New Study Says Psychedelics Are No Better than Antidepressants; We Say There’s More to the Story
A new meta-analysis published March 18 in JAMA Psychiatry is making some waves. The headline: psychedelic-assisted therapy is no more effective than traditional antidepressants for treating major depression.
The story is more nuanced than the headline suggests. As a physician who integrates ketamine-assisted psychotherapy into a broader biopsychosocial treatment model, I think this study raises critical questions that deserve a closer look, not a dismissal of psychedelic medicine.
What the Study Found
Researchers from UCLA and the Centre for Psychedelic Research at Imperial College London, led by clinical data scientist Balázs Szigeti, PhD, pooled data from 24 trials: 8 psychedelic therapy trials (249 patients) and 16 open-label antidepressant trials (7,921 patients). Their goal was to compare the two approaches under what they call “equal unblinding conditions.”
The result: both groups improved by approximately 12 points on the Hamilton Depression Rating Scale (HAM-D 17). The estimated difference between the two was 0.3 points — statistically and clinically negligible.
In Szigeti’s own words, reported by Gizmodo: “What I wanted to show is that even if you compare psychedelics to open-label antidepressants, psychedelics are still much better. Unfortunately, what we got is the opposite result — that they are the same, which is very surprising given the enthusiasm around psychedelics and mental health.”
The Blinding Problem: Why This Comparison Is Inherently Flawed
The central insight of this meta-analysis is also its greatest limitation: the blinding problem.
In traditional drug trials, the gold standard is a double-blind design. This is where neither the patient nor the clinician knows who got the real drug versus the placebo. This controls for the expectancy effect: the phenomenon where believing you’re receiving treatment actually makes you feel better.
Psychedelics break this model entirely. When you take psilocybin, you know. The visual distortions, the altered sense of self, the emotional depth; there is no mistaking it for a sugar pill. Studies show that 90–95% of participants in psychedelic trials correctly guess their treatment allocation, compared to roughly 60% in traditional antidepressant trials.
The researchers’ solution was to compare psychedelic therapy to open-label antidepressant trials — studies where patients know they’re getting the real drug. The logic: if everyone knows they’re getting treatment, the playing field is level.
But here’s the problem many researchers and clinicians are pointing out: knowing you’re taking psilocybin and knowing you’re taking an SSRI are not the same kind of “knowing.”
As Prof. David Owens, emeritus professor of clinical psychiatry at the University of Edinburgh, noted in his Science Media Centre response, these studies address “perhaps THE outstanding issue in the assessment of psilocybin and other hallucinogens as therapeutic tools in treatment-resistant depression — blinding.”
Szigeti himself coined the term “knowcebo effect” to describe what happens when a participant realizes they got the placebo and becomes demoralized, a kind of reverse expectancy that artificially widens the gap between drug and placebo arms. This is a real phenomenon. But the meta-analysis’s workaround, comparing to open-label antidepressant trials with entirely different patient populations, protocols, and therapeutic contexts, introduces its own confounds.
You’re not comparing the same patients. You’re not comparing the same therapeutic frameworks. You’re comparing 249 psychedelic therapy patients who typically receive one or two doses alongside intensive psychotherapy to nearly 8,000 patients in standard antidepressant trials with vastly different support structures.
What the Numbers Don’t Capture: Duration, Side Effects, and Quality of Life
Even if we accept the study’s framing at face value: that psychedelic therapy and traditional antidepressants produce similar reductions in depression scores, that equivalence masks differences in how those outcomes are achieved and what they cost the patient over time.
One or Two Sessions vs. Years of Daily Medication
Psychedelic therapy typically involves one or two dosing sessions paired with preparation and integration psychotherapy. If the outcome is comparable to daily SSRI use, consider what that means: similar relief from depression without the need for a daily pill, potentially for years or indefinitely.
A landmark 6-month follow-up study published in eClinicalMedicine (The Lancet) found that psilocybin and escitalopram (a common SSRI) produced similarly sustained reductions in depression scores over six months, but the psilocybin group showed significantly greater improvements in work and social functioning, connectedness, and meaning in life. The scores may have been the same. The lived experience was not.
The Side Effect Burden
Traditional antidepressants carry a well-documented burden of long-term side effects that profoundly impact quality of life:
Emotional blunting: a reduced ability to feel both positive and negative emotions. Many patients describe feeling “flattened” or “numb,” which is technically an improvement on depression scores but hardly what most people mean by “getting better.”
Sexual dysfunction: reduced libido, difficulty with arousal and orgasm. These effects can persist for months or even years, and in rare cases, sexual dysfunction continues even after stopping the medication.
Weight gain and metabolic changes that compound over time with chronic use.
