A 25-year-old woman presents to her college campus clinic with the complaint of being unable to get up for her morning classes. She says that, because of this, her grades are being affected. For the past 6 weeks, she says she has been feeling depressed because her boyfriend dumped her. She finds herself very sleepy, sleeping in most mornings, eating more snacks and fast foods, and feeling drained of energy. She is comforted by her friend’s efforts to cheer her up but still feels guarded around any other boy that shows interest in her. The patient says she had similar symptoms 7 years ago for which she was prescribed several selective serotonin reuptake inhibitors (SSRIs) and a tricyclic antidepressant (TCA). However, none of the medications provided any long-term relief. She has prescribed a trial of Phenelzine to treat her symptoms. Past medical history is significant for a long-standing seizure disorder well managed with phenytoin. Which of the following statements would most likely be relevant to this patient’s new medication?

“While taking this medication, you should avoid drinking red wine.”

“This medication is known to cause anorgasmia during treatment.”

“You will have a risk for cardiotoxicity from this medication.”

“A common side effect of this medication is sedation.”

“While on this medication, you may have a decreased seizure threshold.”

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 27-year-old man comes to the physician for a follow-up examination. Paroxetine therapy was initiated 6 weeks ago for a major depressive episode. He now feels much better and says he is delighted with his newfound energy. He gets around 8 hours of sleep nightly. His appetite has increased. Last year, he had two episodes of depressed mood, insomnia, and low energy during which he had interrupted his job training and stopped going to the gym. Now, he has been able to resume his job at a local bank. He also goes to the gym three times a week to work out and enjoys reading books again. His temperature is 36.5°C (97.7°F), pulse is 70/min, and blood pressure is 128/66 mm Hg. Physical and neurologic examinations show no abnormalities. On mental status examination, he describes his mood as "good." Which of the following is the most appropriate next step in management?

Continue paroxetine therapy for 2 years

Switch from paroxetine to venlafaxine therapy

Continue paroxetine therapy for 6 months

Switch from paroxetine to lithium therapy

A 17-year-old white female with a history of depression is brought to your office by her parents because they are concerned that she is acting differently. She is quiet and denies any changes in her personality or drug use. After the parents step out so that you can speak alone, she begins crying. She states that school has been very difficult and has been very depressed for the past 2 months. She feels a lot of pressure from her parents and coaches and says she cannot handle it anymore. She says that she has been cutting her wrists for the past week and is planning to commit suicide. She instantly regrets telling you and begs you not to tell her parents. What is the most appropriate course of action?

Explain to her that she will have to be hospitalized as she is an acute threat to herself

Prescribe an anti-depressant medication and allow her to return home

Tell her parents about the situation and allow them to handle it as a family

Prescribe an anti-psychotic medication

Benzodiazepines are clinically useful because of their inhibitory effects on the central nervous system. Which of the following correctly pairs the site of action of benzodiazepines with the molecular mechanism by which they exert their effects?

GABA-A receptors; increasing the frequency of activation of a chloride ion channel

GABA-B receptors; activating potassium channels

GABA-A receptors; increasing the duration of activation of a chloride ion channel

GABA-A receptors; blocking action of GABA

GABA-B receptors; activating a G-protein coupled receptor

Pharmacotherapy for depression for USMLE Step 1: High-Yield Psychiatry Lessons

SSRIs & SNRIs - Happy Pills 101

SSRI Mechanism of Action in Synaptic Cleft

SSRIs (Selective Serotonin Reuptake Inhibitors)
- MOA: ↑ serotonin by blocking 5-HT reuptake.
- Use: First-line for depression, anxiety, OCD, PTSD.
- Agents: Fluoxetine, Sertraline, Citalopram, Escitalopram.
- ADRs: Sexual dysfunction, GI distress, headache. ⚠️ ↑ suicide risk in young adults.
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
- MOA: ↑ serotonin & norepinephrine by blocking their reuptake.
- Use: Depression, diabetic neuropathy (Duloxetine), fibromyalgia.
- Agents: Venlafaxine, Duloxetine.
- ADRs: SSRI profile + hypertension, sweating (NE effects).

⭐ Serotonin Syndrome: A life-threatening emergency from excess serotonergic activity. Presents with a triad of cognitive (agitation), autonomic (hyperthermia, diaphoresis), and somatic (clonus, hyperreflexia) symptoms. Requires immediate drug cessation.

TCAs & MAOIs - Old School Mood Boosters

Tricyclic Antidepressants (TCAs)
- Mech: Block Norepinephrine (NE) & Serotonin (5-HT) reuptake.
- Examples: Amitriptyline, Nortriptyline, Imipramine.
- Toxicity: 📌 Tri-C's: Cardiotoxicity (arrhythmia), Convulsions, Coma. Strong anticholinergic & antihistaminic effects.
Monoamine Oxidase Inhibitors (MAOIs)
- Mech: Irreversibly inhibit MAO → ↑ NE, 5-HT, Dopamine.
- Examples: Phenelzine, Tranylcypromine, Selegiline.
- Toxicity: ⚠️ Hypertensive crisis with tyramine-rich foods (wine, cheese). Risk of serotonin syndrome; requires 2-week washout from SSRIs.

⭐ Exam Favorite: TCA overdose causing a widened QRS complex on ECG is treated with sodium bicarbonate (NaHCO3) to correct acidosis and stabilize cardiac membranes.

Atypical Antidepressants - The Odd Bunch

Bupropion
- Mech: Norepinephrine-Dopamine Reuptake Inhibitor (NDRI).
- Use: Good for patients with fatigue or concerns about sexual side effects; also used for smoking cessation.
- ⚠️ SE: Lowers seizure threshold.
Mirtazapine
- Mech: α2-antagonist (↑NE & 5-HT release) & potent H1-antagonist.
- Use: Ideal for depression with insomnia and weight loss.
- SE: Sedation, ↑ appetite, significant weight gain. 📌 "Meal-tazapine".
Trazodone
- Mech: Primarily a 5-HT2, α1, and H1 antagonist.
- Use: Mainly for insomnia at lower doses.
- SE: Sedation, orthostatic hypotension, and ⚠️ priapism. 📌 "Trazo-BONE".

⭐ Exam Favorite: Bupropion is absolutely contraindicated in patients with seizure disorders or current/prior eating disorders (anorexia, bulimia) due to the increased risk of seizures.

Treatment Algorithm - The Game Plan

First-line: SSRI/SNRI + psychotherapy. Choice depends on side-effect profile & comorbidities.
- Bupropion: good for smoking cessation, ↓sexual dysfunction.
- Mirtazapine: useful for insomnia & anorexia.
Assessment: Re-evaluate at 4-8 weeks. If response is inadequate, switch agent or augment.
Continuation: After remission, continue treatment for an additional 4-9 months to prevent relapse.

⭐ Switching to or from an MAOI requires a 2-week washout period (5 weeks for fluoxetine due to its long half-life) to prevent serotonin syndrome.

High‑Yield Points - ⚡ Biggest Takeaways

SSRIs are first-line treatment; full effect takes 4-6 weeks.

Sexual dysfunction is a very common side effect of SSRIs.

Avoid serotonin syndrome by allowing a 2-week washout period between SSRIs and MAOIs.

TCAs are cardiotoxic; treat overdose with sodium bicarbonate.

MAOIs can cause hypertensive crisis when combined with tyramine-rich foods.

Bupropion is an atypical antidepressant that does not cause sexual dysfunction.

Mirtazapine's primary side effects are sedation and increased appetite.

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