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 23-year-old woman is brought to the physician by her father because of irritability, mood swings, and difficulty sleeping over the past 10 days. A few days ago, she quit her job and spent all of her savings on supplies for a “genius business plan.” She has been energetic despite sleeping only 1–2 hours each night. She was diagnosed with major depressive disorder 2 years ago. Mental status examination shows pressured speech, a labile affect, and flight of ideas. Throughout the examination, she repeatedly states “I feel great, I don't need to be here.” Urine toxicology screening is negative. Which of the following is the most likely diagnosis?

Attention-deficit hyperactivity disorder

A 28-year-old woman is brought to the emergency department by her friends. She is naked except for a blanket and speaking rapidly and incoherently. Her friends say that she was found watering her garden naked and refused to put on any clothes when they tried to make her do so, saying that she has accepted how beautiful she is inside and out. Her friends say she has also purchased a new car she can not afford. They are concerned about her, as they have never seen her behave this way before. For the past week, she has not shown up at work and has been acting ‘strangely’. They say she was extremely excited and has been calling them at odd hours of the night to tell them about her future plans. Which of the following drug mechanisms will help with the long-term management this patient’s symptoms?

Inhibition of inositol monophosphatase and inositol polyphosphate 1-phosphatase

Increase the concentration of dopamine and norepinephrine at the synaptic cleft

Modulate the activity of gamma-aminobutyric acid receptors

Acts as an antagonist at the dopamine, serotonin and adrenergic receptors

Inhibit the reuptake of norepinephrine and serotonin from the presynaptic cleft

First episode management for USMLE Step 1: High-Yield Psychiatry Lessons

Initial Workup - Spotting the Storm

Assess Episode Type: Is it Mania or Hypomania?
- Mania: Symptoms ≥ 1 week, causing marked functional impairment, hospitalization, or psychosis.
- Hypomania: Symptoms ≥ 4 days, observable change in function, but no marked impairment/hospitalization/psychosis.
Evaluate Symptoms: Use the 📌 DIGFAST mnemonic:
- Distractibility
- Indiscretion (risky behaviors)
- Grandiosity
- Flight of ideas
- Activity increase
- Sleep deficit
- Talkativeness
Rule Out Other Causes:
- Substances: Cocaine, amphetamines, high-dose steroids. Order a UDS.
- Medical: Hyperthyroidism, neurologic conditions. Order a TSH.

⭐ Always screen for substance use (UDS) and thyroid dysfunction (TSH) in a patient with new-onset manic symptoms.

Acute Mania - Taming the Tempest

Immediate Goal: Rapid stabilization & ensure safety. Prioritize de-escalation.
Severe Mania / Agitation: Hospitalization is paramount.
- For acute agitation, use intramuscular (IM) medication:
  - Olanzapine
  - Ziprasidone

Rapid Tranquilization Protocol for Psychotic Illness

Pharmacotherapy First-Line:
- Mood Stabilizers: Lithium (acute target: 0.8-1.2 mEq/L) or Valproate.
- Second-Gen Antipsychotics (SGAs): Risperidone, Olanzapine, Quetiapine. Can be used as monotherapy or adjunctively with mood stabilizers for quicker symptom control.

⭐ For an acutely agitated manic patient, a combination of an antipsychotic (e.g., olanzapine) and a benzodiazepine (e.g., lorazepam) is often used for rapid tranquilization.

Bipolar Depression - The Other First Face

Often the initial presentation of Bipolar I or II. Misdiagnosis as unipolar depression is common and dangerous.
Primary Goal: Treat depression without inducing mania.
First-Line Pharmacotherapy:
- Monotherapy with Second-Generation Antipsychotics (SGAs): Quetiapine, Lurasidone.
- Combination therapy: Olanzapine-fluoxetine.
Maintenance, Not Acute:
- Lamotrigine is effective for maintenance to prevent future depressive episodes.
- ⚠️ Requires slow titration due to the risk of Stevens-Johnson Syndrome (SJS).

⭐ Antidepressant monotherapy (e.g., SSRIs) is contraindicated. It can precipitate a manic or hypomanic episode in a patient with unrecognized bipolar disorder.

High‑Yield Points - ⚡ Biggest Takeaways

Differentiating from unipolar depression is critical; a history of mania or hypomania is definitional.

For acute mania, first-line agents are mood stabilizers (Lithium, Valproate) or second-generation antipsychotics (SGAs).

Severe mania often requires combination therapy: a mood stabilizer PLUS an SGA.

Antidepressant monotherapy is contraindicated due to the risk of precipitating a manic episode.

If mania emerges while on an antidepressant, taper and discontinue the antidepressant immediately.

Treat bipolar depression with mood stabilizers or specific SGAs (e.g., quetiapine, lurasidone), not antidepressants alone.

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