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How to present patient cases

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• Peer review
• Mary Ni Lochlainn , foundation year 2 doctor 1 ,
• Ibrahim Balogun , healthcare of older people/stroke medicine consultant 1
• 1 East Kent Foundation Trust, UK

A guide on how to structure a case presentation

This article contains...

-History of presenting problem

-Medical and surgical history

-Drugs, including allergies to drugs

-Family history

-Social history

-Review of systems

-Findings on examination, including vital signs and observations

-Differential diagnosis/impression

-Investigations

-Management

Presenting patient cases is a key part of everyday clinical practice. A well delivered presentation has the potential to facilitate patient care and improve efficiency on ward rounds, as well as a means of teaching and assessing clinical competence. 1

The purpose of a case presentation is to communicate your diagnostic reasoning to the listener, so that he or she has a clear picture of the patient’s condition and further management can be planned accordingly. 2 To give a high quality presentation you need to take a thorough history. Consultants make decisions about patient care based on information presented to them by junior members of the team, so the importance of accurately presenting your patient cannot be overemphasised.

As a medical student, you are likely to be asked to present in numerous settings. A formal case presentation may take place at a teaching session or even at a conference or scientific meeting. These presentations are usually thorough and have an accompanying PowerPoint presentation or poster. More often, case presentations take place on the wards or over the phone and tend to be brief, using only memory or short, handwritten notes as an aid.

Everyone has their own presenting style, and the context of the presentation will determine how much detail you need to put in. You should anticipate what information your senior colleagues will need to know about the patient’s history and the care he or she has received since admission, to enable them to make further management decisions. In this article, I use a fictitious case to show how you can structure case presentations, which can be adapted to different clinical and teaching settings (box 1).

Box 1: Structure for presenting patient cases

Presenting problem, history of presenting problem, medical and surgical history.

Drugs, including allergies to drugs

Family history

Social history, review of systems.

Findings on examination, including vital signs and observations

Differential diagnosis/impression

Investigations

Case: tom murphy.

You should start with a sentence that includes the patient’s name, sex (Mr/Ms), age, and presenting symptoms. In your presentation, you may want to include the patient’s main diagnosis if known—for example, “admitted with shortness of breath on a background of COPD [chronic obstructive pulmonary disease].” You should include any additional information that might give the presentation of symptoms further context, such as the patient’s profession, ethnic origin, recent travel, or chronic conditions.

“ Mr Tom Murphy is a 56 year old ex-smoker admitted with sudden onset central crushing chest pain that radiated down his left arm.”

In this section you should expand on the presenting problem. Use the SOCRATES mnemonic to help describe the pain (see box 2). If the patient has multiple problems, describe each in turn, covering one system at a time.

Box 2: SOCRATES—mnemonic for pain

Associations

Time course

Exacerbating/relieving factors

“ The pain started suddenly at 1 pm, when Mr Murphy was at his desk. The pain was dull in nature, and radiated down his left arm. He experienced shortness of breath and felt sweaty and clammy. His colleague phoned an ambulance. He rated the pain 9/10 in severity. In the ambulance he was given GTN [glyceryl trinitrate] spray under the tongue, which relieved the pain to 5/10. The pain lasted 30 minutes in total. No exacerbating factors were noted. Of note: Mr Murphy is an ex-smoker with a 20 pack year history”

Some patients have multiple comorbidities, and the most life threatening conditions should be mentioned first. They can also be categorised by organ system—for example, “has a long history of cardiovascular disease, having had a stroke, two TIAs [transient ischaemic attacks], and previous ACS [acute coronary syndrome].” For some conditions it can be worth stating whether a general practitioner or a specialist manages it, as this gives an indication of its severity.

In a surgical case, colleagues will be interested in exercise tolerance and any comorbidity that could affect the patient’s fitness for surgery and anaesthesia. If the patient has had any previous surgical procedures, mention whether there were any complications or reactions to anaesthesia.

“Mr Murphy has a history of type 2 diabetes, well controlled on metformin. He also has hypertension, managed with ramipril, and gout. Of note: he has no history of ischaemic heart disease (relevant negative) (see box 3).”

Box 3: Relevant negatives

Mention any relevant negatives that will help narrow down the differential diagnosis or could be important in the management of the patient, 3 such as any risk factors you know for the condition and any associations that you are aware of. For example, if the differential diagnosis includes a condition that you know can be hereditary, a relevant negative could be the lack of a family history. If the differential diagnosis includes cardiovascular disease, mention the cardiovascular risk factors such as body mass index, smoking, and high cholesterol.

Highlight any recent changes to the patient’s drugs because these could be a factor in the presenting problem. Mention any allergies to drugs or the patient’s non-compliance to a previously prescribed drug regimen.

To link the medical history and the drugs you might comment on them together, either here or in the medical history. “Mrs Walsh’s drugs include regular azathioprine for her rheumatoid arthritis.”Or, “His regular drugs are ramipril 5 mg once a day, metformin 1g three times a day, and allopurinol 200 mg once a day. He has no known drug allergies.”

If the family history is unrelated to the presenting problem, it is sufficient to say “no relevant family history noted.” For hereditary conditions more detail is needed.

“ Mr Murphy’s father experienced a fatal myocardial infarction aged 50.”

Social history should include the patient’s occupation; their smoking, alcohol, and illicit drug status; who they live with; their relationship status; and their sexual history, baseline mobility, and travel history. In an older patient, more detail is usually required, including whether or not they have carers, how often the carers help, and if they need to use walking aids.

“He works as an accountant and is an ex-smoker since five years ago with a 20 pack year history. He drinks about 14 units of alcohol a week. He denies any illicit drug use. He lives with his wife in a two storey house and is independent in all activities of daily living.”

Do not dwell on this section. If something comes up that is relevant to the presenting problem, it should be mentioned in the history of the presenting problem rather than here.

“Systems review showed long standing occasional lower back pain, responsive to paracetamol.”

Findings on examination

Initially, it can be useful to practise presenting the full examination to make sure you don’t leave anything out, but it is rare that you would need to present all the normal findings. Instead, focus on the most important main findings and any abnormalities.

“On examination the patient was comfortable at rest, heart sounds one and two were heard with no additional murmurs, heaves, or thrills. Jugular venous pressure was not raised. No peripheral oedema was noted and calves were soft and non-tender. Chest was clear on auscultation. Abdomen was soft and non-tender and normal bowel sounds were heard. GCS [Glasgow coma scale] was 15, pupils were equal and reactive to light [PEARL], cranial nerves 1-12 were intact, and he was moving all four limbs. Observations showed an early warning score of 1 for a tachycardia of 105 beats/ min. Blood pressure was 150/90 mm Hg, respiratory rate 18 breaths/min, saturations were 98% on room air, and he was apyrexial with a temperature of 36.8 ºC.”

Differential diagnoses

Mentioning one or two of the most likely diagnoses is sufficient. A useful phrase you can use is, “I would like to rule out,” especially when you suspect a more serious cause is in the differential diagnosis. “History and examination were in keeping with diverticular disease; however, I would like to rule out colorectal cancer in this patient.”

Remember common things are common, so try not to mention rare conditions first. Sometimes it is acceptable to report investigations you would do first, and then base your differential diagnosis on what the history and investigation findings tell you.

“My impression is acute coronary syndrome. The differential diagnosis includes other cardiovascular causes such as acute pericarditis, myocarditis, aortic stenosis, aortic dissection, and pulmonary embolism. Possible respiratory causes include pneumonia or pneumothorax. Gastrointestinal causes include oesophageal spasm, oesophagitis, gastro-oesophageal reflux disease, gastritis, cholecystitis, and acute pancreatitis. I would also consider a musculoskeletal cause for the pain.”

This section can include a summary of the investigations already performed and further investigations that you would like to request. “On the basis of these differentials, I would like to carry out the following investigations: 12 lead electrocardiography and blood tests, including full blood count, urea and electrolytes, clotting screen, troponin levels, lipid profile, and glycated haemoglobin levels. I would also book a chest radiograph and check the patient’s point of care blood glucose level.”

You should consider recommending investigations in a structured way, prioritising them by how long they take to perform and how easy it is to get them done and how long it takes for the results to come back. Put the quickest and easiest first: so bedside tests, electrocardiography, followed by blood tests, plain radiology, then special tests. You should always be able to explain why you would like to request a test. Mention the patient’s baseline test values if they are available, especially if the patient has a chronic condition—for example, give the patient’s creatinine levels if he or she has chronic kidney disease This shows the change over time and indicates the severity of the patient’s current condition.

“To further investigate these differentials, 12 lead electrocardiography was carried out, which showed ST segment depression in the anterior leads. Results of laboratory tests showed an initial troponin level of 85 µg/L, which increased to 1250 µg/L when repeated at six hours. Blood test results showed raised total cholesterol at 7.6 mmol /L and nil else. A chest radiograph showed clear lung fields. Blood glucose level was 6.3 mmol/L; a glycated haemoglobin test result is pending.”

Dependent on the case, you may need to describe the management plan so far or what further management you would recommend.“My management plan for this patient includes ACS [acute coronary syndrome] protocol, echocardiography, cardiology review, and treatment with high dose statins. If you are unsure what the management should be, you should say that you would discuss further with senior colleagues and the patient. At this point, check to see if there is a treatment escalation plan or a “do not attempt to resuscitate” order in place.

“Mr Murphy was given ACS protocol in the emergency department. An echocardiogram has been requested and he has been discussed with cardiology, who are going to come and see him. He has also been started on atorvastatin 80 mg nightly. Mr Murphy and his family are happy with this plan.”

The summary can be a concise recap of what you have presented beforehand or it can sometimes form a standalone presentation. Pick out salient points, such as positive findings—but also draw conclusions from what you highlight. Finish with a brief synopsis of the current situation (“currently pain free”) and next step (“awaiting cardiology review”). Do not trail off at the end, and state the diagnosis if you are confident you know what it is. If you are not sure what the diagnosis is then communicate this uncertainty and do not pretend to be more confident than you are. When possible, you should include the patient’s thoughts about the diagnosis, how they are feeling generally, and if they are happy with the management plan.

“In summary, Mr Murphy is a 56 year old man admitted with central crushing chest pain, radiating down his left arm, of 30 minutes’ duration. His cardiac risk factors include 20 pack year smoking history, positive family history, type 2 diabetes, and hypertension. Examination was normal other than tachycardia. However, 12 lead electrocardiography showed ST segment depression in the anterior leads and troponin rise from 85 to 250 µg/L. Acute coronary syndrome protocol was initiated and a diagnosis of NSTEMI [non-ST elevation myocardial infarction] was made. Mr Murphy is currently pain free and awaiting cardiology review.”

