Psychedelics may be no better than antidepressants for depression

Psychedelics may be no more effective than traditional antidepressants in treating depression. Drugs like psilocybin, LSD, and DMT have recently shown tremendous promise in treating a variety of mental health conditions, but a persistent problem in this research is that people can often judge whether they received these drugs or a placebo, based on the hallucinogenic effects of the former. When this is taken into account, it appears that psychedelics may be effective for depression, but not more so than antidepressants.

“Our results do not refute the exciting findings regarding psychedelic treatments,” says Balázs Szigeti of the University of California, San Francisco (UCSF). “We also show that psychedelics are effective in treating depression; it’s just that they are no more effective than open-label medications. [unblinded] traditional antidepressants, which seems disappointing given the attention [on psychedelics].”

Hallucinogens have shown promise in treating depression, anxiety, and obsessive-compulsive disorder. The gold standard in drug development is usually testing a treatment against a placebo. This overcomes the placebo effect, when a person’s medical symptoms are alleviated through the power of suggestion and expectation. But in psychedelic research, people are often able to perceive whether they are in the treatment group.

To get around this problem, Szigeti and colleagues studied 24 trials, eight of which focused on psychedelic-assisted therapy (PAT) – the combined treatment of psychotherapy and psychedelics. The remaining 16 were open trials of traditional antidepressants. This means that researchers and participants knew which treatment was being administered, eliminating the “blinding” that is also considered the gold standard in most trials.

The team found that traditional antidepressants appeared to outperform PAT by only 0.3 points on a 52-point depression rating scale, which is neither statistically nor clinically significant.

Psychedelics have typically outperformed a placebo by 7.3 points in previous trials, compared with about 2.4 points when antidepressants are pitted against a placebo. But researchers say much of that benefit could come from participants being able to determine whether they were given a psychedelic. “Our studies and others provide new evidence that unblinding suppresses the placebo response,” says Szigeti.

“This is an interesting review with a clever approach to answering the question of placebo in psychedelic trials for depression,” said Matthew Johnson of John Hopkins University in Maryland, who was involved in some of the studies the team reviewed. Some researchers have “a religious zeal to show that psychedelics are effective, rather than a principled approach of trying to actually test hypotheses,” he says.

But Rayyan Zafar of Imperial College London says psychedelics need to be compared head-to-head with antidepressants, not just placebos, to understand their effects: “The jury is still scientifically out. » Only one trial has done so, testing psilocybin against escitalopram, a selective serotonin reuptake inhibitor antidepressant – and it found no significant difference in relieving depression.

Robin Carhart-Harris, also at UCSF – who participated in the escitalopram trial – has a common criticism of the methodology behind the latest study: Comparing multiple trials with different designs, including varying sample sizes and inclusion criteria, generally does not yield a conclusive result. “It is proposed to compare apples to apples, when in reality it is more like comparing apples to oranges,” he says.

Last September, a study investigating LSD to treat anxiety sought to reduce the likelihood of blindness being relieved by administering lower doses of the drug to the control group, so as to induce hallucinogenic effects without necessarily having an impact on mental health. And in a psilocybin trial, people were given a sedative that can cause amnesia and erase their memory of the trip.