Management of Depression and Anxiety in Perioperative Medicine.

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Published in final edited form as: Anesthesiology. 2024 Oct 1;141(4):765–778. doi: 10.1097/ALN.0000000000005076 Search in PMC Search in PubMed View in NLM Catalog Add to search Management of Depression and Anxiety in Perioperative Medicine Megan L Rolfzen Megan L Rolfzen , M.D. a Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, USA Find articles by Megan L Rolfzen a , Peter Nagele Peter Nagele , M.D., M.Sc. b Department of Anesthesiology, University of Chicago, Chicago, IL, USA Find articles by Peter Nagele b , Charles Conway Charles Conway , M.D. c Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, USA Find articles by Charles Conway c , Robert Gibbons Robert Gibbons , Ph.D. d Center for Health Statistics, University of Chicago, Chicago, IL, USA Find articles by Robert Gibbons d , Karsten Bartels Karsten Bartels , M.D., Ph.D., M.B.A. a Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, USA Find articles by Karsten Bartels a Author information Copyright and License information a Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, USA b Department of Anesthesiology, University of Chicago, Chicago, IL, USA c Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, USA d Center for Health Statistics, University of Chicago, Chicago, IL, USA ✉ Corresponding Author: Karsten Bartels, M.D., Ph.D., M.B.A., University of Nebraska Medical Center, 984455 Nebraska Medical Center, Omaha, NE 68198-4455, [email protected] PMC Copyright notice PMCID: PMC13092319  NIHMSID: NIHMS2157545  PMID: 39136627 The publisher's version of this article is available at Anesthesiology Summary Statement: This Clinical Focus Review summarizes contemporary best practices, recent clinically relevant research, and pertinent unanswered questions related to perioperative screening and treatment of anxiety and depression. Introduction Mental illness is defined by the Substance Abuse and Mental Health Services Administration (SAMHSA) as diagnosable mental, behavioral, or emotional disorders other than developmental or substance use disorders. 1 Mental health disorders are ranked among the most disabling and burdensome public health problems as measured by disability-adjusted life years. 2 The burden of anxiety and depression has increased in recent years, likely due to social isolation, occupation disruption, and substance use, all of which were likely accelerated by the COVID-19 pandemic. 3 , 4 Indeed, the most recent national prevalence study conducted by SAMHSA and the Research Triangle Institute (RTI) International reports 1-year prevalence rates of major depressive disorder (MDD) at 15.5% and generalized anxiety disorder (GAD) at 10.0% in adults aged 18–65. 5 Interestingly, but perhaps unsurprisingly, estimated rates of depression and anxiety in surgical patients differ by specialty ( Figures 1 and 2 ). 6 , 7 Mental health disorders are associated with increased postoperative pain, 8 more frequent hospital readmissions, 9 higher incidence of postoperative delirium, 10 and increased 30-day mortality. 11 , 12 Furthermore, they predispose to long-term negative consequences such as decreased quality of life, functional disability, and persistent pain. 13 However, only 47.2% of those diagnosed with a mental illness in 2021 received any mental health services, including inpatient or outpatient treatment, prescription medication, or telehealth. 14 As the demand for behavioral health professionals increases, but the supply remains steady or slightly decreases, 15 perioperative clinicians may need to contribute to addressing this urgent and unmet need. Figure 1. Presence of postoperative depression in select observational studies stratified by surgical specialty. Open in a new tab Figure was produced from data presented in BJA Open 2023; 8:100223, 127 J Clin Neurosci 2022; 104:91–5. 128 Clinically significant depression is defined by International Classification of Diseases codes and validated screening assessments. Open thoracic procedures are defined by the presence of a thoracotomy, thoracoscopic thoracic are video-assisted thoracoscopic (VATS) procedures, non-elective orthopedic are comprised of hip fracture surgeries, elective othopedic are total hip arthroplasties, general surgery is mainly laparoscopic cholecystectomy, and spine surgery is comprised of spinal fusions. Figure 2. Presence of preoperative anxiety in select observational studies stratified by surgical specialty. Open in a new tab Figure was produced from data presented in Heart Vessels 2017; 32:1458–68, 12 Asia Pac J Oncol Nurs 2019; 6:440–5, 129 Spine 2014; 39:e111–22, 130 Int J Surg Open 2020; 25:6–16, 131 BMJ Open 2024; 14:e071231. 6 Clinically significant depression is defined by International Classification of Diseases codes and validated screening assessments. The cardiac surgery category includes coronary artery bypass grafts, valve repairs, or replacements, oncologic surgery includes any intervention for the outpatient surgical removal of cancer, spine surgery encompasses fusions and laminectomies, orthopedic surgery includes both total hip and knee arthroplasties, and bariatric includes gastric bands, bypass, or sleeve gastrectomies. This review aims to summarize current perioperative behavioral health management approaches that may improve long-term outcomes in patients with depression and anxiety. It simultaneously calls for perioperative clinicians to conceptualize mental health as an integral part of brain health. 