Originally published as: Student BMJ 2017;25:i4406

Competing interests: None declared.

Provenance and peer review: Not commissioned; externally peer reviewed

• ↵ Green EH, Durning SJ, DeCherrie L, Fagan MJ, Sharpe B, Hershman W. Expectations for oral case presentations for clinical clerks: opinions of internal medicine clerkship directors. J Gen Intern Med 2009 ; 24 : 370 - 3 . doi:10.1007/s11606-008-0900-x   pmid:19139965 . OpenUrl CrossRef PubMed Web of Science
• ↵ Olaitan A, Okunade O, Corne J. How to present clinical cases. Student BMJ 2010;18:c1539.
• ↵ Gaillard F. The secret art of relevant negatives, Radiopedia 2016; http://radiopaedia.org/blog/the-secret-art-of-relevant-negatives .

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• Page 1 of 3

• Introduction
• Conclusions
• Article Information

Flowchart shows sample sizes and corresponding rates of depression screening and management in our study population for the most recent fiscal year. Sample sizes and rates shown in the text differ and reflect observations aggregated from all 4 study years.

a Refers to the 1-year prospective time frame when numbers were obtained.

b Refers to the 6-month retrospective time frame when numbers were obtained.

eTable 1.  ICD-10 Codes Used for Depression Diagnosis

eTable 2. List of Drugs Classified as Antidepressant Medication in Study

eTable 3. Current Procedural Terminology (CPT) Codes for Psychotherapy

eTable 4. VA Clinic Stop Codes for Mental Health Specialty Visits

eTable 5.  ICD-10 Codes Used for Other Mental Health Diagnoses in Study

eTable 6. Associations Between Receipt of Timely Depression Follow-up and Treatment and Various Patient Characteristics (Among All Screen-Positive Patients)

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Leung LB , Chu K , Rose D, et al. Electronic Population-Based Depression Detection and Management Through Universal Screening in the Veterans Health Administration. JAMA Netw Open. 2022;5(3):e221875. doi:10.1001/jamanetworkopen.2022.1875

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Electronic Population-Based Depression Detection and Management Through Universal Screening in the Veterans Health Administration

• 1 Center for the Study of Healthcare Innovation, Implementation, and Policy, VA Greater Los Angeles Healthcare System, Los Angeles, California
• 2 Division of General Internal Medicine and Health Services Research, UCLA David Geffen School of Medicine, Los Angeles, California
• 3 VA Ann Arbor, Center for Clinical Management Research, Ann Arbor, Michigan
• 4 Department of Medicine, University of Michigan Medical School, Ann Arbor
• 5 Department of Psychiatry and Biobehavioral Sciences, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California
• 6 RAND Corporation, Santa Monica, California

Question   Among health care systems that implement universal depression screening, do patients who screen positive for depression receive timely follow-up and treatment?

Findings   In a cohort study of 607 730 patients at 82 Veterans Health Administration primary care clinics from 2015 to 2019, 15 155 patients newly screened positive on the 2-item Patient Health Questionnaire and also were detected by clinicians as having depression; 77% met guidelines for completing at least minimal treatment in 1 year, but only 32% received clinical follow-up within 3 months of screening.

Meaning   These findings suggest that screening paired with integrated services offers a reasonable opportunity to engage primary care patients in depression treatment, supporting collaborative care’s extensive evidence base; yet, access to timely services remains limited.

Importance   In 2016, the US Preventive Services Task Force newly recommended universal screening for depression, with the expectation that screening would be associated with appropriate treatment. Few studies have been able to assess the population-based trajectory from screening to receipt of follow-up and treatment for individuals with depression.

Objective   To examine adherence to guidelines for follow-up and treatment among primary care patients who newly screened positive for depression in the Veterans Health Administration (VA).

Design, Setting, and Participants   This retrospective cohort study used VA electronic data to identify patients who newly screened positive for depression on the 2-item Patient Health Questionnaire at 82 primary care VA clinics in California, Arizona, and New Mexico between October 1, 2015, and September 30, 2019. Data analysis was performed from December 2020 to August 2021.

Main Outcomes and Measures   Receipt of guideline-concordant care for screen-positive patients who were determined by clinicians as having depression was assessed. Timely follow-up (within 84 days of screening) was defined as receiving 3 or more mental health specialty visits, 3 or more psychotherapy visits, or 3 or more primary care visits with a depression diagnosis according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision . Completing at least minimal treatment (within 12 months) was defined as having 60 days or more of antidepressant prescriptions filled, 4 or more mental health specialty visits, or 3 or more psychotherapy visits.

Results   The final cohort included 607 730 veterans (mean [SD] age, 59.4 [18.2] years; 546 516 men [89.9%]; 339 811 non-Hispanic White [55.9%]); 8%, or 82 998 of 997 185 person-years, newly screened positive for depression. Clinicians identified fewer than half with depression (15 155 patients), of whom 32% (5034 of 15 650 person-years) met treatment guidelines for timely follow-up and 77% (12 026 of 15 650 person-years) completed at least minimal treatment. Younger age (odds ratio, 0.990; 95% CI, 0.986-0.993; P  < .001), Black race (odds ratio, 1.19; 95% CI, CI 1.05-1.34; P  = .01), and having comorbid psychiatric diagnoses were significantly associated with timely follow-up. Individual quality metric components (eg, medication or psychotherapy) were associated differently with overall quality results among patient groups, except for age.

Conclusions and Relevance   In this cohort study, most patients met the guidelines for completing at least minimal treatment, but only a minority received timely follow-up after screening positive and being identified as having depression. More research is needed to understand whether the discrepancy between patients who screened positive and patients identified as having depression reflects a gap in recognition of needed care.

Major depressive disorder is the leading cause of disability worldwide. 1 In 2016, the US Preventive Services Task Force (USPSTF) newly recommended universal depression screening in the general adult population, with the expectation that screening would be linked to appropriate treatment. 2 USPSTF recognized that staff-assisted depression care directed at ensuring accurate diagnosis, appropriate follow-up, and effective treatment conferred substantial improvement in clinical outcomes and was increasingly available in primary care settings. Yet, others have disagreed 3 and cited that evidence supporting the benefits of universal depression screening is too limited. For example, 4 2013 guidelines from the Canadian Task Force on Preventive Health Care recommended against routine depression screening to avoid depression overdiagnosis. Knowledge gaps in depression screening remain because few health care systems have been able to pragmatically study the population-based trajectory from screening to follow-up and treatment for those who have depression.

For more than 2 decades, the Veterans Health Administration (VA) has mandated annual depression screening in primary care 5 and currently achieves nearly universal screening rates among clinics nationally. 6 Primary care nurses conduct initial screening; then, primary care clinicians follow up with patients who screen positive for confirmation and treatment of depression. Primary care mental health integration teams also provide diagnostic support and collaboratively treat mental and behavioral health conditions, with a focus on mild-to-moderate severity depression and anxiety. 7 Primary care mental health integration teams (eg, psychologists, psychiatrists, and nurse care managers) are readily available in person or virtually throughout primary care clinics nationally, in addition to more intensive services provided through traditional mental health specialty referrals. The VA system is thereby equipped to address patients who are identified as having mental health needs, especially those with clinical depression.

In the US, there is an increasing call for depression to be addressed at the population level and for its detection and management to be done through public health approaches. 8 Other health care systems similarly embarking on guideline-concordant depression care (via screening, follow-up, and treatment) may benefit from anticipatory guidance on the volume of positive screens and treatment seekers within a primary care population. We use a new method to generate electronic population-based depression care quality measures to add to the limited evidence base on patient outcomes from universal depression screening. This cohort study aims to examine adherence to guidelines for follow-up and treatment among primary care patients who newly screened positive for depression in the VA.

The VA Greater Los Angeles institutional review board approved this study. Because the evaluation efforts were part of an ongoing quality improvement effort at the VA, the institutional review board deemed this study to be nonhuman participants research and, therefore, exempt from informed consent requirements. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.

In a retrospective cohort study, we identified primary care patients among 82 clinics in 1 VA region between October 1, 2015, and September 30, 2019, using VA electronic data. Patient data were drawn from 11 hospital-based and 71 community-based VA clinics in Southern California, Arizona, and New Mexico that administered depression screening via the 2-item Patient Health Questionnaire.

This study expanded on recognized depression care quality metrics 9 by newly incorporating depression screening data using administrative and pharmacy databases from VA’s Corporate Data Warehouse. First, we identified 71 421 patients who screened positive for depression in primary care clinics by scoring 3 or higher on the 2-item Patient Health Questionnaire. Second, we restricted the cohort to patients who visited the same primary care site at least 1 additional time, allowing opportunity for clinical intervention. Third, to isolate patients with a new episode of depression, we further restricted the cohort to those who had not already received a diagnosis of depression (ie, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] depression diagnosis) or engaged in mental health care (ie, ≥60 days of antidepressant prescriptions, ≥4 mental health specialty visits, or ≥3 psychotherapy visits) (eTable 1, eTable 2, eTable 3, and eTable 4 in the Supplement ) within the past 6 months. Among our cohort who screened positive and met the aforementioned criteria, we further identified patients who were also detected by a clinician as having depression via diagnostic coding or antidepressant prescription within 12 months of screening positive ( Figure 1 shows data for fiscal year 2019).

Our 3 study outcomes were population-based depression care quality metrics established and detailed in prior research. 9 Measures were constructed on the basis of VA and National Committee for Quality Assurance guidelines and then were agreed on by a modified Delphi panel of VA and non-VA experts. We used 2 measures of timely follow-up, defined as 3 or more mental health specialty visits, 3 or more psychotherapy visits, or 3 or more primary care visits with a depression ICD-10 diagnosis within (1) 84 days and (2) 180 days. Also, we measured completion of at least minimally appropriate treatment (ie, having ≥60 days of antidepressant prescriptions, ≥4 mental health specialty visits, or ≥3 psychotherapy visits within 12 months of screening positive). Prescriptions with subtherapeutic doses and with nondepression indications (or keywords written on the dosing instructions) were excluded as antidepressant medications. We dichotomized outcomes as patients either having received or not received guideline-concordant depression care in each study year.

