One night in December 2019, Emma Louthan realized in a mild panic that she needed a gift for a child’s birthday party the next day. She grabbed acrylic paint and some of her daughter’s old clothes and began creating an aquatic scene: pink koi swimming beneath white and green water lilies.

The birthday boy wasn’t much impressed by the artful present, but it planted a seed in Ms. Louthan’s mind.

A few months later, she tried her hand at a collection of about a dozen hand-painted adult sweatshirts and found a more appreciative audience. It was the beginning of Covid lockdowns, and Ms. Louthan, an artist in Philadelphia who graduated from Temple University’s Tyler School of Art and Architecture, was working as a freelance textile designer while at home with her husband and 1-year-old daughter.

The sweatshirts, which she had painted in the kitchen of her brick duplex in Germantown, sold out online almost immediately.

“I feel like I just kind of accidentally hit it at the right time,” said Ms. Louthan, 35. Though divisive and terrifying, the pandemic also brought out people’s softer sides. Suddenly, comfort was king. Everyone was baking or crafting. Small-batch ceramics and upcycled quilted coats soared in popularity. There was a compulsory return to the home — and a wholehearted embrace of the homemade.

Noticing that people were drawn to “anything that could replicate a tie-dye look,” Ms. Louthan learned different dyeing techniques: botanical, ice, brush-applied. She traded her stiff acrylic paints for fabric versions, which she used to produce more sweatshirts and loungewear under her brand, Swan Gossip Shop.

As life slowed down during the pandemic, many other artists and independent designers also found success in the niche world of clothes with hand-drawn motifs — a trend spurred in part by Emily Adams Bode Aujla, who repopularized the senior cord tradition, which dates back to the 1900s, with her namesake brand.

Located across the country, these makers use a variety of methods, mediums and styles. In Los Angeles, Juliet Johnstone paints oversize, sherbet-colored flowers, butterflies and peace signs onto T-shirts and fitted work pants; in St. Louis, Lauren dela Roche and Curtis Campanelli of 69 Tearz use 19th-century farmer feed sacks as canvases for gothic hand lettering and rubber-hose-style cartoon characters; and in New York, Nick Williams and Phil Ayers of Small Talk Studio juxtapose imagery like American brand logos and botanical drawings on Japanese cotton.

In an era of mass-produced fast-fashion, these designers and others say they have experienced a growing demand for their meticulously rendered, one-of-a-kind garments.

Today, Ms. Louthan has a monthslong wait-list for her custom hand-painted clothes, which range in price from $250 (for T-shirts and sweatshirts) to $800 (for some pants). She’s partnered with local boutiques; the streetwear brand, Teddy Fresh; and national retailers including Anthropologie, Urban Outfitters and Free People on small batches of shirts, socks, bags and dresses.

“People say they can sense a certain energy in the hand-painted stuff,” Ms. Louthan said one afternoon this summer, while carefully adding green to a tendril on a pair of bluejeans.

Although her brand now has national reach, Ms. Louthan still paints her clothing at home, mostly on her kitchen table. Her process usually takes multiple days and consists of three stages: outlining forms, painting them and then heat-setting everything with an iron.

“I feel like with the rise of A.I., people are swinging the other way pretty intensely,” she said. “I think when everything feels so impersonal, people do gravitate toward art.”

Ms. Louthan’s work is fantastical, depicting off-kilter, edenic scenes of cherubs, rabbits, butterflies, devils, swans, moons and streams. She creates storybook worlds, where the sun smiles and jesters run wild.

She draws inspiration from illustrators of vintage children’s books (like Beatrix Potter and Roald Dahl); the Impressionist artist Mary Cassatt (known for her reverent paintings of domestic life); and ancient art.

Her daily walks to Awbury Arboretum, half a mile from her house, are also creative fodder. “There’s no roadblock,” she said, between what she sees blooming there and what she paints.

Before she had her first daughter, Rosie, in 2018, Ms. Louthan designed prints for mass market brands. Back then, she also painted by hand, but her designs would later be scanned, photoshopped and printed onto fabrics that would then be sold to companies like Gap, Old Navy and Alfred Dunner.

Ms. Louthan said her work today is “kind of the exact opposite of trying to design for thousands of people who want the same thing.”

Though Ms. Louthan occasionally orders plain white shirts or finds light-colored clothes in thrift stores, customers more frequently provide their own garments for her to paint (they have ranged from $800 Acne jeans to favorite old tees). It’s a way of giving clothes a second life, Ms. Louthan said, and making precious garments even more special.

The popularity of hand-drawn designs like hers can pose challenges. Producing a single garment is time consuming for artists and can also be physically taxing.

Ms. dela Roche of 69 Tearz used to joke that she was a “doodle machine.” But now, because of arthritis and bone spurs in her hand, she said, “I literally can’t hand-draw anything anymore.”

Last year, she and Mr. Campanelli, her business partner, began screen-printing outlines of her designs onto garments. Only about 25 items are screen-printed before Ms. dela Roche, 42, switches up the imagery. Mr. Campanelli, 33, still hand sews each garment and hand-paints certain portions, ensuring that each piece is distinct.

“Even if I try my absolute best, I cannot do the same thing twice,” he said.

In 2023, Mr. Williams and Mr. Ayers, the Small Talk Studio designers, expanded their then-three-year-old business to include seasonal, ready-to-wear collections.

“We had all these ideas we wanted to put into motion and we wanted the operation to support more than just these specific hand-drawn garments,” said Mr. Williams, 33. “The other part of it was also that there’s a ceiling to how much you can charge and how much you can put out if that’s all you’re doing.”

