Psychotherapy, selective serotonin-reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) have long been the go-to treatments for adults with depression.
But in recent years, the range of evidence-based options has expanded rapidly to include medications with novel mechanisms of action — and even artificial intelligence (AI).
Serotonin and Beyond: Pharmacotherapy for Depression and Emerging Treatment Options, to be presented June 12 at ASHP Pharmacy Futures 2024 in Portland, Oregon, covers the newest pharmacological treatments for major depression and postpartum depression and gives a preview what could be next for the future of mental and behavioral health care.
Session speakers Mei T. Liu and Daniel J. Greer, clinical assistant professors at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey, previewed some of the session’s highlights for ASHP’s News Center.
One size doesn’t fit all
Depression is highly heterogenic in both etiology and presentation. That’s one reason new treatments are so welcome.
- Patients may require multiple treatments and need to try several options before finding what works best for them.
- Pharmacotherapy has looked beyond the monoamine hypothesis for depression — which gave us SSRIs and SNRIs — to help explain the differences in individual responses to antidepressant medication. Depression has been linked to neuroactive steroids, brain-derived neurotrophic factor, and gut microbiota, which could indicate subtypes of depression with different pathogenesis.
- “As pharmacists, medication is our bread and butter. But treating depression takes a lot of different modalities because patients and the reasons why they develop depression can be very diverse,” Liu said.
New on the scene
Liu and Greer discussed some of the newer antidepressants and antipsychotics that can be used as monotherapy or to augment SSRIs and SNRIs. For example, the combination of dextromethorphan and bupropion was approved in 2022 for the treatment of major depression in adults.
- Some of the chemical formulations are far from new — for example, the hallucinogen ketamine has been available as esketamine for treatment-resistant depression since 2019. The recent acceptance of such therapies has “pivoted the way we treat depression,” Liu said.
- Other hallucinogens and psychedelics have a growing evidence base but have not been approved by the Food and Drug Administration (FDA). Research shows each agent is best indicated for a specific mental health condition. For example, psilocybin holds promise for depression, lysergic acid diethylamide for anxiety, and methylene-dioxymethamphetamine (MDMA) for post-traumatic stress disorder (PTSD). However, on June 4, an FDA advisory panel voted against approving MDMA as a treatment for PTSD, citing insufficient evidence and potential risk to patients.
A focus on postpartum depression (PPD)
PPD is thought to affect 10 to 20% of new mothers worldwide.
- Until recently, the only treatment options were therapy and traditional antidepressants. Now researchers recognize that the physiology of depression is different in new mothers.
- Brexanolone and zuranolone are the first FDA-approved medications specifically for patients with PPD.
- While their mechanism of action is not fully understood, “the exciting thing to me is that these new medications are based on the biomarkers and drops in hormone levels associated with PPD,” Liu said.
- Still, access remains a challenge. Brexanolone is administered as an infusion over 60 hours, posing a barrier for many new mothers. The oral formulation zuranolone is easier to take but can be expensive.
The role of AI
The session also explores how AI could help diagnose depression and serve as a complement to therapy and medication as part of a comprehensive treatment plan.
- Greer gave the example of an AI-powered app that takes a candid photo every time you unlock your smartphone and assesses the image for signs of depression.
- As mental health practitioners and patients have grown comfortable using apps for meditation and to support cognitive behavioral therapy, using AI is a feasible next step. “This is not coming out of nowhere. We’ve been building up to this for years,” Greer said.
- AI software is easy for patients to access and grows smarter with every use — but it’s not a silver bullet. “Because AI is so new, you shouldn’t put all your faith and trust in it,” Greer added.
The standard remains the standard
New options mean a bigger toolbox with which to care for patients with depression. However, established treatments still have their place.
For someone with mild depression, standard psychotherapy is still the recommended first course of action. Meanwhile, a patient with moderate to severe depression would likely benefit from the addition of a first-line SSRI. If they have severe side effects or don’t respond well, it’s time to explore other options.
“The standard remains the standard,” Greer said.
