A 25-year-old woman presents to the psychiatric emergency department in restraints. She was found trying to break into a deli at midnight. The patient claims that she has an idea that will revolutionize the shipping industry. The patient is not violent but seems highly agitated and is speaking very rapidly about her ideas. She is easily distractible and tells you about many of her other ideas. She has a past medical history of depression and hypertension refractory to treatment. Her current medications include captopril, ibuprofen, and melatonin. A neurological exam is deferred due to the patient's current status. Her pulmonary and cardiovascular exams are within normal limits and mild bilateral bruits are heard over her abdomen. The patient is given haloperidol and diphenhydramine and spends the night in the psychiatric inpatient unit. The patient is started on long-term therapy and is discharged 3 days later. At a follow up visit at her primary care physician, the patient is noted to have a blood pressure of 150/100 mmHg. She is started on chlorthalidone and instructed to return in 3 days. When the patient returns her blood pressure is 135/90 mmHg. She exhibits a fine tremor, and complains of increased urinary frequency. Her pulse is 47/minute, and she is afebrile. Which of the following is the best next step in management?

Ultrasound of the renal arteries

Maintain current medication regimen

A 24-year-old woman is brought to the emergency department by her roommate because of bizarre behavior and incoherent talkativeness for the past week. Her roommate reports that the patient has been rearranging the furniture in her room at night and has ordered a variety of expensive clothes online. The patient says she feels “better than ever” and has a lot of energy. She had absence seizures as a child and remembers that valproate had to be discontinued because it damaged her liver. She has been otherwise healthy and is not taking any medication. She is sexually active with her boyfriend. She does not smoke, drink alcohol, or use illicit drugs. Physical and neurologic examinations show no abnormalities. Her pulse is 78/min, respirations are 13/min, and blood pressure is 122/60 mm Hg. Mental status examination shows pressured and disorganized speech, flight of ideas, lack of insight, and affective lability. Which of the following is the best initial step before deciding on a therapy for this patient's condition?

Obtain TSH, β-hCG, and serum creatinine concentration

Obtain CBC, liver function studies, and beta-HCG

Obtain BMI, HbA1c, lipid levels, and prolactin levels

Perform urine drug testing and begin cognitive behavior therapy

Assess for suicidal ideation and obtain echocardiography

A 50-year-old man is brought to his neurologist by his wife for bizarre behavior. On several occasions over the last several days, he had started to complain about ‘bunnies, tigers, and emus’ in the living room. The patient has a history of multiple sclerosis and was last seen by his primary neurologist 2 weeks ago for complaints of new left upper extremity weakness. On physical exam, his temperature is 37.0°C (98.6°F), the heart rate is 70/min, the blood pressure is 126/78 mm Hg, the respiratory rate is 16/min, and the oxygen saturation is 98% on room air. The exam is disrupted by the patient’s repeated comments about various animals in the exam room. His neurologic exam is unchanged from his neurologist's last documented exam. The basic metabolic panel is as follows: Na+ 138 mEq/L K+ 3.9 mEq/L Cl- 101 mEq/L HCO3- 24 mEq/L BUN 10 mg/dL Cr 0.6 mg/dL Glucose 356 mg/dL Which of the following is the most likely etiology of this patient's presentation?

Progression of neurologic disease

A 27-year-old woman is brought to the office at the insistence of her fiancé to be evaluated for auditory hallucinations for the past 8 months. The patient’s fiancé tells the physician that the patient often mentions that she can hear her own thoughts speaking aloud to her. The hallucinations have occurred intermittently for at least 1-month periods. Past medical history is significant for hypertension. Her medications include lisinopril and a daily multivitamin both of which she frequently neglects. She lost her security job 7 months ago after failing to report to work on time. The patient’s vital signs include: blood pressure 132/82 mm Hg; pulse 72/min; respiratory rate 18/min, and temperature 36.7°C (98.1°F). On physical examination, the patient has a flat affect and her focus fluctuates from the window to the door. She is disheveled with a foul smell. She has difficulty focusing on the discussion and does not quite understand what is happening around her. A urine toxicology screen is negative. Which of the following is the correct diagnosis for this patient?