Discontinuation syndrome: when patients try to stop SSRIs, they can experience dizziness, nausea, anxiety, “brain zaps,” and a return of depressive symptoms that make it incredibly difficult to taper off.
Psychedelic-assisted therapy has a fundamentally different side effect profile. Common effects — transient nausea, headache, temporary anxiety during the session — typically resolve within 24 to 48 hours. There is no daily drug in your system. No hormonal disruption from chronic use. No withdrawal when you stop, because there’s nothing to stop taking.
If two treatments produce the same depression score improvement, but one requires a lifetime commitment with significant side effects and the other requires one or two sessions with transient discomfort, are they really equivalent?
Expectancy As Feature, Not a Bug
One of the most thought-provoking critiques emerging from the expert commentary around this study is that the entire framework may be asking the wrong question.
As one expert noted in the Science Media Centre roundup, the research “highlights the limitations of the RCT paradigm in unpicking the undoubted expectancy effects that come with a drug like psilocybin from the more biological effects. However, since both are important in the treatment of depression, psilocybin therapy represents an increasingly intriguing option.”
This is a crucial point. In the biopsychosocial model of pain and mental health — which is the foundation of how we practice at NeuroPain Health — the psychological and social dimensions of healing are not noise to be controlled for. They are the treatment.
When a patient enters a ketamine-assisted psychotherapy session with a trained therapist, in a carefully prepared setting, with intention and openness — that context is not a confound. It’s the therapeutic container that allows neuroplasticity, emotional processing, and behavioral change to take root.
The RCT model was designed to isolate a single pharmacological variable. That works beautifully for blood pressure medication. It works less well for treatments that are, by design, holistic — treatments where the drug, the therapy, the relationship, and the patient’s belief in their own capacity to heal are all part of the mechanism of action.
What This Means for Patients
Szigeti himself stated: “This does not mean psychedelic therapy is not a valuable treatment option, but it’s probably not as effective as early research indicated.” He also noted that “psychedelics will be a useful addition to the clinician’s toolkit.”
I agree — and I’d go further. For many patients, especially those who:
Have not responded to traditional antidepressants (roughly 30% of depression patients)
Are struggling with the side effects of long-term SSRI use
Experience comorbid chronic pain and depression (where the kynurenine pathway and neuroinflammation create a vicious cycle)
Want a treatment that addresses root causes rather than managing symptoms indefinitely
…psychedelic-assisted therapy, and ketamine-assisted psychotherapy specifically, offers something that a daily SSRI cannot: the opportunity for deep psychological work in a condensed timeframe, without the long-term pharmacological burden.
The Bigger Picture: Psychiatry Needs More Options, Not Fewer
Prof. David Owens made a point in his commentary that I think is worth sitting with: interest in psychedelics stems partly from a sense of desperation among mental health professionals. There has been minimal innovation in psychiatric pharmacology in the past 40 years since the introduction of SSRIs. As Owens put it: “Psychiatry is constrained by outdated theories … and we don’t need another SSRI for depression.”
This study is a useful reminder to stay grounded in evidence and resist hype. But it would be a mistake to let a flawed comparison — one that equates “knowing you took psilocybin” with “knowing you’re on Lexapro” — be the reason we slow down a field that millions of treatment-resistant patients are counting on.
The question has never been whether psychedelic therapy is a miracle cure (we know it is not). The question is whether it’s a safe, effective, and durable option that can help people who are suffering — especially those whom traditional medicine has failed. The answer, based on the totality of the evidence, is yes.
Explore Your Options
If you’re considering ketamine-assisted psychotherapy or want to learn more about our integrative approach to pain and mental health, schedule a consultation with Dr. Weiner’s team at NeuroPain Health.
Learn more about our Ketamine-Assisted Psychotherapy (KAP) program.
Read Dr. Weiner’s published research on low-dose ketamine for chronic pain.
References & Sources
1. Szigeti B, et al. “Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions.” JAMA Psychiatry. Published online March 18, 2026. Full text
2. Erritzoe D, et al. “Effect of psilocybin versus escitalopram on depression symptom severity: 6-month follow-up.” eClinicalMedicine (The Lancet). 2024. Full text
3. Science Media Centre. “Expert reaction to two papers on psilocybin and blinding in psychedelic therapy.” March 2026. Expert reactions
4. Gizmodo. “Scientists Pump the Brakes on Psychedelic Antidepressant Hype.” March 2026. Article
5. EurekAlert / UCLA. “Are psychedelics better than antidepressants? New study says no.” March 2026. Press release
6. HCPLive. “Psychedelic Therapy Matches Efficacy of Antidepressants in MDD, With Balázs Szigeti, PhD.” March 2026. Interview