Depression is notoriously difficult to treat, but advances in neuroscience and electromagnetic technology are enabling new options for some chronic cases. One well-established, if not as well-known, treatment is transcranial magnetic stimulation (TMS).

Don’t be fooled by the sci-fi sounding name: TMS — which uses magnetic fields to stimulate the brain’s natural electrical activity — is approved by the U.S. Food and Drug Administration (FDA), produces minimal side effects, and boasts strong efficacy rates.

“It can be a game-changer for people who suffer from chronic depression,” says interventional psychiatrist Suzanne Jasberg, MD, who began treating patients with TMS more than a decade ago. “I became fascinated with neuromodulation during my medical residency, and I’ve continued to use it ever since simply because it’s so effective.”

TMS has also been FDA-approved for obsessive-compulsive disorder, migraine, and smoking cessation (though insurance does not always cover the cost of treatment for these uses). Trials are underway for a range of other mental illnesses, including bipolar disorder and posttraumatic stress disorder.

How does TMS work?

TMS is performed via an electromagnetic coil that’s placed against the scalp and delivers nerve-stimulating pulses to regions of the brain that tend to be compromised in those with depression.

This is a fundamentally different approach from medication. Antidepressant medications influence the brain’s neurochemistry, affecting the release or reuptake of neurotransmitters like serotonin, norepinephrine, and dopamine. TMS affects the brain’s neurocircuitry, the interconnected neural pathways that enable us to process information, regulate emotions, and make decisions.

TMS works well as a means of enhancing rather than replacing traditional treatments: With healthier neuropathways, the brain can make better use of medication and psychotherapy.

What does TMS feel like?

During TMS sessions, a patient dons hearing protection and settles into a reclining chair beneath or beside a magnetic coil. At an initial session, a TMS technician “maps” a patient’s head to identify the regions of the brain to target. Reflexive twitching in the hands and fingers on the opposite side of the body identifies target brain locations. At subsequent sessions, a technician uses measurements gathered from this mapping process to determine treatment locations.

TMS machines are fairly loud, and patients can hear and feel a tapping sensation against their head, even with ear plugs. The tapping can be uncomfortable or even slightly painful, and patients often experience headaches or dizziness after a session. These side effects are generally mild and pass within a few minutes; it’s safe for a patient to drive and go about their day once a session is complete.

Patients will often bring a friend or family member with them to their first sessions to help them cope with the tapping and make the experience less intimidating.

TMS is not a one-and-done treatment. For several weeks, patients typically undergo sessions every weekday, each lasting between 20 and 50 minutes; many return for follow-up sessions after the initial course of treatment.

Why haven’t I heard more about TMS?

This really comes down to marketing dollars, Jasberg explains. “TMS doesn’t have the marketing budget that pharmaceuticals have.”

TMS also carries some stigma. She finds that people associate TMS with electroconvulsive therapy, a far more intrusive treatment that can lead to memory loss. Or, as she puts it, “they may assume TMS must be woo-woo and experimental.”

“Brain stimulation sounds scary,” she acknowledges. But TMS has been FDA-approved for more than a decade and is backed by a large body of research supporting its efficacy and safety. The side effects tend to be mild, and there’s no memory loss, little risk of seizure, and no need for anesthesia.

Still, the treatment is not for everyone. TMS is not recommended for anyone with a magnetically sensitive implant, such as a pacemaker or cochlear implant. A history of seizures, head trauma, or other neurological conditions may also rule out the treatment.

The history and severity of depressive episodes also determines whether an individual qualifies for TMS. The treatment is approved only for major depressive disorder, and some providers and insurance companies OK it only if the depression is deemed resistant to other treatments — which means an individual has undergone at least two unsuccessful medication trials and received a formal diagnosis of major depressive disorder.

To find a TMS provider near you, work with your insurance company or check out provider directories like Brainsway or the Clinical TMS Society.

How well does TMS work?

Studies have shown that about 60 percent of individuals who undergo TMS for depression experience a significant and sustained decrease in symptoms, and one study found remission rates as high as almost 80 percent. By contrast, the average antidepressant offers relief to only 30 percent of those who take it.