This study comprehensively examined available patient and clinic characteristics known or hypothesized to be associated with depression care quality. Data sources included VA’s Corporate Data Warehouse, National Patient Care Database, Vital Status File, and Site Tracking System. Patient covariates consisted of age, sex, self-reported race and ethnicity (ie, non-Hispanic White, non-Hispanic Black, Hispanic, other [American Indian or Alaska Native, Asian, and Native Hawaiian or other Pacific Islander], or unknown or missing), marital status, and income proxies (because patients may be eligible for VA care on the basis of a service-connected disability or exempt from copayment on the basis of having low financial means). Race and ethnicity were assessed in this study because disparities in mental health treatment by racial and ethnic group have been reported. 10 We used ICD-10 codes in outpatient and inpatient visits to identify mental health diagnoses (ie, depression, anxiety, posttraumatic stress disorder [PTSD], alcohol and substance use disorders, and serious mental illness [specifically, schizophrenia and bipolar disorder]) (eTable 5 in the Supplement ) and to calculate Charlson Comorbidity Index scores to risk-adjust physical health for each patient during each study year. Finally, we adjusted for whether patients’ assigned clinics were community-based vs hospital-based, rural vs urban location, and 5000 or more vs fewer assigned primary care patients (as a proxy for clinic size).

For descriptive purposes, we calculated unadjusted, aggregate rates of achieving depression care quality measures across our cohort and then examined patient and clinic characteristics for (1) screen-positive patients and (2) screen-positive patients who were also detected by clinicians as having depression, using t and χ 2 tests. We analyzed patient and clinic characteristics among those who met and did not meet depression care quality outcome measures, using χ 2 tests.

This study used multilevel regression models to examine for associations between depression care quality and the aforementioned patient and clinic characteristics among all study patients. We included year and health care system fixed effects to account for secular trends and invariant organizational characteristics. Patient random effects were included to account for the possibility of patients having multiple nonindependent observations during the 4 study years. SEs were also adjusted to account for clustering of patients within clinics. Given the dichotomous distributions of our quality outcomes, we reported odds ratios (ORs) and 95% CIs from multilevel logistic regressions in adjusted models. Estimates were also presented as probabilities (and SEs were calculated via the delta method), with all covariates held constant at their means. In additional analyses, we examined the contribution of each quality metric component (eg, counts of antidepressant prescriptions and psychotherapy visits) and reported incidence rate ratios (IRRs) and 95% CIs from multilevel negative binomial regression models. Finally, sensitivity analyses were conducted to examine for interactions between patient demographic characteristics (eg, age, sex, race, and ethnicity) and between demographic and clinic variables (eg, rurality, hospital-based vs community-based), to account for known demographic differences among veterans across age groups and clinic locations. For all models, we determined significance by using a 2-tailed α = .05. Data were analyzed in Stata statistical software version 15.1 (StataCorp). Data analysis was performed from December 2020 to August 2021.

Our study included 607 730 veterans (mean [SD] age, 59.4 [18.2] years; 546 516 men [89.9%]; 339 811 non-Hispanic White [55.9%]). Approximately 8% (82 998 of 997 185 person-years, or 71 421 patients) screened positive for new depressive symptoms in VA primary care. Among those who screened positive, 80% (66 305 of 82 998 person-years, or 57 779 patients) continued to receive primary care services that year in the same site, allowing opportunities for clinical intervention. Among those, 56% (37 063 of 66 305 person-years) had not already engaged in mental health care (within the past 6 months). We then examined the remaining 33 694 patients who newly screened positive for depression in our study cohort and noted several patient (ie, age, race, ethnicity, and comorbid conditions) and clinic characteristics to be significantly associated with depression care quality ( Table 1 and eTable 6 in the Supplement ).

However, fewer than one-half of screen-positive patients were detected by clinicians as having depression via diagnosis and/or antidepressant prescription (15 155 patients). When clinicians detected depression among patients who screened positive, 32% (5034 of 15 650 person-years) met treatment guidelines for appropriate timely follow-up by receiving 3 or more mental health specialty visits, 3 or more psychotherapy visits, or 3 or more primary care visits with a depression ICD-10 diagnosis within 84 days of screening; 77% (12 026 of 15 650 person-years) completed at least minimally appropriate treatment by having 60 days or more of antidepressant prescriptions filled, 4 or more mental health specialty visits, or 3 or more psychotherapy visits within 12 months of screening. Figure 1 shows data for fiscal year 2019. Percentages were stable across all 4 study years at the VA ( Figure 2 ).

Certain patient characteristics remained significantly associated with depression care quality among screen-positive patients who were also detected by clinicians as having depression ( Table 2 ). Younger age (OR for receiving treatment, 0.990; 95% CI, 0.986-0.993; P  < .001) and comorbid mental illness were factors significantly associated with higher depression care quality. Probabilities for timely follow-up were 33% among patients younger than 45 years and 21% among patients older than 75 years; probabilities for receiving treatment were 81% among the younger patients and 71% among the older patients. Mental health comorbidities were important factors associated with high-quality depression care; as an example, probabilities for timely follow-up were 38% among patients with PTSD and 24% for patients without PTSD, probabilities for receiving treatment were 85% among those with PTSD and 72% among those without PTSD. Although having physical health comorbidities was not associated with receipt of treatment, it was an important factor associated with not receiving timely follow-up (OR, 0.80; 95% CI, 0.70-0.90; P  < .001), with probabilities of 12% for Charlson Comorbidity Index scores of 2 or higher vs 14% for Charlson Comorbidity Index scores of 0. Black race was significantly associated with higher odds of timely follow-up vs White race (OR, 1.19; 95% CI, 1.05-1.34; P  = .01), but race was not otherwise associated with treatment completion. When controlling for all covariates at their means, probabilities for follow-up among Black and White patients were 32% and 29%, respectively.

Each quality metric component (eg, antidepressant treatment, psychotherapy visits), appeared to contribute differently among patient groups, apart from age. Among patients with and without mental health comorbidities, results were similar across quality metric components, except PTSD. Among patients with and without PTSD, we found that mental health specialty (IRR, 1.18; 95% CI, 1.10-1.27; P  < .001) and psychotherapy visits (IRR, 1.63; 95% CI, 1.52-1.75; P  < .001) were associated with higher rates of timely follow-up; there was no difference in primary care visits. Similarly, among patients with Charlson Comorbidity Index score of 2 or higher vs those with a score of 0, we observed lower rates of timely follow-up through mental health specialty (IRR, 0.89; 95% CI, 0.81-0.99; P  = .04) and psychotherapy visits (IRR, 0.86; 95% CI, 0.77-0.97; P  = .01); there was no difference in primary care visits. For Black veterans compared with White veterans, greater use of mental health specialty care (IRR, 1.12; 95% CI, 1.02-1.23; P  = .01) was associated with differences in timely follow-up. Although we did not see racial or ethnic differences in overall rates of treatment completion, we saw differences in use of different treatment types between White veterans and those from minority groups. Black veterans (IRR, 0.8; 95% CI, 0.76-0.86; P  < .001) and Hispanic veterans (IRR, 0.88; 95% CI, 0.76-0.93; P  < .001) had lower rates of treatment with antidepressant medication but had higher rates of mental health specialty visits (Black veterans, IRR, 1.18; 95% CI, 1.1-1.27; P  < .001) and psychotherapy visits (Hispanic veterans, IRR, 1.11; 95% CI, 1.02-1.20; P  = .01), compared with White veterans. Although no sex differences were observed among quality metrics, we noted that of individual metric components, primary care visits with a depression ICD-10 diagnosis were significantly more likely for women (IRR, 1.82; 95% CI, 1.44-2.31; P  < .001) than men. Finally, no significant interactions were identified among tested patient demographic and clinic variables in sensitivity analyses.

The VA has invested heavily in screening as an important part of the pathway for patients to initiate and access mental health treatment, 11 allowing us to assess results of a primary care population receiving USPSTF guideline-concordant depression care. 2 For some researchers, without more data, routine use of depression screening in medical settings remains controversial. 3 , 4 In the absence of randomized clinical trials, our large observational cohort study attempts to fill knowledge gaps surrounding systemwide implementation of depression screening. We found that 8% of patients screened positive among primary care populations in our integrated VA health care system, but clinicians identified fewer than one-half of screen-positive patients as having depression. Those who were not detected as having depression are likely an unknown mix of patients who were appropriately assessed and were found to not meet the criteria for a depression diagnosis (desired care process) and patients who were never appropriately assessed or assessed with no diagnosis recorded (undesired care process). More research is needed to understand whether this indicates a gap in recognition of needed care or overdetection from universal screening in the VA.

Although most patients with depression met guidelines for completing treatment within a year of screening positive, only a minority received timely clinical follow-up within 3 to 6 months. Trends did not improve over time for the approximately two-thirds and one-half of screen-positive patients who were detected by clinicians as having depression and did not receive follow-up visits within 3 to 6 months. Across all years, approximately one-quarter of these patients did not receive at least minimal treatment within 1 year. As a system that aims to lead in care of PTSD (a common comorbidity to depression) 12 and to prioritize suicide prevention (for which depression is a major risk factor), 13 improving timeliness of follow-up and treatment after a positive depression screen remains necessary in the VA. Similarly, other health care systems have struggled and cited that only 36% of patients with newly diagnosed depression even start medication and/or complete 1 psychotherapy visit during the first 3 months. 14 Nonetheless, screening paired with accessible mental health services generally offered reasonable opportunity to engage VA primary care patients in treatment, supporting the extensive evidence base for collaborative care of depression. 15

This study also highlights notable differences in depression care quality between patient groups. We found that timely follow-up and treatment continued to lag for geriatric patients 16 and those with chronic physical health comorbidities, 17 likely related to competing demands such as specialty care. Patients who had comorbid mental health conditions, however, fared well in the receipt of high-quality depression care, as noted before, 18 likely a testament to VA-specific services for those with PTSD or serious mental illness (eg, Mental Health Intensive Case Management). 19 In a male-dominated health system, we again noted sex differences in mental health care access, seemingly occurring preferentially for women through primary care services. 20 Although some disparities between patient groups have been remedied by an integrated health system that prioritizes mental health care accessibility, efforts to improve the timeliness of care after a positive depression screen and treatment of geriatric patients and patients with physical health comorbidities remain necessary.

