Ketamine, a controlled substance referred to as a party drug by those who abuse it, is now being used in authorized clinical settings in Singapore to treat patients with major depressive disorder (MDD) who are not responding well to other forms of treatment.

Esketamine has been approved by the authorities and used to treat two patients in Singapore. The modified version of ketamine is being administered via a nasal spray.

Separately, The Straits Times (ST) understands a clinical trial is under way to test the effectiveness of oral ketamine to alleviate symptoms of treatment-resistant depression. Dr Johnson Fam, senior consultant in the Department of Psychological medicine at National University Hospital, confirmed that NUH is leading the study. "Patients on the trial are referred from doctors and they must be screened for trial eligibility. For example, subjects must have no history of substance abuse," he said. The tablets must be consumed under direct observation in the hospital and patients are not allowed to take them home.

According to an Institute of Mental Health (IMH) research newsletter published in February, MDD is a debilitating disorder and the leading cause of disability worldwide. Up to 50 per cent of patients are treatment-resistant.

Dr Fam said that the study is being done in collaboration with the IMH and Singapore General Hospital as trial sites. "The clinical effectiveness of ketamine for alleviating symptoms of depression is dependent on proper dosage, an unauthorized consumption is harmful," he added.

The IMH research newsletter noted that ketamine has robust antidepressant properties if given intravenously, for patients with treatment-resistant depression. The onset of antidepressant effects can be as rapid as 24 hours. "However, intravenous treatments are difficult to administer in the outpatient psychiatric setting, so we embarked on a multinational study of oral ketamine for treatment-resistant patients," it said.

The nasal spray manufactured by Johnson & Johnson received the Health Science Authority’s (HSA) approval to treat treatment-resistant MDD patients here in October last year. A spokesperson for Johnson & Johnson told ST that the two patients here receiving the treatment have seen "a significant reduction in their depressive symptoms as fast as the next day, the side effects are transient and manageable, and one of them has commented that it allows him or her to see ‘hope’ in the future".

The spray is administered in the clinic by a psychiatrist in a single use device before it is disposed of following local regulations.

Spravato, the esketamine nasal spray, was approved in March 2019 by the United States Food and Drug Administration to treat adults with treatment-resistant depression. ST spoke to a psychiatrist who is currently treating a middle-aged patient with Spravato. He is believed to be among the first in the Asia-Pacific region to receive the treatment.
"(The patient) has tried various forms of other treatment before, including electrocompulsive therapy, transmagnetic stimulation, as well as various kinds of antidepressants, over the years and they all didn’t work for him," said the psychiatrist with more than three decades of experience.

Speaking on condition of anonymity, he added that his patient has had MDD for at least five years and previously sought help from several other psychiatrists. The patient pays about $6000 to $8000 a month and the recommended treatment is six months long. After receiving the spray, patients are observed in the clinic for about two hours. They cannot leave with the spray.

Illegal possession or consumption of ketamine carries with it a punishment of up to 10 years of imprisonment, a $20,000 fine or both. A spokesperson for the Central Narcotics Bureau told ST: "All such (controlled) drugs must be prescribed by a Singapore doctor, and must be prescribed for the medical condition registered with HSA."

Psychiatrist Thomas Lee, who is also an addiction specialist, and Dr Adrian Wang urged caution in such treatments. Dr Lee said patients are not treatment-resistant until they have tried all other forms of treatment, including psychotherapy, counselling and family therapy. "These clinical trials are very welcome because they inform us of the efficacy, and how to use the drugs… but more information has to be given to the public to not get the impression that ketamine is okay," he added.


Source: The Straits Times
Reproduced with permission.