Precision non-implantable neuromodulation therapies: a perspective for the depressed brain

Summary & key facts

This paper looks at non-implantable brain-stimulation methods as options for people with major depression. The authors say these methods can help when medicines or talking therapies don’t work for about one-third of people, but current non-convulsive methods work only a little and seizure-based methods can harm thinking. They argue for a “precision” approach — tailoring stimulation with personalized mental tasks, real-time brain feedback, better ways to measure who will benefit, computer models to aim and dose the treatment, and machine learning to combine different kinds of data. They also say the evidence is limited because past studies were small, didn’t explain how the treatments work or their costs, and more trials are needed before this approach can be used widely.

Key facts:

• About one-third of people with major depressive disorder still don’t reach remission after trying multiple medications, and psychotherapy can be costly and slow.
• Non-implantable neuromodulation methods include magnetic stimulation to the head, weak electrical stimulation to the head, and seizure-inducing therapies like electroconvulsive therapy and magnetic seizure therapy.
• Non-convulsive methods (the magnetic and weak electrical ones) have shown only modest benefit so far, meaning they help some but not most patients clearly.
• Seizure-inducing (convulsive) treatments can work but are limited by side effects on memory and thinking.
• The authors recommend a precision approach that combines personalized cognitive tasks, real-time (closed-loop) adjustment using brain signals, biomarkers that predict response, computer models to guide where and how strong the stimulation should be, and machine learning to find who will respond.
• Current research is limited: many studies used small groups, didn’t fully study how the treatments work or cause side effects, and did not include cost-effectiveness analyses.
• Because of these limits, the suggested precision framework is promising but not yet proven or ready for routine clinical use.

Abstract

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more "precision-oriented" practice.

Topics

Electroconvulsive Therapy Studies Neurological disorders and treatments Transcranial Magnetic Stimulation Studies

Categories

Life Sciences Neurology Neuroscience

Tags

Biology Brain stimulation Cognition Context (archaeology) Electroconvulsive therapy Major depressive disorder Medicine Modalities Neuromodulation Neuroscience Paleontology Psychology Social science Sociology Stimulation Transcranial direct-current stimulation Transcranial magnetic stimulation

Conditions & symptoms

Depression Lack of energy or motivation Poor sleep Sadness or low mood