According to the 2013 National Ambulatory Medical Care Survey, antidepressants are the third most frequently prescribed class of medications in outpatient clinics [1]. These medications are often prescribed for the treatment for depressive or anxiety disorders, such as major depressive disorder, phobias, panic disorder, generalized anxiety disorder, or obsessive-compulsive disorder [2]. However, they are also prescribed off-label for analgesic purposes, such as treating chronic pain, menstrual symptoms, fatigue, or even postoperative pain [3]. The most common types of antidepressant drugs are tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs) [2]. All antidepressants work by increasing serotonin and/or norepinephrine in CNS synapses [4]. An existing prescription for antidepressants may affect the anesthesia approach if the patient needs to undergo surgery. 

TCA overdose can cause seizures, which are traditionally treated with benzodiazepines. In some cases, this administration may result in respiratory distress and over-sedation during the postictal state (the period immediately after an epileptic seizure). Therefore, in patients experiencing TCA overdose, administering benzodiazepines such as flumazenil to treat seizures can exacerbate the epileptic response [5]. Chronic therapy with TCAs depletes cardiac catecholamine stores, increasing the risk of cardiac depression after anesthetic administration [6]. If a patient on TCAs requires a surgical intervention, it is important to avoid stimulating the sympathetic nervous system, because of the sympathomimetic properties of TCAs in high quantities [6,7]. For this reason, ketamine, pancuronium, meperidine, and epinephrine-containing anesthetics should be avoided to minimize adverse effects [6].  

SSRIs are generally the first drug of choice in treating depressive disorders because of their highly selective nature; they only block reuptake of serotonin, and do not alter adrenergic, cholinergic, histaminergic or other neurochemical systems [6]. Cytochromes (CYP) p450 are a superfamily of monooxygenases, which are critical for processes like hormone synthesis and breakdown [8]. Analgesics for postoperative pain containing codeine or tramadol (prodrugs) are metabolized to their active metabolites, morphine and o-desmethyltramadol respectively by CYP 2D6. However, SSRIs commonly inhibit the CYP system, reducing the amount of prodrug that is converted into active drug, ultimately reducing the effectiveness of analgesia and potentially requiring higher doses of the anesthetic [5].  

Serotonin syndrome is a potentially life-threatening condition resulting from excessive serotonin in the brain stem and spinal cord, leading to behavioral changes (such as agitation), increased motor activity, and loss of autonomic control (manifesting as tachycardia, hyperthermia, or fluctuating blood pressure). In extreme cases, seizures, renal failure, coma, and death may occur. Drugs associated with increased risk of this disorder include SSRIs, SNRIs, TCAs, tramadol, pethidine, and dextromethorphan [6].  

MAOIs are antidepressants that can also have hazardous interactions with anesthesia, including both indirect and direct active sympathomimetics. When patients on MAOI therapy are given anesthetic agents with sympathomimetic properties, systemic hypertension often ensues [9]. Opioids such as meperidine have been shown to have the most damaging effects when combined with MAOI use. MAOIs may also cause a reduction in the hepatic metabolism of barbiturates, meaning a smaller quantity of the anesthetic agent is sufficient to create the intended response [6]. Propofol and etomidate can be used safely, however, ketamine should be avoided since it causes significant sympathetic activation [9].  

While it is generally considered safe to administer anesthesia in patients on antidepressants, the anesthesiologist should be aware of the many intricacies and risks of drug-drug interactions, as well as serotonin syndrome and changes in blood pressure [5]. Taking a thorough medical history is a critical preliminary step towards reducing the risks of adverse outcomes.  

References 

1. National Center for Health Statistics, Centers for Disease Control and Prevention. Therapeutic Drug Use. Available at: https://www.cdc.gov/nchs/fastats/drug-use-therapeutic.htm.  

2. Saraghi, M., Golden, L. R., & Hersh, E. V. (2017). Anesthetic considerations for patients on antidepressant therapy—Part I. Anesthesia Progress, 64(4), 253–261. https://doi.org/10.2344/anpr-64-04-14  

3. Catalani, B., Hamilton, C. S., Herron, E. W., Urman, R. D., Fox, C. J., & Kaye, A. D. (2014). Psychiatric agents and implications for perioperative analgesia. Best Practice & Research Clinical Anaesthesiology, 28(2), 167–181. https://doi.org/10.1016/j.bpa.2014.05.001  

4. Stoelting, R. K., & Hillier, S. C. (2012). Pharmacology and Physiology in Anesthetic Practice. Lippincott Williams & Wilkins.  

5. Saraghi, M., Golden, L., & Hersh, E. V. (2018). Anesthetic considerations for patients on antidepressant therapy – part II. Anesthesia Progress, 65(1), 60–65. https://doi.org/10.2344/anpr-65-01-10  

6. Attri, J. P., Bala, N., & Chatrath, V. (2012). Psychiatric patient and anesthesia. Indian Journal of Anesthesia, 56(1), 8–13. https://doi.org/10.4103/0019-5049.93337  

7. Sympathomimetic drug—An overview | Science Direct topics. Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/sympathomimetic-drug  

8. McDonnell, A. M., & Dang, C. H. (2013). Basic review of the cytochrome p450 system. Journal of the Advanced Practitioner in Oncology, 4(4), 263–268. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093435/  

9. Hines, R. L., & Marschall, K. (2008). Stoelting’s anesthesia and co-existing disease. Elsevier Health Sciences.  

Related posts:

Anesthesia for Electroconvulsive Therapy Halothane: Biological Mechanisms, Surgical Applications and Side Effects Utilization of Operational Analytics in the Perioperative Care Spectrum Opioid Associated Postoperative Nausea