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Why Ketamine could one day be used to treat depression

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Anaesthetic and party drug ketamine is one of a number of medicines that might see a new use in the future.

A third of people with serious depression are unable to find a drug that works to ease their symptoms. That’s a pretty high failure rate and there hasn’t been a major depression drug breakthrough in decades. Now, a New Zealand company may be in the forefront of helping to change that.

At the West Auckland headquarters of Douglas Pharmaceuticals, a phase II trial is about to get under way treating depression with a drug that has been around since the 1970s. Ketamine is used in anaesthesia and for short-term pain relief. Dubbed Special K, it has also been popular as a party drug. Now there is hope it may be able to help at least some of those with treatment-resistant depression.

“There are about three million people in the US alone who are treatment-resistant,” says Peter Surman, the drug company’s chief scientific officer. “The alternative for them is electroconvulsive therapy, but most people would prefer to take a tablet than have a zap of electricity, so we’re trying to offer another medical option.”

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A small seven-patient trial has already shown encouraging results. Now, in collaboration with the University of Otago, the company is widening that to 200-plus patients in three countries, trying to identify the ideal oral dose as well as prove the drug is effective and can be used safely.

“This is the biggest commitment we’ve made in a clinical trial to date, so it’s very exciting,” says Surman, who is still in the final stages of the approval process, and hopes to be able to start the 12-week trial by March.

There are several complications to negotiate. One is that ketamine is a controlled drug, so moving it from country to country involves a fair bit of red tape. There are also issues to do with treating depression; namely, monitoring and safety checks are necessary to make sure the mental health of participants isn’t deteriorating.

“And a really big question patients with depression will ask is, if they feel good on it, what happens after three months when the trial is finished – will they go crashing back down again? Because there is no registered medicine and it’s going to take three or four years before this is approved,” says Surman.

Pete Surman. Photo/Supplied

A compassionate-use programme will mean those participants who feel they have benefited will be able to get the drug through their psychiatrists once the study has finished.

Developing a new drug is a billion-dollar exercise for a pharmaceutical company and there are no guarantees of success. Finding new uses for old drugs is a far less risky business and can still provide huge benefits.

“The advantage of repurposed products is that you know from a safety point of view they are well understood,” says Surman.

Other existing medications that may have exciting new futures include Lopinavir, an antiretroviral drug used to treat HIV. Collaborating with virologists at the University of Manchester, Surman and his team are looking at it as an alternative to surgery for women with early-stage cervical cancer.

They have ethics approval to start a trial with a small number of women in Wellington, Napier and Tauranga and the hope is that applying Lopinavir directly to the cervix will both kill precancerous cells and tackle the HPV virus that causes the disease.

Although there is a vaccine for HPV, it doesn’t work for those who are already infected.

“At the moment, if you’re HPV-positive, there is a chance it could turn into cancer within the next 20 years,” says Surman. “I think for peace of mind a lot of people would rather use a self-administered cream for three weeks.”

More areas of interest for Douglas Pharmaceuticals include repurposing the cancer drug vinorelbine to treat ectopic pregnancy (when an embryo implants somewhere other than the uterus, such as the fallopian tube). It is also partnering with other companies to try to make existing cancer treatments effective for a larger number of patients.

“What Douglas brings to all of this, apart from funding, is that we’re very good at formulating products,” says Surman. “So if someone wants an oral dose or an ointment or cream, that’s like music to our ears.”

This article was first published in the January 26, 2019 issue of the New Zealand Listener.