While there are no guarantees, TMS can be life-changing for those who respond well to the treatment. “Many of my patients have been depressed most of their lives,” Jasberg says. “They may have tried 20 or 30 different medications. Understandably, they come in skeptical. But a few weeks pass, and they find themselves doing things they never thought they could do. The world seems brighter. They’re finally able to enjoy life.”

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Like a certain portion of the American public, I’ve been feeling a little low lately while struggling to find some equilibrium amid what seems like a daily dose of political and cultural chaos. There’s no escaping the zeitgeist, however, so I was oddly pleased the other day to learn that the real source of my sagging spirits may have less to do with current events than with my advanced age.

And though it’s a bit depressing to discover that the simple act of aging may cause depression, recent research has uncovered some novel antidotes.

An estimated 20 percent of older U.S. adults develop what’s called late-life depression (LLD), according to a 2023 study published in the journal Translational Psychiatry. It is, explains lead study author Sarah Szymkowicz, PhD, “a malignant illness that increases disability, contributes to poorer medical outcomes, and is associated with increased suicide risk and mortality.”

Szymkowicz, an assistant professor of psychiatry and behavioral sciences at Vanderbilt University, and her team found that the risk factors for LLD align closely with conditions common to the aging body: inflammation, vascular disease, and neurodegeneration.

Chronic inflammation, for instance, alters the cellular structure in parts of the brain that influence depressive behavior, she explains, citing research linking such neural activity in the brains of depressed individuals who have attempted suicide. Similarly, hypertension, atherosclerosis, and other common age-related vascular afflictions can damage the neural pathways that regulate mood. And as dementia sufferers and their loved ones can attest, cognitive dysfunction eventually affects social behavior, often resulting in depression.

“Vulnerability to developing depressive episodes results from accumulated factors, many of which have an initial onset earlier in life,” Szymkowicz writes. “Other vulnerability factors are unique to later life and may contribute to a new diagnosis of depression or a relapse of symptoms in previously remitted individuals.”

Szymkowicz cites research suggesting that cognitive training — like standard treatment approaches, such as psychotherapy and pharmacotherapy — may repair the neural connections that lead to depressive behavior. In many cases, she notes, a mix of therapies may prove to be most efficient. “Augmenting cognitive training with neuromodulation approaches or other nonpharmacological treatments may provide additional benefit but need study in LLD.”

Some of that research is already underway. A meta-analysis of 27 clinical studies published last month in JAMA Network Open found that an exercise regimen significantly reduced levels of depression among older cancer patients. “These findings suggest that healthcare professionals and policymakers should focus more on implementing exercise interventions to improve mental health outcomes in this vulnerable population,” the authors note.

The workouts described in the various studies range from conventional strength training and aerobics to mind-body exercises such as Qi Gong, yoga, and tai chi. Researchers suspect that the physical activity releases neurotransmitters that stimulate areas of the brain that improve mood control. It also tends to boost sleep quality, which has been shown to ease depression and anxiety.

And a study published last week in Nature Mental Health touts the antidepressive benefits of engaging with others in various artistic endeavors. A team of researchers from Queen Mary University of London reviewed 39 studies involving more than 4,000 participants from 21 countries and found that joining a group to paint, play music, dance, write, or simply wander through a museum eased depression and anxiety — especially among older adults in nursing homes and assisted-care facilities. The results were comparable to other, more conventional treatment approaches, such as antidepressants, talk therapy, and even exercise.

Citing the “social identity approach to health,” Janelle Jones, PhD, and her team suggest that connecting with peers through these activities offers tangible and intangible resources that ease anxiety and promote mental health. “Arts interventions are accessible, cost-effective, and enjoyable,” Jones explains. “They offer a way to address mental health challenges that doesn’t rely solely on medication or traditional therapy. This is particularly important for older adults, who may face barriers to accessing conventional treatments.”

I’ll take all this as good news for me and My Lovely Wife. She meets regularly with a group of fellow artists to share their work and chat about the artistic process. And I’d like to think the collaborative nature of magazine work — including the weekly polishing of this column — may qualify as a modestly artistic effort.

So, I guess there’s a chance that my currently sagging spirits may have less to do with the mundane malfunctioning of my aging brain than with the uncontrollable chaos of current events. And that is depressing.

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Jacqueline had gone through therapy and been on antidepressants for years, yet she still felt numb, stuck, and disengaged. She was struggling to move past childhood trauma and had become disconnected from her emotions.

