Should ketamine be used to treat depression?
Laurel Barr had tried 13 antidepressants, electroconvulsive therapy and everything else doctors prescribed to try to restore her life to normal, but the treatments brought only temporary benefits and some made her severe depression worse.
The disorder drained her energy, confining her to her home and bed when she wanted to be at work or with her two young sons and husband, said Barr, 40, who grew up in West View and lives in New Zealand.
A month and a half ago in Pittsburgh she received six infusions of the drug ketamine, an anesthetic often used as a party drug that is being tested against treatment-resistant depression. She started to feel brighter after the second treatment, she said. She went for walks, looked forward to seeing friends, enjoyed watching birds.
“It seemed to have really significantly helped,” said Barr, who has returned to New Zealand. “For how long, I’m not exactly sure.”
No long-term clinical trials of the Schedule 3 drug have been completed. It is FDA-approved as an anesthetic and some doctors prescribe it off-label for the most severe depression.
Short-term trials show it acts more quickly than any other depression treatment, sometimes within hours, and that its benefits last up to a few weeks. It acts on a different part of the brain than antidepressant medications, fueling hopes that it could be a good alternative for people who haven’t responded to other treatments.
“It definitely has a role to play in the treatment options we have currently; for a specific patient this can be lifesaving,” said Dr. LalithKumar Solai, director of UPMC’s Center for Interventional Psychiatry.
But, Solai added, “Once we get them better, we don’t know what to do with them.”
Doctors don’t have any evidence from clinical trials about what might be the effects of repeated ketamine infusions over time, or whether putting patients on antidepressants after a ketamine course might be a good idea, Solai and other doctors said. Adding to the uncertainty are concerns about side effects, which so far range from hallucinations and discomfort during infusions to bladder and liver problems associated with recreational use of the drug.
Those concerns have kept many doctors from embracing the drug, and insurers don’t cover it as a depression treatment. UPMC doesn’t prescribe it but plans to start offering it for treatment-resistant depression soon. Allegheny Health Network doctors prescribe it rarely, according to the head of the health system’s psychiatry department.
Other doctors believe that patients with few remaining options should be able to try ketamine. One is Dr. Hank Macler, who opened Pittsburgh Ketamine a year ago in White Oak. Barr was treated there during a Pittsburgh visit scheduled around the birth of her brother’s baby.
Macler administers six infusions of the drug to patients in his clinic over two weeks. Patients receive the drug and sit in padded chairs while it takes effect. White noise plays in the background. Macler prescribes oral ketamine pills for patients to take twice a day after the infusions.
He estimates about two-thirds of patients respond positively to the infusions, some experiencing dramatic transformations, and the effects can last months or longer. Patients can come in for a booster treatment when the effects wear off.
“We just know it works,” said Macler, who completed a residency at the Harvard hospital now known as Brigham and Women’s Hospital and used ketamine as an anesthetic while treating severe burn victims. “We know how to use it, to use it safely, (and) get a good result.”
Barr said her depression became most apparent when she was in college at Syracuse University, where she received undergraduate and graduate degrees in arts and art education.
She found herself lacking energy to focus on details or accomplish basic tasks and started to isolate herself. She moved to New Zealand in 2000, about a year after she received her graduate degree. Her condition got worse, and she found herself sometimes unable to get out of bed or hold a train of thought.
“It’s a very hard life, because every tiny thing becomes very overwhelming,” she said.
She sought treatment on the advice of friends. Some combinations of antidepressants and other therapies helped for brief periods, enabling her to do things like cook dinner or drive her kids to school, but didn’t cure her. There were hospitalizations and suicide attempts, she said.
“I have a wonderful family, I have wonderful job,” she said. “I’m on the school board; I’ve got three degrees … I’ve got a pretty content life, but my brain can’t function in a proper way. And it’s very, very, very frustrating, because there’s nothing I can do to make it come right.”
Google searches on treatment-resistant depression led her to ketamine. In addition to helping her depression, the treatment eliminated chronic pain in her hip from torn cartilage that she had been treating with pain killers.
The drug’s apparent benefits have led to descriptions of it as a wonder drug or miracle drug, which can be problematic, said Dr. Christopher Ryan, a clinical associate professor of psychiatry at the University of Sydney who wrote a paper on ketamine that appeared in April in The Lancet Psychiatry.
“The only trouble is, at this point, there’s no actual evidence of that. At least no trial evidence,” Ryan said.
He is concerned that patients who experience great benefits from ketamine and then lose them may end up in a worse condition than they started, he said. If the drug turns out to have more significant side effects than is now known, regulators in different countries could take a harder stance than they might have if it were to go through full testing before broader use, he said.
Longer-term trials are underway, and Ryan said he supports waiting for their results before prescribing the drug without well-vetted guidelines to follow.
“Ironically, by using it early you could actually stop anybody getting some potential benefit in the future,” he said.
Macler said he warns patients about the risk, including that the drug might not work for them. The first infusion costs $525 and subsequent treatments cost $475 each.
Allegheny Health Network ran a small trial about 10 years ago that showed some short-term benefits in treating severe depression, said Dr. PV Nickell, system chairman of AHN’s Department of Psychiatry.
While promising due to its fast action and its targeting of a different part of the brain than other antidepressants, Nickell remains cautious about the drug. He and Solai each said they would recommend electroconvulsive therapy and transcranial magnetic stimulation before ketamine.
“It still is experimental as far as I’m concerned,” Nickell said.
Emailing from New Zealand this week, Barr said the drug is still keeping suicidal thoughts at bay and allowing her to feel “normal” and suppressing the pain in her hip.
“I constantly worry when the effects will wear off, but trying to focus on the here and now and enjoying the time I have bought with the treatment,” Barr said in an email.
The drug is more difficult to get in New Zealand than in America, but she said she might seek special approvals to use it if it wears off.