NEW YORK — When you think of Ellen DeGeneres, Conan O'Brien, David Letterman and Robin Williams, the first word that comes to mind isn't depression.
But the four comedians have all struggled with the disease suffered by an estimated 350 million people worldwide, according to their own comments or those close to them. Williams, a comedian known for his manic energy, committed suicide Aug. 11 at age 63. He had suffered a period of severe depression, his publicist Mara Buxbaum said in a statement.
"Not everybody who has a depression disorder gets recognized," Paul Summergrad, the president of the American Psychiatric Association, said in a telephone interview. "It affects rich people, it affects poor people, it affects people across the spectrum."
Symptoms vary and can include feelings of hopelessness, extreme anxiety, appetite changes, insomnia or excessive sleeping, and suicide risk, according to the National Institute of Mental Health in Washington. Depression often occurs in concert with substance abuse, according to the institute.
Treatment can include a combination of prescription drugs and talk therapy, said Jeff Borenstein, president of the Brain and Behavior Research Foundation. For a number of people, multiple drugs must be tried, or a combination of drugs, before finding a treatment that works, he said.
"It is a physical condition that affects the brain," Borenstein said. "The symptoms include feeling depressed, obviously. But it also can include difficulty functioning at work, home or at school, inability to enjoy oneself, and low level of energy, difficulty concentrating and, most importantly, thoughts of wanting to kill oneself."
Drugs used to treat the disease include Eli Lilly's Prozac, Pfizer's Zoloft and GlaxoSmithKline's Paxil. Side effects can include nausea, dizziness, insomnia and weight gain or loss. They belong to a class of drugs called selective serotonin reuptake inhibitors, which build up levels of a chemical in the brain, serotonin, the lack of which has been associated with depression.
It's a class of drugs that's been controversial in the past because of a link to suicidal thoughts. They now carry warning labels that advise close monitoring when patients first start on the medication.
Recently, investigators at Johns Hopkins University in Baltimore published research on a gene tied to negative thoughts and impulses. It may lead to a blood test predicting suicide risk, they said. The research, published in the Journal of Psychiatry in July, adds to recent genetic discoveries in psychiatry that promise to advance treatment and diagnostics in the field.
Suicide is the 10th-leading cause of death in the United States, according to the Centers for Disease Control and Prevention. While there are known risk factors, such as mental illness, drug abuse or distressful life events, there is no consistent way to predict suicide, researchers said.
The greatest risk comes when people who are severely depressed don't get treated, or when treatment is inadequate or sporadic, according to Summergrad. Those also dealing with substance abuse or other illnesses need to have that care coordinate with their depression treatment, he said.
"When a treatment is started, people need to be monitored very, very carefully," he said.
Just half of Americans diagnosed with major depression are treated and only 20 percent are cared for according to practice guidelines, according to the National Institutes of Health.
David Letterman is expected to address Robin Williams' passing in his late night show on Aug. 18, according to a spokesman. In interview with "CBS This Morning" in 2012, Letterman said he avoided treatment initially because he feared the drugs could make some symptoms worse.
"I thought it would make me loopy or make me hallucinate or make me drowsy," Letterman said in 2012. "It's different than, 'Oh I don't feel good today.' It's different than feeling sad, it's different than feeling blue."
O'Brien's depression deepened after losing his job as the host of NBC Universal's "The Tonight Show" in 2010, he told Rolling Stone magazine. "I felt like I'd just been in a car accident," he was quoted as saying.
DeGeneres said her depression settled in during a lull in her career in 1997 after she first came out as a lesbian, facing a slowdown in advertisers on her show and tabloid attention, according to a report in the Guardian.
Williams had film roles touching on mental illness. As the title character in Patch Adams, he portrayed a man who committed himself to a mental institution and became a doctor. He also played a therapist in Good Will Hunting.
Being highly successful is no protection against depression, said Scott Krakower, a psychiatrist at Zucker Hillside Hospital in Glen Oaks, New York, in a telephone interview. In fact, it may be a contributor, he said.
"They do have a really nice life," Krakower said. "But there's always a lot of pressure on them being in the spotlight constantly, and sometimes you need almost an escape from that."
Actors, in particular, may feel the extreme level of anxiety that is symptomatic of the disease, according to Krakower. "When they go on the stage they want to be perfect," he said. "There's a lot of pressure on them and they put a lot of pressure on themselves."
Williams was released from a rehab center last month, according to published reports. He has commented in the past on his struggles with both alcoholism and drug addiction, a troubling situation that can lead to difficulties in treating depression, according to Summergrad.
Substance abuse "can change the way depression appears," making it "harder to treat," Summergrad said. "In some cases you need to treat the mental health illness, the addictions and general health issues all at the same time."