September 2023 Newsletter: Zuranolone for Postpartum Depression, Algorithm for the Pharmacotherapy of OCD, and BSMs for Mental Health

This newsletter presents the future of postpartum depression treatment with zuranolone, the first-ever oral treatment option approved by the FDA. Unlike SSRIs, zuranolone may work within days and requires only short-term, 2-week use.

We also discuss a pharmacologic algorithm for OCD, key points from a presentation on what clinicians need to know for using broad-spectrum micronutrients in mental health, and our practical research summaries of adult, child, and adolescent psychiatry (Quick Takes and CAP Smart Takes).

Zuranolone for Postpartum Depression

On August 4, 2023, the FDA approved zuranolone (Zurzuvae) for treating postpartum depression. This represents the inaugural oral treatment option available for this condition.

What are the main characteristics of postpartum depression (PPD)?
- Symptoms of major depressive disorder
- Occurs within 4 weeks of childbirth
- Anxiety is a prominent feature, often presenting as obsessions.
- If an episode begins prior to birth, it is categorized as peripartum onset (DSM-5-TR). Learn more here.
How does zuranolone work?
- Zuranolone is a neuroactive steroid that adjusts GABA receptors’ activity. It acts as a positive allosteric modulator of the GABA-A receptor, thereby assisting in reestablishing equilibrium in the brain’s neural activities.
What do we know about its efficacy?
- The efficacy of zuranolone for the treatment of PPD was demonstrated in 2 randomized, double-blind, placebo-controlled, multicenter studies.
- Study 1:
  - Patients received 50 mg of zuranolone once daily in the evening for 14 days.
  - Patients who received zuranolone showed significantly more improvement in depressive symptoms, measured using the Hamilton Depression Rating Scale (HAMD-17) at day 15, than those who received the placebo. Learn more here.
- Study 2:
  - Patients were administered 40 mg of zuranolone for 14 days.
  - Treatment effect was maintained at day 42—4 weeks after the last dose of zuranolone—indicating sustained improvement in patients’ depressive symptoms. Learn more here.
What are the most common side effects?
- Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection
How does zuranolone differ from SSRIs?
- SSRIs take weeks to show effects, whereas zuranolone may work within days.
- SSRIs require long-term daily use, whereas zuranolone is being tested for short-term use of 2 weeks.
How does zuranolone differ from brexanolone?
- Zuranolone is being developed as an oral medication that could be taken at home, unlike brexanolone, which requires a continuous 60-hour IV infusion at a certified healthcare facility.
When will it be available?
- Zurzuvae is anticipated to launch in the fourth quarter of 2023, although the pricing details remain uncertain at this point.

Early studies show zuranolone’s potential for treating PPD, but more research is needed to assess recurrence risks. The pharmaceutical company has also sought approval to use this drug in treating major depressive disorder. However, no efficacy was observed in this particular disorder, necessitating further exploration and analysis.

Algorithm for the Pharmacotherapy of Obsessive-Compulsive Disorder, With David Osser, M.D.

In this interview, Dr. David Osser discusses an evidence-based psychopharmacology algorithm for the treatment of obsessive-compulsive disorder (OCD). He explores various treatment strategies, including SSRIs; possible combination options; and neuromodulatory options for the treatment of patients with OCD.

Interview highlights include the following:

SSRIs remain first-line pharmacologic options for the management of OCD. It is best to maximize SSRI dose before augmenting these with other agents.
Deep TMS is now an FDA-approved option as an adjunctive strategy for the treatment of OCD. For patients with treatment-resistant OCD, neurosurgical interventions can be an effective option.

Learn more and earn 0.5 CME credits here.

Broad-Spectrum Micronutrients (BSMs) for Mental Health: What You Need to Know for Clinical Use

In this video lecture, Dr. Amelia Villagomez elucidates all the critical concepts for correctly using BSMs in treating mental disorders. She describes the available formulas, including the research concerning their safety and tolerability. Furthermore, Dr. Villagomez deliberates on contraindications, their prominent interaction with psychotropic medication, and essential considerations when discussing risks and benefits with patients.

Practical Tips for Using BSMs in Clinical Practice

No consistent predictors of response have been identified for BSMs.
To minimize side effects, BSMs should be taken with a meal.
Try to maintain a 2-hour separation between doses.
There are available recipes for patients who are unable to swallow pills.

Learn more and earn 0.75 CME credits here.

Quick Takes: Research, Digested

Effect of Brexanolone on Postpartum Depressive Symptoms, Anxiety, and Insomnia

Dr. Vivien Burt discusses brexanolone, a medication approved by the FDA for postpartum depression treatment. The medication shows promise in rapidly improving core depressive symptoms, anxiety, and insomnia, although further studies are needed to evaluate these effects rigorously. Learn more.

Listen to or read the full volume, and earn 0.5 CME credits here.

CAP Smart Takes: Research, Digested

Managing Adverse Effects of Antidepressants in Youth

GI symptoms, insomnia, low energy/fatigue, and activation are commonly reported side effects in youth treated with antidepressants. These symptoms can often be managed through treatment, behavioral interventions, or dose adjustments.
Establish baseline functioning and symptomatology before starting medication to distinguish between antidepressant side effects and symptoms of depressive or anxiety disorders. Learn more.