16 Depression Major depressive disorder is defined by clinically significant depressed mood or loss of interest over a two-week period that is not attributable to another medical condition. 17 It is a common but heterogeneous psychiatric disorder with an annual prevalence of 10.4% and a lifetime prevalence of 20.6% in the non-institutionalized civilian adult US population. 18 Evidence suggests that postoperative depressive symptoms occur in 20–40% of older adults, and 50% of these patients have no prior history of depression, reflecting that this mental illness exists on a dynamic continuum. 19 , 20 The increased perioperative prevalence is likely multifactorial and related to acute illness or stress reaction, inadequately treated depression, medical stressors, and polypharmacy. 21 , 22 Depression and anxiety are not binary diagnoses, with severity classifications based on number of symptoms, level of distress, and the degree of impairment. Depression severity has been shown to modulate clinical outcomes, including but not limited to procedural success rates, 23 digital mental health treatment responses, 24 and thoughts of harm. 25 Further, treatment-resistant depression (TRD) represents a common subgroup of major depressive disorder that exhibits a lack of response to two adequate dose-duration trials of established pharmacotherapy or psychotherapy. 26 Perioperative depressive symptoms, depression, and treatment-resistant depression are separate entities. It is essential to distinguish between them because prevention of symptoms after surgery is different from treatment of refractory depression as an outpatient. Preoperative psychological care begins with assessing patients using validated screening tools ( Table 1 ). Notably, the perioperative use of these tools is still infrequent, but their incorporation into electronic health record systems can facilitate operability and tracking. 27 – 29 Depression evaluations may include self-administered ratings, 30 personality characteristics, 31 perceived social support scores, 32 and disability screenings. 33 Limited evidence exists to suggest the superiority of any one measure, but proper screening and intervention can potentially change recovery trajectories. 22 Short-form questionnaires identify “high-risk” individuals who may benefit from targeted preventive perioperative planning to alter pain and recovery outcomes. 34 Table 1. Mental health screening tools available for use in the perioperative period. Tool Scale Description Hospital Anxiety and Depression Scale (HADS) 120 0 – 42 numerical scale, 0 – 21 for each subscale; 8 cut-point 14-items. Subscales distinguish between symptom severity without ‘noise’ from somatic or serious mental disorders. Most widely used scale. Generalized Anxiety Disorder-7 0 – 21 numerical scale; 8 cut-point 7-item validated tool, based on the DSM-IV criteria. Low discriminant validity among elderly patients. Restrictions on patients with physical symptoms. Generalized Anxiety Disorder-2 0 – 6; 3 cut-point Shorter version of GAD-7. Uses two core anxiety symptom questions to identify the need for further evaluation. Amsterdam Preoperative Anxiety and Information Scale (APAIS) 72 4 – 20 scale; 11 cut-point 4-items. Specifically used to evaluate surgical patients. Computerized Adaptive Test – Anxiety Inventory (CAT-ANX) 121 0 – 100; <35 normal, >65 severe symptoms Assesses anxiety severity based on 431 possible questions adaptively administered. Patient Health Questionnaire-9 0 – 27 numerical rating severity score, 19 cut-point 9-item quick depression assessment. Consider disorder if 4 check marks in shaded section. Use numerical scale for severity. Patient Health Questionnaire-2 0 – 6; 3 cut-point 2-item assessment of depressed mood and anhedonia over past 2 weeks. First 2 items of PHQ-9. Computerized Adaptive Test – Major Depressive Disorder (CAD-MDD) 122 Decision tree and random forest Average of 4 self-report items. Screens for Major Depressive Disorder; validated against DSM-V. Computerized Adaptive Test – Depression Inventory (CAT-DI) 123 0 – 100; <35 normal, >75 severe symptoms Assesses depression severity based on 389 possible questions adaptively administered. Concerns About Pain Scale 73 Raw summed score transformed into item response theory-based T-score 6-item short form is reliable. Computer adaptive testing available. Removed the word catastrophizing to reduce stereotype. Pain Catastrophizing Scale 124 0 – 52; 30 cut-point 13-item pain catastrophizing measure validated in pain patients and controls. Includes rumination, magnification, and helplessness subscales. 2-Item Coping Strategies Questionnaire 74 Likert scale 0 – 6; 2 questions for each subscale. A 2-item version of the 27-item questionnaire. Assesses chronic pain coping strategies. NIH Toolbox Loneliness v3.0 32 5-point scale; “never” to “always”. Raw score converted to T-score. 