Psychiatric Annals

Case Report 

Prednisone-Induced Psychosis, and Homicidal and Suicidal Attempts in a Man Recently Diagnosed with Temporal Arteritis

Yekaterina Angelova, MD; Archna Sarwal, MD

Abstract

Temporal arteritis is a systemic vasculitis seen in older adults (incidence peaks in the seventh decade1) that typically affects the small arteries of the head and neck. Signs and symptoms of this condition may include new-onset headaches, changes in vision, tenderness over the temples, jaw claudication, constitutional symptoms, and elevated erythrocyte sedimentation rate and/or C-reactive protein levels. The definitive diagnosis is obtained by temporal artery biopsy, and the standard treatment is a lengthy course (typically 1 to 2 years) of high-dose corticosteroids such as prednisone.2

Corticosteroids have been widely prescribed since the 1950s to treat a myriad of allergic, inflammatory, and immunologic conditions. Despite their benefits, numerous adverse effects, including psychiatric and cognitive, have been attributed to this class of medication. Mild euphoria and anxiety are common early in the course of steroid therapy, whereas depression is more likely to occur during prolonged therapy.3 More alarming psychiatric symptoms, such as mania, severe depression, and psychosis, have been observed in patients receiving high doses of corticosteroids and/or receiving corticosteroids for a prolonged period of time. A daily prednisone-equivalent dose of ≥40 mg appears to significantly increase the risk of corticosteroid-induced neuropsychiatric disturbances.4

In this report, we present the case of a man with newly diagnosed temporal arteritis who developed acute insomnia, anxiety, and depressed mood after the initiation of high-dose corticosteroids, which rapidly progressed to psychosis, homicidality, and suicidality. We also discuss the patient's hospital course and complexity of simultaneously treating his medical and psychiatric conditions.

Information used in this report was gathered via interviews with the patient, his family, emergency department trauma team, primary treatment team, and consulting rheumatologist. Chart review was conducted.

The patient, a 73-year-old married man, with no significant psychiatric history, substance use history, or functional impairment, was brought to the emergency department under police custody after sustaining deep cuts to bilateral wrists and a stab wound to the chest resulting in a pneumothorax. The patient's injuries were self-inflicted. Prior to harming himself, the patient admitted to attacking his sleeping wife and attempting to strangle her.

Approximately 2 weeks prior, the patient had been diagnosed with temporal arteritis after experiencing new-onset headaches and blurry vision for several weeks. He was admitted to the hospital at that time for a 3-day course of intravenous (IV) methylprednisolone and discharged on oral prednisone at a dose of 80 mg daily. He soon began to experience symptoms of anxiety and worsening insomnia. He began to feel increasingly depressed, making occasional statements to his family about wanting to die. He began to experience auditory hallucinations, which he described as “a man, maybe a demon,” instructing him to kill his wife and himself. On the day of admission, the patient had succumbed to his distressing perceptual disturbances and attacked his wife while she slept. After his wife's escape from his grasp, he attempted to end his own life.

The patient was evaluated by our consultation-liaison team in the emergency department. He presented with anxiety and depressed affect, although he was oriented and coherent, with grossly intact cognition. He was fully aware of his actions prior to arrival to the hospital and expressed feelings of guilt, remorse, and helplessness. Collateral information obtained from his daughter revealed that before beginning corticosteroid treatment 2 weeks prior, the patient had never attempted to harm himself or others nor had he exhibited or endorsed any perceptual disturbances to the family's knowledge. He was described as having stable, loving relationships with his wife and children.

