Explainer: Trials to fight treatment-resistant depression in Singapore — why these could be a game-changer

SINGAPORE — Two clinical trials are currently underway to fight treatment-resistant depression — where patients do not respond well to medication — which, if successful, could significantly improve remission rates for people who suffer from severe depression.

Both trials, conducted by the Institute of Mental Health (IMH) and the National University of Singapore’s (NUS) Yong Loo Lin School of Medicine, involve the use of magnetic fields to target specific regions of the brain.

Singapore is the first country in Southeast Asia to embark on such trials.

IMH and NUS said in a media statement on Friday (April 12) that the trials will run concurrently from March 2024 to 2026.

Both trials are aided by a grant of S$1 million each from Temasek Foundation and the National Medical Research Council, which was set up by the Ministry of Health to fund medical research.

TODAY takes a closer look at what the trials will involve.

WHY ARE IMH AND NUS CONDUCTING THESE TRIALS?

One in 16 adults aged 18 and above — or 6.3 per cent of the entire adult population here — has experienced depression at some point in their lives, according to a 2016 Singapore Mental Health Study.

It is the most common psychiatric disorder among Singapore adults.

Symptoms may include persistent sadness, insomnia (or sleeping more than normal), loss of interest, lethargy, irritability, poor concentration and, in severe cases, suicidal thoughts.

Depression is a treatable condition. Mild cases may be managed with psychotherapy, while moderate to severe cases are typically managed with antidepressant medication to alleviate the symptoms.

However, some people do not respond well to medication, and may see an alleviation but not a remission in their symptoms despite regularly taking their medication.

This is known as treatment-resistant depression. It is usually managed through a treatment approach that includes optimising medication dosage, switching to a different class of medications, and augmenting or combining treatments, IMH and NUS said in their statement.

Those who suffer from treatment-resistant depression could also undergo what is known as standard Transcranial Magnetic Stimulation (TMS), a non-invasive procedure where an insulated coil is placed on the patient’s scalp.

The coil generates brief magnetic pulses that directly stimulate specific areas of the brain.

WHAT GOES ON DURING THE TRIALS?

Standard TMS delivers stimulation to the same spot on the brain for all patients, but what the trials are aimed at is to personalise a treatment plan for each individual patient.

For this "personalised" TMS, participants will have to undergo functional magnetic resonance imaging scans.

This is to find the ideal location in each patient's brain that should be stimulated to treat his or her depression.

As this spot is unique to each individual, advanced analytics will be performed on the brain scan to identify it.

Data from the scans is then integrated with an advanced "neuro-navigation robotic arm" to mount the magnetic coil on the precise spot on the patient’s head.

Standard TMS is able to achieve a remission rate of 33.6 per cent after six weeks of treatment.

However, a pilot in the United States has shown that personalised TMS results in a significant improvement: A remission rate of about 80 per cent after one week.

A total of 90 individuals who have undergone conventional psychiatric treatment for depression and failed to achieve remission will be recruited for both trials. They will be screened for suitability.

HAS IT BEEN DONE ELSEWHERE?

Personalised TMS is modelled after the so-called Stanford Accelerated Intelligent Neuromodulation Therapy protocol, which is used in the US for treatment-resistant depression.

In pilots done on Americans, about 80 per cent of patients achieved remission after one week.

In England, a clinical trial conducted from 2019 to 2022 revealed that MRI-guided TMS significantly eased symptoms of severe depression for at least six months.

IMH and NUS said that the trials conducted in Singapore will "pair IMH’s clinical expertise in standard TMS with NUS Medicine’s expertise in brain MRI" to personalise a treatment plan for each participant, study its efficacy and make recommendations on implementing this as a mainstream treatment.

“With these clinical trials, we hope to validate the efficacy of this precision modality in helping persons with treatment-resistant depression achieve remission and improve their quality of life,” said Dr Tor Phern Chern, senior consultant of the department of mood and anxiety, and head of neurostimulation service at IMH.