5-item fixed form for perceptions of social isolation. Sheehan Disability Scale 33 0 – 30 total score 3-item composite assessing functional impairment in 3 major life domains: work, social life, and family life. Distress Thermometer 31 0 – 10 Likert scale resembling a thermometer; 4 cut-point Single-item tool. Considered the 6 th vital sign in oncology care. Open in a new tab Cut points represent thresholds for further evaluation or referral. Abbreviations: DSM, Diagnostic and Statistical Manual of Mental Disorders Evidence-based guidance on nonpharmacologic treatment for depression in the context of a surgical encounter is lacking, and many of the systemic changes needed to affect long-term outcomes are extraneous to the perioperative sphere of influence. However, a stepped-care approach to address comorbid depression in patients undergoing surgery may be extrapolated from interventions in similar settings. 35 Brief interventions administered in the perioperative period do not necessarily require the presence of mental health professionals (i.e., education, music medicine, and mindfulness intervention), though collaboration with psychiatrists, geriatricians, psychologists, and neurologists is encouraged. Examples of tools tailored to non-mental health subspecialized clinicians are Problem Management Plus 36 for adults who struggle with depression, anxiety, and stress and the Thinking Healthy manual, which addresses peripartum depression. 37 Moreover, evidence suggests that individuals with perceived emotional support from a social network are more likely to engage in health-promoting behaviors. 38 As the risk of depression is higher (odds ratio 2.60; 95% CI 1.84, 3.69) in adults with poor overall relationship quality, 39 reinforcing the perioperative advantage of social support is important. This may involve a simple educational conversation with family members in the preoperative context or with the patient and family members in the recovery room. The sustainability and feasibility of low-intensity psychological interventions adapted to the perioperative period have been demonstrated in surgical patients. 40 – 43 Perioperative 90-minute group psychotherapy sessions once a week for eight weeks improved both depression (62.9% reduction) and anxiety (61.6% reduction) in patients with lung cancer undergoing gamma knife surgery immediately after treatment and at three months follow-up. 40 For older adults who are cognitively intact, brief preoperative cognitive behavioral therapy for four 15–60 minute individual sessions has been shown to decrease depression indices in coronary artery bypass graft patients (adjusted mean difference −7.79, p=0.008). 44 The differential group effects did not persist six months post-surgery, but both anxiety and depression reduction persisted (mean differences −9.50, p<0.001; −25.13, p<0.001, respectively). 44 Furthermore, providing information about the surgical procedure and social connection paired with postoperative pain normalization, psychological comfort, and coping strategies effectively decreased self-rating anxiety and depression scores in 78 surgical lung cancer patients. 45 For more information, Table 2 tabulates the results of recent meta-analyses and systematic reviews of non-pharmacologic interventions customized to perioperative settings. 46 Table 2. Selected systematic reviews, meta-analyses, and narrative reviews regarding nonpharmacological interventions for perioperative depression, anxiety, and related disability. Study Authors Study Type (Size) Intervention(s) Outcomes Follow-Up Timing Comment Nadinda et al. 2022 77 Systematic Review and Meta-Analysis of RCTs (21 studies, N = 2,288) Psychological interventions including: - cognitive behavioral therapy acceptance and commitment therapy psychoeducation - mindfulness-based stress reduction guided imagery Psychological interventions reduced subacute postoperative pain (d = −0.26) and chronic postoperative pain (d = −0.33). Psychological interventions reduced subacute (d = −0.43) and chronic (d = −0.43) disability. Subacute: 1 day – 3 months after surgery Chronic: 3 – 12 months after surgery Small to moderate effect sizes. Postoperative interventions were more effective than only preoperative at reducing chronic disability. McCann et al. 2023 42 Narrative Review (39 studies, N ~ 200,000) Preoperative education Physical activity Social connection Rehabilitation Education associated with moderate reduction in depression and large reduction in anxiety. Social connection associated with small reduction in depression, family relationships associated with large reductions in anxiety and stress. N/A Cardiac surgical patients between 1983 and 2022. Preoperative education and social connection have the most robust evidence. Powell et al. 2016 78 Meta-Analysis and Narrative Review of RCTs (105 studies, N = 10,302) Psychological preparation techniques including: - procedural information - sensory information - behavioral instruction - cognitive intervention - relaxation techniques - hypnosis - emotion-focused intervention Lower postoperative pain (SMD −0.20). Reduced length of stay (mean difference −0.52 days). Reduced negative affect (SMD −0.35). 1 – 30 days post-surgery Low quality evidence limiting consensus. Negative affect defined as mood states: anxiety, stress, and depression. No evidence that behavioral instruction reduced pain outcome. Wang et al. 2018 46 Meta-Analysis of RCTs (15 studies, N = 2,220) Active psychological interventions including cognitive behavioral therapy and relaxation. Psychoeducation including support and provision of information. Active psychological interventions significantly reduced chronic postsurgical pain (WMD −1.06; 95% CI −1.56, −0.55) and disability (WMD −9.87; 95% CI −13.42, −6.32). Education interventions were ineffective. 