Question 36: A 22-year-old college student is brought to the emergency department by friends after taking MDMA (ecstasy) at a party. He is agitated, confused, has a temperature of 104°F (40°C), tachycardia, hypertension, dilated pupils, and muscle rigidity. What is the most likely diagnosis?
A) Neuroleptic malignant syndrome
B) Serotonin syndrome
C) Malignant hyperthermia
D) Anticholinergic toxicity
Answer: B) Serotonin syndrome
Explanation:
This patient has serotonin syndrome, a potentially life-threatening condition caused by excessive serotonergic activity in the central nervous system, in this case from MDMA (3,4-methylenedioxymethamphetamine, “ecstasy”).
Serotonin Syndrome Pathophysiology:
* Excessive serotonin in CNS and peripheral serotonin receptors
* Caused by medications/drugs that: Increase serotonin synthesis, release, or directly activate receptors; Decrease reuptake or metabolism.
Common Causative Agents:
* Illicit drugs: MDMA (ecstasy) ← THIS PATIENT, Cocaine, Amphetamines, LSD.
* Psychiatric medications: SSRIs (fluoxetine, sertraline, etc.), SNRIs (venlafaxine), MAOIs (phenelzine, etc.), TCAs (clomipramine), Trazodone, Lithium, Buspirone.
* Other medications: Tramadol, Meperidine, Fentanyl, Dextromethorphan (cough suppressant), Linezolid (antibiotic with MAOI activity), Metoclopramide, Ondansetron.
* Supplements: St. John’s Wort, Tryptophan.
* Highest risk: Combination of agents (e.g., SSRI + MAOI is contraindicated!).
Hunter Serotonin Toxicity Criteria:
Required: Patient has taken a serotonergic agent PLUS one of the following:
1. Spontaneous clonus
2. Inducible clonus + (agitation OR diaphoresis)
3. Ocular clonus + (agitation OR diaphoresis)
4. Tremor + hyperreflexia
5. Hypertonia + temperature >38°C + (ocular clonus OR inducible clonus)
Classic Triad:
1. Mental status changes: Agitation, confusion, restlessness.
2. Autonomic hyperactivity: Hyperthermia, tachycardia, hypertension, diaphoresis, dilated pupils (mydriasis).
3. Neuromuscular abnormalities: Tremor, clonus, hyperreflexia, muscle rigidity.
Differential Diagnosis Table:
* NMS: Caused by Antipsychotics. Onset is days to weeks (slow). Features “Lead pipe” rigidity, normal reflexes, and normal pupils. Resolves in 1-2 weeks.
* Serotonin Syndrome: Caused by Serotonergics. Onset is hours (rapid). Features Hyperreflexia/clonus and dilated pupils. Resolves in 24-72 hours.
* Malignant Hyperthermia: Triggered by anesthetic agents (succinylcholine, volatile gases). Severe rigidity and high CK. Treatment is Dantrolene.
* Anticholinergic Toxicity: “Mad as a hatter, dry as a bone.” Key distinction: Anticholinergic = DRY (no sweating). Serotonin syndrome = DIAPHORESIS (profuse sweating).
Treatment:
1. Discontinue agent immediately.
2. Supportive care: IV fluids, Oxygen, cooling (ice packs). Avoid antipyretics (don’t work here).
3. Benzodiazepines: For agitation/rigidity (Lorazepam/Diazepam).
4. Cyproheptadine: Serotonin antagonist (12 mg initial, then 2 mg q2h).
5. Complications: Rhabdomyolysis → aggressive IV fluids; Renal failure → dialysis.
Question 37: A 45-year-old man with schizophrenia has been taking haloperidol for 2 years. He now presents with involuntary, repetitive movements of his tongue, lips, and jaw, including lip smacking and tongue protrusion. What is the most likely diagnosis?
A) Acute dystonia
B) Akathisia
C) Parkinsonism
D) Tardive dyskinesia
Answer: D) Tardive dyskinesia (TD)
Explanation:
This patient has tardive dyskinesia (TD), a potentially irreversible movement disorder that develops after chronic use (months to years) of dopamine receptor blocking agents (antipsychotics).
Pathophysiology:
* Dopamine receptor supersensitivity in the basal ganglia after chronic blockade.
Causative medications:
* 1st Gen (Typical): Haloperidol (Highest risk), Chlorpromazine, Fluphenazine.
* 2nd Gen (Atypical): Risperidone, Olanzapine, Quetiapine (Lower risk).
* Others: Metoclopramide (can cause TD even with short-term use), Prochlorperazine.
