A BREAKTHROUGH OR HAZARD?
Millions of people worldwide suffer from depression. Ketamine has emerged in the west as a promising antidepressant, but its use raises safety and security questions, write TAN TECK BOON and NANDHAKUMAR GUNASEKARAN
WITH fancy names like Special K, Vitamin K or Kit Kat, ketamine is a popular street drug among substance abusers in Asia. Ketamine first appeared on the recreational drug scene in the mid-1970s, mainly in the United States when it was discovered that a small dose of the anaesthetic induces hallucinations and a sense of disconnect between the body and mind. In 2006, it was further discovered that ketamine could be used off-label to treat severe mood disorders like depression.
As ketamine has been approved by the US Food and Drug Administration for use as an anaesthetic, physicians are permitted under US laws to prescribe it for medical conditions which they believe the drug to be effective against. Depression is one of them.
A debilitating disease, depression causes one to feel a deep sense of sadness and hopelessness. According to the World Health Organisation (WHO), more than 300 million people of all ages worldwide suffer from depression. The standard treatment includes selective serotonin re-uptake inhibitor (SSRI) prescription drugs like Prozac and Zoloft.
These antidepressants work by increasing the levels of serotonin in the brain to alter patients’ dark moods. Helping to regulate one’s mood, serotonin is a neurotransmitter that carries signals between different parts of the body for, among other things, psychological functions.
Yet, in about 30 per cent of the cases for patients with treatment-resistant depression (TRD), SSRI antidepressants are ineffective. It can take weeks, or even months, before an improvement is seen in patients. But, with a small ketamine hydrochloride infusion, results are seen within a few hours with two-thirds of TRD patients reporting an improvement in their moods that last up to a week.
Depression is also often associated with suicide. Studies as far back as the 1980s in US and Europe suggest that 50 to 60 per cent of those who committed suicides may have suffered from depression or related disorders. For those at risk of suicide, recent studies have suggested that ketamine demonstrates potential as a fast-acting treatment.
The apparent efficacy of ketamine in TRD therapy caught the attention of pharmaceutical companies and doctors. Additionally, several private clinics in US and Australia have sprung up in recent years offering ketamine therapy for TRD patients. Meanwhile, a global pharmaceutical company has patented esketamine — a ketamine-derivative nasal spray that will soon become available in US.
Yet, questions remain over the use of ketamine for TRD therapy. Could the widespread use of ketamine turn it into a health hazard? FIRST is drug safety. Although the ketamine dose administered during therapy is low (about onetwelfth of an anaesthesia dose), it is unclear what side effects from frequent infusions of the drug can have over time. Long-term use of ketamine can cause damage to the liver, kidneys and bladder. Cognitive impairment has also been observed in recreational users of the drug. With that in mind, ketamine infusion for TRD therapy is akin to taking small doses of a powerful anaesthesia repeatedly over extended periods.
SECOND, drug addiction. Repeated use can lead to drug dependence. The worst outcome is that TRD patients could end up substituting their mental condition with drug addiction. The ongoing opioid epidemic in US is an example. Patients become opioid addicts because physicians prescribe opioids like OxyContin for pain management before stopping the prescriptions at the end of the treatment period, forcing them to seek alternatives. Addicted, they simply turn to synthetic opioids or heroin for relief. One should not dismiss the possibility of ketamine use producing similar results.
THIRD, the market-readiness of ketamine. Ketamine has only been given to a small (at US$500 [RM1,958] per dose), often wealthy group of TRD patients. Before a drug is ready for the market, it needs to undergo many years of clinical trials, often involving thousands of participants. With fewer than 400 TRD patients having received ketamine in published clinical trials, its efficacy can, at best, be described as preliminary. More trials are needed before it can be certified ready for the market.
If the esketamine nasal spray is made commercially available, authorities in countries where ketamine is a controlled substance, like Malaysia and Singapore, will have to deal with it crossing their borders through international travellers, who may have such drugs in their possession, with or without a prescription. Malaysia and Singapore would have to invest in the kind of sophisticated detection capabilities needed to prevent this ketamine-derivative from being smuggled across sea, air and land checkpoints.
There is also the potential for misuse since esketamine nasal sprays can be inhaled in large doses to induce a hallucinogenic high. For countries where off-label use of ketamine is legal, the emergence of a new class of ketamine addicts cannot be ruled out, especially if the drug were suddenly made unavailable to TRD patients.
If there is one lesson from the opioid epidemic in the US, it is that prescription medications can turn out to be a source of a deadly drug problem. Close monitoring of those who use esketamine is, therefore, crucial.
Hence, authorities around the world would have to address this emerging issue as ketamine gains legitimacy in the West as a quickacting antidepressant. The sooner they prepare for it, the less likely they will be caught offguard.
Although the ketamine dose administered during therapy is low (about onetwelfth of an anaesthesia dose), it is unclear what side effects from frequent infusions of the drug can have over time. Long-term use of ketamine can cause damage to the liver, kidneys and bladder.
Tan Teck Boon is Research Fellow and Coordinator of the Science and Technology Studies Programme (STSP) in the S. Rajaratnam School of International Studies, Nanyang Technological University, Singapore. Nandhakumar Gunasekaran is Senior Analyst in STSP