Accelerating Transcranial Magnetic Stimulation Treatment for Depression

What's the science?

Thirty percent of people with depression are resistant to treatments like anti-depressant medication or psychotherapy. Some people with treatment-resistant depression respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This technique involves inducing a magnetic field using pulses from a magnetic coil in a device resting on the scalp. However, it might take a patient many weeks of rTMS to see mood improvement, so having a faster acting treatment for those with severe depression is optimal. This week in Neuropsychopharmacology, Fitzgerald and colleagues tested a new ‘accelerated rTMS’ paradigm, to see if the same effects could be achieved faster.

How did they do it?

The authors conducted a randomised controlled trial, in which adults with depression received 63 00 rTMS pulses in total over the course of several rTMS sessions. Pulses were targeted at the dorsolateral prefrontal cortex, known to be involved in emotion regulation.  Fifty-eight adults followed the accelerated schedule: They received 3 treatments per day, for 3 days the first week, 3 treatments over 2 days the second week, and 3 treatments in one day the third week. Fifty-seven adults followed a standard schedule (not accelerated): one treatment per day, 5 days a week, for 4 weeks. They measured depression scores 1, 2, 3, 4, and 8 weeks after treatment.

What did they find?

Depression scores slowly decreased over the 8-week period in both the accelerated and standard treatment groups. The accelerated treatment did not appear to improve mood faster than the standard treatment, and participants in the accelerated group were more likely to experience discomfort such as headache. There were no differences in the efficacy of the accelerated treatment versus the standard treatment, indicating the accelerated treatment worked just as well as the standard treatment.

What's the impact?

This is the first randomised controlled trial to test whether accelerated rTMS could be used as a treatment for depression. This study clarifies the effectiveness of  accelerated rTMS as a treatment for depression. Accelerated rTMS might be a viable option for individuals with depression who cannot commit to long periods of daily rTMS treatment. Depression comes in many different forms, so determining which treatments work best for which patients, and their potential side effects, is critical for treatment optimization.

Reach out to study author Dr. Paul Fitzgerald on Twitter @PBFitzgerald

P.B. Fitzgerald et al., Accelerated repetitive transcranial magnetic stimulation in the treatment of depression. Neuropsychopharmacology. (2018). Access the original scientific publication here.

Ketamine Blocks Burst Firing to Provide Depression Relief

What's the science?

Ketamine is a drug that binds to and blocks NMDA receptors found on neurons. It provides fast acting and sustained relief of depression symptoms, however, the mechanisms underlying ketamine’s effectiveness are unknown. A brain region called the lateral habenula, involved in reward processing and negative emotions, is known to have abnormal “burst” activity in patients with depression. This week in Nature, Yang and colleagues determine whether abnormal activity in the lateral habenula can drive depression-like behaviours, and how this might be reversed by ketamine.

How did they do it?

They tested to see if ketamine infusion into the lateral habenula relieved depression symptoms (improved mobility in the forced swim test) in learned helpless (depressed) rats. Next, they performed whole-cell patch-clamp (a method used to measure the electrical currents in a neuron) on lateral habenula neurons to determine : 1) whether the spontaneous neuronal activity in these cells is abnormal in depressed rats, 2) whether these abnormalities could be reversed by NMDA blockers and, 3) if changing the resting state membrane potential of the cell can alter the pattern of spiking activity in the lateral habenula. They then used optogenetic techniques to mimic the bursting activity seen in the lateral habenula of depressed mice to determine whether this activity was sufficient to induce depression behaviours.

What did they find?

Ketamine administered in the lateral habenula alleviated the depression symptoms in rats. Increased burst firing occurred in neurons in the lateral habenula of depressed rats. These burst patterns were completely blocked by ketamine, but not by other typically used antidepressant drugs. The bursting properties of the lateral habenula could be altered by changing the membrane potential of the cell, suggesting a new potential therapeutic target, the T-type calcium channel. They were also able to induce depression-like symptoms in rats by using optogenetics to control the pattern of burst firing in the lateral habenula.

What's the impact?

This is the first study to describe the mechanisms by which ketamine has fast acting depression relief. We now know that burst firing underlies depressive symptoms in rats, and that this can be blocked with ketamine. Understanding how and where ketamine acts in the brain is an important step towards developing new therapies for depression.  

Yang et al., Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature. (2018). Access the original scientific publication here.

Rachel Bosma, PhD contributed to this BrainPost