Risk Factors:
* Older age, female gender, longer duration of use, diabetes mellitus, African American ethnicity.
* Incidence with Typical antipsychotics: ~5% per year of exposure.
Clinical Features (Classic Movements):
* Orofacial (Most common): Tongue protrusion, lip smacking, puckering, chewing movements, facial grimacing.
* Limb: Choreiform (jerky), athetoid (writhing), finger movements (piano-playing).
* Trunk: Rocking, pelvic thrusting.
* Characteristics: Involuntary, purposeless, worse with stress, disappears during sleep.
Extrapyramidal Symptoms (EPS) Timeline:
1. Acute Dystonia (Hours to Days): Muscle spasms, torticollis, oculogyric crisis. Tx: Benztropine.
2. Akathisia (Days to Weeks): Restlessness, pacing. Tx: Beta-blockers (Propranolol).
3. Parkinsonism (Days to Weeks): Tremor, rigidity, bradykinesia. Tx: Lower dose, switch to atypical.
4. Tardive Dyskinesia (Months to Years): Involuntary repetitive movements.
Treatment of TD:
* Step 1: Reevaluate need for antipsychotic. If possible, stop or taper (TD may improve in 30-50% of cases). Switch to Clozapine or Quetiapine (lowest risk).
* Step 2 (FDA-Approved): VMAT2 Inhibitors (Valbenazine/Ingrezza and Deutetrabenazine/Austedo). These are now considered FIRST-LINE.
* Step 3: Clonazepam, Amantadine, or Ginkgo biloba.
* What NOT to do: Do NOT increase the antipsychotic dose (this masks symptoms but worsens the underlying TD).
Question 38: A 50-year-old man presents with depressed mood, anhedonia, insomnia, fatigue, and feelings of worthlessness for the past 3 weeks. He also reports significant unintentional weight loss. Physical examination reveals a pulse of 110 bpm, blood pressure 150/95 mmHg, and hand tremor. What should be the next step in management?
A) Start SSRI antidepressant
B) Refer for psychotherapy
C) Check thyroid function tests
D) Start benzodiazepine for anxiety
Answer: C) Check thyroid function tests
Explanation:
This patient presents with depressive symptoms along with physical signs suggestive of hyperthyroidism (tachycardia, hypertension, tremor, weight loss). Medical causes must be ruled out before diagnosing primary psychiatric illness.
Critical Principle:
Must rule out medical causes (especially in first episode or atypical presentations) before attributing symptoms to a primary psychiatric disorder.
Hyperthyroidism (Thyrotoxicosis) Psychiatric Manifestations:
* Mood: Anxiety (most common), Depression (especially in elderly), Irritability.
* Cognitive: Poor concentration, racing thoughts.
* Apathetic Thyrotoxicosis: In the elderly, hyperthyroidism can present with apathy and depression rather than hyperactivity.
Physical Signs in this Patient:
* Tachycardia (Pulse 110), Hypertension (150/95), Hand tremor, Unintentional weight loss.
Thyroid Function Tests (TFTs):
1. TSH (Best Initial Test): Low TSH suggests hyperthyroidism; High TSH suggests hypothyroidism.
2. Free T4/T3: Checked if TSH is abnormal.
* Hyperthyroidism: Low TSH + High T4/T3.
* Hypothyroidism: High TSH + Low T4. (Hypothyroidism is a very common cause of depression).
[Image of Hypothalamic-Pituitary-Thyroid Axis]
Other Medical Causes of Depression to Consider:
* Endocrine: Cushing’s, Addison’s, Diabetes.
* Neurological: Stroke, Parkinson’s, MS, Brain tumors.
* Infections: HIV, Neurosyphilis, Lyme, Hepatitis C.
* Nutritional: Vitamin B12, Folate, Vitamin D, Thiamine deficiency.
* Malignancy: Pancreatic cancer (depression is often the first symptom).
* Meds: Corticosteroids, Beta-blockers (propranolol), Interferon, Isotretinoin.
Basic Workup for New-Onset Depression:
* CBC, CMP (electrolytes/glucose), TSH (Essential), Vitamin B12, Folate, Vitamin D.
Why other options are incorrect:
* A) SSRI: Premature. If symptoms are due to hyperthyroidism, SSRIs may be ineffective and can worsen tremor/anxiety.
* B) Psychotherapy: Premature. Will not address the underlying physiological cause.
* D) Benzodiazepine: Inappropriate. Can worsen depression and does not address the medical cause.
