Can an undiagnosed brain tumor present with symptoms mimicking new anxiety, leading to failure of the current medication regimen, particularly in a patient with a complex medical history, including recent discontinuation of escitalopram (SSRI) and use of multiple medications without proper tapering?

Can a Brain Tumor Present as New Anxiety and Cause Medication Failure?

Yes, brain tumors can present with isolated psychiatric symptoms including new-onset anxiety without neurological signs, and this should be considered when anxiety symptoms are atypical or treatment-resistant, particularly with abrupt onset, cognitive changes, or personality shifts.

Clinical Presentation of Brain Tumors with Psychiatric Symptoms

Brain tumors can be "neurologically silent" and present exclusively with psychiatric manifestations 1. The key clinical features include:

• Depression is the most common psychiatric presentation (24% of brain tumor patients), followed by anxiety disorders (27% of patients have some psychiatric symptom) 2
• Frontal lobe tumors are particularly associated with psychiatric symptoms due to disruption of frontal-subcortical circuits 3
• Psychiatric symptoms may be the sole presenting complaint for months to years before diagnosis 1, 4
• Sudden onset without clear stressor, psychomotor retardation, speech fluency difficulties, and cognitive changes (memory, attention) are red flags 3

When to Suspect Brain Tumor vs. Primary Anxiety

Red Flags Requiring Neuroimaging:

• Recent-onset psychiatric symptoms (especially in younger patients without psychiatric history) 4
• Atypical features: personality changes, cognitive slowing, speech difficulties, or apathy accompanying anxiety 3
• Treatment resistance: failure to respond to standard anxiolytic therapy 5
• Abrupt onset without identifiable psychosocial stressor 3
• Progressive worsening despite appropriate treatment 1
• Age of onset: new psychiatric symptoms in patients without prior psychiatric history warrant higher suspicion 4

Important Caveat:

Patients with pre-existing psychiatric diagnoses are at particular risk for delayed brain tumor diagnosis, as symptoms may be attributed to their known condition 4. One case report documented a patient treated for PTSD and borderline personality disorder for over 4 years before glioblastoma was discovered 1.

Why Anxiety Medications Would Fail

If a brain tumor is the underlying cause:

• Structural brain pathology cannot be corrected by neurotransmitter modulation alone 6
• Peritumoral edema and mass effect disrupt normal neural circuits regardless of pharmacologic intervention 2
• Malignant tumors (particularly high-grade gliomas) are more commonly associated with psychiatric symptoms 2
• The location matters: frontal lobe lesions disrupt orbitofrontal and dorsolateral prefrontal circuits that regulate mood and anxiety 3

Diagnostic Approach

Obtain brain MRI with contrast if:

• New psychiatric symptoms with cognitive changes (attention, memory, speech fluency) 3
• Treatment failure after 8 weeks of appropriate pharmacologic/psychological intervention 5
• Any subtle neurological findings on examination 1
• Personality changes or apathy accompanying anxiety 3

Before attributing symptoms to primary anxiety disorder:

• First treat medical causes of anxiety symptoms (pain, fatigue, metabolic derangements) 5
• Assess for delirium (infection, electrolyte imbalance) 5
• Consider neuroimaging for atypical presentations 1, 4

Management Implications

If brain tumor is found:

• Do NOT prescribe prophylactic antiepileptic drugs if the patient has never had a seizure (Level A recommendation) 5
• Psychiatric symptoms often improve after tumor resection 4
• Standard depression/anxiety treatment guidelines still apply, but address the underlying tumor first 6

If no tumor is found:

• Reassess compliance with anxiety treatment and barriers to adherence 5
• After 8 weeks without improvement, alter treatment course (add psychological intervention, change medication, or refer to specialist) 5
• Consider tapering benzodiazepines if used, as they carry abuse risk and cognitive impairment 5

Critical Clinical Pearls

• Prevalence: Depression occurs in 21.7% of intracranial tumor patients and significantly worsens quality of life and survival 3
• Frontal tumors: Right frontal lesions typically cause disinhibition/irritability, but left-sided lesions can present with depression (though our evidence shows exceptions exist) 3
• Medication withdrawal: Abrupt SSRI discontinuation (as mentioned in your context) can cause withdrawal symptoms that mimic anxiety, but would not explain progressive cognitive decline or treatment resistance 5
• Apathy vs. depression: Frontal tumors may cause "sorrowless depression" with emotional blunting and reduced goal-directed behavior, which differs from primary major depression 3

The bottom line: In a patient with new anxiety, multiple medication failures, recent SSRI discontinuation, and particularly if there are ANY cognitive changes (memory, attention, speech), brain MRI is warranted to exclude structural pathology before attributing symptoms solely to psychiatric illness.