The patient was admitted to the surgical floor for management of his injuries. At time of presentation, his home medications consisted of simvastatin at…

Temporal arteritis is a systemic vasculitis seen in older adults (incidence peaks in the seventh decade1) that typically affects the small arteries of the head and neck. Signs and symptoms of this condition may include new-onset headaches, changes in vision, tenderness over the temples, jaw claudication, constitutional symptoms, and elevated erythrocyte sedimentation rate and/or C-reactive protein levels. The definitive diagnosis is obtained by temporal artery biopsy, and the standard treatment is a lengthy course (typically 1 to 2 years) of high-dose corticosteroids such as prednisone.2

Corticosteroids have been widely prescribed since the 1950s to treat a myriad of allergic, inflammatory, and immunologic conditions. Despite their benefits, numerous adverse effects, including psychiatric and cognitive, have been attributed to this class of medication. Mild euphoria and anxiety are common early in the course of steroid therapy, whereas depression is more likely to occur during prolonged therapy.3 More alarming psychiatric symptoms, such as mania, severe depression, and psychosis, have been observed in patients receiving high doses of corticosteroids and/or receiving corticosteroids for a prolonged period of time. A daily prednisone-equivalent dose of ≥40 mg appears to significantly increase the risk of corticosteroid-induced neuropsychiatric disturbances.4

In this report, we present the case of a man with newly diagnosed temporal arteritis who developed acute insomnia, anxiety, and depressed mood after the initiation of high-dose corticosteroids, which rapidly progressed to psychosis, homicidality, and suicidality. We also discuss the patient's hospital course and complexity of simultaneously treating his medical and psychiatric conditions.

Methods

Information used in this report was gathered via interviews with the patient, his family, emergency department trauma team, primary treatment team, and consulting rheumatologist. Chart review was conducted.

Case Report

The patient, a 73-year-old married man, with no significant psychiatric history, substance use history, or functional impairment, was brought to the emergency department under police custody after sustaining deep cuts to bilateral wrists and a stab wound to the chest resulting in a pneumothorax. The patient's injuries were self-inflicted. Prior to harming himself, the patient admitted to attacking his sleeping wife and attempting to strangle her.

Approximately 2 weeks prior, the patient had been diagnosed with temporal arteritis after experiencing new-onset headaches and blurry vision for several weeks. He was admitted to the hospital at that time for a 3-day course of intravenous (IV) methylprednisolone and discharged on oral prednisone at a dose of 80 mg daily. He soon began to experience symptoms of anxiety and worsening insomnia. He began to feel increasingly depressed, making occasional statements to his family about wanting to die. He began to experience auditory hallucinations, which he described as “a man, maybe a demon,” instructing him to kill his wife and himself. On the day of admission, the patient had succumbed to his distressing perceptual disturbances and attacked his wife while she slept. After his wife's escape from his grasp, he attempted to end his own life.

The patient was evaluated by our consultation-liaison team in the emergency department. He presented with anxiety and depressed affect, although he was oriented and coherent, with grossly intact cognition. He was fully aware of his actions prior to arrival to the hospital and expressed feelings of guilt, remorse, and helplessness. Collateral information obtained from his daughter revealed that before beginning corticosteroid treatment 2 weeks prior, the patient had never attempted to harm himself or others nor had he exhibited or endorsed any perceptual disturbances to the family's knowledge. He was described as having stable, loving relationships with his wife and children.

The patient was admitted to the surgical floor for management of his injuries. At time of presentation, his home medications consisted of simvastatin at 20 mg daily for hyperlipidemia and prednisone at 80 mg daily for his newly diagnosed temporal arteritis. Differential diagnoses at this time included delirium secondary to a metabolic disturbance or infection, psychosis secondary to another medical condition such as seizure, stroke, or temporal arteritis itself (which can, albeit rarely, present with neuropsychiatric manifestations), psychosis secondary to substance intoxication or withdrawal, or exacerbation of an underlying psychiatric disorder. Results of routine blood tests, including complete blood count, complete metabolic panel, liver function tests, thyroid function tests, glucose, vitamin B12, and folate were within normal limits. Urinalysis was unremarkable and urine toxicology was negative. A computed tomography scan of his head was unremarkable. The patient's family did not endorse any prior psychiatric illness or substance abuse.

Prednisone was withheld as steroid-induced psychosis was strongly suspected based on the chronology of symptoms and aforementioned history and clinical evaluation. Lorazepam at a dose of 1 mg every 6 hours as needed was recommended to address the patient's anxiety; no antipsychotic medication was started at this time as the patient did not exhibit any frank symptoms of psychosis. One-to-one observation was maintained for safety.

