New Drug Combination Shows Promise For SSRI-Resistant Depression Treatment

A combination of two existing drugs that could be used as a potential new treatment for depression has been identified by scientists at University of Bath.

The researchers found that using buprenorphine, a painkiller used post-surgery, combined and naltrexone, a drug used for treating addiction, produced antidepressant-like responses in mice.

Most of the current generation of antidepressants, SSRIs, are believed to wok by increasing the amount of serotonin in the brain; the exact mechanism by which they work is still unclear. But around 30-50 per cent of these patients do not respond to treatment, it can take several weeks before the drugs take effect, and many patients suffer significant side effects.

This new drug combination targets a different pathway in the brain, so may offer hope for those for whom SSRIs don’t work.

Urgent Need for New Treatments

Dr Sarah Bailey, Senior Lecturer in the Department of Pharmacy & Pharmacology, explained:

“Whilst SSRIs work for a lot of people, they can cause serious side effects and don’t work for everyone.

No new drugs for depression have been developed for decades – they all work in a similar way – so there’s an urgent need to develop new treatments for this condition that affects around 4 million adults in the UK.”

Since both of these drugs have a proven safety record as they are already licensed for other conditions, the researchers believe this could reduce the time it would take to perform clinical trials and gain regulatory approval, so that patients can benefit from this new treatment sooner.

Naltrexone and Buprenorphine

Buprenorphine reduces the patient’s response to stress by blocking a receptor in the brain called the kappa opioid receptor. However it also stimulates a related receptor called the mu opioid receptor which could cause addictive effects if taken long term or used by depressed patients.

To counter this, the researchers used the anti-addiction drug naltrexone, which blocks the mu receptor. They found for the first time that in mice this combination gave an antidepressant effect.

Dr Bailey noted:

“Our study shows that using a combination of naltrexone and buprenorphine gives an antidepressant effect in mice, but without the problems of addiction that could be caused by using buprenorphine alone.

Developing new drugs is a lengthy process, with lots of safety tests and trials to go through. These two drugs have already gone through that process individually, so we know they are safe. There still need to be further trials of the combination in humans, but the whole process of developing this as a new treatment would be greatly reduced.”

Co-author Professor Steve Husbands added

“It may be hard to deliver this combination in the clinic because of the properties of these drugs. We have also been working on changing the chemistry of buprenorphine so that it has the properties of this combination treatment in one molecule which should simplify drug delivery”

Abdulrahman Almatroudi, Stephen M Husbands, Christopher P Bailey, Sarah J Bailey
Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice
J Psychopharmacol July 2015 vol. 29 no. 7 812-821 doi: 10.1177/0269881115586937

Illustration: Rowena Dugdale, Wellcome Images, Creative Commons by-nc-nd 4.0