What is the differential diagnosis and recommended evaluation and treatment for a patient presenting with fatigue, nausea, dizziness, vertigo (motion‑related symptoms), headache, and hot flashes?

Differential Diagnosis and Management of Fatigue, Nausea, Dizziness, Motion Sickness, Headache, and Hot Flashes

Primary Consideration: Drug-Induced Adverse Reaction

The constellation of fatigue, nausea, dizziness, headache, and hot flashes strongly suggests an adverse drug reaction (ADR), particularly if the patient is taking serotonergic medications, as these symptoms align with SSRI discontinuation syndrome or early serotonin syndrome. 1

Key Diagnostic Features of SSRI Discontinuation Syndrome

• Dizziness, fatigue, lethargy, general malaise, headaches, nausea, vomiting, insomnia, imbalance, vertigo, and sensory disturbances characterize this syndrome, particularly with shorter-acting SSRIs like paroxetine, fluvoxamine, and sertraline 1
• Symptoms typically occur following missed doses or acute discontinuation 1
• Hot flashes may represent autonomic dysregulation associated with serotonergic medication effects 1

Critical First Step: Medication History

Obtain a detailed medication history focusing on:

• Recent initiation, dose changes, or discontinuation of SSRIs, SNRIs, TCAs, or other serotonergic drugs (antidepressants, tramadol, meperidine, methadone, fentanyl, dextromethorphan) 1
• Over-the-counter products including St. John's wort, L-tryptophan, diet pills 1
• Timing of symptom onset relative to medication changes (typically within 24-48 hours) 1
• Polypharmacy in older patients, as ADRs cause nonspecific symptoms in 10% of emergency department presentations and are missed 60% of the time 2

Secondary Differential Diagnoses

Vestibular Disorders

If dizziness is episodic and positional, consider Ménière's disease or benign paroxysmal positional vertigo (BPPV):

• Ménière's disease: Two or more episodes of vertigo lasting 20 minutes to 12 hours, with fluctuating hearing loss, tinnitus, or ear fullness 1
• BPPV: Brief episodes triggered by specific head position changes 1
• Perform Dix-Hallpike maneuver to diagnose BPPV 1
• Obtain audiogram when assessing for Ménière's disease 1

Orthostatic Hypotension and Autonomic Dysfunction

If symptoms worsen upon standing and improve when lying down:

• Measure orthostatic vital signs (blood pressure and heart rate supine and after 3 minutes of standing) 1
• Classical orthostatic hypotension: BP drop starts immediately on standing with sustained low BP 1
• Delayed orthostatic hypotension: BP drop occurs beyond 3 minutes of standing 1
• Autonomic neuropathy may present with orthostatic hypotension, nausea, sweating abnormalities, and GI difficulties 1

Migraine

If headache is the predominant symptom with associated nausea and dizziness:

• Migraine commonly presents with headache, nausea, vomiting, and dizziness 1
• Vestibular migraine can cause motion-related symptoms 1

Perimenopause/Menopause (if applicable)

• Hot flashes combined with fatigue and headache may indicate hormonal transition in women of appropriate age
• However, this would not explain acute dizziness or nausea unless combined with another condition

Serotonin Syndrome (if on multiple serotonergic agents)

Monitor for progression to severe symptoms:

• Combining two or more serotonergic drugs increases risk 1
• Early symptoms include nausea, dizziness, headache, and autonomic instability 1
• Caution is required especially in the first 24-48 hours after dosage changes 1

Diagnostic Evaluation Algorithm

Step 1: Immediate Assessment

• Vital signs including orthostatic measurements 1
• Complete medication reconciliation including timing of recent changes 1, 2
• Neurological examination to exclude central causes 1

Step 2: Targeted Testing Based on History

If medication-related:

• No specific testing required; diagnosis is clinical 1
• Consider electrolytes if vomiting is severe 1

If vestibular symptoms predominate:

