Work with drugs like ketamine, psilocybin, and MDMA feels almost titillating. We now have scientists working with cutting edge compounds that, because they can also be abused, have a daring side to them. We may also be finally breaking free from the serotonin/noradrenaline handcuffs and embarking on new and more rational strategies for antidepressant medication development. Finally, and of course most important, there are some signs–although much more research on both effectiveness and safety must be done–that these new drugs can help depressed people in some ways that currently available medications do not.

The prospect of a new medication for depression always seems to generate enthusiastic public and media attention. Not surprisingly, therefore, many stories about the crop of potential new drugs have appeared, whetting our appetite with hope for a breakthrough. There is a kind of “we told you so” theme to some of these stories: drugs that were heralded in the 1960s as the road to higher consciousness only to be demonized and banned are once again being looked upon as possible breakthroughs. But if the idea that drugs considered illicit may now become prescribable medicines seems strange and surprising, so perhaps do findings that strategies once associated with gurus, yogis, and fitness advocates that do not involve any drugs may also be effective antidepressants.


Who’s Your Guru?

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By now most of us have gotten the message that exercise is good for just about everything. Mood is no exception; many studies have clearly documented that exercise improves mood and may reduce the symptoms of depression. Although systematic reviews of the literature reach conflicting conclusions about just how potent an antidepressant exercise is, there is emerging evidence that exercise can be considered as part of the treatment plan for any patient with depression who can safely engage in physical activity. There is also evidence that exercise can prevent depression.

It is sometimes assumed that only medications have a biological basis for the treatment of psychiatric illnesses, but we are coming to understand that psychosocial interventions of various kinds also have demonstrable effects on brain function. There is now work, for example, showing that exercise has effects on the brain that may be relevant to its antidepressant effects, like increasing the size of the hippocampus, a structure critical for learning and memoryAccording to evolutionary biologist Herman Pontzer, exercise may blunt the effects of cortisol, the stress hormone known to play an important role in both depression and anxiety disorders. Pontzer argues that exercise is an evolutionary development that distinguishes humans from their nearest genetic relatives, the great apes. Exercise is uniquely essential for humans because “we evolved a faster metabolism, [requiring] fuel for increased physical activity and the other energetically costly traits that set humans apart, including bigger brains.”

Another “wellness” practice that also appears to have biologically-based antidepressant effects is mindfulness meditation. Although once again there are conflicting opinions about just how effective meditation is for treating depression, studies have shown that meditation normalizes connections between two brain areas critically involved in fear, anxiety, and depression—the amygdala and the prefrontal cortex. Preliminary evidence also indicates that yoga may play a role in treating depression.

Science in Silos

All of these new approaches to treating depression are exciting, but we also note that the medication and non-medication ones seem to be developed by scientists who operate in silos and rarely communicate with each other. So if you are a person suffering from depression, should you go to a psychiatrist who offers ketamine, even though it has not yet been approved by the FDA as an antidepressant? Or would it be better for you to hire a trainer and begin exercising? Or perhaps both?

Of course, a lot of the answer to this question depends on an individual’s exact circumstances. Someone who is already a marathon runner might not benefit from more exercise. Ketamine seems to be helpful for the immediate treatment of severe depression, but we do not know yet if it is safe or effective for longer-term treatment of more moderate forms of depression. Hence, the most useful thing would be to see a mental health clinician who knows about all of these different approaches to treatment, understands which have the best evidence supporting them, and is prepared to offer an intervention plan that combines both somatic and psychosocial elements.

New medications are typically evaluated by comparing them to placebos, identically appearing but physiologically inert pills. This is a straightforward and rigorous way of determining if a new drug works and in cases like ketamine for depression the answer is almost certainly that it does. But for a person suffering from depression knowing that a drug works better than nothing is informative. He or she might ask “is this pill better for me than if I start meditating or doing yoga?”

Answers to a question like that will require breaking down some of the silos that often exist in science and getting scientists from very different fields to communicate with each other. How about a study comparing psilocybin to yoga? Or Ecstasy to meditation? And maybe add brain imaging to see to what extent the treatments normalize brain function in depressed people? This may seem like “science joins the psychedelic age,” but bold approaches are exactly what we need for serious and difficult to treat illnesses like depression. As daring as it may be to study psychedelics and strategies originally developed by Eastern practitioners as approaches to treating a medical condition, breaking down some walls that separate scientists working on the same problem might be even bolder.