The patient was rechallenged with 80 mg daily of prednisone in a controlled setting on the day after admission, which led to re-emergence of delirium, psychosis, and severe agitation requiring mechanical restraint and IV haloperidol and lorazepam. Ophthalmology and rheumatology consultation was requested to evaluate the patient's current vision deficits and discuss the risks, benefits, and possible alternatives to treatment for his temporal arteritis. Ophthalmology and rheumatology both recommended that the patient be restarted on oral prednisone, as significant loss of vision was noted on examination.

A discussion was held with the patient and his family regarding the risks and dangers of his condition if untreated, the potential benefits and adverse effects of the proposed treatment plan, and alternatives to treatment (which were few in this case). The patient agreed to be restarted on prednisone with a reduction in dose from 80 mg daily to 60 mg daily. Methotrexate at a dose of 5 mg daily was added with hopes of reducing the duration and toxicity of steroid treatment. Haloperidol at a dose of 2 mg twice daily was started to prevent recurrence of psychotic symptoms. No further psychosis or agitation were noted during the admission; however, the patient continued to endorse anxiety, restlessness, depressed mood, and feelings of helplessness. He was started on 10 mg daily of escitalopram and 0.5 mg of lorazepam in the morning and 1 mg at bedtime, which alleviated some of his symptoms.

The patient was deemed medically and psychiatrically stable for discharge on day 11 of admission and returned home on prednisone at 60 mg daily, methotrexate at 5 mg daily, haloperidol at 2 mg daily, escitalopram at 10 mg daily, and lorazepam at 0.5 mg in the morning and 1 mg at night. Prior to discharge, the patient and his family were provided with extensive education on his condition, warning signs of possible recurrence of steroid-induced psychosis were discussed, and a detailed safety plan was formulated (Table 1, Table 2). The patient was provided with outpatient follow-up appointments with a psychiatrist and psychotherapist, who would continue to monitor him for re-emergence of any psychotic or mood symptoms and provide support, counseling, and coping strategies for him and his family. The patient was strongly advised to continue his antipsychotic regimen for the duration of corticosteroid treatment and to discuss any future medication adjustments with his outpatient psychiatrist.

Warning Signs of Steroid-Induced Psychosis After Initiation or Prolonged Use of High-Dose Corticosteroids

Table 1.

Warning Signs of Steroid-Induced Psychosis After Initiation or Prolonged Use of High-Dose Corticosteroids

Discharge Recommendations for Patients with Steroid-Induced Psychosis

Table 2.

Discharge Recommendations for Patients with Steroid-Induced Psychosis

One month after discharge, the patient remained stable on this medication regimen, attended his follow-up appointments regularly, and had shown significant improvement in his mood and hopefulness for the future.

Discussion

Changes in mood, behavior, and cognition in patients treated with corticosteroids date back as early as the 1950s, when use of these medications first became widespread.5 There is a wide range of reported incidence of steroid-induced neuropsychiatric symptoms (2%–60%), likely due to variations in definitions of symptoms and doses of corticosteroids, as well as tendency of most studies to focus primarily on medical side effects.6

Multiple studies have shown that corticosteroid dose and duration of treatment correlate with the severity and type of psychiatric symptoms (as discussed at the start of this case report). Although neuropsychiatric effects have been reported in patients taking doses as low as 2.5 mg per day of prednisolone, dosage appears to be the most significant risk factor.6 In this patient's case, treatment with IV methylprednisolone at 1 mg for 3 days followed by 2 weeks of oral prednisone at 80 mg daily (which is a relatively high dose over a prolonged period of time) resulted in his alarming symptoms.

