What is the best course of action for a patient with anxiety, weight loss, paresthesias, and cognitive impairment, who is taking fluoxetine, escitalopram, divalproex, buspirone, dextroamphetamine-amphetamine, and Lybalvi (olanzapine and samidorphan), and is suspected of having a brain tumor?

Immediate Diagnostic Workup for Suspected Brain Tumor

This patient requires urgent brain MRI with contrast to confirm or rule out a brain tumor, as cognitive impairment with paresthesias and weight loss warrant immediate neuroimaging regardless of psychiatric medication burden. 1

Critical First Steps

Obtain contrast-enhanced brain MRI immediately as this is the gold standard for detecting brain tumors and determining their number, size, and location. 2 MRI can reliably rule out a brain tumor when performed properly and interpreted by experts. 3

Key Clinical Context

• Cognitive impairment is present in 90% of patients with primary brain tumors and 91% with brain metastases before any treatment begins. 1
• Depression and psychiatric symptoms can be the sole presenting feature of frontal lobe tumors, particularly in younger patients, even without obvious neurological signs. 4, 5
• The combination of cognitive impairment, weight loss, and paresthesias in this clinical context demands imaging before attributing symptoms to psychiatric illness or medication side effects. 1

Medication Review and Management

Immediate Medication Concerns

Review and potentially reduce the polypharmacy burden, as multiple psychotropic medications can contribute to cognitive impairment, though this should not delay neuroimaging. 1

• Olanzapine (in Lybalvi) carries high risk for weight gain, not weight loss, making the weight loss in this patient more concerning for organic pathology. 6
• Divalproex is an enzyme-inducing anticonvulsant that should be avoided if a brain tumor is confirmed, as it interferes with chemotherapy metabolism. 1
• The combination of fluoxetine and escitalopram (both SSRIs) is redundant and increases serotonin syndrome risk, particularly with other medications. 7

If Brain Tumor is Confirmed

Switch divalproex to levetiracetam or lamotrigine immediately if the patient has a seizure history, as these are non-enzyme-inducing options preferred in brain tumor patients. 1, 8

Do NOT start prophylactic antiepileptic drugs if the patient has never had a seizure, as this is contraindicated (Level A recommendation). 1, 8

Addressing Cognitive Impairment

Initial Approach

Screen for and address reversible contributors to cognitive dysfunction before attributing symptoms solely to a potential tumor:

• Depression (already being treated, but inadequately with dual SSRIs)
• Pain (assess for headaches or other pain)
• Fatigue (common with both psychiatric medications and brain tumors)
• Sleep disturbance (multiple medications affect sleep)
• Medication effects (polypharmacy burden is substantial) 1

If Tumor-Related Cognitive Impairment is Confirmed

Memory and executive functioning are the most frequently impaired domains in brain tumor patients, caused by both the tumor itself and disruption of cognitive networks. 1

Prioritize nonpharmacologic interventions first for cognitive rehabilitation, including:

• Cognitive rehabilitation therapy
• Exercise programs
• Structured cognitive training 1

Consider stimulant therapy only as last-line treatment after nonpharmacologic interventions fail:

• Modafinil 100-200 mg daily is the preferred first choice, with more consistent evidence for improving memory, attention, and psychomotor speed in brain tumor patients. 1, 8
• Titrate up to 600 mg daily as needed, with 83% of patients reporting improvement in fatigue. 8
• Alternative: Methylphenidate 10 mg twice daily, increasing to 20-30 mg twice daily if tolerated, though evidence is more mixed. 1, 8
• Monitor for insomnia, agitation, headache, nausea, and anorexia. 8

Management Algorithm if Tumor is Confirmed

Acute Symptom Management

Start dexamethasone 16 mg/day in divided doses if there is moderate to severe mass effect or cerebral edema causing symptoms. 2, 9

• Higher doses up to 100 mg/day may be needed for acute neurologic deterioration or impending herniation. 2, 9
• Taper steroids as quickly as clinically possible to minimize toxicity including personality changes, immunosuppression, metabolic derangements, and insomnia. 2, 9

Seizure Prophylaxis Decision

If the patient has had a seizure:

• Start antiepileptic treatment immediately
• Levetiracetam or lamotrigine are first-line choices due to efficacy and tolerability 1
• Continue secondary prophylaxis until local tumor control is achieved 1

If the patient has never had a seizure:

• Do NOT prescribe prophylactic antiepileptics (Level I, Grade A recommendation) 1, 8

Critical Pitfalls to Avoid

Never attribute new-onset cognitive impairment and weight loss solely to psychiatric illness without neuroimaging, especially when symptoms are atypical or sudden in onset. 4, 5

Never continue enzyme-inducing anticonvulsants (like divalproex) in confirmed brain tumor patients, as they interfere with chemotherapy and targeted therapy metabolism. 1

Never delay imaging because psychiatric medications "explain" the symptoms—brain tumors frequently present with psychiatric symptoms as the initial or sole manifestation, particularly with frontal lobe involvement. 4, 5

Never use prophylactic antiepileptic drugs in brain tumor patients without seizure history, as this provides no benefit and adds medication burden. 1, 8

Follow-Up Monitoring

Serial MRI scans are essential to assess treatment response if a tumor is confirmed. 2

Question patients about seizure occurrence at each follow-up visit if they have a seizure history. 1

Reassess cognitive function and medication efficacy at 2-4 week intervals, discontinuing stimulants if no benefit is observed. 8