2.5 – 30 months Moderate to high quality of evidence. Effects significantly differed between active psychotherapy and education. Kakar et al. 2021 91 Systematic Review and Meta-Analysis (16 studies, N = 987) Perioperative music session, 30-minute median duration Reduction in postoperative anxiety (SMD −0.50, p<0.01) after first session and at 8 days after multiple days of music (SMD −0.39, p<0.01). Reduction in postoperative pain after the first session (SMD −0.51, p<0.01) but not after multiple days of music (SMD −0.40, p<0.10). Up to 8 days postoperatively No significant effects on hemodynamic parameters. Álvarez-García & Yaban, 2020 43 Meta-Analysis of RCTs (8 studies) Pre-surgical guided imagery in adults and children vs standard care Moderate effect reduction in preoperative trait anxiety in adults (N=333, d=−0.64; 95% CI −0.97, −0.31). Low effect reduction in postoperative pain in adults (N=318, d=−0.24; 95% CI −0.46, −0.02). 1 day postoperatively Only four studies included in each meta-analysis, but relative lack of bias. Bradt et al. 2013 82 Systematic Review (26 studies, N = 2,051) 10–60-minute preoperative music listening vs standard care Reduction in state anxiety (−5.72; 95% CI −7.27, −4.17). Reduction in anxiety using other standardized scales (SMD −0.60; 95% CI −0.90, −0.31). N/A Overall low quality of evidence. No significant effects on physiological responses other than small effect on heart rate. Tas et al. 2022 94 Systematic Review and Meta-Analysis (27 studies, N = 1,695) Virtual reality for distraction or exposure in pediatric patients undergoing medical procedures Used for distraction to reduce pain (SMD −0.67; 95% CI −0.89, −0.45) and anxiety (SMD −0.74; 95% CI −1.00, −0.48). Used as exposure to reduce anxiety (SMD −0.58; 95% CI −1.15, −0.01). During and immediately after procedure Small number of exposure studies. Virtual reality is easy to use and personalize. Open in a new tab Abbreviations: CI, confidence interval; d, Cohen’s d; MD, mean difference; NA, not applicable; RCT, randomized controlled trial; SMD, standardized mean difference; WMD, weighted mean difference. Successful implementation of non-pharmacological interventions for perioperative mood disorders often requires thoughtful interdisciplinary coordination. Systemic change at this scale undoubtedly requires efforts beyond anesthesiologists. An example of such systematic restructuring is the mental health bundle that Abraham and colleagues developed and adapted to the perioperative setting. 47 Enacted by social workers, pharmacists, psychiatrists, behavioral scientists, registered nurses, anesthesiologists, and surgeons, this intervention bundle concurrently employs behavioral activation and medication optimization for older surgical patients with anxiety and depression. Behavioral activation is a flexible, patient-centered treatment predicated on increasing positive interactions between patients and their environment to maintain engagement. It is a simple psychological treatment alternative that is non-inferior to traditional cognitive behavioral therapy. 48 Iterations to the bundle are ongoing, but early work to ensure sustainability, feasibility, and reach is promising. As exemplified, behavioral interventions are low-risk, feasible, and scalable to perioperative care. Despite effective treatment options in the outpatient setting (i.e., pharmacotherapy, psychotherapy), these therapies are typically not widely initiated in the perioperative period due to time constraints, staffing limitations, and lack of recognition. Granted, existing pharmacotherapy regimens that have been thoughtfully titrated by psychiatric colleagues are typically continued perioperatively when enteral access is available. Abrupt cessation of most pharmacological agents for anxiety and depression can precipitate withdrawal or disease relapse. 49 Therefore, the decision to taper or stop long-term drug therapy preoperatively should be carefully considered. In the US, there are five main classes of oral antidepressants: selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and atypical antidepressants. Fundamentally, these medications increase central nervous system neurotransmitters and network activity involved in learning, motivation, mood, and emotion. Based on the modulation of similar molecules (gamma-aminobutyric acid and 5-hydroxytryptamine), the implications of pairing anesthetics with these oral antidepressants are important to consider. 50 Clustered co-administration of multiple serotonergic agents predisposes to serotonin syndrome, which may be challenging to differentiate from malignant hyperthermia, neuroleptic malignant syndrome, thyrotoxicosis, and sepsis in the operating room. 51 Furthermore, perioperative serotonergic antidepressant use has been associated with an increased transfusion requirement (odds ratio 1.19, 95% CI 1.09, 1.30) but not reoperation (odds ratio 1.48, 95% CI 0.84, 2.62), 52 except in breast cancer surgery (adjusted relative risk 2.30, 95% CI 1.40, 3.90). 53 Aside from partnering with pharmacists and psychiatrists to optimize traditional oral formulations around the time of surgery, there is interest in repurposing anesthetic agents to alter the trajectory of clinically significant depression. Both ketamine and nitrous oxide are N -methyl-D-aspartate (NMDA) receptor antagonists that have historically been applied intraoperatively for analgesic and anesthetic purposes. Evidence suggests that the NMDA receptor-mediated glutamatergic signaling provides the basis for rapid antidepressant effects. 