She wasn’t quite sure how to regain that connection, but she knew antidepressants weren’t doing the trick. “I need something different,” she told me.

After nearly a decade practicing traditional talk therapy, I began integrating ketamine into my practice in 2023. Ketamine was first synthesized in 1962; it’s since been used as a surgical anesthetic and at times misused as a recreational psychedelic drug. But it turns out that this molecule offers much in the way of mental health treatment. It has shown enormous promise in treating both acute and chronic depression, as well as addiction, PTSD, and other mental health disorders.

Though ketamine isn’t for everyone and is not a silver bullet — beware of anyone who claims otherwise — I’ve seen some pretty astonishing results.

Jacqueline (who asked we use only her first name to preserve her privacy) seemed wary when she arrived in my office; she had never used psychedelics before. But she had researched the science behind ketamine-assisted psychotherapy (KAP) and decided it wouldn’t hurt to try. The explanation and preparation put her at ease. “There was so much thought put into the process,” she recalls.

She settled into a zero-gravity armchair with an eye mask blocking external light. Ambient electronica music played in her headphones. She says she felt comfortable and safe. The nurse took her blood pressure, reviewed dosage options, and, after receiving a final confirmation, injected 50 mg of ketamine into Jacqueline’s right biceps.

“There’s no good way to describe what happened next,” Jacqueline says. For the next hour or so, Jacqueline was immersed in colorful imagery, stimulating all five senses. “I felt like I was in a happy daydream. It was the first time I’d felt joy in years.”

The real impact came afterward.

That night, Jacqueline slept better than she had in years. “I have always had trouble sleeping due to nightmares and anxiety: I was having them two to three times a week,” she says.

During the summer months following the KAP, she had just three nightmares. “So, it [was] the summer of good sleep for me — which has impacted both my mood during the day and my relationships. I think having such a consistent effect from the treatment is important; and once I started talking with other adults, I discovered this issue is more common than I thought.”

The day after her first KAP therapy, Jacqueline found herself opening up to her husband in ways she’d never felt able to before. It was as though the emotional blockage in her life was finally melting away.

How Does Ketamine Work to Support Depression?

To appreciate how and why ketamine works, it’s helpful to understand how and why traditional antidepressants work — and why they often don’t.

Ketamine works differently from traditional antidepressants, says John Lichtsinn, MD, a board-certified psychiatrist who offers KAP in his outpatient practice. He explains the difference with an analogy: Imagine the brain is a series of interconnected roads and highways. Traditional antidepressants are like gas stations along the road; for people who don’t produce enough feel-good “fuel” naturally, these medications top off the neurotransmitters dopamine, serotonin, or norepinephrine at certain signaling pathways in the brain.

If someone doesn’t have healthy neuropathways to begin with, the effect of the antidepressants can be limited, he says.

Ketamine enhances those neural networks — it maintains, rebuilds, and improves those roadways in the brain. This not only makes travel easier but also expands the ways one can get from point A to point B.

This is because ketamine acts on a different neurotransmitter: glutamate. The brain’s most abundant excitatory neurotransmitter, glutamate is critical to neurological changes involved in learning and memory. Studies have found that ketamine helps stimulate the brain to regrow synapses that may have been lost due to chronic stress, as well as to form new synapses. This effect, called synaptogenesis, seems especially profound in areas of the brain associated with depression and chronic stress.

Speed of impact is another benefit. Antidepressants can take weeks to begin working, while ketamine’s effects are nearly immediate. That makes it effective in treating acute conditions, such as suicidal ideation. It can also enable brief but intense transcendent experiences when administered via certain routes and doses (more on that later).

While it remains unclear just how long the newly formed synapses survive, it appears that the cognitive and behavioral benefits — new ways of seeing things, new ways of reacting to things — can sustain over time. With more routes to choose from, the brain can break out of ingrained mental habits to form new ways of thinking and reacting, a process known as neuroplasticity.

How long that neuroplasticity lasts remains a complicated question. Some effects, like synaptogenesis — the formation of new connections between neurons — seem to peak within a day, while the enhanced learning and processing enabled by increased neural connectivity may last for several weeks.

