A 7-year-old boy is brought to the physician because of spells of unresponsiveness and upward rolling of the eyes for 2 months. The episodes start abruptly and last a few seconds. During that time he does not hear anyone’s voice or make any purposeful movements. When the episodes end, he continues what he was doing before the spell. He does not lose his posture or fall to the ground. Episodes occur multiple times during the day. Physical examination shows no abnormal findings. An EEG following hyperventilation shows 3 Hz spike-and-slow-wave discharges. Which of the following is the most appropriate pharmacotherapy at this time?

No pharmacotherapy at this time

A 24-year-old male comes into the psychiatric clinic complaining of consistent sadness. He endorses feelings of worthlessness, anxiety, and anhedonia for the past couple months but denies feeling suicidal. He further denies any past episodes of feeling overly energetic with racing thoughts. Confident of the diagnosis, you recommend frequent talk therapy along with a long-term prescription of a known first-line medication for this disorder. What is the drug and what are some of the most frequently encountered side effects?

Selective serotonin reuptake inhibitor; anorgasmia, insomnia

Selective serotonin reuptake inhibitor; hypomania, suicidal thoughts

Tricyclic antidepressants; hypomania, suicidal thoughts

Monoamine oxidase inhibitors; Orthostatic hypotension, weight gain

Tricyclic antidepressants; Orthostatic hypotension, anticholinergic effects

A 38-year-old woman presents to her primary care physician for complaints of insomnia. She states that for the last 8 months, she has had difficulty falling asleep. Additionally, she awakens in the middle of the night or early morning and cannot fall back to sleep. When further questioned, she reports decreased appetite with a 12-lb. weight loss in the last 6 months. She was recently demoted at her work as a baker due to trouble focusing and coordinating orders and excess fatigue. She feels she is to blame for her family's current financial status given her demotion. She is given a prescription for fluoxetine at this visit with follow-up 2 weeks later. At the follow-up visit, she reports no improvement in her symptoms despite taking her medication consistently. What is the most appropriate next step in management?

Increase dose of current medication

ECT and neuromodulation therapies — USMLE Lesson

ECT - The Gold Standard Shock

ECT Electrode Placement: Bifrontal, Bilateral, Unilateral

Indications:
- Treatment-Resistant Depression (TRD)
- Catatonia
- Acute suicidality
- Refusal to eat/drink
- Depression with psychotic features
Mechanism: Neurotransmitter modulation
- ↓ β-adrenergic receptors
- ↑ 5-HT₂ and GABA receptors
Contraindications: None absolute. Relative contraindications include:
- Space-occupying CNS lesion
- Recent MI or CVA
- High anesthetic risk (ASA class 4/5)
Procedure & Seizure Goal: Induce a generalized seizure lasting 25-60s.

Adverse Effects:
- Post-ictal confusion & delirium
- Headache, nausea
- Anterograde & retrograde amnesia (often transient)
- 📌 Mnemonic (Side Effects): ECT = Electrical Current Therapy causes Headache, Amnesia, Delirium (HEAD).

⭐ High-Yield: The most common adverse effect is temporary amnesia, both anterograde (trouble forming new memories) and retrograde (loss of memory for events preceding treatment). Unilateral placement may reduce memory loss.

Neuromodulation - Beyond the Current

Newer therapies modulate neural circuits implicated in depression, offering alternatives when medications fail.

Vagus Nerve Stimulation (VNS) Device Placement

Therapy	Mechanism	Indication	Key Side Effects
rTMS	Repetitive magnetic pulses stimulate focal areas (e.g., DLPFC).	Treatment-Resistant Depression (TRD), especially with inadequate response to ≥1 antidepressant.	Headache, scalp pain, rare seizures.
VNS	Implanted device intermittently stimulates the left vagus nerve.	Adjunctive therapy for chronic TRD (≥4 failed treatments).	Hoarseness, cough, dyspnea.
DBS	Electrodes implanted in specific brain regions (e.g., subgenual cingulate).	Highly refractory TRD (investigational).	Surgical risks (infection, hemorrhage), stimulation-related mood changes.
MST	Magnetic fields induce a more focal seizure than ECT.	TRD; aims for ECT's efficacy with fewer cognitive side effects.	Headache, nausea; less memory impairment than ECT.

Therapy Face-Off - Compare & Contrast

Feature	ECT (Electroconvulsive)	rTMS (Transcranial Magnetic)	VNS (Vagus Nerve)
Invasiveness	Most	Non-invasive	Invasive (implant)
Anesthesia	General	No	Yes (for implant)
Seizure	✅ Induced	❌ No (rare risk)	❌ No
Efficacy	↑↑↑ Highest	↑↑ Moderate	↑ Modest (adjunct)
Onset	Rapid (1-2 wks)	Slow (4-6 wks)	Very Slow (months)
Side Effects	Cognitive (amnesia)	Local (scalp pain)	Local (hoarseness)

High‑Yield Points - ⚡ Biggest Takeaways

ECT is the most effective treatment for severe, treatment-resistant depression, especially with psychotic features or catatonia.

The most significant adverse effect is anterograde and retrograde amnesia, which is typically transient.

There are no absolute contraindications to ECT, but relative contraindications include conditions that increase intracranial pressure.

TMS is a non-invasive option for depression that does not require anesthesia or induce seizures.

VNS is an adjunctive therapy for chronic, treatment-resistant depression.

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