The psychiatric medication pipeline: What’s the latest?

by | Mar 14, 2024

psychiatric medication pipeline

For some, psychiatric medications are the difference between life and death. For others, they’re the difference between life and chaos. There’s a lot at stake for a whole lot of people, and that’s why following the medication pipeline is crucial.

Ah, those college days of taking “shrooms” and going to the planetarium. Who knew we’d be talking about psilocybin 50 years later?

It’s believed that one in five adult Americans use psychiatric medications. The United Kingdom numbers are similar.

Now, there are those who claim psych meds are not only useless, they’re harmful. But for the sake of folks who believe in – and rely upon – them, as well as continuing the quest for improved efficacy and fewer side effects, we need to do this.

We’re going to review the pipeline according to disorder. And as you can imagine, there’s a ton of info and no way to do it justice in one piece.

So we’ll handle generalized anxiety disorder, major depressive disorder, and post-traumatic stress disorder here. And we’ll come back for part two and hit attention-deficit/hyperactivity disorder and schizophrenia.

As long as we’re on the subject, if you’re interested in participating in a US Food and Drug Administration (FDA) clinical trial for a drug in development anywhere in the world, hit the database. The UK offers the same at ScanMedicine.

Let’s – get – busy…

The psychiatric medication pipeline: The latest

I’ve tried to make the info you’re about to read simple and brief. If you want every minute detail, there are links to my sources at the end.

Generalized anxiety disorder (GAD)

MM120

Mind Medicine has received breakthrough therapy designation from the FDA for its lysergide d-tartrate therapy, MM120, for GAD. The company announced positive data from a phase 2b (out of four) study.

MM120 is a tartrate salt form of lysergide, a semi-synthetic hallucinogen commonly known as, yep, LSD.

According to study investigator David Feifel, MD, PhD…

I’ve conducted clinical research studies in psychiatry for over two decades and have seen studies of many drugs under development for the treatment of anxiety. That MM120 exhibited rapid and robust efficacy, solidly sustained for 12 weeks after a single dose, is truly remarkable.

The study also showed that MM120 was generally well-tolerated, with most adverse events rated as mild to moderate, transient, and occurring on dosing day.

Mind Medicine intends to begin a phase 3 clinical trial of MM120 in the second half of 2024.

Major depressive disorder (MDD)

The first two drugs we’re going to discuss influence NMDA (N-methyl-D-aspartate) receptors in the brain. Simply, NMDA is a glutamate receptor, glutamate being our most abundant excitatory (rev things up) neurotransmitter.

What makes glutamate receptors a great target is they’re involved in a lot of important brain activities and illnesses. One of the activities is neuroplasticity, responsible for the brain’s ability to adapt to varying conditions – “neurons that fire together wire together.” Glutamate receptors are also one of a few that process opiate/opioid painkillers in the brain.

Currently, there are two FDA-approved NMDA-targeting psych meds: esketamine (Sprovato) and the combination of dextromethorphan and bupropion (Auvelity).

Esmethadone

Esmethadone is a NMDA receptor antagonist that’s believed to modulate the glutamate system, generating antidepressive effects

We’ve all heard of methadone. Esmethadone is structurally different enough to remove the opioid effect while adding antidepressive action. It also increases levels of critically important BDNF.

In a phase 2a study, participants being psychiatric inpatients with MDD, esmethadone significantly outperformed placebo. Phase 3 studies are underway.

Navacaprant

Navacaprant, being developed by Neumora Therapeutics, targets κ-opioid receptors. In a recent phase 2 study, it demonstrated a significant improvement in depressive symptoms, including anhedonia, in patients with moderate to severe MDD.

The impact of assorted neurochemicals on the κ-opioid system has been known to generate degrees of depression and anhedonia. The reverse action navacaprant has on the system likely reduces those symptoms.

Neumora has begun phase 3 studies.

Psilocybin

Ah, those college days of taking “shrooms” and going to the planetarium. Who knew we’d be talking about psilocybin 50 years later?

