Is there an association between underlying depressive mood and patients with fever of unknown origin (pyrexia of unknown origin)?

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From the Guidelines

Depression should be addressed alongside the physical workup in patients with pyrexia of unknown origin (PUO) to improve quality of life and potentially enhance recovery. Patients with prolonged, unexplained fever often experience anxiety, frustration, and depression due to diagnostic uncertainty, multiple medical investigations, and disruption to daily life. A comprehensive approach includes screening for depressive symptoms using tools like the PHQ-9 while continuing the fever investigation. Initial management may include supportive counseling, cognitive behavioral therapy, and in moderate to severe cases, antidepressant medication such as an SSRI.

  • Key considerations in managing depression in PUO patients include:
    • Routine screening using a validated questionnaire is good practice, as seen in other conditions like heart failure 1
    • Selective serotonin reuptake inhibitors are thought to be safe and can be used as a first-line treatment
    • A multidisciplinary approach involving both medical and mental health professionals provides the best outcomes for these patients, treating both the underlying fever and its psychological consequences simultaneously. The psychological impact of PUO stems from both the physical discomfort of persistent fever and the emotional toll of an uncertain diagnosis. Addressing depression can improve quality of life and potentially enhance recovery, as psychological stress can influence immune function and inflammation.

From the Research

Underlying Depressive Mood in Patients of Pyrexia of Unknown Origin

  • The provided studies do not directly address the topic of underlying depressive mood in patients with pyrexia of unknown origin (PUO) 2, 3, 4, 5.
  • However, it is known that patients with PUO often experience significant psychological burden due to the uncertainty of their diagnosis and prognosis 3.
  • Depression is a common comorbidity in patients with chronic illnesses, and it is possible that patients with PUO may also experience depressive symptoms 6.
  • A study on fluoxetine versus other types of pharmacotherapy for depression found that fluoxetine was as effective as tricyclic antidepressants (TCAs) in reducing depressive symptoms, but was less effective than some other antidepressants such as sertraline, mirtazapine, and venlafaxine 6.
  • The relationship between PUO and depressive mood is not well-studied, and more research is needed to understand the underlying mechanisms and to develop effective treatment strategies for patients with PUO who experience depressive symptoms 2, 3, 4, 5.

Possible Causes and Investigation of PUO

  • PUO is a syndrome that can be caused by a variety of factors, including infective, inflammatory, neoplastic, and miscellaneous conditions 2, 5.
  • The investigation of PUO requires a systematic approach, including the use of modern diagnostic techniques such as positron emission tomography-computed tomography (PET-CT) 2, 3.
  • The diagnostic strategy for PUO should be tailored to the individual patient, taking into account their medical history, physical examination, and laboratory results 4, 5.

Management of PUO

  • The management of PUO depends on the underlying cause of the condition, and may involve the use of antimicrobial agents, anti-inflammatory medications, or other treatments 2, 5.
  • In some cases, the cause of PUO may not be identified despite extensive investigation, and the patient may require ongoing monitoring and supportive care 3, 4.
  • The psychological burden of PUO should not be underestimated, and patients may benefit from counseling or other forms of psychological support 3, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pyrexia of unknown origin.

Clinical medicine (London, England), 2018

Research

Fluoxetine versus other types of pharmacotherapy for depression.

The Cochrane database of systematic reviews, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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