A new and noteworthy observation pertains to the absence of and possible reversal of oft-seen racial disparities in overall mental health care access across health care systems. Although it was again noted that Black veterans were treated with antidepressant medication at lower rates than White veterans, 10 we did not see racial disparities in overall rates of treatment completion when we fully accounted for veterans who chose to seek nonmedication treatment through mental health specialty care. The VA has striven for increasing accessibility of psychotherapy as part of integrated primary care teams, 7 which is the treatment modality that is preferred by patients, especially those in racial and ethnic minority groups. 21 Such systemwide changes may have resulted in previously documented racial and ethnic disparities in guideline-concordant depression treatment 10 to seemingly be eliminated in the VA. Depression is often underdetected and undertreated among minoritized groups in the US. 22 This study continues to support that systematic quality improvement of screening and treatment are potential tools to mitigate racial and ethnic disparities in mental health care. 23

To our knowledge, this study is one of the first to examine timely follow-up and treatment for primary care patients who screen positive for depression in an integrated health care system, but several limitations are worth noting. First, because we leveraged existing electronic databases, we were unable to investigate patient-reported quality outcomes, such as depression symptoms or quality of life. Second, our study excluded fewer than 20% of patients who did not return for primary care after screening. Our study cohort was designed to assess care quality for patients who had the opportunity to receive continuity primary care. Focusing on patients who drop out of VA care, often because they have had an acute problem when traveling, are switching VA clinics, or are seeking non-VA care, requires a different study approach and lead to different implications than were the case for this study. Third, similar to other studies based on administrative data, coding inaccuracies (eg, inactive depression diagnoses being incorrectly recoded, possible discrepancies related to antidepressant prescriptions without listed indications) may be limitations. Fourth, although the results may not be generalizable beyond our study population of mostly male veterans in 1 VA region, prior studies show that the large majority of mental health services are delivered to veterans by the VA. 24

With increasing recognition of population-level impacts of mental health disorders, an epidemiological framework for mapping access to care for patients who screen positive for depression in VA primary care is methodologically crucial. In the VA, we observed that universal screening yields a stable proportion of patients who screen positive for depression, of whom the minority receive timely follow-up but the majority receive guideline-concordant treatment. Although the VA’s investments in depression screening and subsequent follow-up care and treatment have seemingly closed some disparity gaps (in mental health comorbidities and race), several others remain (in age and in physical health comorbidities). Continued research in mapping access to care pathways for patients who screen positive for depression is needed to ultimately improve upon patient health outcomes for VA and other health care systems.

Accepted for Publication: January 23, 2022.

Published: March 10, 2022. doi:10.1001/jamanetworkopen.2022.1875

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2022 Leung LB et al. JAMA Network Open .

Corresponding Author: Lucinda B. Leung, MD, PhD, Center for the Study of Healthcare Innovation, Implementation, and Policy, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd (111G), Los Angeles, CA 90073 ( [email protected] ).

Author Contributions: Dr Leung and Ms Chu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Leung, Wells, Rubenstein.

Acquisition, analysis, or interpretation of data: Leung, Chu, Rose, Stockdale, Post.

Drafting of the manuscript: Leung, Rubenstein.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Leung, Chu, Rose.

Obtained funding: Leung, Stockdale.

Administrative, technical, or material support: Leung, Chu, Post, Wells.

Supervision: Leung, Stockdale, Wells, Rubenstein.

Conflict of Interest Disclosures: Dr Rubenstein reported receiving nonfinancial support from the Department of Veterans Affairs (VA) during the conduct of the study. No other disclosures were reported.

Funding/Support: Dr Leung is supported by Career Development Award IK2 HX002867 from the VA Health Services Research and Development Service.

Role of Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the VA or the US government. This work was undertaken as part of the Veterans Health Administration’s Primary Care Analytics Team (Seattle, Washington), supporting and evaluating the VA’s transition to a patient-centered medical home. Funding for the Primary Care Analytics Team is provided by the VA Office of Primary Care (Washington, DC).

Additional Contributions: Michael McClean, BA (VA Greater Los Angeles Healthcare System), assisted with data management, and Jessica Severin, BA (VA Greater Los Angeles Healthcare System), assisted with manuscript preparation. Neither of them was compensated for this work beyond their normal salaries.

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A Case Study on Polypharmacy and Depression in a 75-Year-Old Woman with Visual Deficits and Charles Bonnet Syndrome

José caamaño-ponte.

1 Grupo de Investigación Dependencia, Gerontología, y Geriatría, Universidade Santiago de Compostela, 15782 Santiago de Compostela, Spain; moc.liamtoh@sojamaac

Martina Gómez Digón

2 Servicio Enfermería EOXI Lugo, 27003 Lugo, Spain; moc.liamg@42anittram

Mercedes Pereira Pía

3 Servicio Farmacia EOXI Lugo, 27003 Lugo, Spain; [email protected] (M.P.P.); [email protected] (A.d.l.I.C.)

Antonio de la Iglesia Cabezudo

Margarita echevarría canoura.

4 Sanitas Hospitales A Coruña, 15005 A Coruna, Spain; se.satinas@cairravehcem

David Facal

5 Departamento de Psicología Evolutiva y de la Educación, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain

Associated Data

The data presented in this study can be requested to the corresponding author. The data are not publicly available due to confidentiality and anonymity.

Depression is one of the most prevalent pathologies in older adults. Its diagnosis and treatment are complex due to different factors that intervene in its development and progression, including intercurrent organic diseases, perceptual deficits, use of drugs, and psycho-social conditions associated with the aging process. We present the case of a 75-year-old woman (who lives in the community) with a diagnosis of major depression with more than 10 years of history, analyzing her evolution and therapeutic approach.

1. Introduction

Depressive disorders are the most common psychiatric pathology in old adulthood. It is associated with various mental and biological stressors that affect the functional capacity and independence of old adults, reducing their quality of life. International studies show variable prevalences that range between 8.8% and 23.6% in Europe [ 1 , 2 ], could reach 60% in Latin America, and would exceed 38% in rural Asian populations. This geographical variability is due to methodological, clinical, and sociocultural differences. Recent studies in Spain inform that up to 36% of older people living in urban areas in the community suffer from depression [ 3 , 4 , 5 ]. Depression seems to be more frequent in the female sex. However, this observation could be biased because women present a greater longevity and/or a greater tendency to go to medical services than men, whereas men present a more severe somatic expression of psychiatric symptoms and/or a higher reluctance to express psychiatric symptoms than women [ 6 ].

Depressive symptoms include affective disorders such as sadness, apathy, emotional lability and crying, anhedonia, and nihilism; behavior modifications such as anxiety, irritability, insomnia, and hyporexia; and alterations in the course and content of thought, as well as cognitive and physical frailty. Among all the symptoms, autolytic ideation requires a specific comment, since depression is the main suicide risk factor in old age. Suicide constitutes one of the 10 main causes of death in the old adults, mainly in men aged 65 and over who use more lethal methods conditioned by loneliness and isolation [ 7 , 8 ]. In old populations, the etiology of depression is multifactorial: there are psychosocial causes derived from the aging process (family losses, work life, loneliness, environmental barriers, lack of resources, lack of social support) in addition to genetic and biological factors that contribute to the increase in frailty, geriatric syndromes, and dependency [ 9 , 10 ].

Its diagnosis is clinical, following the criteria included in the International Classification of Diseases (ICD-10) or the Diagnostic and Statistical Manual of Mental Disorders (DSM-5, APA 2014). In old adults, the diagnosis can be complex due to comorbidity and drugs that potentially induce psychiatric symptoms and iatrogenic complications, to adaptive disorders following age-related changes and/or to incipient cognitive impaiments. In any case, it can be an underdiagnosed disease due to circumstances related to its own nature, personality factors, and, also, because of the peculiarities of the healthcare systems [ 11 ].

To optimize its treatment, a transdisciplinary approach is required based on antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SSNRIs), which have shown different therapeutic efficacy. It may also require, in many cases, mood stabilizers, anxiolytics, antipsychotics, tricyclic antidepressants (TCAs), or monoamine oxidase inhibitors (MAOIs) [ 12 , 13 , 14 ], plus psychosocial approaches (cognitive-behavioral psychotherapy, supportive psychotherapy), occupational techniques (re-education in activities of daily living, training in the use of technical aids), and physical training, which help to improve the prognosis and prevent relapses [ 15 ].

Within the different age-related conditions that can interfire with the diagnosis of depression in old age, Charles Bonnet syndrome is characterized by the presence of complex visual hallucinations, triggered by vision deprivation in the absence of neurological, psychiatric, and/or systemic disorders. The patient usually perceives the hallucinations as not real, which reduces anxiety, although the content, duration, and frequency are variable. Charles Bonnet syndrome can be associated with age-related entities such as enucleation, optic neuritis, diabetic retinopathy, macular degeneration, cataracts, and glaucoma, among others. Accordingly, its prevalence is relatively high in geriatric patients. In patients with major depression, a differential diagnosis with psychotic disorders is required [ 16 , 17 ].

The main objective of the study has been to facilitate deliberation on the frequent interrelation between organic pathologies, depressive symptomatology, and their overlap in time in old patients, as well as to present the heterodox therapeutic approach in this case, taking into account the complexity of the health care model of the Autonomous Community of Galicia (northwest Spain) and the patient’s therapeutic choices.

2.1. Personal History

A 75-year-old woman, who is right-handed, and a resident of the urban area of the province of A Coruña (Galicia, NW of Spain). She is married and has two children (one female and one male) and two male grandchildren. She lives with her husband (74 years old), who provides care support for the patient’s visual deficits. A medium education of schooling is possessed, along with an administrative profession and adequate social resources.

2.2. Ethical Standards

The study was conducted in accordance with the “Request for authorization for access and publication of health data as clinical case/case series” as provided in the General Data Protection Regulation (EU Regulation 2016/679 of the European Parliament and of the Council, 27 April 2016) and the Spanish regulations on personal data protection in force. Written informed consent was obtained from the participant. Due to visual deficits in the patient, the informed consent was read aloud and supervised by the caregiver.

2.3. Medical History

According to medical records, during this study the patient presented hypothyroidism, dyslipidemia, type II diabetes mellitus, macular degeneration, glaucoma, arterial hypertension, hypertensive heart disease, ChadsVasc4 persistent atrial fibrillation, extensive calcification of the mitral annulus, mild mitral regurgitation, moderate tricuspid regurgitation, lacunar stroke, vertigo, peripheral vascular disease, bronchial asthma, and acute bronchitis progressively diagnosed. The patient demonstrates no toxic habits.

The patient has been followed by the family medicine (FM) service of the center since the end of 2013, with the aim of carrying out a preventive approach, in coordination with doctors from other specialties such as cardiology, endocrinology, ophthalmology, neurology, and psychiatry.

In the initial clinical evaluation, previously diagnosed diseases were treated with levothyroxine sodium, Armolipid Plus, a nutraceutical based on berberine, red yeast, policosanols, coenzyme Q10, astaxanthin and folic acid, and Bimatoprost solution, to which clonazepam and duloxetine were added to treat anxiety-depression symptoms. The general physical examination showed no data of interest. A control analysis was requested, whose most significant results were glucose in serum/plasma 156 mg/dL, total cholesterol 300 mg/dL, HDL 48 mg/dL, LDL 232 mg/dL, TSH 0.93 mIU/L, and the need was emphasized for diet and physical exercise to adjust lipid levels, explaining that the patient ruled out lipid-lowering drug treatment due to fear of liver damage. The FM insisted on the convenience of carrying out a scheduled follow-up.

