart Function in Depression Treatment?

What you need to know

• Adding lithium to antidepressant treatment (lithium augmentation) did not cause any serious heart rhythm problems or major changes in electrocardiogram (ECG) measurements in this study.
• Some minor ECG changes were observed, including flattening of T waves in some patients, but these are not considered clinically concerning.
• The study found lithium augmentation did not prolong the QT interval, which is an important measure of heart rhythm that can indicate increased risk for dangerous arrhythmias when prolonged.
• More research is still needed on the long-term cardiac effects of lithium augmentation, but this study suggests it is generally safe for the heart in the short-term when used at proper doses.

Understanding lithium augmentation for depression

Depression is a common and serious mental health condition that can be challenging to treat effectively. While antidepressant medications help many people, some individuals do not get adequate relief from antidepressants alone. In these cases of treatment-resistant depression, doctors sometimes recommend adding lithium to the antidepressant regimen, a strategy called lithium augmentation.

Lithium has been used for decades as a mood stabilizer, particularly for bipolar disorder. When added to antidepressants, it can boost their effectiveness for some patients with major depressive disorder who haven’t responded well to antidepressants on their own. However, lithium does come with some side effects and safety considerations that need to be monitored.

One area of concern has been lithium’s potential effects on heart function. At very high levels in the blood, lithium can cause serious heart rhythm problems. But less was known about whether lithium causes any concerning changes to heart function when used at normal therapeutic doses in combination with antidepressants. This study aimed to examine that question by looking at electrocardiogram (ECG) measurements before and after adding lithium to ongoing antidepressant treatment.

What is an ECG and what can it tell us?

An electrocardiogram, or ECG, is a non-invasive test that records the electrical activity of the heart. It provides information about heart rate, rhythm, and other aspects of cardiac function. Some key measurements from an ECG include:

• Heart rate: How fast the heart is beating
• PQ interval: The time it takes for an electrical impulse to travel from the atria to the ventricles
• QRS interval: The time it takes for the ventricles to contract
• QT interval: The time from the start of ventricular contraction to the end of relaxation
• QTc interval: The QT interval corrected for heart rate
• QT dispersion: A measure of variability in ventricular repolarization

Changes in these measurements can sometimes indicate problems with the heart’s electrical system or other cardiac issues. For example, prolongation of the QT interval beyond normal limits is associated with increased risk of dangerous arrhythmias.

How the study was conducted

The researchers recruited 33 patients who were starting lithium augmentation for treatment-resistant depression. All patients were already taking an antidepressant medication. The patients underwent ECG testing before starting lithium and again after reaching a therapeutic lithium level in their blood (between 0.5-0.8 mmol/L).

The average time between the first and second ECG was about 32 days. The researchers compared various ECG measurements before and after lithium augmentation to look for any significant changes. They also recorded any visible changes in the shape of ECG waves.

Key findings on ECG changes

Overall, the study found no major concerning changes in ECG measurements after starting lithium augmentation. Specifically:

• There were no significant changes in heart rate, PQ interval, QRS interval, or QTc interval.
• QT dispersion actually decreased significantly, which may indicate more uniform repolarization of the heart ventricles.
• No patients developed any serious cardiac side effects or potentially dangerous arrhythmias.

The researchers did observe some minor ECG changes:

• 9 patients developed flattened T waves (known as isoelectric T waves)
• 2 patients developed U waves (an extra wave sometimes seen after the T wave)

However, these types of minor T wave changes have been seen before with lithium use and are not considered clinically concerning on their own.

What do these results mean?

This study provides reassuring evidence that adding lithium to antidepressant treatment does not cause major concerning changes in heart function, at least in the short term. Importantly, it did not lead to QT interval prolongation, which has been a theoretical concern with some psychotropic medication combinations.

The lack of serious cardiac effects aligns with previous research on lithium monotherapy (lithium used on its own). This suggests that combining therapeutic doses of lithium with antidepressants does not substantially increase cardiac risk compared to using either medication alone.

The observed decrease in QT dispersion was an interesting finding. The researchers speculate this could potentially reflect improvement in depression symptoms leading to more balanced autonomic nervous system function. However, this is just a hypothesis that would need further study to confirm.

Limitations and future research needs

While these results are encouraging, there are some important limitations to keep in mind:

• The study had a relatively small sample size of 33 patients.
• It only looked at short-term effects over about a month of lithium use.
• There was no control group for comparison.
• The study did not use long-term ECG monitoring that might detect brief arrhythmias.

More research is still needed on the long-term cardiac effects of lithium augmentation in larger groups of patients. Studies comparing lithium augmentation to antidepressant monotherapy would also be valuable. Additionally, research focused specifically on higher-risk patients with pre-existing heart conditions would provide important safety data.

Conclusions

• This study found no evidence of serious ECG abnormalities or increased arrhythmia risk when lithium augmentation was added to antidepressant treatment at therapeutic doses.
• The findings are reassuring for the cardiac safety of lithium augmentation in the short-term for most patients without pre-existing heart conditions.
• Regular ECG monitoring is still recommended when using lithium augmentation to detect any potential long-term effects.
• Patients and doctors can be cautiously optimistic about the cardiac safety of lithium augmentation, but should continue to weigh the overall risks and benefits for each individual case.