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Antidepressants are my grandfather’s legacy. But with mental illness, they aren’t enough

November 13, 2022


My grandfather, Harry Salzer, was a psychiatrist in Cincinnati who, along with his colleague Max Lurie, reported in a 1953 paper that isoniazid — a medication developed to treat tuberculosis — had a positive impact on two-thirds of their depressed patients.

This was the first time researchers had identified a drug with so-called antidepressant effects. With that, a new era in psychiatric treatment was born.

Growing up, I knew my grandfather was a psychiatrist. But I didn’t know he’d published any scientific papers until I began my own training in clinical psychology. When researching treatments for a patient with panic attacks and poor diet, I came across my grandfather’s studies where he claimed low blood sugar could underlie some psychiatric conditions. Roughly 10 years ago, I found his 1953 paper about antidepressants. It was a shocking revelation.

The 1953 finding was consistent with a growing belief that mental illnesses are rooted in biology, which has led to 70 years of efforts to identify those causes, and drugs to address them. The optimism underlying these ideas was so great that the 1990s was declared the “decade of the brain” by then-President George Bush, in anticipation of discoveries identifying the genetic and brain mechanisms associated with mental disorders, and the development of medications to cure them.

But the 1990s are now well behind us and we are far away from those anticipated cures.

So perhaps it’s time to expand our thinking about the causes and cures for depression and other mental illnesses. Maybe primarily focusing on treatments that target biological underpinnings to mental illness isn’t the best idea?


How to find help

If you or anyone you know is thinking of suicide, help is available 24/7:

  • The National Suicide Prevention Talk Line offers help in over 150 languages. Call 1-800-273-8255 or text HELLO to 741741. En Español, marque al 1-888-628-9454. If you’re deaf or hard of hearing, call 1-800-799-4889.
  • The Philadelphia Suicide and Crisis Center offers guidance and assessment about depression, self harm, hopelessness, anger, addiction, and relationship problems, at 215-686-4420.
  • Veterans Crisis Chat is available at 1-800-273-8255 or by text at 838255.
  • The Trevor Project offers crisis support to LGBTQ+ youth 25 and under. Call 1-866-488-7386, text START to 678678, or start a chat.

Thomas Insel, a former head of the National Institute of Mental Health — the federal agency that funded much of this research — has recently asked a similar question. For all the agency’s focus on genetics and brain chemicals that might drive mental illnesses, there are still too many people suffering from those conditions who need more immediate help. In a recent book, Insel writes about a man who talked about his son with schizophrenia, who told Insel: “Our house is on fire, and you are talking about the chemistry of the paint. What are you doing to put out this fire?”

The man has a point.

Millions of Americans take antidepressants, and their use has risen in recent years. Many swear that escitalopram (brand name: Lexapro) or sertraline (Zoloft) changed their lives, and I would never suggest that anyone stop taking their antidepressants without a long conversation with their prescriber. But research has generally been unkind to my grandfather’s notion of antidepressants as a cure-all that targets the biological roots of mental illness.

Research has generally been unkind to my grandfather’s notion of antidepressants as a cure-all.

Several clinicians and researchers have proposed that most of the positive impacts of antidepressants at least partly result from the placebo effect — namely, people feel better because they’ve taken a pill that they expect to help them, regardless of whether the pill targets the desired brain mechanisms. Today’s antidepressants often work by helping raise brain levels of serotonin, known as the “feel good” hormone. But a recent evaluation of research found that depression isn’t related to serotonin levels at all.

If treatments that target our biology, including serotonin levels in the brain, aren’t the cure we were hoping for, what can we turn to?

Seventy years after my grandfather pioneered the use of drugs to treat depression, I believe it’s time to expand our approaches.

For instance, some depression experts have been suggesting non-drug interventions. There is, of course, talk therapy, but that can be expensive and also takes time to result in benefits.

Johann Hari, in his book Lost Connections, refers to ample research showing that depression may result from the loss of meaning and purpose in life — including a lack of satisfying interpersonal relationships, and contact with nature. Loss of contact with nature, in particular, sounds implausible as a cause of depression, but just remember that humans essentially lived outside during most of our history, and it has only been the last 100 years or so when we have started to spend most of our days inside homes and buildings. This deprives us of the demonstrated positive impacts that the sights and smells of nature have on our bodies and mental health.

» READ MORE: Exercise can relieve depression – even at lower doses than you’d think

As a result of such thinking, health-care providers outside the United States have considered what these might mean for treating depression. In the United Kingdom, clinicians offer social prescribing, including recommending activities that provide meaning and enhance participation in society, such as volunteering, engaging in the arts, participating in sports, learning about healthy cooking, and spending time with others. In Japan, they suggest shinrin-yoku, also known as “forest bathing.” Physicians in Canada prescribe nature walks and give their patients free yearlong passes to Canada’s national parks system.

To be clear: I’m not suggesting that anyone ditch their prescription for a nature walk. But I am suggesting we look beyond medications when treating mental health. I’m proud of my grandfather’s legacy, but I also believe that, in many cases, depression can’t be treated by antidepressants alone. It’s time to shift focus to a broader range of approaches to effectively treat depression and other mental health issues.

Mark Salzer is a psychologist and professor of social and behavioral sciences and director of the Collaborative on Community Inclusion of Individuals with Psychiatric Disabilities at Temple University.



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