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 33-year-old man visits his psychiatrist with feelings of sadness on most days of the week for the past 4 weeks. He says that he is unable to participate in his daily activities and finds it hard to get out of bed on most days. If he has nothing scheduled for the day, he sometimes sleeps for 10–12 hours at a stretch. He has also noticed that on certain days, his legs feel heavy and he finds it difficult to walk, as though there are bricks tied to his feet. However, he is still able to attend social events and also enjoys playing with his children when he comes home from work. Other than these simple pleasures, he has lost interest in most of the activities he previously enjoyed. Another troubling fact is that he had gained weight over the past month, mainly because he eats so much when overcome by these feelings of depression. His is prescribed a medication to treat his symptoms. Which of the following is the mechanism of action of the drug he was most likely prescribed?

Inhibit the uptake of serotonin and norepinephrine at the presynaptic cleft

Activates the γ-aminobutyric acid receptors

Works as an antagonist at the dopamine and serotonin receptors

Non-selectively inhibits monoamine oxidase A and B

Stimulates the release of norepinephrine and dopamine in the presynaptic cleft

A 65-year-old woman presents with memory problems for the past few weeks. Patient vividly describes how she forgot where she put her car keys this morning and did not remember to wish her grandson a happy birthday last week. Patient denies any cognitive problems, bowel/bladder incontinence, tremors, gait problems, or focal neurologic signs. Patient mentions she wants to take Ginkgo because her friend told her that it can help improve her brain function and prevent memory loss. Past medical history is significant for an acute cardiac event several years ago. Current medications are aspirin, carvedilol, and captopril. Patient denies any history of smoking, alcohol or recreational drug use. Patient is a widow, lives alone, and is able to perform all activities of daily living (ADLs) easily. No significant family history. Patient is afebrile and vital signs are within normal limits. Physical examination is unremarkable. Which of the following would be the most appropriate response to this patient’s request to take Ginkgo?

"No, taking ginkgo will increase your risk for bleeding."

"Yes, ginkgo is widely used for improving brain function and memory."

“No, you have Alzheimer's disease and need to start donepezil.”

“No, herbal preparations are unsafe because they are not regulated by the FDA.”

Yes, ginkgo may not help with your memory, but there is no risk of adverse events so it is safe to take.

Alternative treatments for anxiety — USMLE Lesson

Herbal Supplements - Nature's Prozac?

Patient interest is high, but evidence varies; FDA does not regulate for safety or efficacy.
Kava (Piper methysticum):
- Acts on GABA-A receptors.
- ⚠️ Warning: Associated with severe hepatotoxicity; monitor LFTs.
St. John's Wort (Hypericum perforatum):
- Used more for depression; weak MAOI/SSRI activity.
- ⚠️ Warning: Potent CYP450 inducer (especially CYP3A4).
Valerian Root & Passionflower:
- Milder options for insomnia and anxiety, also via GABA modulation.

⭐ Exam Favorite: St. John's Wort significantly reduces the concentration of many drugs-including oral contraceptives, warfarin, and antiretrovirals-by inducing CYP3A4. Always check for drug interactions.

St. John's Wort herbal supplement

Mind-Body Therapies - Zen & the Brain

Core Principle: Non-judgmental awareness of the present moment (mindfulness).
Techniques:
- Mindfulness-Based Stress Reduction (MBSR): Structured program integrating meditation and Hatha yoga.
- Vipassanā & Zen Meditation: Focus on breath, bodily sensations, and observing thoughts without attachment.
Neurobiological Effects:
- ↓ Amygdala activity (fear center).
- ↑ Prefrontal Cortex (PFC) activity (emotional regulation).
- Promotes neuroplasticity in key networks.

Neurobiological Changes After Mindfulness

⭐ High-Yield: Mindfulness meditation is strongly associated with decreased activity in the Default Mode Network (DMN), the brain's "autopilot" network active during mind-wandering and self-referential thought, which is often hyperactive in anxiety disorders.

Lifestyle & Other Methods - Body as Pharmacy

Exercise: Aerobic activity (e.g., running, swimming) for ≥30 mins, 3-5 days/week.
- Mechanism: ↑ endorphins, ↑ serotonin, ↑ BDNF, ↓ cortisol.
Sleep Hygiene: Crucial for emotional regulation. Consistent sleep-wake cycles are key.
Dietary Modification:
- ↓ Caffeine & alcohol intake.
- Consider omega-3 fatty acids & probiotics.
Mind-Body Therapies:
- Yoga & Tai Chi: Improve GABA levels.
- Meditation/Mindfulness: Strengthens prefrontal cortex control over amygdala.
- Controlled breathing (e.g., box breathing).

Aerobic Exercise's Neurochemical Effects on Brain Health

⭐ Regular aerobic exercise demonstrates anxiolytic effects comparable to SSRIs in some studies, by boosting endorphins and modulating the HPA axis.

High‑Yield Points - ⚡ Biggest Takeaways

Kava kava carries a significant risk of severe hepatotoxicity and is generally not recommended.

St. John's Wort is a potent CYP450 inducer, which can reduce the efficacy of many medications and risks serotonin syndrome if combined with SSRIs.

Valerian root, used for insomnia and anxiety, can cause significant sedation and dizziness.

S-adenosyl-L-methionine (SAMe) lacks strong evidence and may precipitate mania in patients with bipolar disorder.

Always ask about herbal supplement use to avoid dangerous drug interactions.

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