Patients with major depressive disorder (MDD), which affects an estimated 15% of adults in the United States and more than 300 million people worldwide, face elevated risks of morbidity and mortality in the perioperative setting compared to those without MDD.
Because anesthetic agents and other drugs used perioperatively may affect the same neurotransmitters as antidepressant medications, MDD patients are more likely to experience cardiovascular effects including arrhythmias and hypotension, as well as postoperative cognitive dysfunction and other adverse events during and after surgery. Thus, it is critical for clinicians to be aware of the unique risks and potential drug interactions that may affect MDD patients in this context.
“Major depression is the most common mental disorder in the US, and its prevalence is projected to increase with the ongoing coronavirus pandemic,” said Edwin N. Aroke, PhD, CRNA, assistant professor in the School of Nursing at the University of Alabama at Birmingham (UAB), and associate scientist at the Minority Health and Health Disparities Research Center and the Comprehensive Arthritis, Musculoskeletal, Bone, and Autoimmunity Center at the UAB School of Medicine. “Healthcare providers must take active steps to decrease their patients’ risk of postoperative complications,” he stated.
In a paper published in April 2020 in the Journal of Perianesthesia Nursing, Dr Aroke and colleagues described perioperative considerations for patients taking antidepressants who are undergoing elective surgery.1 Selected points from their review are highlighted below, focusing on 3 widely prescribed types of medications.
1. Selective serotonin reuptake inhibitors (SSRIs) should be continued in the perioperative period to prevent the development of discontinuation syndrome, which is characterized by symptoms such as dizziness, lethargy, confusion, and delirium. These symptoms may be mistaken for other conditions such as postoperative cognitive dysfunction.
Certain SSRIs inhibit the cytochrome P450 2D6 enzyme and may increase plasma levels of benzodiazepines, barbiturates, and other drugs.2 Inhibition of this enzyme can also reduce the conversion of tramadol, codeine, oxycodone, and their active metabolites, thus reducing their analgesic effects.
Studies have linked SSRIs with an increased risk of bleeding in patients undergoing procedures such as cardiac and breast cancer surgery.3,4 These findings underscore the need to closely monitor bleeding in these patients and to exercise caution when administering NSAIDs for pain management. Commonly used perioperative medications, including fentanyl, tramadol, and methadone, can increase the risk of serotonin syndrome when used concurrently with SSRIs.
2. While tricyclic antidepressants (TCAs) should also be continued perioperatively to prevent discontinuation syndrome, caution is needed to avoid TCA toxicity when TCAs are also used for postoperative pain control. TCA toxicity is relatively common due to the rapid absorption of these drugs from the gastrointestinal tract.
“Given that TCAs inhibit the reuptake of norepinephrine, the increased availability of catecholamines in the central nervous system may increase anesthetic requirement,” and “care must be taken to avoid sympathetic stimulation and activities that increase the release of catecholamines,” the study authors wrote.1
Depletion of cardiac catecholamines may result from chronic administration of TCAs, and the cardiac depressant effects of anesthetic medications may be magnified in patients taking TCAs.5 Close perioperative monitoring for arrythmias is recommended for patients taking TCAs.
3. While there is currently no formal guidance or consensus regarding the continuation of Monoamine Oxidase Inhibitors (MAOIS) during the perioperative period, they are often continued to avoid complications, including withdrawal symptoms and patient suicide. If the care team and patient agree to taper and discontinue MAOIs before surgery, they should be resumed immediately following surgery.
The coadministration of opioids and MAOIs may lead to depressive reactions that are reversible with naloxone.2 Tramadol, dextromethorphan, and meperidine can cause serotonin syndrome and should thus be avoided. Indirect-acting sympathomimetics such as ketamine, ephedrine, and pancuronium should not be used in patients taking MAOIs due to associated risks of fatal hypertensive crises.
MAOIs impair the hepatic metabolism of barbiturates and should be used at reduced dosages in patients taking MAOIs. Drug classes that can be safely used in these patients during anesthesia include propofol, etomidate, anticholinergic drugs, volatile anesthetic agents, and several others.
4. Additionally, Aroke et al discussed considerations for patients taking atypical antidepressants, which can generally be continued perioperatively. Lithium should be discontinued at least 24 hours before minor procedures and up to 3 days before major surgeries. The coadministration of lithium and certain agents used in the perioperative setting, including angiotensin converting enzyme inhibitors, NSAIDs, thiazide diuretics, and tramadol, can result in severe lithium toxicity and associated complications.
We interviewed Dr Aroke to learn more about managing perioperative risks in patients with MDD.
What is known thus far about perioperative risks in individuals with MDD?
MDD is a strong predictor of chronic postoperative pain. It is associated with increased length of stay, wound infections, myocardial infarction, and opioid use disorder after surgery. Many patients with MDD are treated with SSRIs and TCAs. While SSRIs are associated with increased risk of bleeding and readmission after surgery, TCAs may increase the risk of perioperative cardiac arrhythmias.
In your paper, you and your colleagues note that the mechanisms driving these risks are not yet known, but what does the research point to as a few potential mechanisms?
Altered levels of neurotransmitters such as serotonin, dopamine, and norepinephrine may contribute to the risk of postoperative complications. We also know that the etiology of MDD is related to genetics and environmental factors, so various gene-environment interactions may increase the risk of postoperative complications.
Studies have shown an increased risk of depression following cardiac surgery. What does the available evidence suggest about outcomes among patients with depression who undergo cardiac surgery?
Patients with moderate to severe depression have been shown to have worse outcomes after cardiac surgery, including a greater likelihood of experiencing major adverse cardiac events postoperatively.6 The good news is that many patients who continue to take their antidepressants, especially SSRIs, usually have better outcomes.
Also, patients who are initiated on an antidepressant and anxiolytic after cardiac surgery tend to do better. Of course, caution must be exercised when using arrhythmogenic antidepressants such as MAOIs in patients with underlying cardiac disease. SSRIs may be safer for this population.
What are some ways in which providers can help to manage these risks?
Providers should optimize depressive symptoms before scheduling patients for elective surgery. In emergency procedures, careful selection of medication to minimize the risk for cardiovascular effects is essential.
What are remaining research needs regarding this topic?
Ketamine is an intravenous anesthetic medication that has excellent analgesic and antidepressant effects. Large scale randomized controlled trials are needed to investigate whether perioperative ketamine use modulates the risk for postoperative complications. Additional studies could investigate different combinations of perioperative medications and their effect on postoperative morbidity and mortality.
Current ongoing studies include the use of cognitive behavioral therapy, multidisciplinary teams, and risk-stratified scoring systems.
2. Attri JP, Bala N, Chatrath V. Psychiatric patient and anaesthesia. Indian J Anaesth. 2012;56(1):8‐13.
3. Eckersley MJ, Sepehripour AH, Casula R, Punjabi P, Athanasiou T. Do selective serotonin reuptake inhibitors increase the risk of bleeding or mortality following coronary artery bypass graft surgery? A meta-analysis of observational studies. Perfusion. 2018;33(6):415‐422.
4. Gärtner R, Cronin-Fenton D, Hundborg HH, et al. Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study. BMC Surg. 2010;10:3.
5. Saraghi M, Golden LR, Hersh EV. Anesthetic considerations for patients on antidepressant therapy-part I. Anesth Prog. 2017;64(4):253‐261.
6. Horne D, Kehler S, Kaoukis G, et al. Depression before and after cardiac surgery: do all patients respond the same?. J Thorac Cardiovasc Surg. 2013;145(5):1400‐1406.