A potential breakthrough in the treatment of depression is emerging, offering the possibility of significantly shortening the duration of therapy from weeks to just days. According to a comprehensive mental health report published in The Lancet, severe depression affected 236 million people worldwide in 2023—more than double the number from 1990. Traditional treatments, such as antidepressant medications, often require several months of daily use and can cause side effects like reduced libido, sleep problems, and chronic fatigue. These treatments fail to provide relief for nearly a third of patients, leaving them stuck in a therapeutic dead end. A 2022 study in the British Medical Journal found that antidepressants showed a significant effect over a placebo in only 15 percent of participants in clinical trials. Researchers are now exploring entirely new methods to treat depression by targeting the brain's neural circuits directly. Techniques like focused ultrasound, accelerated transcranial magnetic stimulation, and the use of psychedelic substances such as psilocybin (found in hallucinogenic mushrooms) are showing promise. If these methods prove effective, they could achieve results in just a few days that previously required weeks of treatment. At the Institute of Physics for Medicine in Paris, a team led by Jean-François Aubry has developed a device that uses high-frequency sound waves to stimulate the brain. This method is inspired by electroconvulsive therapy (ECT), a treatment historically used for severe depression, but it aims to avoid ECT’s significant side effects. In a preliminary study published in Brain Stimulation in May 2025, five patients experienced a 60 percent reduction in depression symptoms over five days. The device uses a silicone acoustic lens to tailor the signal to the thickness of each patient's skull. Initially, the device required 512 cables to manually adjust the timing of each signal, but it has since been improved by the company SonoMind. The next step is to test the device on a larger group of patients in a clinical trial, with the goal of obtaining regulatory approval for commercial use by 2029. Researchers at universities in Bristol, Cambridge, and University College London have also explored a new approach using immunotherapy to target chronic inflammation in patients with treatment-resistant depression. A clinical trial published in JAMA Psychiatry in May found that an infusion of the antibody tocilizumab helped reduce symptoms such as fatigue, lack of concentration, and low energy. While the results are encouraging, more studies are needed to confirm the effectiveness of this method. This approach could potentially be used alongside other treatments for patients who do not respond well to traditional therapies. Psilocybin, the active ingredient in hallucinogenic mushrooms, is showing strong potential as a treatment for treatment-resistant depression. Psychiatrist Michel Sabé describes psilocybin as a "super antidepressant," noting its powerful and rapid effects. He and his team have treated hundreds of patients under Swiss law allowing compassionate access to psychedelic substances. A trial involving 100 patients, published in A Psychiatry Research, found that a single dose of psilocybin reduced depression symptoms in most participants, with a third experiencing a more than 50 percent reduction. Psilocybin activates a serotonin receptor called 5-HT2A, which may shift brain activity to favor positive emotions. It also affects the brain's "default mode" network, reducing rumination and mental loops common in depression. The effects on brain plasticity can last for weeks, which may support long-term recovery and psychotherapy. Unlike esketamine, which has shorter-lasting effects and can cause a sense of disconnection, the benefits of psilocybin may last several weeks to months, helping patients reconnect with their environment. In February, researchers at the University of California, Los Angeles (UCLA), introduced a new method of magnetic stimulation that achieves results in five days that would typically take six to eight weeks. This technique involves delivering intermittent magnetic pulses through the skull to stimulate neurons in the dorsolateral prefrontal cortex, a brain region involved in reasoning and planning. The new accelerated version increases the number of pulses per session—from 600 to 1800—over five days. This approach has been shown to reduce depression severity by up to 70 percent, but it is still unclear whether these effects are long-lasting. More long-term studies are needed to confirm the durability of this treatment's benefits.