Amisulpride: The Antipsychotic Americans Can’t Have (But Maybe Should)
Amisulpride is a second-generation antipsychotic that’s been used for decades abroad for the treatment of schizophrenia and, at lower doses, persistent dysthymia.
“Maybe they’re no longer depressed…they just don’t care anymore.”
It’s a chilling reflection shared by many of us in psychiatry — and it strikes at the heart of one of the most misunderstood symptoms in depression: anhedonia. Patients complete treatment. Their scores improve. But they aren’t living. They aren’t engaging. They simply don’t care anymore.
At the 2025 NEI Spring Congress, Dr. Roger McIntyre, a global leader in mood disorders research, delivered a groundbreaking session titled “A More Tailored and Swift Approach? Using Clinical Endophenotypes to Address Major Depressive Disorder in All of Its Variations.” In it, he tackled the limitations of conventional treatment models and emphasized the urgent need to address core, under-recognized drivers of poor outcomes—chief among them: anhedonia.
But he didn’t stop there.
Dr. McIntyre introduced the field to SAINT — the Stanford Accelerated Intelligent Neuromodulation Therapy protocol, a theta-burst TMS regimen that delivers 10 sessions per day over five days. The results?
This protocol isn’t a hopeful future. It’s a reality. And for the first time, we’re seeing targeted interventions that address not just depression, but the loss of reward and meaning that defines anhedonia.
Dr. McIntyre didn’t frame anhedonia as a secondary issue. He position edit as a core endophenotype—a biological and clinical signature that may one day earn its own diagnostic classification. And for good reason.
Anhedonia comes in at least two distinct forms:
This is the inability to anticipate or look forward to pleasure. Patients withdraw not because they feel bad—but because they expect nothing at all.
“Even if I go, I won’t enjoy it.” This subtype is strongly associated with dopaminergic dysfunction and is one of the strongest predictors of suicidality, according to Dr. McIntyre’s analysis.
This is the inability to enjoy pleasure in the moment. Patients may go through the motions of life but experience no reward.
“I used to love music. Now it just sounds like noise.” Consummatory deficits are linked to hedonic hotspots in the brain, including the nucleus accumbens and prefrontal cortex.
These two profiles aren’t just theoretical—they map directly onto why conventional antidepressants often fail to deliver functional recovery.
In discussing pharmacologic strategies, vortioxetine (Trintellix) was discussed as a unique agent that targets the complex neurobiology of anhedonia more effectively than traditional SSRIs.
Vortioxetine:
The presented data showed that vortioxetine significantly improves MADRS anhedonia subscale scores, and that this change correlates directly with gains in functionality, engagement, and motivation.
For patients who say, “I’m not sad. I just feel nothing,” vortioxetine is not just an antidepressant—it’s a pathway back to meaning.
In addition to vortioxetine, several other pharmacologic treatments with emerging or established efficacy for treating anhedonia and difficult-to-treat depression (DTD) were discussed:
These agents represent a shift toward mechanism-based prescribing, rooted in neurocircuitry rather than checklists.
Dr. McIntyre made clear that medication alone isn’t enough—and that the future of treatment lies in interdisciplinary, circuit-level approaches, including:
Dr. McIntyre concluded by reminding clinicians that anhedonia is not secondary. It is primary, it is predictive, and it is often the most disabling feature our clients face—even after other symptoms improve.
The takeaway? If we’re not treating anhedonia, we’re not treating depression.
Whether it’s vortioxetine, AXS-05, SAINT TMS, or behavioral activation, we now have a growing arsenal of tools to intentionally restore joy, purpose, and motivation.
Our job isn’t just to reduce symptom scales. Our job is to help people reconnect with their lives. As Dr. McIntyre so powerfully demonstrated at NEI, we’re entering a new chapter in psychiatry—one where we stop asking “Are they less depressed?” and start asking:
“Do they care again?”
Schedule an appointment today to get diagnosed, receive a prescription, and continue your journey towards mental peace.