Between 2014 and 2018, the patient went to her FM and specialist doctors on different occasions to control her chronic diseases (mainly hypothyroidism, dyslipidaemia, Diabetes Mellitus, and Glaucoma). Acute diseases such as respiratory infection, viriasis, oral candidiasis, lump infectious breast, sciatica, or sacral-coccygeal trauma were successfully treated. She also received systematic immunization against the influenza virus. She underwent surgery for her visual pathology in 2016, with relative success and maintenance treatment consisting of Lutein, Bimatoprost, and Brinzolamide. Bronchial asthma with treated with Budesonide/Formoterol. Table 1 shows the main pharmacological treatment modifications made to date.

Evolutive drug adjustments.

Note: 2021-1 (February 2021). 2021-2 (October 2021). Boi-K: Potassium hydrogen carbonate 1001 mg and ascorbic acid 250 mg, with dose in mgs. c: capsule.

2.4. History of the Disease

The prevalent symptomatology referred to by the patient and her family throughout the depressive process consists of sadness, emotional lability and crying, low self-esteem, negativism, apathy, anxiety, insomnia, ruminant thinking, and occasional autolytic ideation. Regarding the loss of visual capacity and the secondary dependence to it, the diagnosis of glaucoma and macular degeneration has been subsequent to the onset of depressive symptoms.

Over the years, an evolution characterized by periods of emotional well-being with a significant reduction in symptoms and different relapses that required therapeutic adjustments has been observed. Monitoring of the depressive disorder is carried out by a psychiatrist outside the primary care center, who adjusts the psychotropic drugs periodically ( Table 1 ).

From a non-pharmacological perspective, she was treated in the center’s psychology department. Psychologists detected family problems, poor socialization, and a lack of acceptance of the disease with reactivity to support proposals, such as technical aids for ambulation or functional independence. She also attended therapeutic programs of the Spanish National Organization for the Blind (ONCE), where she currently receives supportive psychotherapy and participates in activities such as gymnastics and choir. Regarding physical activity, ONCE provides cardiorespiratory and muscular maintenance as well as psychomotor coordination training.

2.5. Supplementary Tests

The patient’s multiple pathologies and her evolution have required the performance of different complementary tests, the chronology and results of which are summarized in Table 2 and Table 3 . In August 2019, a routine electrocardiogram (ECG) was performed, showing atrial fibrillation (AF) at 120 bpm, initiating treatment with digoxin, diltiazen, and low molecular weight heparin (LMWH). Examined by the cardiology service, an echocardiogram was performed, which showed multiple valve disease, adjusting the treatment ( Table 1 ).

Control serum parameters.

Note: 2021-1 (February 2021). 2021-2 (October 2021). Parameters in mg/dl. Hgb A1c in %. Digoxinemia in nanograms/mL. niop: not included or provided.

Control cardiac and psychological paremeters.

Note: 2021-1 (February 2021). 2021-2 (October 2021). AF (Atrial Fiblilation). GADS: Goldberg Anxiety and Depression Scale. niop: not included or provided.

Assessed in August 2020, in neurology outpatient clinics in relation to a double episode of nocturnal disorientation, a cranial CT scan was requested that found a “small cerebellar hemorrhage” requiring hospitalization for neurological surveillance. Treatment with edobaxan is preventedly suspended due to its anticoagulant properties. A brain study is completed with MRI that does not clearly show the presence of hemorrhage, ruling out malformations or other lesions that cause bleeding. There was good evolution during the hospital stay. A control cranial CT scan was performed that showed a punctiform image in the right cerebellar hemisphere corresponding to calcification, so the patient was discharged and the edobaxan regimen was restarted.

During the COVID-19 pandemic, a SARS CoV-2 antigen screening was performed (November 2020) with a negative result.

2.6. Follow-Up during 2021

In December 2020, the patient went to the new FM service of the center showing a defective speech related to her visual difficulties, including a negativistic discourse with complaints as well as a nihilistic view of her circumstances and her future. She also maintained her heart disease, brain damage, anxiety-depressive symptoms, side effects of drug treatment, and secondary functional dependence. The clinical examination showed a temperature of 35.7 °C, heart rate of 70 bpm (atrial fibrillation), blood pressure of 150/75 mmHg, and O 2 saturation of 96%, resulting in normal physical and neurological examination. She reports complex visual hallucinations (people, animals, and objects) in the absence of cognitive impairment that appears to be Charles Bonnet syndrome.

During the months of January and June 2021, she attended four times for analytical control, assessment of the evolution and therapeutic adjustment (see Table 1 , Table 2 and Table 3 ), in coordination with her cardiologist and her psychiatrist. Different analytical parameters have been requested including hemogram, proteinogram, kidney function tests, and glomerular filtration. Hepatopancreatic, ionogram, markers of heart failure such as NT pro-BNP, iron metabolism, and anemias screening have shown data suggestive of normality.

The SARS-COVID-19 immunization is carried out between the months of March and April 2021.

In consultation with her FM and carried out in October 2021, the patient attends in the company of her husband; she is very cooperative, smiling, and showing emotional stability, with absence of parasuicidal ideation and Charles Bonnet syndrome, which she associates with increased physical activity and psychotherapeutic as well as to correct pharmacological control, despite the fact that anxiety levels remain high, referring to fear of loss of family support (the results are shown in Table 1 , Table 2 and Table 3 ).

3. Case Management from Family Medicine

Since it is a patient who lives in the community, the FM department of the health center has acted, coordinating the needs of monitoring of the different pathologies that she presents with the support of her family as a basic element of well-being. It is a classic FM strategy, implemented with the aim of achieving primary, secondary, and tertiary prevention.

4. Discussion

In the present case, the following areas of deliberation are raised: 1. Multifactorial etiology of the disease; 2. Diagnostic certainty; 3. Efficacy of psychopharmacological treatment; and 4. Role of the family in the patient’s care.

4.1. Multifactorial Etiology of the Disease

The main risk factors for depressive disorder in old adults have been frequently studied and include psychosocial circumstances of the aging process, personality factors, previous psychiatric pathology, intercurrent illnesses, and the interactions of associated treatments, although the level of influence of each factor is difficult to discriminate [ 18 , 19 ].

The present case could constitute a paradigm of the multicausality of depressive disorder in old adulthood, since, in a progressive and continuous way, several of the main factors associated with depressive symptoms that contribute to chronicity have been presented. In the psychosocial level, losses and grief, loneliness, environmental changes, and maladjustment stand out as potential etiological factors [ 20 ]. In this case, she is a person with a high cultural level, economic resources, comfortable habitat, and very stable social and family support. Regarding personality factors, some authors suggest that traits such as neuroticism increase the risk of presenting depressive symptoms in old adulthood [ 21 ]. It was not considered necessary to assess personality factors in a structured way, since an evolution of 10 years and the previous therapeutic approaches seem to be advisable, although it is true that the patient frequently refers to “a change in personality, from shyness to a certain disinhibition in the last years” associated with the general clinical picture that could be the result of antidepressant treatment. In the medical history, no references to previous psychiatric pathologies, consumption of toxic substances, or adjustment disorders were observed, with a stable work environment until her retirement.

Different studies associate metabolic diseases such as hypothyroidism and diabetes mellitus, or cardio and cerebrovascular disease, with an increased risk of suffering from depression, relating it to the multiple neuroimmunoendocrine changes in depressive patients. It has been observed that patients with depressive symptoms experience increased platelet activation that could predispose them to thromboembolic episodes. They also experience immune activation (NK cells and leukocytes) and hypercortisolemia, along with an increased adrenocorticotropic hormone (ACTH) and ACTH-releasing factor. In addition, they experience decreased insulin resistance, increased endogenous production of steroids, and the release of catecholamines, associated with an increase in arterial pressure and coronary vasoconstriction. Moreover, depressive symptoms constitute a poor prognostic factor in cardiovascular and metabolic diseases [ 22 , 23 , 24 , 25 ]. In this case, the protocol-based examinations showed no alteration justifying the role of physical factors in the depressive simptomatology. On the other hand, the polypharmacy used to control these diseases constitutes a known precipitating factor of depressive symptoms in old adults. Thus, drugs such as digoxin, diuretics, oral antidiabetics, and antihypertensives have been frequently associated with a greater risk of depression in these populations [ 26 ]. We cannot determine the level of influence of these drugs on the prognosis, but we can consider that their interactions with antidepressant drugs could make remission of the depressive symptomatology difficult.

In the clinical evolution of the patient, we consider the loss of vision to be key in the chronification of depressive symptoms due to the psychological repercussions as a factor of anxiety, insecurity, and fear; the functional repercussions for the instrumental and basic activities of daily life that limit self-care and potentiate iatrogenic risks; and the social repercussions related to leisure activities and increased consumption of resources, all of which favor frailty and limit self-perception of health status.

On the other hand, we consider the presence of a Charles Bonnet syndrome characterized by hallucinations to be of interest, which are commonly perceived as real by the patients and are related to visual deficits. Although the underlying mechanism is not well understood, it seems to be related to a brain’s continuous adjustment to significant vision loss. Old adults affected with Charlet Bonnet syndrome can avoid reporting to their doctor because of fear that the hallucinations could be related to a severe mental disorder. The clinical management consists of health education, explaining to the patient the nature of the disorder, the prevalent symptomatology, making them aware of the symptoms, and explaining that it is part of their visual deficit and not relevant to their depressive symptomatology. Eventually, pharmacological treatment with neuroleptics, benzodiazepines, antidepressants, and antiepileptics is required [ 16 , 17 ].

4.2. Diagnosis of Depression

As a complex diagnosis, major depression in old age involves assessing cognitive functions, behaviors, and the impact of any affective disorder on the functional capacity and quality of life of the patient. Following the DSM-5 criteria [ 11 ] facilitates the discrimination between a depressive disorder and a mixed adjustment disorder that could be better explained according to the current situation of the process. For the diagnosis of major depressive disorder, the criterion of temporality greater than two weeks, the presence of a depressed mood most of the day, and anhedonia, or a marked decrease in interest or a displeasure in almost all activities, are included; in addition, the presence of at least five additional symptoms are included, such as insomnia, hyporexia, loss of energy, inappropriate feelings of guilt and worthlessness, and self-destructive ideation, among others. In the case of mixed adjustment disorder, the diagnostic criteria include five groups (A–E), so that the anxiety-depressive symptoms occur in response to an identifiable stressor or factors that occur in the following three months. At the beginning of the stressor (A), the symptoms are clinically relevant with an intense and disproportionate discomfort in relation to the intensity of the stressor, generating a significant deterioration of social functioning or of other areas (B), other mental disorders are excluded (C), the symptoms do not represent a normal grief (D), and once the stressful event or its consequences have ended, the symptoms do not persist for more than another six months (E). In the case reported, it is not possible to fulfill criterion E because the most significant stress factors, those that generate the most discomfort and maladjustment, have become chronic so their resolution is not possible. Structured cognitive assessment has not been carried out because of the absence of progressive decline.