In the case of temporal arteritis, various immunosuppressive agents continue to be explored as alternatives or adjuncts to steroid treatment in hopes of reducing the risk for severe adverse effects such as those described in this case. Methotrexate is often used as a steroid-sparing agent with hopes of reducing steroid toxicity and length of steroid therapy; however, evidence for its efficacy is scarce.7 Infliximab and other anti-tumor necrosis factor-alpha agents have shown mixed results.8,9 Newer biological therapies have shown some promise in the treatment of giant cell arteritis, with the most significant being tocilizumab.9 Nonetheless, high-dose corticosteroids remain the backbone of temporal arteritis treatment for now.

Evidence-based guidelines for the treatment of steroid-induced psychiatric conditions are lacking, and most treatment recommendations are drawn from case reports and small studies.10,11 Educating patients and their families about the potential neuropsychiatric effects prior to initiating treatment with corticosteroids is crucial (Table 1). If and when symptoms do occur, underlying medical causes or contributions should be carefully assessed for and managed. For example, withdrawal from alcohol or benzodiazepines, infection, metabolic disturbances, and psychosocial stressors may result in or worsen psychiatric disturbances.10

Treatment of steroid-induced psychosis usually involves discontinuation or tapering of the steroid, although emergence of acute psychosis after corticosteroid discontinuation has also been reported.12 Several strategies of preventing steroid-induced neuropsychiatric effects have been discussed in the literature, including the use of lithium and olanzapine.13 Symptomatic treatment of the neuropsychiatric effects of steroids with antipsychotics, mood stabilizers, anxiolytics, and antidepressants has been successful.10,14 In this patient's case, a combination of a first-generation antipsychotic, an antidepressant, and a benzodiazepine was warranted due to the severity of his presentation.

This case report has several limitations. A sample size of one makes the results impossible to generalize to a larger population. Furthermore, although the diagnostic conclusions discussed above were highly suspected, no cause-effect relationship can be established with certainty. Multiple barriers to timely and efficient management of this patient were encountered during the hospital course, including conflicting recommendations from consultants and disagreement among family members while assisting the patient with medical decisions.

Conclusion

This case report illustrates the potential severity of neuropsychiatric effects of prolonged, high-dose steroid treatment in new-onset temporal arteritis. Unfortunately, high-dose corticosteroids remain the mainstay of temporal arteritis treatment. Although several alternatives and adjuncts to corticosteroid treatment have been explored, few options have shown promising results. Patients who develop adverse psychiatric effects on corticosteroids are often tapered off steroids if possible and managed symptomatically with antidepressants, anxiolytics, mood stabilizers, and first- or second-generation antipsychotics. Few guidelines exist for the treatment of corticosteroid-induced psychosis, and most clinical guidance is derived from case reports such as presented here. Further studies are required to explore management and prevention of this potentially life-threatening condition.

