Question 1

A 22-year-old woman with depression is brought to the emergency department by ambulance after a suspected intentional overdose. She is obtunded with a heart rate of 120 bpm. Her ECG shows a QRS duration of 140 milliseconds. Her roommate found an empty bottle of amitriptyline. What is the most appropriate immediate intervention?

Accepted Answer

A wide QRS complex (greater than 100 ms) in the setting of TCA overdose is a medical emergency that requires immediate sodium bicarbonate. The bicarbonate provides a sodium load that competes with the TCA at myocardial sodium channels, narrowing the QRS and reducing the risk of ventricular arrhythmias. Alkalinization of the blood also decreases the ionized fraction of the drug. Flumazenil (answer C) is a benzodiazepine antagonist and is not relevant here — and is in fact dangerous in mixed overdoses because it can precipitate seizures. Activated charcoal (answer A) may have a role if the patient presents within 1-2 hours of ingestion, but it is not the priority when the QRS is already widened. Supportive care alone (answer D) is insufficient given the QRS prolongation, which predicts progression to arrhythmia.

Question 2

A 34-year-old man with OCD has failed adequate trials of fluoxetine (80mg for 12 weeks) and fluvoxamine (300mg for 12 weeks) with only partial response. His psychiatrist is considering adding a medication to augment or switching to a different class. Which of the following is the most evidence-based next step for treatment-resistant OCD?

Accepted Answer

Clomipramine is the most potent serotonin reuptake inhibitor among the TCAs and the only TCA with FDA approval for OCD. Multiple studies suggest it may be more effective for OCD than SSRIs, though its side effect burden makes SSRIs the first-line choice. After failure of two adequate SSRI trials, clomipramine is a well-supported next step. Venlafaxine (answer A) is an SNRI with limited evidence for OCD specifically. Buspirone augmentation (answer C) has weak evidence in OCD. Benzodiazepines (answer D) do not treat the core symptoms of OCD.

Question 3

A resident asks why SSRIs replaced TCAs as first-line antidepressants, given that TCAs have comparable efficacy for major depression. Which of the following is the most accurate explanation?

Accepted Answer

The shift from TCAs to SSRIs was driven primarily by safety, not efficacy. TCAs and SSRIs have roughly comparable antidepressant efficacy in head-to-head trials. The critical difference is that a two-week supply of a TCA can be lethal in overdose due to sodium channel blockade in the heart, while SSRIs have a far wider safety margin. Add to that the anticholinergic side effects, orthostatic hypotension, sedation, and weight gain of TCAs, and the clinical calculus strongly favors SSRIs as first-line treatment. SSRIs do have side effects (answer B is wrong), and not all TCAs require blood level monitoring — only nortriptyline has a well-defined therapeutic window (answer D is wrong).

Tricyclic Antidepressants (TCAs)

Side Effects Worth Knowing

Cardiac toxicity in overdose

Anticholinergic effects

Orthostatic hypotension

Sedation

Weight gain

Seizure threshold lowering

Sexual dysfunction

References & Further Reading