Deep brain stimulation (DBS), a surgical procedure that implants electrodes in the brain to deliver electrical stimulation, may offer hope for people with severe depression that has not responded to multiple treatments.
However, larger and more rigorous studies are still needed to confirm its benefits and long-term safety.
Key Facts:
- DBS targets areas of the brain thought to be involved in depression. Most research has focused on the subcallosal cingulate gyrus.
- A meta-analysis found DBS had a 56% response rate and 35% remission rate in open-label studies. But only 2 small randomized trials have been done, with conflicting results.
- While DBS appears relatively safe so far, 67% of patients experienced adverse effects. Suicidal thoughts and behavior have occurred in some patients after DBS.
- How DBS improves depression symptoms is still unknown. It may modulate activity in brain circuits involved in mood regulation.
- More research is needed on optimal brain targets, long-term outcomes, safety, and mechanisms of action before DBS can be considered a standard depression treatment.
The Devastating Toll of Treatment-Resistant Depression
Major depressive disorder is one of the leading causes of disability worldwide.
While antidepressant medications and psychotherapy help many people, up to 30% do not adequately respond to multiple depression treatments.
This is known as treatment-resistant depression (TRD).
People with TRD experience prolonged depressive episodes and a lower quality of life.
They have a high risk of relapse, even when taking maintenance antidepressants.
As depression persists, the brain may undergo harmful changes that make recovery more difficult. Tragically, TRD is linked to an increased risk of suicide.
Clearly, better treatments are desperately needed for the estimated 100 million people worldwide who have TRD.
Could Deep Brain Stimulation offer new hope?
Understanding Deep Brain Stimulation (DBS)
DBS has been used since the 1990s to reduce tremors and motor symptoms in Parkinson’s disease.
More recently, doctors have tried using DBS to treat psychiatric disorders like TRD.
Here’s how it works:
- Electrodes are surgically implanted into specific brain regions believed to be involved in depression.
- A pacemaker-like device is placed under the skin of the chest to deliver electrical pulses through the electrodes.
- Doctors program the device to continuously stimulate areas such as the subcallosal cingulate gyrus, which may regulate mood and emotions.
- Patients can have the stimulation adjusted as needed. The effects are reversible by turning it off.
By modulating abnormal activity in mood-related brain circuits, DBS aims to provide long-term depression relief with minimal side effects.
But does the evidence support its use so far?
Reviewing the Research on DBS for Depression
To better understand the efficacy and safety of DBS for difficult-to-treat depression, researchers conducted a meta-analysis of studies through January 2019.
Their goal was to pool together results from early stage trials.
The analysis included 17 studies on 233 patients with TRD.
The trials tested DBS targeted to 7 different brain regions, most commonly the subcallosal cingulate.
In the 16 open-label studies, patients and doctors knew they were receiving active DBS.
These found DBS had:
- 56% response rate – defined as at least 50% improvement in depression scores
- 35% remission rate – defined as minimal or no depression symptoms
- 14% recurrence rate of depression symptoms in the first year
However, only 2 small randomized controlled trials (RCTs) compared DBS to a sham control.
They had conflicting results on whether DBS was better than placebo.
Two-thirds of patients experienced adverse effects from DBS, like pain and anxiety.
A few patients tragically died by suicide despite DBS treatment.
This highlights the need to carefully screen candidates and monitor suicide risk.
Overall, DBS appears relatively safe so far, although controlled trials with longer follow-up are needed.
But efficacy results are harder to interpret without larger RCTs.
Currently, it’s unknown if benefits are due to electrical stimulation or a placebo effect.
Exploring How DBS May Work for Depression
Scientists still aren’t sure exactly how DBS improves depression, but they have some theories.
Depression involves dysregulation in brain circuits and structures that process mood and emotion.
DBS likely modulates the abnormal activity within these neural networks.
For example, stimulating the subcallosal cingulate may regulate downstream areas involved in depression like the amygdala, hypothalamus, and prefrontal cortex through white matter connections.
By altering neurotransmission and blood flow in areas that are underactive or overactive in depression, DBS may help rebalance mood-regulating circuits.
Ongoing Challenges in DBS for Depression
While DBS represents an exciting new direction, many unknowns remain:
- It is unclear which brain target results in the best antidepressant effect and fewest side effects. Most research has focused on the subcallosal cingulate, but other areas may hold promise.
- Ideal stimulation parameters have not been defined and likely need customization for each patient.
- Sham-controlled trials are limited by the invasive nature of DBS surgery, making large RCTs ethically challenging.
- Long-term impacts on mood, cognition, and brain function require further study through 5-10 years of follow-up monitoring.
- Biomarkers are needed to identify which patients are most likely to benefit from DBS.
- Neuroimaging and neurophysiology studies should clarify DBS mechanisms of action in the brain.
While DBS appears relatively safe so far, the surgical risks and stimulation of brain tissue can cause side effects.
Careful screening and informed consent are essential.
Additional controlled trials are critical before DBS can be recommended as an established therapy for TRD.
Hope on the Horizon for Treatment-Resistant Depression
In conclusion, DBS offers tentative hope for people struggling with severe TRD who have cycled through medications and therapies without relief.
Early results are promising, but enthusiasm must be balanced with realistic expectations until further research is conducted.
For now, patients with TRD should not view DBS as a miracle cure or alternative to standard treatments.
While DBS may someday be a breakthrough, we need a better understanding of its long-term outcomes, safety, brain effects, and optimal use.
Rigorous controlled trials in coming years will help clarify its role.
In the meantime, scientists continue working to uncover DBS mechanisms and identify which neural circuits make the best targets for modulating mood.
As we learn more about safely manipulating brain activity, refined DBS technologies could transform how we treat severe, chronic depression.
References
- Study: Deep brain stimulation in treatment-resistant depression (systematic review and meta-analysis on efficacy and safety)
- Authors: Youliang Wu et al. (2021)
