‘Club Drug’ Ketamine Provides Hope in Fight Against Depression

Scientists are increasingly convinced that ketamine, a popular “club drug,” may be a viable treatment option for people who suffer from depression. The drug could hold particular promise for people who are suicidal, according to the results of one small study.

Scientists are increasingly convinced that ketamine, a popular “club drug,” may be a viable treatment option for people who suffer from depression. The drug could hold particular promise for people who are suicidal, according to the results of one small study.

Depression is so common that people in the U.S. spend about $11 billion each year to relieve their symptoms. Most antidepressants work by adjusting the brain chemicals that can affect our mood, and while some are effective, the drugs are far from perfect. They typically take up to two months to work, and even then, only 30% of people will respond to any given drug. That leaves most people to cycle from one prescription to the next until, hopefully, one starts to lift their feelings of hopelessness and helplessness.

But beginning in the 1990s, researchers started studying a compound called ketamine that seems to sweep away depressive symptoms with almost miraculous ease and speed. “Honestly, it was unlike anything I had ever seen when I first saw its effects four years ago,” says Dr. Dawn Ionescu, a staff psychiatrist at Massachusetts General Hospital. “We were seeing patients who were depressed for years and tried many different medications, sometimes even electroconvulsive therapy, and nothing worked. But a single infusion improved their depression within hours.”

Ketamine is approved by the Food and Drug Administration (FDA) as an anesthetic and for treating certain types of pain. In just the right doses, however, it can trigger hallucinatory and out-of-body experiences, which also makes it a popular club drug.

As more studies are starting to show, ketamine can also be a highly effective way to lift mood. But giving people with depression doses of ketamine could also set them up for addiction; while it rebalances certain brain chemicals pertaining to mood, ketamine also triggers dopamine, a substance with direct links to the reward system. Hits of ketamine make the brain crave even more of the drug, and since depression is a chronic condition that requires consistent treatment, a drug that has the potential to cause dependence is far from ideal.

Still, two recent papers add stronger evidence to the idea that ketamine could be a new option for treating depression.

In one study, published in the journal Nature, researchers led by Carlos Zarate from the National Institute of Mental Health used animals to figure out how ketamine works in the brain and how it affects depression. They studied ketamine, as well as the byproducts it releases after it’s broken down by the body, to understand how the drug affects depression. They found that ketamine leads to the side effects of dependence and dissociative thinking by blocking a brain pathway called NMDA, which affects mood. But they also made an important discovery about one of ketamine’s byproducts—one metabolite in particular—which remain in the body for days after the drug is taken. This metabolite appears to trigger the antidepressant effects of ketamine, but without the side effects and addictive potential.

That explains why previous studies found that ketamine’s ability to relieve depression occurred so quickly and lasted for days, often up to a week. Zarate is particularly encouraged by the fact that the metabolite he found doesn’t seem to activate the pathway that’s responsible for ketamine’s addictive effects as well.

That means that if drug developers can find a way to mimic the metabolite, and provide it in just the right dose, ketamine could become an appealing treatment. Theoretically, it could even be used early in a person’s depression history, and, because it acts quickly, might save millions of people from unnecessary suffering.

That may be especially true of people with severe depression who also experience suicidal thoughts. In a small separate study, published this year in the Journal of Clinical Psychiatry, Ionescu found that among 14 people with depression and suicidal thoughts, a few infusions of ketamine helped them to lessen their suicidal ideations considerably after three weeks. While there is still debate over whether suicidal thoughts are part of depression or in a separate category, having a compound that could address them is critical. “Suicide is the only top 10 cause of death that is increasing, not decreasing,” says Dr. Charles Nemeroff, chairman of psychiatry and behavioral sciences at the University of Miami and chair of the American Psychiatric Association task force on biomarkers and novel treatments. “Most of that is due to untreated, under-treated or treatment-resistant depression.”

“We definitely need to understand the addictive potential and side effects of ketamine more before it becomes a prime time treatment for depression,” says Ionescu. “But what we’re excited about is the fact that we may have something that is helping very sick patients in a relatively short period of time.”

Nemeroff is equally encouraged by the findings, but warns that the number of patients studied in ketamine trials is still small, and the sample may not be representative of all people with depression. Most of the people currently in ketamine trials are there as a last resort; they’ve failed other antidepressant therapies, including numerous medications and electroconvulsive therapy.

He’s also concerned about the growing number of ketamine clinics that are popping up around the country, where people with depression can receive infusions of ketamine via IV. Some of those clinics aren’t run by psychiatrists or mental health professionals, he says, but by anesthesiologists and pain physicians who may not have as refined training about how best to use ketamine for depression. “I worry about how well people are screened, and because this is a drug of abuse, whether people are screened for drug abuse as well,” he says.

Even though doctors can prescribe ketamine for depression off label, huge questions still remain about how much of the drug to give, and for how long, says Nemeroff. There is also no data on the safety or efficacy of using ketamine long-term. “If we give ketamine to someone who is suicidal, and they’re no longer suicidal, do we let them go? What happens the next day or two days later? Does the suicidality come back? These are the kinds of questions we need to know the answer to,” says Nemeroff.

Some of those answers may come from a trial that Johnson & Johnson is conducting on a type of ketamine they’ve developed as an intranasal medication. That study will provide more data on what dose might help people with depression, how long the drug should be given and whether there are long-term side effects. If those results are positive, then groups like the American Psychological Association will need to help doctors decide who might benefit most from the drug by coming up with guidelines for how best to administer the medication. “It would be terrific to have new targets to treat depression,” says Nemeroff. “I’m just saying that I want us to be cautious.”

Original Article Found Here.

