‘No One Thing’: Different Symptoms, Different Treatments and the Murky Path of Treating Depression

In many ways—and much to the chagrin of psychiatrists—mental illness remains a mystery, Psych Congress co-chair Charles Raison, MD, said in a lengthy interview published by The Sun magazine this month.

While there have been significant advances in the field since the first DSM was published in 1980, Raison says two hurdles remain: Identify and develop more-effective treatments for various mental health conditions, and figure out which treatments should be given to which patients.

Raison noted that one of the biggest challenges in treating major depression is that it can present in vastly different ways between patients.

“According to the DSM you have to have five out of nine possible symptoms to be diagnosed with major depression,” he said. “That means two people can both have major depression and have only one symptom in common.”

Raison spoke with The Sun both before and during the COVID-19 pandemic. In his interviews for the magazine’s feature, Raison discussed various treatments for depression:

Psilocybin. In his research, Raison said he has observed that patients’ narratives about themselves and the world seem to become more positive after receiving psilocybin. “Depression has elements of a narrative disorder, one that arises from the stories we tell ourselves about our lives: difficult childhood stories; stories of adversity and loss, of not getting the love we need at key points. Studies suggest that a psychedelic experience, if done in a proper, clinical context, radically changes people’s personal stories.”

With regards to the effects of psilocybin, Raison pointed to a pair of studies conducted by New York University and Johns Hopkins. Patients in each study had been diagnosed with potentially life-threatening cancer and clinically significant anxiety and depression. They were provided with six to eight hours of psychological preparation before receiving their psilocybin (or placebo) doses.

“The results were quite striking,” he said. “In both studies a single dose of psilocybin induced a powerful antidepressant response that was maintained for five weeks. Six months after the crossover, 70% to 80% of people were in remission from their depression without other treatments. 

Later studies at Imperial College London and Johns Hopkins produced similar results.

Ketamine. While it won’t work for all patients, Raison said ketamine has demonstrated an effect compared to a placebo in some patients for whom standard antidepressants have failed. Many patients who were depressed felt “considerably better within an hour or two after a ketamine treatment,” he said.

Raison added that although ketamine isn’t a psychedelic, it can produce hallucinations, and it has shown direct effects on the brain that reduce depression with or without being paired with psychotherapy.

Ayahuasca. Used in ceremonies in South America for decades, ayahuasca has demonstrated antidepressant effects in small studies. However, because of the way it is produced and some of the side effects it causes, ayahuasca is not approved in the U.S.

Ultimately, Raison said, the lack of new accepted treatments for depression is a result of a lack of new pharmaceuticals.

“Until ketamine came along, all antidepressants operated on some combination of norepinephrine, serotonin, and dopamine,” Raison said. “None of these antidepressants is appreciatively different from the others when tested on large groups. Still, it’s good to have many options available, because people respond idiosyncratically to antidepressants. It can take some trial and error before you hit upon one that really makes a difference for you.”