References

  1. Kermani TA, Schäfer VS, Crowson CS, et al. Increase in age at onset of giant cell arteritis: a population-based study. Ann Rheum Dis. 2010;69(4):780–781. doi:10.1136/ard.2009.111005 [CrossRef] PMID:19854712
  2. Proven A, Gabriel SE, Orces C, O'Fallon WM, Hunder GG. Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes.Arthritis Rheum. 2003;49(5):703–708. doi:10.1002/art.11388 [CrossRef] PMID:14558057
  3. Bolanos SH, Khan DA, Hanczyc M, Bauer MS, Dhanani N, Brown ES. Assessment of mood states in patients receiving long-term corticosteroid therapy and in controls with patient-rated and clinician-rated scales. Ann Allergy Asthma Immunol. 2004;92(5):500–505. doi:10.1016/S1081-1206(10)61756-5 [CrossRef] PMID:15191017
  4. Bhangle SD, Kramer N, Rosenstein ED. Corticosteroid-induced neuropsychiatric disorders: review and contrast with neuropsychiatric lupus. Rheumatol Int. 2013;33(8):1923–1932. doi:10.1007/s00296-013-2750-z [CrossRef] PMID:23588411
  5. Clark LD, Bauer W, Cobb S. Preliminary observations on mental disturbances occurring in patients under therapy with cortisone and ACTH. N Engl J Med. 1952;246(6):205–216. doi:10.1056/NEJM195202072460601 [CrossRef] PMID:14890837
  6. Dubovsky AN, Arvikar S, Stern TA, Axelrod L. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53(2):103–115. doi:10.1016/j.psym.2011.12.007 [CrossRef] PMID:22424158
  7. Hoffman GS, Cid MC, Hellmann DB, et al. A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum.2002;46(5):1309–1318. doi:10.1002/art.10262 [CrossRef]
  8. Pipitone N, Salvarani C. Improving therapeutic options for patients with giant cell arteritis. Curr Opin Rheumatol. 2008;20(1):17–22. doi:10.1097/BOR.0b013e3282f31769 [CrossRef] PMID:18281852
  9. Samson M, Espígol-Frigolé G, Terrades-García N, et al. Biological treatments in giant cell arteritis and Takayasu arteritis. Eur J Intern Med. 2018;50:12–19. doi:10.1016/j.ejim.2017.11.003 [CrossRef] PMID:29146018
  10. Kenna HA, Poon AW, de los Angeles CP, Koran LM. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011;65(6):549–560. doi:10.1111/j.1440-1819.2011.02260.x [CrossRef] PMID:22003987
  11. Ismail MF, Lavelle C, Cassidy EM. Steroid-induced mental disorders in cancer patients: a systematic review. Futur Oncol. 2017;13(29). doi:10.2217/fon-2017-0306 [CrossRef]
  12. Mercadante S, Villari P, Intravaia G. Withdrawal acute psychosis after corticosteroid discontinuation. J Pain Symptom Manage. 2007;34(2):118–119. doi:10.1016/j.jpainsymman.2007.03.005 [CrossRef] PMID:17555921
  13. West S, Kenedi C. Strategies to prevent the neuropsychiatric side-effects of corticosteroids: a case report and review of the literature. Curr Opin Organ Transplant. 2014;19(2):201–208. doi:10.1097/MOT.0000000000000065 [CrossRef] PMID:24553497
  14. Corbett B, Nordstrom K, Vilke GM, Wilson MP. Psychiatric emergencies for clinicians: emergency department diagnosis and management of steroid psychosis. J Emerg Med. 2016;51(5):557–560. doi:10.1016/j.jemermed.2016.05.055 [CrossRef] PMID:27553921

Warning Signs of Steroid-Induced Psychosis After Initiation or Prolonged Use of High-Dose Corticosteroids

<list-item>

Disturbances in sleep, insomnia

</list-item><list-item>

Changes in mood, such as euphoria, depression, or irritability

</list-item><list-item>

Confusion or disorganization

</list-item><list-item>

Perceptual disturbances, such as auditory or visual hallucinations

</list-item><list-item>

Delusions, such as paranoia or grandiosity

</list-item><list-item>

Aggression or agitation

</list-item><list-item>

Suicidal or homicidal ideation, gestures, or attempts

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Discharge Recommendations for Patients with Steroid-Induced Psychosis

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Prior to discharge from the hospital, patients should be evaluated for resolution of acute symptoms of psychosis, mood episode, and/or other presenting symptoms

</list-item><list-item>

Thorough suicide risk and violence risk assessments should be completed

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Education should be provided to patient, family, caregivers, and outpatient providers regarding patient's presenting symptoms, the recommended treatment and follow-up, and warning signs of re-emerging symptoms

</list-item><list-item>

Patients should be provided with clear outpatient follow-up instructions for their underlying medical condition requiring the use of corticosteroids

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Authors

Yekaterina Angelova, MD, is a Consultation-Liaison Psychiatry Fellow, Mount Sinai Beth Israel. Archna Sarwal, MD, is the Chief of Consultation-Liaison Psychiatry, and the Clerkship Director for Medical Students, Richmond University Medical Center.

Address correspondence to Yekaterina Angelova, MD, Department of Consultation-Liaison Psychiatry, Mount Sinai Beth Israel, 281 1st Avenue, 6 Linsky, New York, NY 10003; email: katie.angelova@gmail.com.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00485713-20200507-01

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