Schizotypal personality disorder

A 23-year-old man presents to the emergency department with a chief complaint of being assaulted on the street. The patient claims that he has been followed by the government for quite some time and that he was assaulted by a government agent but was able to escape. He often hears voices telling him to hide. The patient has an unknown past medical history and admits to smoking marijuana frequently. On physical exam, the patient has no signs of trauma. When interviewing the patient, he is seen conversing with an external party that is not apparent to you. The patient states that he is afraid for his life and that agents are currently pursuing him. What is the best initial response to this patient’s statement?

It sounds like you have been going through some tough experiences lately.

I think you are safe from the agents here.

You have a mental disorder but don’t worry we will help you.

I don’t think any agents are pursuing you.

What medications are you currently taking?

Psychosis due to medical conditions — USMLE Lesson

Core Concepts - Not Just Delirium

Distinguished from delirium by a clear sensorium and normal level of consciousness. Psychotic symptoms are the core feature, not a consequence of attentional deficits.
Requires evidence from history, physical exam, or labs that hallucinations/delusions are a direct physiological result of a specific medical condition.
A close temporal association between the medical illness (onset, exacerbation) and psychotic symptoms is essential for diagnosis.
Common etiologies:
- Neurologic: Seizures (post-ictal), CNS tumors, stroke, Huntington's disease
- Endocrine: Cushing's syndrome, thyroid/parathyroid disorders
- Autoimmune/Inflammatory: SLE, anti-NMDA receptor encephalitis

⭐ Visual hallucinations are more common than auditory ones, a key feature distinguishing it from primary psychotic disorders like schizophrenia.

Common Culprits - The Body's Rebellion

Neurologic Causes
- CNS Infections (e.g., HSV encephalitis, neurosyphilis)
- Cerebrovascular Disease (Strokes, vasculitis)
- Degenerative Disorders (Huntington's, Lewy Body Dementia)
- Seizure-related (ictal, post-ictal)
- Space-occupying lesions (neoplasms)
- Autoimmune (e.g., Anti-NMDA receptor encephalitis, SLE cerebritis)
- Traumatic Brain Injury (TBI)
Endocrine & Metabolic
- Thyroid dysfunction (thyrotoxicosis, myxedema madness)
- Adrenal disorders (Cushing's, Addison's)
- Electrolyte imbalance (↓Na+, ↑Ca2+)
- Hypoglycemia
- Organ failure (uremia, hepatic encephalopathy)
Systemic & Nutritional
- Infections (HIV, sepsis)
- Vitamin deficiencies (B12, B1, B3)

⭐ Anti-NMDA Receptor Encephalitis: A critical diagnosis to consider in young patients (especially women) with new-onset psychosis, seizures, dyskinesias, and autonomic instability. Frequently paraneoplastic, associated with ovarian teratomas.

Workup & Management - Sleuthing & Soothing

Core Principle: Identify and treat the underlying medical etiology. Psychosis should resolve as the medical condition improves.
Initial Workup:
- History & Physical: Focus on new medications, substance use, and systemic signs of illness.
- Labs: CBC, CMP, TSH, Vitamin B12/folate, urinalysis, urine drug screen.
- Targeted Tests: RPR/VDRL (syphilis), HIV screen, ANA (lupus), ceruloplasmin (Wilson's), LP (if CNS infection/inflammation suspected).
- Imaging/Function: Brain CT/MRI, EEG.

Management:
- Primary: Address the root medical cause (e.g., antibiotics for infection, steroids for autoimmune).
- Symptomatic: Use low-dose, short-term antipsychotics (e.g., Haloperidol, Risperidone) for agitation/psychosis.
- Environment: Ensure patient safety and provide a calm, structured setting.

⭐ Exam Favorite: Always consider anti-NMDA receptor encephalitis in young women presenting with new-onset psychosis, psychiatric symptoms, and subtle neurological signs (e.g., seizures, dyskinesias).

Brain MRI: FLAIR hyperintensity in limbic encephalitis

High-Yield Points - ⚡ Biggest Takeaways

This is a diagnosis of exclusion, requiring a thorough workup to rule out other causes.

A clear temporal relationship between the general medical condition and the psychosis is essential for diagnosis.

Be suspicious with atypical features like late age of onset, visual hallucinations, or fluctuating consciousness.

Key causes include CNS disease (tumors, seizures), endocrinopathies, autoimmune disorders (SLE), and metabolic disturbances.

Management priority is to treat the underlying medical condition first and foremost.

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