Of the current interest in such pieces, Mr. Ayers, 34, added, “We don’t know whether this is like a trend or not — you know, that people are into hand-drawn clothing.”

Ms. Louthan has had to make some adjustments, too. When she works with brands like Anthropologie and Free People, she is often tasked with fulfilling bulk orders of the same garment — 60 pairs of natural-dyed socks, for example, or 40 T-shirts emblazoned with kittens.

“They know that it won’t be all the same, but it’s as similar as possible,” she said. “I just work in batches, you know, kind of assembly-line style.”

Recently, Ms. Louthan has re-embraced the idea of licensing artwork to be scanned and printed on clothes. “I kind of hope to shift more into that in the future,” she said. “Honestly, just because hand-painting everything is physically — it’s just a lot.”

She’s striving to find a balance.

“There’s always at least one moment of, I would say, growth in every single thing I paint,” she said, pointing to a small area on a T-shirt where the red paint of a tomato bled into the blue paint of a stream. “I always make sure to have a few moments where I tell myself, even if no one else notices or no one else appreciates, I just think it’s really cool.”

Barrie Miskin was newly pregnant when she noticed her appearance was changing. Dark patches bloomed on her skin like watercolor ink. A “thicket” of hairs sprouted on her upper lip and chin.

The outside world was changing, too: In her neighborhood of Astoria, Queens, bright lights enveloped objects in a halo, blurring her vision. Co-workers and even her doctors started to seem like “alien proxies” of themselves, Ms. Miskin, 46, said.

“I felt like I was viewing the world through a pane of dirty glass,” she added. Yet Ms. Miskin knew it was all an illusion, so she sought help.

It took more than a year of consulting with mental health specialists before Ms. Miskin finally found an explanation for her symptoms: She was diagnosed with a dissociative condition called depersonalization/derealization disorder, or D.D.D. Before her pregnancy, Ms. Miskin had stopped taking antidepressants. Her new psychiatrist said the symptoms could have been triggered by months of untreated depression that followed.

While Ms. Miskin felt alone in her mystery illness, she wasn’t. Tens of thousands of posts on social media reference depersonalization or derealization, with some likening the condition to “living in a movie or a dream” or “observing the world through a fog.”

People who experience depersonalization can feel as though they are detached from their mind or body. Derealization, on the other hand, refers to feeling detached from the environment, as though the people and things in the world are unreal.

Those who are living with D.D.D. are “painfully aware” that something is amiss, said Elena Bezzubova, a psychoanalyst who specializes in treating the condition. It’s akin to seeing an apple and feeling that it is so strange it doesn’t seem real, even though you know that it is, she added.

The disorder is thought to occur in about 1 to 2 percent of the population, but it’s possible for anyone to experience fleeting symptoms.

Mental health providers have sometimes dismissed D.D.D. as its own diagnosis not only because of a lack of familiarity with the disorder, but also because its symptoms overlap with conditions like depression, anxiety or panic disorder.

As new research has emerged, it has become more widely acknowledged and discussed. The second edition of “Feeling Unreal,” a primer on D.D.D. originally published in 2006, was released in 2023. And Ms. Miskin published a memoir on the subject titled “Hell Gate Bridge” last June. The same month, the novel “Please Stop Trying to Leave Me” came out, featuring a protagonist with D.D.D. The author, Alana Saab, knows the disorder well: She was diagnosed several years ago.

“It’s kind of what I would imagine a drug trip would be,” she said of her experience with the disorder. “But it’s 2 in the afternoon and I’m completely sober.”

The Cambridge Depersonalization Scale is widely considered the most reliable measure of the disorder. Patients are asked to rate how often and how long 29 different experiences occur. Examples include feeling like “a robot,” losing bodily sensations like hunger or thirst and seeing a world that now looks “flat” or “lifeless,” like a picture.

People with D.D.D. may feel disconnected from themselves and their surroundings for months or even years at a time. Less commonly, they may also experience auditory distortions — like muffled or louder sounds.

D.D.D. is often associated with a history of emotional abuse or neglect. The symptoms can be brought on by anxiety, depression, the resurfacing of early trauma, major life stressors, cannabis and hallucinogens like LSD, said Dr. Daphne Simeon, an expert on the disorder and the co-author of “Feeling Unreal.”

In some people, there can be multiple triggers, particularly if there is an underlying propensity to dissociate.

“You can meet a person whose first episode was triggered by panic and then it happened again when they got depressed and then it happened a third time when they had a terrible divorce,” Dr. Simeon said.

Researchers have hypothesized that depersonalization/derealization might be part of the mind’s defense system.

“Your body and your mind are telling you something,” Dr. Simeon added. “You’re having an intolerable experience, essentially, from which you then have to detach.”

Jeffrey Abugel, Dr. Simeon’s co-author on “Feeling Unreal,” dealt with D.D.D. for more than a decade before finally getting a diagnosis. He knows exactly where it stemmed from: “Pot, plain and simple,” he said. The drug pushed him “over the edge,” he added, creating a “massive panic attack.”

Mr. Abugel, who is a health and wellness coach, eventually found help. He now offers private consultations and virtual support groups for people with the disorder.

Ms. Miskin’s symptoms improved with a combination of psychotherapy and medication. She restarted her antidepressant and also began taking lamotrigine, or Lamictal, a medicine best known for treating seizures and bipolar disorder.

Recovery was a painful process.

“You have to relearn how to be in the world,” she said, even though “you just want to lay in bed and pull the covers over your head and never come out.”