4.3. Efficacy of the Psychopharmacological Treatment

As has been reported, the pharmacological approach in this case is highly complex. Until the advent of SSRIs, the treatments of choice were TCA and tetracyclic (ATTC) antidepressants, but the potential induction of anticholinergic effects can cause cardiovascular alterations (orthostatic hypotension, arrhythmias, electrocardiographic alterations), changes in intestinal motility (constipation, paralytic ileus), urinary retention, and pupillary dilatation, among others, discouraging their use. Currently, SSRIs and SSNRIs are the dominant pharmacological approaches for depression in old adults, motivated by their ease of use, versatility, efficacy, and safety, in addition to their cost-effectiveness.

SSRIs (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) work by blocking the reuptake of serotonin (5-HT) through inhibition of the adenosine triphosphatase (ATPase)-dependent sodium/potassium transporter (NA+/K+) in presynaptic neurons. With some differences between them, they have effects on other neurotransmission systems such as noradrenergic or dopaminergic. They are metabolized by liver enzymes, especially cytochrome P450 2D6, and have different pharmacokinetic characteristics. The main indication is major depression, although they are also useful in conditions such as obsessive-compulsive disorder or anxiety disorders. The most frequent side effects are gastrointestinal (nausea, burning, diarrhea), related to intestinal 5-HT receptors, which are minimized with a staggered dosage of medication. A variable percentage of patients treated with SSRIs manifest a sensation of activation of the central nervous system with agitation, nervousness, and insomnia that usually responds to moderate doses of benzodiazepines, such as alprazolam, lorazepam, or clonazepam. In general, they present a moderate risk of pharmacological interactions, and they are very safe drugs, as studies of lethal overdose show [ 27 , 28 , 29 , 30 , 31 , 32 ].

SSNRIs, such as duloxetine and venlafaxine, are a second group of drugs especially useful in the treatment of depression in old adulthood. SSNRIs may have a faster onset of action than other antidepressants by modulation of beta-adrenergic receptors. Duloxetine is a potent 5-HT and norepinephrine reuptake inhibitor with low affinity for muscarinic or histamine receptors, whereas venlafaxine shares 5-HT reuptake potency with moderate effects on norepinephrine reuptake and few effects on other neurotransmission systems. In addition, they present a low risk of pharmacokinetic interactions due to low potency in the inhibition of liver enzymes of cytochrome P450, a factor that facilitates their use. The FDA indications for this group of drugs are major depression, generalized anxiety disorder, and social anxiety disorder. Since they have a mechanism of action similar to that of tricyclic antidepressants, SSNRIs have shown their usefulness in some pain disorders, which makes them especially useful in older patients and in depression associated with neuropathic comorbidity. They share some of the gastrointestinal side effects with SSRIs, however, they differ from these in the moderate risk of increased blood pressure, somewhat less frequently in prolonged-release venlafaxine, which requires periodic monitoring in the first months of treatment and is solved by adjusting the dose. Other side effects described are syncope, ortostatic hypotension, and anticholinergic symptoms, such as dry mouth, urinary retention, and constipation, which in old patients must be monitored. Exceptional cases of fatal overdose have been described. Its level of efficacy compared to SSRIs seems somewhat higher, even though the data are discrepant [ 33 , 34 , 35 , 36 , 37 , 38 ].

In recent years, the approval of mirtazapine for the treatment of depression has led to its frequent use in old adults. It is an antagonist of alpha 2-adrenergic receptors that acts by increasing the release of norepinephrine that achieves a rapid increase in 5-HT levels, achieving modulation of the serotonergic system. Mirtazapine is metabolized through cytochrome P450 enzymes without being an inducer or inhibitor of these enzymes, so there are no interactions with other psychotropic agents, which facilitates the combination. Its main indication is major depression, used alone or in association with SSRIs/SSNRIs. Compared with paroxetine, it showed a faster response and fewer dropouts associated with adverse effects. Among the most frequent side effects are drowsiness (which advises its use at night) and increased appetite and weight. Furthermore, it seems to increase the levels of cholesterol and triglycerides secondarily, which, associated with its potential cardiovascular effect, makes it necessary to monitor blood pressure [ 39 , 40 , 41 ].

The therapeutic strategy is of great interest in this case. Since it is a highly complex case, the management of psychotropic drugs had to be careful, requiring consideration not only of the efficacy and probability of remission, but also of the minimization of secondary organic complications, to guarantee safety. In addition, the progressive appearance of comorbid, cardio, and cerebrovascular factors has required pharmacological adjustment. The potential interactions of the treatment must be considered, with the aim being its optimization. We consider the combined use of venlafaxine and mirtazapine to be successful due to its efficacy and safety, as evidenced by the adequate adherence of the patient to treatment and medical controls. In the case of duloxetine, its potential modification of blood pressure levels could question its use in this case [ 42 ]. The Goldberg Anxiety and Depression Scale (GADS) carried out in October 2021 suggests a remission of depressive symptoms and an improvement in the patient’s attitude. However, based on the results of the interview and the GADS (A7/D0), the use of benzodiazepines to control anxiety and insomnia symptoms does not seem clear.

4.4. Role of the Family in the Patient’s Care

This case presents many of the specific challenges in managing geriatric patients in the Galician health care model (northwest Spain). The guarantee of citizens’ health rights has been defined in the Spanish constitution since 1978. However, in 2002 there was a decentralization of competences in different areas, including health, according to the Law of Cohesion and Quality of the National Health System, which established a framework in the 17 autonomous communities of the Spanish State, but with peculiarities according to each territory. Regardless of this framework, the citizens, using their freedom, choose in each health situation whether to be treated in the public health system (in Galicia, the Servicio Galego de Saúde, or SERGAS) or in the free market system (private clinical services companies and/or consultations by private professionals), or both. The reality is that this mixed system can condition the efficiency of geriatric and psychiatric interventions in complex cases, hindering actions from primary health care because decision-making is dispersed. In this context, relevant information for therapeutic optimization is frequently lost.

The socioeconomic context of the patient allows clinical follow-up with good health resources, within a dual system (private and public) that contributes to effective health care, although its efficiency is limited by the heterogeneity of clinical opinions. As it has been mentioned above, the health care model in Galicia is based on a public, universal system in coexistence with private companies and entities of the social sector that provide health and care services, in addition to freelance professionals in health areas such as ophthalmology, psychiatry, internal medicine, or psychology, among many others. Between 2020 and 2021, the COVID-19 pandemic has required the adoption of restrictive measures in terms of prevention and mobility attitudes that seem to increase the incidence of psychiatric pathology in old populations [ 43 , 44 ], although in this case it does not seem to have conditioned the evolution of the patient.

We believe that a more intensive non-pharmacological approach would contribute to improving the prognosis; specifically, it would reduce anxiety-type symptoms and achieve a more objective self-perception of health. It would be an area for improvement using some of the usual techniques in similar cases, from cognitive behavioral to supportive or family therapy. In recent years, third generation behavioral therapies seem to contribute to intervention in psychogeriatrics. These include Acceptance and Commitment Therapy, Dialectical Behavioral Therapy, Mindfulness-Based Therapy, Behavioral Activation Therapy, Integral Behavioral Couple Therapy, or Functional Analytical Psychotherapy, which share an integrative vision of the psychological problems of old patients, considering their functional structure relevant, that is, the psychological functions of maladaptive behaviors in the context in which they occur [ 45 ]. These types of approaches may probably contribute to improve the quality of life and the health perception of the patient.

The evolution of the depressive disorder is linked to the role that her husband plays in psychological care and functional support for her activities of daily living. The long duration of the disease and the appearance of associated pathologies increase the intensity of care. The parallel aging of the husband and the incidence of medical and psychological problems could contribute to a potential claudication or the development of caregiver burnout [ 46 , 47 ].

5. Conclusions

The present work discusses the complexity of the diagnosis and treatment of depression in the geriatric patient. It is illustrated with the case of a patient (a 75-year-old woman) with depressive symptomatology with more than 10 years of evolution, also affected by different concomitant organic pathologies including visual deficits and Charles Bonnet syndrome. The interventions of different medical specialties are shown, and some psychopharmacological treatment options are discussed. The interactions of the different pharmacological treatments and the mixed care approaches are considered, with the aims of improving the case management and maximizing the quality of life of the patient in this type of complex clinical condition. The complexity of the healthcare system in Galicia (northwest Spain) and how difficult it is to handle complex geriatric cases in this context are discussed. In this regard, the most relevant limitation of this case in the lack of a specific approach, substituted for this patient by a mixed care model. Other limitations include the lack of a personality assessment using psychometrically valid tests, the lack of an explicit frailty assessment beyond the clinical observation of an increased bio-psycho-social vulnerability, and the lack of an objective assessment of the caregiver burden.

Author Contributions

J.C.-P. and M.G.D. conceived and designed the case report; J.C.-P., M.G.D., M.P.P., A.d.l.I.C. and M.E.C. collected the data and prepared the case report; D.F. critically reviewed the case report and prepared contributions regarding depression disorders and psycho-social care. All authors reviewed and revised the manuscript. All authors have read and agreed to the published version of the manuscript.

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki. As a single case report, ethical review and approval was not applicable.

Informed Consent Statement

Informed consent, following the recommendation of the Galician Clinical Research Ethics Committee, was obtained from the participant.

Data Availability Statement

Conflicts of interest.

All authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

• Case Report
• Open access
• Published: 04 June 2024

Caution for psychiatrists: malignant hyperthermia risks with the anesthetic agent succinylcholine (Suxamethonium) during electroconvulsive therapy

• Masaki Nakano 1 , 2 ,
• Michitaka Funayama 1 , 2 ,
• Taketo Takata 1 ,
• Riko Wakisaka 1 , 2 ,
• Genki Koyama 1 , 2 ,
• Akihiro Koreki 2 , 3 ,
• Takuto Ishida 2 , 4 ,
• Hiroyuki Uchida 2 &
• Masaru Mimura 2  

BMC Psychiatry volume  24 , Article number:  411 ( 2024 ) Cite this article

Metrics details

Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine (Suxamethonium). Despite the frequent use of succinylcholine with electroconvulsive therapy (ECT), there has been no reported case of potentially lethal malignant hyperthermia following ECT. In addition, the time interval between the administration of succinylcholine and the onset of malignant hyperthermia has not been outlined in the context of ECT.