Psychiatrists Call For Special Clinics To Prescribe Ketamine As Anti-Depressant

The party drug ketamine can have powerful beneficial effects on severely depressed patients who have struggled for years to recover, and the drug should be developed responsibly as a psychiatric medicine, British experts said on Thursday.

In a study published in the Lancet Psychiatry journal, specialists from Oxford University said there is an urgent need for ethical and innovative action by doctors to prescribe the drug under controlled conditions.

“We think patients’ treatment should be in specialist centers and formally tracked in national or international registries,” said Rupert McShane, a consultant psychiatrist and researcher at Oxford who has led a series of ketamine studies.

Ketamine is a licensed medical drug, widely used as an anesthetic and to relieve pain. But it is also used as a recreational drug – sometimes known as Special K – and can lead some people into addiction and drug abuse.

Several research teams around the world have been trialling ketamine use in chronic and recurring depression, since many patients with the psychiatric condition fail to respond to currently available antidepressants such as Prozac and Seroxat.

“I have seen ketamine work where nothing has helped before,” McShane said at a briefing in London.

The U.S. pharmaceutical company Johnson & Johnson is developing an intranasal form of the drug, called esketamine. Its results so far have been promising enough for Food and Drug Administration officials to award esketamine “breakthrough” status to speed its progress through regulatory hurdles.

McShane and his co-researcher Ilina Singh, a psychiatry professor at Oxford University, told the briefing there had been a worrying sharp rise in the past year in the number of private ketamine clinics in the United States.

There are wide variations in the clinical checks before a patient receives treatment, they said, and there is a need for clear guidelines and registries to track how patients respond.

Last month, the American Psychiatric Association issued a consensus statement on ketamine in a bid to guide safe, appropriate prescribing of the drug for severe patients who do not respond to regular antidepressants.

McShane stressed that the ketamine doses used in the Oxford depression treatment trials are given in controlled conditions and are very different from those taken by street or club users.

On the street, users often take several grams a day and can suffer severe bladder problems and impaired brain function. The doses used in medical trials are a fraction of that – around 80 milligrams – and given once a week in a monitored setting.

Singh said ketamine has such great potential to help a small group of very ill patients that it would be wrong not to find a way of allowing them to benefit from it: “This drug is available, it’s out there, and if we can help patients get treatment responsibly, it’s our duty to do so,” she said.

Treating patients in specialist centers should help doctors spot potential problems early, she said, as well as picking up any abuse problems with longer term use and narrowing down what dose, frequency, route and duration of treatment works best.

Original Article Found Here.

Ketamine For Severe Depression: ‘How Do You Not Offer This Drug To People?’

Gerard Sanacora, a professor of psychiatry at Yale University, has treated hundreds of severely depressed patients with low doses of ketamine, an anesthetic and popular club drug that isn’t approved for depression.

This sort of “off-label” prescribing is legal. But Sanacora says other doctors sometimes ask him, “How can you be offering this to patients based on the limited amount of information that’s out there and not knowing the potential long-term risk?”

Sanacora has a simple answer.

“If you have patients that are likely to seriously injure themselves or kill themselves within a short period of time, and they’ve tried the standard treatments, how do you not offer this treatment?” he says.

More and more doctors seem to agree with Sanacora.

Depression Treatments Inspired By Club Drug Move Ahead In Tests

Dozens of clinics now offer ketamine to patients with depression. And a survey of providers in the U.S. and Canada showed that “well over 3,000” patients have been treated so far, Sanacora says.

A number of small studies have found that ketamine can do something no other drug can: it often relieves even suicidal depression in a matter of hours in patients who have not responded to other treatments.

Ketamine’s potential as an antidepressant was recognizedmore than a decade ago. And studies done since then provide “compelling evidence that the antidepressant effects of ketamine infusion are both rapid and robust, albeit transient,” according to a consensus statement from a task force of the American Psychiatric Association. Sanacora is one of the task force members.

But there are still a lot of unanswered questions about ketamine, says James Murrough, an assistant professor of psychiatry and neuroscience at the Icahn School of Medicine at Mt. Sinai in New York.

“We haven’t had large-scale trials. We don’t know how much or how often it should be given for it to be effective or safe,” says Murrough, who is an author of a review of ketamine published in the journal Nature Reviews Drug Discovery.

Doctors know a lot about the short-term effects of ketamine because it has been used as an anesthetic in emergency rooms for decades. But there’s still not much information about the effects of using ketamine for years.

A vial of ketamine, an anesthetic and club drug that is sometimes used to treat severe depression.Wikipedia

That’s worrisome because ketamine’s antidepressant effect tends to wear off after a few days or weeks, meaning patients need repeated infusions to keep depression at bay, Murrough says.

Still, Murrough thinks the case for using ketamine is much stronger than it was just a few years ago.

“There’s warranted caution that’s balanced with an optimism that says we’ve never had a new medication for depression since the era of Prozac,” Murrough says.

Prozac arrived in the 1980s, and became the first of a new class of depression drugs that target the neurotransmitter serotonin.

Ketamine acts on a different neurotransmitter called glutamate. The drug’s success has pharmaceutical companies excited about the possibility of creating a whole new class of drugs for depression, Murrough says.

“Companies are reopening programs,” he says. “They are pulling [old] drugs off the shelf that they know act on the glutamate system.”

One promising candidate is a chemical sibling of ketamine called esketamine. It’s now in the final phase of testing before consideration by the Food and Drug Administration, which designated esketamine as a breakthrough therapy.

And esketamine is just one of several ketamine-like drugs in development, says Sanacora, who consults for companies developing these drugs.

“This is probably the most interesting and exciting new development that I’ve seen in my career, and probably going back over the past 50 to 60 years,” he says.

Original Article Found Here.