54 , 55 However, there is conflicting evidence regarding the long-term benefit in patients with different forms of depression when administered perioperatively. For example, single ketamine boluses of 0.25–0.5 mg/kg administered during Cesarean section have been found to be associated with both no effect 56 and a reduction in postpartum depression at one week 57 and six weeks. 58 An international randomized clinical trial comparing the anti-depressant effects of intraoperative subanesthetic ketamine boluses with saline placebo in adults 60 or older undergoing major surgery with general anesthesia found no difference in postoperative depressive symptoms. 20 In fact, postoperative hallucinations and nightmares were seen with escalating doses of ketamine. 59 Notably, only 9.6% of the patients enrolled met the screening criteria for baseline depression, and the intraoperative ketamine was administered as a single bolus rather than an infusion. Extensive and compelling literature supports intravenous (typically 0.5 mg/kg over 40 minutes) and intranasal ketamine as being as efficacious as rapid antidepressants in treatment-resistant depression. 55 , 60 Intranasal esketamine (Spravato; Janssen, Raritan, New Jersey, USA), the S(+) enantiomer of ketamine, is the only FDA-approved formulation of ketamine for treatment-resistant depression and major depressive disorder with acute suicidal ideation in conjunction with an oral antidepressant. Esketamine in combination with an oral antidepressant, has been found to be more effective in preventing relapse of depressive symptoms in non-surgical patients with treatment-resistant depression compared to an oral anti-depressant alone. 61 While preliminary studies of esketamine administered during Cesarean section have confirmed its analgesic potential and not detected untoward neonatal depression, 62 determining the utility of perioperative esketamine on postpartum depression will require additional research. There is some suggestion that the racemic mixture of ketamine is superior to the s-enantiomer alone. 63 In fact, a recent 403-patient open-label, randomized trial comparing ketamine with electroconvulsive therapy (ECT), considered the “gold standard” treatment in treatment-resistant depression, found ketamine to be non-inferior (difference 14.2%; 95% CI 3.9, 24.2). 64 In the postoperative setting, a prolonged ketamine infusion regimen (96 hours) is feasible, but an adequately powered clinical trial is warranted to assess efficacy on depressive symptoms. 65 Alternatively, nitrous oxide may confer rapid-onset antidepressant effects without the adverse effect profile associated with ketamine. In a phase 2 prospective, randomized, double-blind, crossover trial of 24 non-surgical patients with treatment-resistant depression, nitrous oxide reduced depressive symptoms for up to two weeks after a single 1-hour inhalation session. 66 , 67 The 2-week efficacy of 25% nitrous oxide was similar to 50% (−5.19 Hamilton Depression Rating Scale points, p=0.02 [25% nitrous oxide]; −7.00 points, p=0.001 [50% nitrous oxide]), with fewer adverse effects. 67 Investigation into the enduring effects of four-cycle nitrous oxide treatment programs and the perioperative use of this medication in people with major depressive disorder is ongoing ( NCT03869736 ). Like intravenous ketamine, inhaled nitrous oxide is not currently approved by the U.S. Food and Drug Administration for the treatment of any psychiatric disorder. Both ketamine and nitrous oxide permit rapid administration and exert a swift therapeutic effect without requiring weeks-long medication monitoring and readjustment requisite to traditional antidepressants or non-pharmacologic therapy. Rehabilitation is frequently needed after major surgery, rendering these rapid-acting antidepressants potentially valuable for the acute postoperative period to improve functionality in the long term. However, before repurposing anesthetic agents for neuropsychiatric disorders in perioperative medicine, continued research is needed, especially regarding the nuanced effects on postoperative depressive symptoms, major depressive disorder, and treatment-resistant depression. Anxiety Anxiety is likely the most common clinically appreciated perioperative mental health challenge. Preexisting anxiety is frequently intensified around the time of surgery, as patients anticipate the imminent procedure, loss of control, unconsciousness, invasion, pain expectance, and an unknown recovery course. Indeed, a diagnosed anxiety disorder has been associated with higher hospital readmission rates after cardiac surgery 9 and increased mortality in postsurgical patients. 11 It is difficult to separate the manifestations of anxiety and depression because they are frequently comorbid and have similar negative affective underpinnings. 68 Further compounding this complexity is the comorbidity of chronic anxiety with substance use disorders, pain catastrophizing, and chronic pain. 69 , 70 Identifying patients who could benefit from further evaluation or brief intervention for anxiety can be done using any number of validated and reliable scales ( Table 1 ). The Generalized Anxiety Disorder 7-item or 2-item scales are common and convenient self-report instruments. 