“Because the effects diminish over time, people generally benefit from additional treatment,” says Lichtsinn, noting that this often entails psychotherapy or other healing modalities — not just more ketamine. “I see the most change in clients who view the medicine as a catalyst rather than the ‘main event.’”

How Is Ketamine Administered?

Ketamine can be administered in various ways, each offering distinct amounts of bioavailability — the amount of the medicine absorbed into the system. This allows for flexibility in treatment. What follows are the three most common methods of delivery.

1) Sublingual ketamine lozenges that dissolve beneath the tongue generate mild enough side effects that they can be taken at home. Available via online prescribers at a relatively low cost, this is perhaps the most accessible form of ketamine on the market.

Efficacy rates are on par with infusions — in one study, about half of patients logged significant decreases in anxiety and depression scores after just three doses of sublingual ketamine — and may further improve with extended use.

2) Intranasal ketamine spray is based on a more potent form of ketamine called esketamine and is extremely fast-acting, capable of relieving depression symptoms in under an hour.

Esketamine is still under patent and quite expensive for patients, says Lichtsinn, so its use is currently limited. “Once it becomes available as less-expensive generic drugs, I think it will be more broadly used, including for ketamine-assisted therapy,” he explains. “It checks a lot of boxes and has advantages — no needle, no bad taste like with oral form, good absorption into the bloodstream. Given this relative ease of drug delivery, some people have discussed whether it has [a] potential role in acute care (like in emergency rooms) for acute relief of severe depression or for people who are suicidal.”

Because it can distort perception for up to two hours, esketamine is administered in a medical setting where patients are monitored until the side effects pass.

3) Intravenous ketamine infusions can provide rapid relief from depression as well as long-term improvements. Under supervision, patients receive a subanesthetic dosage but may still feel disoriented and euphoric for up to two hours.

Patients often undergo a series of infusions spread out over several weeks or months. One study found that 55 percent of patients who underwent ketamine infusions experienced long-term improvements in depression symptoms.

What Is Ketamine-Assisted Psychotherapy?

In ketamine-assisted psychotherapy (KAP), form — how the ketamine is administered — matters less than function: The intention is to bring patients into either a psycholytic or psychedelic state.

In a psycholytic state (achieved through lower doses like lozenges), the patient experiences an altered state of consciousness yet remains in touch with the present moment. They can still interact with their therapist, but with a “looser” state of mind.

Typically achieved via intramuscular injection, a psychedelic state is much deeper and transcendent — an out-of-body experience that can give rise to powerful memories, images, or sensations.

In either case, it’s the unique combination of neuroplasticity and psychotherapy that makes KAP so beneficial. A therapist can help the client make meaning of their experience and translate new perspectives into long-term healthy mental habits. For example, clients often tell me they “never thought of things that way” until undergoing a ketamine session. We use this realization — that there are many ways of perceiving a situation — to establish and reinforce cognitive restructuring skills, such as reframing assumptions or challenging all-or-nothing thinking.

I tell clients that ketamine is like adding motor oil to the brain, greasing the wheels of rigid thoughts, beliefs, and behaviors that have been contributing to their depression.

Who Should Avoid Ketamine, and What Are the Risks?

Ketamine is not a good fit for everyone. People with a history of or genetic risk for psychosis may want to avoid it; so might those who have certain medical conditions, including uncontrolled hypertension or cardiovascular disease.

Though ketamine is not recommended for individuals who are actively abusing drugs or alcohol, it can be a helpful component of substance-use treatment. But this poses another conundrum: the risk of addiction to ketamine itself.

Using ketamine — at least in certain doses — feels good. After all, it is a drug, and some people may abuse it.

“Clinics are popping up quickly and the regulatory agencies can’t keep up,” Lichtsinn warns. “So do your research before you choose a provider.”

Then there’s ketamine’s murky legal status. Esketamine nasal spray is the only form currently approved by the U.S. Food and Drug Administration for treatment of depression. But because ketamine has long been approved for surgical use, medical providers can legally access and administer the off-label version.

It’s a convenient loophole that presents some challenges. Insurance rarely covers treatment, and out-of-pocket costs can reach hundreds of dollars. With the actual cost of ketamine amounting to little more than pocket change, the profit margin can be enormous, hence the booming market.

“Clinics are popping up quickly and the regulatory agencies can’t keep up,” Lichtsinn warns. “So do your research before you choose a provider.”