Case presentation

We present the case of a 79-year-old woman suffering from severe depression, who experienced severe malignant hyperthermia due to succinylcholine administration during an ECT session. She presented with a high fever of 40.2 °C, tachycardia of 140/min, hypertension with a blood pressure exceeding 200 mmHg, significant muscle rigidity, and impaired consciousness. These symptoms emerged two hours after ECT, which occurred in a psychiatric ward rather than an operating room, and reached their peak in less than 24 h. She was given 60 mg of dantrolene, which quickly reduced the muscular rigidity. Subsequently, she received two additional doses of 20 mg and 60 mg of dantrolene, which brought her fever down to 36.2 °C and completely eased her muscle rigidity within two days after ECT.

Conclusions

This is the first reported case of potentially lethal malignant hyperthermia after ECT. In addition, it highlights the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the necessity for psychiatrists to recognize its onset even after the treatment. In the light of potentially lethal consequences of malignant hyperthermia, it is critically important for psychiatrists to closely monitor both intraoperative and postoperative patient’s vital signs and characteristic physical presentations, promptly identify any symptomatic emergence, and treat it immediately with dantrolene.

Peer Review reports

Malignant hyperthermia is a sudden and serious medical condition triggered by the use of volatile anesthetic inhalants or depolarizing muscle relaxants, such as succinylcholine (Suxamethonium), commonly employed during electroconvulsive therapy (ECT). Without prompt and effective intervention, the progression of malignant hyperthermia can lead to fatal outcomes, with a mortality rate of 9.5% [ 1 , 2 ]. Dantrolene is recognized as the primary drug specifically designed to treat malignant hyperthermia [ 1 ] and should be administered quickly when this disorder is suspected. Considering succinylcholine’s regular use in ECT, there is a potential risk of malignant hyperthermia on ECT. Despite the widespread use of succinylcholine in ECT, only one very mild case of malignant hyperthermia occurring during or after ECT has been reported [ 3 ]. There is recognition among psychiatrists that succinylcholine may induce malignant hyperthermia. However, given that there is only one documented instance of its actual onset and considering that malignant hyperthermia is more commonly recognized among anesthesiologists than among psychiatrists, it is likely that some psychiatrists may not routinely consider this potential side effect. Additionally, the precise time interval between the ECT and the onset of malignant hyperthermia in the previous case was unclear [ 3 ], as was the question of whether the psychiatrist was the first to identify its onset.

We report a case of potentially lethal malignant hyperthermia that manifested in our psychiatric ward rather than in the operating room, occurring two hours after ECT which was performed with the use of succinylcholine. In this case, the patient exhibited abnormal vital signs, such as severe hyperthermia, as well as acute muscle rigidity and compromised consciousness. This case illustrates the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the need for psychiatrists to be vigilant in identifying its emergence within psychiatric wards.

Medical history

The patient is a 79-year-old female who experienced persistent insomnia starting at the age of 50, which lasted for five years. At the age of 55, she received a diagnosis of major depressive disorder at a psychiatric clinic. She was prescribed tricyclic antidepressants, which significantly alleviated her symptoms in six months.

At 76, she experienced a significant emotional disturbance following the sudden death of a close friend. This incident, which occurred 24 days before her first hospital admission, triggered severe anxiety symptoms: heart palpitations, restlessness, and an overwhelming fear of meeting a similar fate, leading her to wander aimlessly. She also exhibited agitated behavior, continuously pacing around her room. Additionally, she experienced sleep disturbances, a significant decrease in appetite, and cognitive decline, resulting in difficulty comprehending the contents of television programs. These symptoms prompted her to seek medical attention at our facility precisely two weeks before her subsequent hospitalization. According to DSM-5 diagnostic criteria standards, she was diagnosed with major depressive disorder, with a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 53, indicating severe depression [ 4 ]. Outpatient treatment initiated with duloxetine (20 mg), lorazepam (1 mg), and lemborexant (5 mg). However, due to a lack of improvement and increased suicidal thoughts, she was admitted to our psychiatric unit.

• Malignant hyperthermia

Upon hospitalization, her medication was discontinued except for lemborexant (5 mg) orally. On the second day of hospitalization, ECT was administered due to the patient’s unresponsiveness to medication and intense suicidal ideation coupled with agitation. Notably, the patient’s physical condition, including vital signs and a Body Mass Index of 18.6 kg/m², had been entirely normal before the anesthesia induction. Anesthesia induction was carried out using 150 mg of sodium thiopental, an ultra-short-acting barbiturate, and 50 mg of succinylcholine, an ultra-short-acting depolarizing muscle relaxant. Additionally, 0.5 mg of atropine, a muscarinic antagonist, 20 mg of landiolol hydrochloride, an ultra-short-acting β-blocker, and 1 mg of nicardipine, a calcium channel blocker, were administered to manage side effects associated with ECT, such as excessive salivation, tachycardia or bradycardia, and elevated blood pressure. ECT procedures were executed without any issues. Her postoperative consciousness improved without complications, reaching a Glasgow Coma Scale score of 13 (Eye, 3; Verbal, 4; Motor, 6).

However, two hours post-ECT, her Glasgow Coma Scale deteriorated to 7 (Eye, 1; Verbal, 1; Motor, 5). At the same time, she exhibited marked muscular rigidity in her limbs, along with mydriasis in both eyes and diminished light reflexes. Given the potential for a brain disorder, a computed tomography scan and magnetic resonance imaging of brain were performed, which revealed no abnormalities. Blood tests showed elevated white blood cell counts to 24,400/µL, but no other abnormal findings. After analyzing the electroencephalogram obtained the same day, we found that the amplitude was markedly reduced without any detectable epileptic waveforms, which indicated an impaired state of consciousness. Approximately seven hours post-ECT, her vital signs became abnormal: her temperature rose to 39 °C, heart rate increased to 140 beats per minute, and systolic blood pressure sharply surged above 200 mmHg. To counter these abnormalities, strategies including continuous intravenous hydration, temperature management, and acetaminophen infusion were employed. Simultaneously, nicardipine, a calcium channel blocker, was used to treat hypertension. However, on the subsequent day post-ECT (the third day of hospitalization), 21 h after the ECT, her temperature further increased to 40.2 °C, and her Glasgow Coma Scale deteriorated to 6 (Eye, 1; Verbal, 1; Motor, 4), with ongoing muscular rigidity. Symptoms of dehydration and hyponatremia, resulting from sustained hyperthermia, were noted, as evidenced by elevated serum creatinine at 1.42 mg/dL, urea nitrogen at 33.9 mg/dL, and a reduced sodium level of 114 mEq/L. Furthermore, due to decreased consciousness resulting from hyponatremia, aspiration pneumonia developed as a complication. These conditions were managed with enhanced fluid resuscitation and the commencement of broad-spectrum antibiotics, specifically piperacillin-tazobactam at 3.375 g every six hours. A concurrent metabolic acidosis due to dehydration-induced circulatory inadequacy and a counteracting respiratory alkalosis were inferred from arterial blood gas results, which showed pH 7.490, PO2 65.9 mmHg, PCO2 24.2 mmHg, Base Excess − 3.4, HCO3- 18.2 mmol/L, and Lactate 3.2 mmol/L.

These clinical signs, including a rapid rise in body temperature, extensive muscular rigidity, and inconsistent sinus tachycardia, corresponded with the diagnostic criteria for malignant hyperthermia as defined by Larach et al. 1994 [ 5 ]. It is noteworthy, however, that the peak creatine kinase level, a key marker for malignant hyperthermia, displayed only a slight increase at 171 U/L on the third day of hospitalization (with the normal upper limit being 80 U/L) [ 6 ].

Dantrolene administration

To treat malignant hyperthermia, dantrolene (60 mg) was intravenously introduced 23 h following the ECT on the third hospital day. Remarkably, following the dantrolene administration, muscular rigidity notably decreased within an hour, and her temperature dropped to 38 °C within four hours. Additional doses of 20 mg and 60 mg of dantrolene were administered on the third and fourth hospital days, respectively, led to a decrease of her temperature to 36.2 °C and the complete resolution of muscular rigidity. Subsequently, dehydration, its associated hyponatremia, and aspiration pneumonia were all successfully resolved. The state of her consciousness showed significant improvement, reaching a Glasgow Coma Scale score of 11 (Eye: 3; Verbal: 4; Motor: 4) on the seventh hospital day. This improvement coincided with an enhanced electroencephalogram displaying alpha waves, denoting lucid consciousness. No side effects associated with dantrolene were detected. By the seventh hospital day, she demonstrated the capability for basic conversations and began feeding on the seventeenth hospital day. Her depressive symptoms improved without the need for additional ECT or psychotropic interventions, and no residual cognitive deficits were observed. She was discharged from our institution on the thirty-second hospital day.

Discussion and conclusions

This case represents the first instance of severe malignant hyperthermia after ECT. Compared with the previous report of malignant hyperthermia after ECT [ 3 ], our case is deemed more severe as the fever persisted for several days and was accompanied by impaired consciousness, which required the administration of dantrolene. Our case also highlights the delayed onset of malignant hyperthermia following an ECT session, emphasizing the need for psychiatrists to be vigilant in identifying its emergence in psychiatric wards. The symptom relief provided by dantrolene underscores its pivotal role in the therapeutic approach to malignant hyperthermia.