71 However, their use in perioperative medicine is less well studied. The Amsterdam Preoperative Anxiety and Information Scale is a brief 4-item instrument created to identify anxious surgical patients in the preoperative setting. 72 Other scales measuring pain concern, 73 coping strategies, 74 and distress 31 can provide indirect evidence of heightened sympathetic activation that could be briefly addressed perioperatively or by referral to clinical psychology or psychiatry colleagues. Perhaps overlooked and underappreciated is the importance of clinician empathy and continuity of care during an anesthetic. A factorial trial in 136 ambulatory gynecologic surgery patients evaluated continuity of care (same versus different anesthesiologists conducting the preoperative visit and the anesthetic) and clinician attitude (empathy versus neutral) towards the patient. 75 Maybe not surprisingly, the anesthesiologist’s continuity of care and empathy positively affected patient satisfaction and anxiety. 75 Shared decision-making regarding surgical procedures, recovery plans, and patient goals is associated with greater satisfaction and reduced anxiety in the right population. 76 Sedative medications such as benzodiazepines are frequently administered for anxiolysis preoperatively, but a personalized approach may make pharmacologic interventions unnecessary. Anesthesia care providers should leverage non-traditional techniques to optimize perioperative mental health, as psychological preparation has the ability to improve outcomes. 77 , 78 Perioperative psychological support and education in a cohort of 67 orthopedic surgical adolescents improved functional status, anxiety, and resiliency as assessed via self-report ratings at one year post-surgery. 79 Non-pharmacologic interventions, including music medicine, 80 – 82 mindfulness exercises, 83 brief motivational interviewing, 84 and even medically trained clowns, 85 have shown utility in reducing pre-procedural anxiety. Music therapy is an intervention implemented by a trained music therapist. Alternatively, music medicine, or passive listening to pre-recorded music, represents a lower barrier to initiation via portable devices or in-room television sets and has minimal side effects. A systematic review of 26 trials (N=2,051) evaluating 10 to 60-minute preoperative sessions of pre-recorded music found a moderate reduction in postsurgical anxiety (standardized mean difference −0.60, p<0.0001). 82 In a group of 69 women undergoing pelvic reconstructive surgery, 30 minutes of preoperative music listening reduced perioperative anxiety (−6.69 vs. −1.32; p=0.01) and improved satisfaction ratings six weeks after surgery compared to usual care (p = 0.03). 81 Physiologically, short music listening periods in mechanically ventilated patients reduce subjective anxiety, 86 sedative requirements, 86 and laboratory cortisol levels. 87 In fact, critical care medicine guidelines suggest offering music therapy for both procedural and nonprocedural pain conditions in critically ill adults, albeit with low-quality evidence. 88 As anxiety is a common predictor of acute postoperative pain, 89 the extrapolation of applying “acousticeuticals” to both conditions is relevant. 90 , 91 Another avenue that can be exploited in the perioperative period is the application of virtual reality technologies for education, distraction, and exposure therapy. In adult surgical patients, a prospective randomized clinical trial evaluating an 8-minute immersive virtual reality video tour compared to standard care found that the intervention significantly reduced preoperative anxiety (mean change −5.46, p<0.001) and increased postoperative satisfaction (mean difference 16.07, p<0.001), but did not diminish postoperative pain scores. 92 If available, virtual reality and augmented reality tools can enhance distraction and procedural education for patients with anxiety, but recommendation strength is limited by low-quality evidence and a lack of follow-up analysis. 93 , 94 Other noninvasive neuromodulation techniques, such as repetitive transcranial magnetic and direct current stimulation, constitute an experimental and clinical priority. Transcranial magnetic stimulation was approved by the US Food and Drug Administration in 2008 for the treatment of major depressive disorder in adults who did not respond satisfactorily to prior antidepressants. Since then, numerous devices have been developed for broad-ranging indications such as smoking cessation, obsessive-compulsive disorder, and anxiety comorbid with major depressive disorder. 95 In a network meta-analysis based on 46 randomized controlled trials (N=5,143), electrical current stimulation demonstrated antidepressant efficacy (mean difference −3.30, 95% CI −5.94, −0.73 using the Cornell Scale for Depression in Dementia) in patients with mild cognitive impairment. 96 The long-term therapeutic effects (reduced chronic pain and improved mental health) are theorized to be related to cortical reorganization and synaptic plasticity. 97 However, the currently available clinical data surrounding these modalities remain inconsistent and, as such, require more extensive confirmatory trials before widespread implementation for neuropsychiatric disorders. 