According to Lichtsinn, reputable clinics conduct a full medical assessment prior to treatment and ensure that patients have access to immediate medical support while taking ketamine, especially if they’re taking it remotely.

“We’re seeing the best and worst of ketamine’s potential,” he adds. “Navigate cautiously.”

How Ketamine and Therapy Can Transform Mental Health

Jacqueline and I met a few days after her initial ketamine treatment in an integration session to explore ways she could build on her newfound mental flexibility. She committed to spending more time outdoors, taking a chance on new friendships, and really being present with her young daughter — all things that seemed unattainable beforehand.

“Trauma and depression trick you into thinking that’s all you’ll ever feel; ketamine woke me up from that,” Jacqueline says. “I remembered that I’ve felt joy before, and more importantly, I realized that I could feel it again.

“Rediscovering joy has improved everything in my life, but especially my relationships. I had always kind of assumed the worst with people, but now I don’t carry that negative perspective. As my daughter put it: ‘Mom, you don’t have a sad face anymore!’”

While crediting the ketamine for loosening her mental joints, Jacqueline considers the psychotherapy component equally important. “It helped me clarify what I wanted to get from the experience so I could go in with a clear intention. And more importantly, having built that therapeutic relationship allowed me to trust that I could surrender to whatever happened.”

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Much has been made about the mental health crisis among today’s teenagers — a very real and growing issue — but it’s actually young adults who are suffering the most. Conducted in 2022, a Harvard Graduate School of Education survey of 1,843 teens, young adults, and parents found that Americans aged 18 to 25 are roughly twice as likely as their teenage counterparts to report struggling with anxiety or depression: Thirty-six percent of young adults reported anxiety; 29 percent reported depression; and 58 percent reported they lacked “meaning or purpose” in their lives.

“Young adults’ mental health hasn’t been on our public radar in the way that teens’ mental health has been since the pandemic,” report coauthor Milena Batanova, PhD, states in a press release.

While some of this can be chalked up to the stressors young adults have always faced, there’s reason to believe young adults from Gen Z faces unique vulnerabilities.

This is a generation that lost formative developmental years to the COVID-19 pandemic. Many were stuck at home or in some form of lockdown during high school or college — when they most needed the opportunity to establish independence.

This is also a generation that’s never known a time when the country wasn’t politically polarized; when college, home ownership, or raising a child was more reasonably affordable for the average American; or when social media wasn’t amplifying the discord surrounding these matters.

In response to various issues, Gen Z has raised its voice: Almost a third of Gen Zers are regularly involved in activism or social-justice work compared with roughly a quarter of millennials, according to a 2023 United Way of the National Capital Area survey. And while it’s admirable to see so many young people advocating for social change, engagement takes a toll: 45 percent of the young adults surveyed by the Harvard Graduate School of Education attributed some aspect of their mental health issues to a “sense that things are falling apart” in the world.

Young adulthood can be a tough time, both exhilarating and intimidating. Gone are the restrictions and limitations of youth. Gone, too, are the long-held routines and daily relationships that can support mental well-being and prevent bad decisions.

For many individuals, their 20s mark the first time they’ll live with roommates rather than with parents; the first time working a “real” job rather than a summer gig or part-time position; the first time paying rent, balancing a budget, buying groceries, or owning a car.

All this can leave even the most well-adjusted young adults uniquely vulnerable to a range of mental health issues. These are some of the most common risks, plus tips for effectively navigating this life stage.

Relationships in Flux

Most people enter young adulthood having been surrounded by familiar faces their entire lives. Then high school ends and the graduates scatter. Parents, siblings, neighbors, and friends may no longer be routinely present in their lives, replaced by a barrage of new relationships: professional colleagues, roommates, romantic interests, maybe even children of their own.

Adjusting to these new dynamics can be challenging, especially since most young adults are still figuring out who they are and what they need, as well as how to communicate those things. A study published by the Journal of Adult Development found that stress stemming from interpersonal relationships — particularly with friends and romantic partners — accounts for between 46 and 82 percent of the everyday stressors that emerging adults encounter.

Yet plenty of young adults struggle with the opposite problem: loneliness. Although it’s an issue that affects people of all ages, chronic loneliness is more common in young adulthood than it is in middle adulthood. A lack of close, supportive relationships can trigger or exacerbate depression and increase stress.