Psilocybin has become a household word. Heck, I’ve even written about it. But keep  in mind, notoriety can evoke misconception, including psilocybin being declared safe and effective for the treatment of depression.

Now, I know of several folks currently using it for a variety of emotional and mental woes. But fact is, although psilocybin is registered with the FDA, and is being aggressively studied, it’s still under investigation.

Psilocybin is a naturally occurring molecule that exists in more than 200 species of Basidiomycota mushrooms. Clinical trials use either psilocybin extracted from these mushrooms or a synthetic form.

psychiatric medication pipeline

Eyes are on you, folks. Keep up the great work.

Psilocybin is classified as a Schedule 1 hallucinogen. Similar to lysergic acid diethylamide (LSD) and mescaline, psilocybin’s primary mechanism of action appears to be its agonism at the serotonin 5-HT2A  receptor.

The action of this receptor is highly significant in psychopharmacology, as many drugs currently used to treat depression and psychotic disorders act upon serotonin 5-HT2A  receptors. They include the antidepressants mirtazapine {Remeron) and trazodone (Desyrel), as well as most atypical antipsychotics – e.g., aripiprazole (Abilify).

As mentioned earlier, the Schedule 1 hallucinogen LSD is also being investigated by the FDA.

A phase 2 controlled trial compared psilocybin to escitalopram (Lexapro) in patients with moderate to severe MDD. The outcome favored psilocybin, but not by much. Phase 3 studies are underway for MDD and treatment-resistant depression (TRD).

Important: It seems as though there’s a lot of momentum behind the eventual FDA-approval of psilocybin for the treatment of depression – along with other clinical applications being investigated.

Post-traumatic stress disorder (PTSD)

A handful of psychotherapies are currently the primary treatment for PTSD: exposure-based therapy, trauma-focused cognitive behavioral therapy, cognitive therapy, and eye movement desensitization and reprocessing therapy (EMDR).

Frustratingly, there are only two medications that are FDA-approved for the treatment of PTSD: sertraline (Zoloft) and paroxetine (Paxil). Frankly, neither provide much to write home about.

Current research supports a model that primarily uses a custom-designed psychotherapy, and includes the administration of 3,4-methylenedioxymethamphetamine (MDMA). It’s known as MDMA-assisted psychotherapy.

Yes, that MDMA – “ecstasy” – a Schedule 1 drug.

MDMA is an empathogen – a drug that increases a person’s feeling of empathy and benevolence towards others, as well as feelings of being socially accepted and connected.

Empathogens do their work by increasing the presynaptic release of serotonin, as well as the release of neurohormones oxytocin, prolactin, and cortisol.

But key here is the hypothesis that MDMA enhances fear extinction, modulates fear memory reconsolidation, increases trust, and amps up emotional learning.

Now, this medication-assisted psychotherapy model has created an important template to be used in other treatments. I’m thinking psilocybin for sure. And I’d be willing to bet MM120 and esmethadone if they’re approved.

Huge: on December 12, 2023, MAPS Public Benefit Corp submitted an application to the FDA requesting approval of the combination of MDMA with psychotherapy for the treatment of PTSD. The drug’s generic name is midomafetamine (capsules).

In response, the FDA granted priority review status on February 13, 2024. Looks like a done deal to me.

Watch for part two

Worked up a sweat putting this one together. But you know what? You’d do the same for me.

Hopefully, you’ve learned a thing or two and found some comfort in knowing the research wheels continue to roll.

Be sure to read part two, in which we’ll turn our attention to meds in development for ADHD and schizophrenia.


Primary info sources: Psychiatric Times: Medication Pipeline: Schizophrenia and PTSD, Medication Pipeline; Antidepressants and ADHD Rx and Drug Topics: FDA Grants Breakthrough Therapy Designation to LSD-Based Treatment for Generalized Anxiety Disorder.

A variety of emotional and mental health info and inspiration articles are at your fingertips. Peruse the titles.

Bill White is not a physician and provides this information for educational purposes only. Always contact your physician with questions and for advice and recommendations.

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