98 , 99 Future Directions While many perioperative mental illness interventions are limited by small study sizes, lack of follow-up, and ill-defined terminology or severity, we compiled recommendations based on the evidence discussed ( Table 3 ). Below, we introduce approaches that warrant more research, especially in the context of preoperative and postoperative care. Table 3. Summary of evidence-informed recommendations for perioperative anxiety and depression. Recommendation Category * Recommendation Screening Utilize adaptive tests for improved precision, efficiency, and reduced burden of measurement 121 , 122 , 125 Integrate reliable and feasible screening tools in the electronic health record Increase frequency of sampling by adapting smartphone-based ecological momentary assessments 103 Refer to comprehensive collaborative care plan when screening is positive Prevention Preoperative education about the procedure and expected timeline of recovery Enhance social support 42 Modify illness and pain expectations Multidisciplinary care coordination for mental health therapies Nonpharmacological Interventions Virtual reality-based exposure and distraction 94 Relaxation techniques including mindfulness-based stress reduction Brief cognitive behavioral intervention Physiotherapy techniques (massage and exercise) 96 Music medicine in preoperative and recovery areas 81 , 82 Noninvasive neuromodulation devices Pharmacologic Interventions Continue oral antidepressants through perioperative period Optimize multimodal pain regimen Consider low dose ketamine and nitrous oxide in the context of treatment-resistant depression Research Incorporate mental health variables in multicenter clinical registries and robust prediction models Include mental illness severity when evaluating clinically meaningful outcomes 23 Increase methodological rigor in evaluating psychological interventions Open in a new tab * All recommendations should be considered to have low- to moderate-quality evidence for implementation in the perioperative care of patients with depression and anxiety. The table was modified from tables in: Srifuengfung M, Abraham J, Avidan MS, Lenze EJ: Perioperative anxiety and depression in older adults: epidemiology and treatment. Am J Geriatr Psychiatry 2023;31(11):996–1008 126 and Jin B, Xv Y, Zhang B, Qiao L, Liu H: Comparative efficacy and acceptability of treatments for depressive symptoms in cognitive impairment: A systemic review and Bayesian network meta-analysis. Front Aging Neurosci 2022;14:1037414. 96 Screening Mental illness is common in surgical patients, but it is likely underassessed due to the time-consuming nature of the screening tools that currently exist ( Table 1 ). Although less cumbersome, truncated scales inherently lose reliability. Artificial intelligence is transforming the automatization of screening tools that previously required in-person clinical assessment. For example, machine learning can be applied to previously collected electronic health record data and contextual clues on social media 100 to predict future risk of severe mental illness or suicidal behavior that necessitates early intervention. 101 Using these precision medicine assessments, theoretical “practice” treatments can then be applied to a “perioperative human digital twin” without physical perturbation to conceptualize the individualized treatment paradigm. 102 Apart from future risk prediction, adaptive computerized tests harness item response theory to synthesize diagnostic phenotypes. Specific responses guide the presentation of each subsequent question, resulting in an individualized and targeted approach. Algorithmic tools, such as the computerized adaptive test-mental health (CAT-MH ® ), provide reliability across various measures and do not require a trained interviewer. 28 Indeed, in a sample of 100 patients undergoing elective surgery, the CAT-MH ® permitted quick and precise assessment of mental health disorders, including anxiety and depression, with a median completion time of three minutes. 28 The National Quality Forum explicitly recommends these adaptive tests for optimal preventive care and screening in primary care. Alternatively, the application of smartphone-based ecological momentary assessments can increase the number and frequency of collected data points. This psychological evaluation method continues to gain traction because of its potential to reliably document mental illness fluctuations around the time of surgery. 103 Future refinement of this technology will complement perioperative mental illness identification efforts. Postoperative The recovery period in the hospital is typically a period of relational isolation. The absence of social support was especially noticed during the pandemic when infection mitigation protocols limited visitors. Social isolation predicts depression and other consequences, including cardiovascular risk, increased mortality, and pain. 104 , 105 During a hospital stay, volunteer visitation organizations focused on providing consistent individual care can help move patients beyond recovery siloes. The Hospital Elder Life Program, a multicomponent program to prevent functional and cognitive decline for older people, effectively reduces delirium incidence (odds ratio 0.47; 95% CI 0.37, 0.59) and decreases hospital costs by $1,600–3,800 (2018 US dollars) per patient. 106 From a public health perspective, installing a program that starts in the postoperative recovery room and extends throughout the hospital stay is intuitive. Initiation of de-novo antidepressant medications has mainly been studied in the context of postoperative pain. One study found that preanesthesia to postoperative day six administration of escitalopram (10 milligrams) was superior to placebo for postoperative pain on days two through six in patients with high pain catastrophizing scores undergoing knee arthroplasty. 