Risky Behavior, Fewer Guardrails

We tend to associate high-risk behavior with the teenage years, when a not-yet-adult brain craves adult freedom. Yet young adults can be similarly vulnerable: The prefrontal cortex, responsible for impulse control and complex problem-solving, typically isn’t fully developed until roughly age 25.

Parents, teachers, and federal laws help curtail high-risk behavior during adolescence, but many of those checks and balances fall away in early adulthood. Now there’s less preventing a young adult from buying beer or skipping school; there’s no parent making sure they make it home by midnight or shaking them awake when they sleep past their alarm.

Meanwhile, some of the potentially moderating structures and responsibilities of adulthood — a full-time job, a live-in partner, the burden of paying for quality health insurance — typically remain on the horizon.

The intersection between sudden freedom and a still underdeveloped prefrontal cortex can be dangerous: Those in their 20s are at a much greater risk of developing substance-use disorders and of dying by injuries caused by accidents or violence than are their older counterparts. And though the majority pass through their 20s without incurring any permanent scars, the stress that comes from making adult decisions without adult wisdom is mentally and emotionally taxing in and of itself.

Onset of Major Mental Illness

The onset of serious mental illnesses such as major depressive disorder, bipolar disorder, and schizophrenia typically occurs in the late teens or early 20s for men, although the average age of onset for women with schizophrenia is in the 20s to early 30s. It’s difficult timing: This is when young people may become more distant from the parents, teachers, and other supports most likely to notice warning signs.

It’s also when people begin to confront the kinds of major stressors — job loss, breakups of serious relationships, and so on — that can precipitate a first episode of major depression or psychosis among those predisposed to these conditions. Moreover, those who are young and whose lives haven’t yet established a predictable rhythm (it’s pretty normal, say, for a young person’s sleep and eating schedules to be all over the map) are going to be less attuned to changes in the baseline. So, someone still finding their footing in life tends to be less attuned to disruptions in their psychological and physiological patterns — sleep, appetite, mood — that can signal oncoming decompensation.

Mental illness doesn’t have to derail one’s life, but early diagnosis and treatment can make all the difference. Without self-knowledge and support, young adults are at risk of falling through the cracks. (For signs that your mental health may need attention, see “7 Signs That Your Mental Health Needs Attention.”)

How to Survive Your 20s

Successfully navigating this life stage boils down to balancing risk with responsibility, independence with connection, and engagement with enjoyment. Tap into these strategies to survive these years and prepare for thriving in the years ahead.

1) Build healthy habits now. Sure, your body is more resilient than it’ll ever be, and you’ve probably got another half-dozen decades to get things together. But your 20s are a golden window to begin building healthy habits. Consider this a great time to start exercising, meditating, questioning your relationship with alcohol, or establishing any other habits you’ll appreciate down the road.

2) Balance social advocacy with self-care. Young people have long been at the forefront of social movements, and while it’s essential to stand up for what you believe in, doing so shouldn’t come at the cost of your own well-being. Find a balance between staying informed and staying mentally healthy, whether by limiting social media, setting boundaries when you’re burned-out, or making time for things that fuel an optimistic view of the world. (For more on self-care for activists, see “Self-Care for Activists.”)

3) Maintain connections. Relationships can come and go throughout this stage of life, so make sure to maintain a few anchors of support amid those waves of change. Who provides that support — a parent, sibling, childhood friend — matters less than whether you can count on them to be there when you need help and to know you well enough to point out concerning changes in mood or behavior. (For more on the importance of friends and connections, see “Why Friends Are Essential to Our Well-Being.”)

4) Be an explorer. For all its challenges, young adulthood can and should be a time for exploration and self-discovery. Because young adults are typically unburdened by kids, a mortgage, or serious career obligations, the time is ripe to try new things, take (healthy) risks, and begin identifying what matters to you.

If there’s a silver lining to the collective struggle, it’s that Gen Z seems much more comfortable discussing it. Studies have shown that members of this cohort are not only more likely than their older counterparts to openly acknowledge mental health issues but also more likely to seek professional treatment. And that means this generation of young adults may be the one that makes young adulthood a little less treacherous for the next.

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