Difference in symptoms between malignant hyperthermia, serotonin syndrome, and neuroleptic malignant syndrome

In this case, the patient exhibited fever, altered consciousness, and limb muscle rigidity, symptoms also observed in serotonin syndrome [ 7 ] as well as neuroleptic malignant syndrome [ 8 ]. Considering the differential diagnosis of serotonin syndrome is crucial, especially since the patient had been undergoing duloxetine treatment until two days before the ECT session. Given its half-life of 10–12 h (Knadler et al., 2011) [ 9 ], duloxetine’s effectiveness at the receptor level would have been present, albeit quite low, during the ECT procedure. Serotonin syndrome is a serious complication that can occur as a result of treatment with selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and other serotonergic medications (Mason et al. 2000) [ 10 ]. The syndrome is characterized by the sudden onset of cognitive/behavioral changes (confusion, agitation, lethargy, and coma), autonomic instability (hyperthermia, tachycardia, diaphoresis, nausea, vomiting, diarrhea, and dilated pupils), and neuromuscular changes (myoclonus, hyperreflexia, rigidity, and trismus) [ 10 ]. The present case exhibited coma, autonomic instability, and rigidity following the administration of a serotonin-norepinephrine reuptake inhibitor until two days before, potentially meeting the criteria for serotonin syndrome diagnosis [ 11 ]. Despite this, the likelihood of serotonin syndrome diagnosis in this case is quite low, primarily due to the timing of the patient’s symptoms and the notable efficacy of dantrolene. Firstly, it is generally unlikely for serotonin syndrome to emerge post-discontinuation of antidepressants [ 11 ]. Mason et al. (2000) reported that 74.3% of serotonin syndrome cases typically develop within 24 h of initiating medication, overdosing, or changing dosage [ 10 ], due to excessive serotonergic activation in both central and peripheral nervous system receptors [ 11 ]. Conversely, only 12.8% of cases emerge after 48 h [ 11 ]. Additionally, many cases of the serotonin syndrome typically resolve within 24 h after discontinuation of serotonergic drugs [ 11 ]. Secondly, the significant effectiveness of dantrolene does not indicate serotonin syndrome; instead, it strongly suggests a diagnosis of malignant hyperthermia. Dantrolene is recognized as the primary drug specifically designed to treat malignant hyperthermia [ 1 ], while Jones et al. (2005) highlight its unproven effectiveness in treating serotonin syndrome [ 12 ]. Additionally, this case lacked some symptoms that are frequently observed in serotonin syndrome, such as diarrhea, vomiting, and myoclonus [ 10 , 11 , 13 ]. The significant effectiveness of dantrolene treatment in this case may also indicate the improbability of neuroleptic malignant syndrome, as White et al. (2000) noted the limited therapeutic efficacy of dantrolene in neuroleptic malignant syndrome [ 14 ]. Conversely, malignant hyperthermia can readily explain this case and is the most plausible explanation, particularly considering the onset, which occurred immediately after the administration of the anesthetic agent succinylcholine during the ECT session, and the pronounced response to dantrolene. Mydriasis, which is one of the symptoms of serotonin syndrome [ 11 , 13 ], can also be present in cases of malignant hyperthermia (Larach et al., 2006; Sheila et al., 2014; Sold et al., 1986) [ 15 , 16 , 17 ]. Thus, we diagnosed this patient with malignant hyperthermia rather than serotonin syndrome.

Regarding the distinction between malignant hyperthermia and neuroleptic malignant syndrome, historically, the similar symptomatology of these conditions has led to theories of a shared pathogenetic mechanism [ 18 ]; however, this hypothesis has not been definitively confirmed. Neuroleptic malignant syndrome and serotonin syndrome are believed to originate neurogenically rather than myogenically [ 11 , 19 ], while the pathogenesis of malignant hyperthermia has been shown to be myogenic, specifically involving an abnormal release of Calcium from the sarcoplasmic reticulum [ 1 ]. Symptomatically, serotonin syndrome presents distinctive symptoms not typically found in malignant hyperthermia, including altered consciousness, behavioral changes, myoclonus, hyperreflexia, diarrhea, and vomiting [ 10 , 11 , 13 , 20 ]. Rosenberg et al. (2015) observed no cross-susceptibility between malignant hyperthermia and neuroleptic malignant syndrome [ 1 ], and a review by Ortiz et al. (2020) found no genetic association between malignant hyperthermia, serotonin syndrome, and neuroleptic malignant syndrome [ 18 ].

However, in terms of treatment methods, there is some overlap between malignant hyperthermia, serotonin syndrome, and neuroleptic malignant syndrome. Immediate discontinuation of responsible agents and hydration are common practices in all of these conditions. Dantrolene administration is often performed as well. Psychiatrists may have mistakenly diagnosed malignant hyperthermia during ECT treatment as serotonin syndrome or neuroleptic malignant syndrome and administered dantrolene for treatment. Ironically, this misdiagnosis could have led to clinical improvement despite the error. The scarcity of reported cases of malignant hyperthermia during ECT treatment has been acknowledged in prior research [ 21 , 22 ]. Some researchers have speculated that some ECT-related fatalities might have resulted from undetected malignant hyperthermia [ 22 ]. Alternatively, in our opinion, another explanation could be the misdiagnosis of malignant hyperthermia as serotonin syndrome or neuroleptic malignant syndrome by psychiatrists.

Still, it remains crucial to always consider the possibility of malignant hyperthermia during and after ECT, especially considering that psychiatrists more commonly encounter conditions like neuroleptic malignant syndrome and serotonin syndrome, which often take precedence in differential diagnoses. A misdiagnosis could lead to a delay in appropriate treatment due to differences in the discontinuation of triggering agents and the effectiveness of dantrolene.

Characteristics of malignant hyperthermia in this potentially lethal case

Our case did not manifest a high level of creatine kinase, masseter muscle rigidity, and severe acidosis, which have been regarded as hallmarks of malignant hyperthermia [ 5 ]. It is well-recognized in malignant hyperthermia that tissue hypoxia and muscle breakdown can lead to increased serum creatine kinase levels. However, in this case, the serum creatine kinase level rose modestly to 171 U/L on the third hospital day, which may be considered to be an atypical presentation. This observation might be ascribed to generally lower creatine kinase values in females than males [ 23 ] and the association between muscle mass and creatine kinase levels [ 24 ]. Notably, this patient exhibited a slender build with a Body Mass Index of 18.6 kg/m². According to the study by Sheila et al. in 2014, approximately 35% of 129 patients diagnosed with malignant hyperthermia exhibited peak creatine kinase values below 1000 [ 16 ]. Additionally, the current case did not exhibit severe acidosis or masseter spasm shortly after the administration of succinylcholine, which are commonly observed in malignant hyperthermia [ 5 ]. However, these symptoms are not mandatory for the diagnosis of malignant hyperthermia [ 5 ]. Regarding acidosis, while our case did not demonstrate severe acidosis, the HCO3- level of 18.2 mmol/L and PCO2 level of 24.2 mmHg in arterial blood gas analysis suggest metabolic acidosis with respiratory compensation [ 25 ], a finding consistent with metabolic acidosis observed in malignant hyperthermia [ 5 ].

According to Larach et al. 2006, only 9.4% of 181 malignant hyperthermia patients showed disturbance of consciousness [ 15 ]. However, this patient experienced a prolonged alteration in consciousness. The extent of consciousness impairment due to malignant hyperthermia considerably varies, with reported cases ranging from a rapid recovery within 90 min [ 26 ] to prolonged cognitive disruption exceeding 40 days, ultimately resulting in the sequelae of severe cognitive dysfunction [ 27 ]. This case was complicated by dehydration and its associated hyponatremia, which may also have affected the disturbance of consciousness.

Calcium channel blockers we used to treat severe hypertension (over 200 mmHg) might have intensified malignant hyperthermia symptoms by increasing calcium concentrations in skeletal myocytes, along with associated muscle rigidity [ 1 ]. A more suitable approach could have employed an antihypertensive agent without calcium channel inhibitory effects.

Mechanisms of malignant hyperthermia

The underlying mechanisms of malignant hyperthermia involve the excessive release of calcium from the sarcoplasmic reticulum, a crucial calcium store within skeletal muscle cells, into the cytoplasm. This dysregulation is provoked by depolarizing neuromuscular blocking agents, predominantly succinylcholine, and volatile inhalation anesthetics [ 1 ]. This disruption results in a marked increase in skeletal muscle metabolic processes, leading to enhanced muscle fiber contraction, increased oxygen consumption, elevated carbon dioxide production, and accelerated depletion of adenosine triphosphate, alongside associated heat production [ 1 ]. These physiological changes give rise to the clinical presentations observed, including hyperthermia and muscle rigidity.

Succinylcholine is routinely employed as a muscle relaxant during ECT due to its rapid onset of action and ultra-short duration, making it suitable for the brief anesthesia required in ECT procedures that typically last only a few minutes (Dao et al., 2023) [ 28 ]. However, it is important to note that depolarizing muscle relaxants like succinylcholine, along with volatile inhalational anesthetics, are known to trigger malignant hyperthermia [ 1 ]. Patients with a known or suspected history of malignant hyperthermia should be administered anesthetics that do not pose a risk of triggering this condition to prevent the onset of malignant hyperthermia. For example, rocuronium, along with its antagonist sugammadex, should be used instead of succinylcholine, as the study by Sumitani et al. (2011) found that the use of rocuronium was not statistically or significantly associated with malignant hyperthermia [ 29 ].

Warning to psychiatrists

Detection and diagnosis of malignant hyperthermia significantly depend on the judgment of psychiatrists. In the case we observed, malignant hyperthermia manifested two hours after ECT, aligning with prior research findings. Visoiu et al. (2014) noted a median time of 76.5 min from the induction of anesthesia to the onset of malignant hyperthermia in cases reported since 1998 [ 30 ]. Furthermore, they reported that the upper third quartile duration from the initiation of anesthesia to the onset of malignant hyperthermia was 148.3 min. Given the considerably shorter duration of ECT compared to general surgery, the probability of postoperative malignant hyperthermia after ECT might be higher.

Therefore, malignant hyperthermia after ECT is primarily considered to occur in a psychiatric ward and be detected by psychiatrists, rather than in the operating room by anesthesiologists. It is therefore critically important to closely monitor for indicators of malignant hyperthermia, including abnormal vital signs, such as elevated temperature, tachycardia, high blood pressure, and tachypnea, as well as characteristic physical presentations, such as muscle rigidity, masseter spasm, and cola-colored urine [ 5 ], for a few hours after ECT in a psychiatric ward.

Given the potential lethality of malignant hyperthermia following ECT, it is essential for psychiatrists to rigorously monitor both intraoperative and postoperative vital signs and physical presentations. Identification at the earliest opportunity and timely intervention with dantrolene are crucial in managing malignant hyperthermia.

Data availability

The data of this case report are available from the corresponding author (MN) upon request.

Abbreviations

• Electroconvulsive therapy

Montgomery-Åsberg Depression Rating Scale

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Acknowledgements

We express our gratitude to the patient and her family members for their participation in this case report.

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Masaki Nakano, Michitaka Funayama, Taketo Takata, Riko Wakisaka & Genki Koyama

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Masaki Nakano, Michitaka Funayama, Riko Wakisaka, Genki Koyama, Akihiro Koreki, Takuto Ishida, Hiroyuki Uchida & Masaru Mimura

Department of Psychiatry, National Hospital Organization Shimofusa Psychiatric Medical Center, Chiba, 266-0007, Japan

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MN, RW, GK and TT acquired case data. MN and MF drafted the manuscript. MM, HU, TT, TI, and AK revised the manuscript. All authors read and approved the final manuscript.

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Nakano, M., Funayama, M., Takata, T. et al. Caution for psychiatrists: malignant hyperthermia risks with the anesthetic agent succinylcholine (Suxamethonium) during electroconvulsive therapy. BMC Psychiatry 24 , 411 (2024). https://doi.org/10.1186/s12888-024-05846-5

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Received : 02 February 2024

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DOI : https://doi.org/10.1186/s12888-024-05846-5

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