107 Secondarily, depression scores were lower in patients on the escitalopram regimen, but there was no difference in anxiety scores. 107 Several trials have examined the efficacy of perioperative antidepressant (i.e., duloxetine, venlafaxine, fluradoline) administration on acute and chronic postoperative pain reduction. 108 A meta-analysis of 24 randomized controlled trials with 2,197 surgical patients supports that serotonin-norepinephrine reuptake inhibitors minimally reduce acute and chronic pain 48 hours after surgery (−0.73 points on 10-point visual analog scale; 95% CI −1.22, −0.23) and six months after surgery (−0.95; 95% CI −1.64, −0.25). 109 Generally, lower doses and shorter timeframes are required to realize the analgesic benefits of oral antidepressants, tricyclic agents in particular. 110 Pain, depression, and anxiety are frequently comorbid, explained by common central and peripheral neural pathways that are modulated by antidepressant agents through opioid, histamine, nicotinic, adenosine, 5-hydroxytryptamine, and N -methyl-D-aspartate mechanisms. 111 Starting oral pharmacotherapy in the perioperative period is challenging due to co-occurring medical conditions, unknown chronicity of mental disease after the time-limited stress of the surgical period, and insufficient time to identify the most effective option. The adoption of artificial intelligence-assisted machine learning models for antidepressant treatment response prediction may be able to provide decision support in the near future. 102 , 112 Selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and some antipsychotics predispose to the development of drug-induced hyponatremia from syndrome of inappropriate antidiuretic hormone secretion, especially in the first 2–4 weeks after initiation. 113 This laboratory derangement and other side effects have implications for postsurgical recovery. Given the necessity for monitoring and follow-up when initiating antidepressant pharmacologic therapy, collaboration with primary care and mental health specialists is advised. Postdischarge Besides integrating mental health care into the current perioperative care model while patients are in the hospital, telemedicine facilitates longitudinal follow-up without prohibitive transportation and cost burdens. Similarly, mobile technology can display cognitive training games, problem-solving modules, and daily health tips for mental health. 114 Digital mental health treatments have proven helpful in all depression severity subtypes. 24 However, retention, engagement, and effectiveness have yet to be consistently demonstrated for mobile technology applications. While time, budget, and staffing constraints may limit the feasibility of incorporating virtual postoperative visits with providers in a perioperative clinic, a thoughtful interdisciplinary approach with concomitant pain, mental health, and medical comorbidity management can add value. 47 , 115 Clinical Research There is compelling evidence regarding the societal and individual burden of mental illness, but there is less evidence regarding implementation strategies for prevention and treatment in surgical patients. This gap highlights the need for transdisciplinary treatment approaches that can be adapted to perioperative settings. Historically, individuals diagnosed with a mental illness have constituted an understudied group. For example, from 2002 to 2010, half of the top-cited clinical trials contained psychiatric exclusion criteria. 116 The underrepresentation of patients with a mental illness in perioperative clinical trials is multifactorial; perceived vulnerability, consent capacity, purposive sampling, and statistical power augmentation all likely contribute to this issue. Although sometimes unavoidable, psychiatric exclusion criteria have perpetuated health disparities. Intentionally including patients diagnosed with mental illness in rigorous trials is imperative to generate valid conclusions on how to make effective mental health care a routine part of perioperative care. Conclusion Surgical care encounters allow clinicians to initiate interventions targeted toward treating medical issues unrelated to the procedure. While initiation of treatments for frequently encountered chronic medical conditions is common, perioperative treatment of mental health disorders is still rare. Previous work has shown that undergoing a major surgical procedure can be a catalyst for behavior modification, such as smoking cessation. 117 An opportunity to change health behaviors may be especially significant for patients who are otherwise unlikely or unable to pursue regular care or who may lack trust in their health system. Capitalizing on teachable moments before and after surgery to improve patients’ psychological well-being is part of the innovative “fourth branch of anesthesiology”. 118 , 119 Indeed, managing comorbidities, including depression and anxiety in the perioperative setting may be an underutilized opportunity for improving population health. Funding Statement: This work was supported in part by the Agency for Healthcare Research and Quality (AHRQ) Award Number R01HS027795 (to KB). 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