• Dix-Hallpike maneuver for BPPV 1
• Audiogram if hearing symptoms present 1
• Consider MRI brain only if central causes suspected (focal neurological signs, severe headache, altered consciousness) 1

If autonomic dysfunction suspected:

• Screen for diabetes, adrenal insufficiency, HIV, parproteinemia, amyloidosis 1
• Consider neurology consultation for electrodiagnostic studies 1

Step 3: Exclude Serious Causes

• Rule out cardiac arrhythmias if syncope or presyncope occurred 1
• Exclude CNS pathology (stroke, tumor, infection) if focal neurological signs, altered mental status, or severe progressive headache 1
• Consider pulmonary embolism if acute dyspnea or chest pain present 1

Management Approach

If Drug-Induced (Most Likely Scenario)

For SSRI Discontinuation Syndrome:

• Reinitiate the discontinued SSRI at the previous dose or switch to a longer-acting SSRI like fluoxetine 1
• Taper slowly over weeks to months rather than abrupt discontinuation 1
• Symptoms typically resolve within days of reinitiation 1

For Early Serotonin Syndrome:

• Immediately discontinue all serotonergic agents 1
• Provide supportive care 1
• Monitor closely for progression 1

If Vestibular Disorder

For BPPV:

• Perform particle repositioning maneuvers (Epley maneuver) as first-line treatment, which demonstrates 4.1 times greater symptom resolution compared to observation 3
• Do NOT use vestibular suppressants (meclizine, promethazine) routinely, as they interfere with central compensation and prolong recovery 3, 4
• Limited use of vestibular suppressants (12.5-25 mg promethazine IV slowly) only for severe, intractable nausea/vomiting in acutely symptomatic patients who cannot tolerate repositioning 3

For Ménière's Disease:

• Offer limited course of vestibular suppressants for acute episodes 1
• Consider intratympanic steroids or gentamicin for refractory cases 1

If Orthostatic Hypotension

• Increase fluid and salt intake 1
• Review and adjust medications that may contribute (antihypertensives, diuretics) 1
• Compression stockings and physical countermaneuvers 1

If Migraine

• NSAIDs (aspirin, ibuprofen, naproxen sodium) as first-line therapy for acute attacks 1
• Triptans or DHE if NSAIDs ineffective 1
• Antiemetics for nausea (not restricted to patients actively vomiting) 1
• Consider preventive therapy if attacks occur ≥2 times per month 1

Critical Pitfalls to Avoid

Do Not Use Promethazine or Meclizine as Primary Treatment for Dizziness

• These medications do not treat the underlying cause and may interfere with vestibular compensation 3, 4
• In older adults, promethazine causes hypotension, CNS depression, and increased fall risk—particularly dangerous when dizziness already predisposes to falls 3
• Anticholinergic effects (dry mouth, blurred vision, urinary retention) are problematic in elderly patients 3

Do Not Miss Drug-Induced Causes

• ADRs are responsible for 10% of nonspecific symptom presentations but are correctly identified in only 40% of cases 2
• Patients do not report all suspected ADR symptoms to physicians, and physicians do not document all reported symptoms 5
• Patient expectations, anxiety, and prior conditioning can amplify nonspecific side effects 6

Do Not Overlook Serious Causes

• Cardiac syncope from arrhythmias requires ECG and cardiac monitoring 1
• Central nervous system causes (stroke, tumor, infection) require neuroimaging if focal signs or altered consciousness present 1
• Posterior reversible encephalopathy syndrome (PRES) can present with headache, visual disturbances, and altered consciousness, requiring urgent blood pressure control and MRI 1

Reassessment Timeline

• Reassess within 1 month after initial treatment to confirm symptom resolution 3
• If symptoms persist or worsen despite appropriate treatment, reconsider the diagnosis and evaluate for concurrent conditions 1
• Monitor for sequelae if drug-induced hypersensitivity syndrome suspected 7