Every patent piece in this series has been about compounds nobody can sell yet — psilocybin, MDMA, ibogaine, LSD, all still Schedule I, all still trials-only. This one is the opposite: the drugs already approved, already prescribed, already generating real revenue for treating the same three conditions — depression, anxiety, and PTSD — that psychedelics are trying to break into. The split in this market is stark: the drugs almost everyone takes make pharma almost nothing, and the drugs making real money are ones most patients have never heard of.
As we've covered elsewhere, none of this works for everyone — I've written before about flushing my own antidepressants down a toilet in another country, one of a lot of personal reckonings with a system that measures success in market share more readily than it measures fit for the person taking the pill.
What's Actually Prescribed
By prescription volume, this category is dominated by decades-old generics. Sertraline (Zoloft) leads antidepressant prescriptions at roughly 7.7% of the total, followed by bupropion (Wellbutrin) and escitalopram (Lexapro). Fluoxetine (Prozac), citalopram (Celexa), trazodone, venlafaxine (Effexor), duloxetine (Cymbalta), and paroxetine (Paxil) round out the rest of the top tier for depression. For anxiety, gabapentin — not even an anxiety drug on-label — is the single most common prescription, followed by bupropion again, then trazodone, alprazolam, and clonazepam. For PTSD specifically, only sertraline and paroxetine carry FDA approval for the indication; prazosin, a blood-pressure drug repurposed for PTSD nightmares, is the most-prescribed off-label option.
Every one of those has been off-patent for years, several for decades. That's not incidental — it's the whole story of this market.
Where the Money Actually Is
| Drug | Company | Indication | FY2025 Revenue | US Patent Status |
|---|---|---|---|---|
| Vraylar (cariprazine) | AbbVie | Bipolar depression, adjunct MDD | $3.62B | Protected to ~2029 |
| Spravato (esketamine) | Johnson & Johnson | Treatment-resistant depression | $1.1B (+56% YoY) | Protected to ~2040 |
| Auvelity (dextromethorphan-bupropion) | Axsome Therapeutics | MDD | $507M | Protected to ~2043 |
| Trintellix (vortioxetine) | Takeda / Lundbeck | MDD | Declining; core patent expires June 2026 | Generic entry expected 2027 |
| Rexulti (brexpiprazole) | Otsuka / Lundbeck | Adjunct MDD, agitation | ~$400–450M (2024 base, growing) | Patent expires April 2026 |
Trintellix and Rexulti are the softest numbers in that table — both are co-marketed across two companies reporting in different currencies on different fiscal calendars, and neither publishes one clean combined global figure, so those are ranges built from the pieces available rather than a single reported total.
Five drugs, none older than the mid-2010s, none facing generic competition until at least next year — and two of them, Trintellix and Rexulti, are about to lose that protection within the next twelve months, which is worth watching as its own story.
The Pattern
This is the same story the psychedelic patent series has been telling from the other direction. Once a drug goes generic, the money leaves — that's just as true for sertraline as it will eventually be for whatever psilocybin or MDMA drug gets approved first. Big Pharma's actual play in mental health right now isn't defending old molecules, it's building the next five-year window of exclusivity: AbbVie with cariprazine, J&J with the esketamine-enantiomer workaround, Axsome with a genuinely novel dextromethorphan combination. Psychedelics are trying to join that same club from a standing start, decades behind on approval but with virgin patent territory nobody's touched yet. Given how fast Rexulti's and Trintellix's windows are closing, it's not hard to see why pharma is looking for the next thing.
This is business and market reporting, not medical advice. Revenue figures are as reported by the companies for FY2025 unless noted; patent expiration dates are estimates based on public patent-tracking sources and can shift with litigation, pediatric exclusivity, or settlement agreements.
Sources
- AbbVie Reports Full-Year and Fourth-Quarter 2025 Financial Results
- Johnson & Johnson Reports Q4 and Full-Year 2025 Results
- Axsome Therapeutics 8-K, FY2025 results (AUVELITY)
- Lundbeck FY2025 Corporate Release
- Otsuka Pharma Sales Rise 7.1% in 2025, Driven by Rexulti — Pharma Japan
- Vraylar Patent Expiration — PharmaCompass
- Trintellix Patent Expiration Date and Generic Timeline — LegalClarity
- Rexulti Patent Expiration — Pharsight
- Spravato / Auvelity Patent Expiration — Pharsight
- Most Common Antidepressants by Prescription Volume — Definitive Healthcare
- Most Commonly Prescribed Anti-Anxiety Drugs — Definitive Healthcare
- Clinician's Guide to Medications for PTSD — VA National Center for PTSD
- Altitude: I Flushed My Antidepressants in Paradise