404 ‒ Mental health beyond neurotransmitters: hormones in psychiatry, psychedelic therapies, & more

KEYPOINTS

• 01

  Good psychiatry starts with understanding the person, not just picking a molecule.

  Abrams, a psychiatrist with nearly 35 years in practice, deliberately trained at a Harvard program that taught both psychotherapy and psychopharmacology so he wouldn't split a patient's care. He still does a lot of psychotherapy and approaches every consultation similarly, whatever the diagnosis, because each patient is more complex than any provider's model of them.

• 02

  Antidepressant classes are more of a continuum than tidy categories.

  He jokes that if a drug scores 10/10 on serotonin and 3–4/10 on norepinephrine, at some point we just call it an SNRI. Effects involve receptor up- and down-regulation over time rather than simply 'adding' a neurotransmitter. Older MAOIs required tyramine-restricted diets that made patients anxious; escitalopram (Lexapro) is typically used at 10 or 20 mg.

• 03

  Modern life likely creates far more anxiety, and plausibly more depression, than ancestral life.

  Asked to imagine 10,000 years ago, Abrams thinks we'd see much less anxiety. Then it was impossible to live in isolation; people were outdoors by default; sleep wasn't necessarily 8 hours but fit natural rhythms. Loss of community, nature and movement are risk factors he weighs alongside biology.

• 04

  Distress tolerance shrinks when foundational biology is off.

  Peter offers a 'window' analogy: sleep loss, pain or hormonal disruption narrow the window of what you can tolerate, so irritability rises. He recalls being irritable two weeks into an injury until someone pointed out untreated pain makes anyone irritable. Abrams focuses on nutrition, exercise, sleep and especially endocrinology.

• 05

  Abrams thinks of hormones as four axes: sex hormones, thyroid, cortisol and more.

  Sex-hormone and thyroid problems are usually deficiencies that we know how to fix; the cortisol axis is hardest because most people have too much, driven by chronic hyperarousal, and there's no pill that is an antidote.

• 06

  Estradiol and progesterone shape brain chemistry, and rapid drops drive mood disorders.

  Estradiol supports neuroplasticity via BDNF, NMDA and glutamate. In PMDD, allopregnanolone, a progesterone derivative, falls late in the luteal phase. After delivery, estradiol may fall from around 30,000 to about 30 pg/mL and progesterone from several hundred to under 1 within 24–48 hours, contributing to postpartum depression. Severe postpartum psychosis is under 1%.

• 07

  Women's testosterone matters, and units obscure it.

  Testosterone is reported in ng/dL and estradiol in pg/mL—a 1,000-fold difference. Normalized, a woman's testosterone is about 10 times her estradiol, though about a tenth of a man's.

• 08

  For men, exogenous testosterone generally beats clomiphene.

  Abrams sees limited rationales for clomiphene/enclomiphene and considers hCG superior to clomiphene because it acts peripherally. Both discuss that estrogen is not 'bad' for men—it's important for male brain and body function.

• 09

  A 'normal' thyroid panel can hide a deficiency that presents as depression.

  TSH of 2.5–5 is often dismissed, but Abrams pays most attention to free T4: if it's suboptimal in a depressed patient, he refers to endocrinology or prescribes himself. He prefers combined T4 and T3, avoids compounded time-release T3, and doses immediate-release T3 twice daily—morning and 6–8 hours later—sometimes starting as low as 2.5 mcg twice daily, and sometimes uses T3 alone for treatment-resistant depression.

• 10

  Ketamine can rapidly defuse suicidality.

  He describes patients on the edge of hospitalization whose suicidal risk dissipates dramatically after a ketamine infusion, usually given at partially dissociative doses. He worries about recreational use and has friends who refer patients for ketamine addiction.