The future of major depressive disorder treatment

Over the past two decades, significant progress has been made in the treatment options for major depressive disorder (MDD). It is now recognised that depression varies from person to person, and efforts are being made to identify and diagnose the specific neurochemical imbalances in individuals in order to tailor treatment accordingly.

Advances have been made in evidence-based treatments, particularly in drug therapy. More selective and specialised antidepressants, such as citalopram, escitalopram, fluoxetine, and sertraline, have been developed, offering improved efficacy and fewer side effects. Combining drug therapy with psychotherapy, specifically cognitive-behavioural and psychodynamic therapy, has been shown to be the most effective approach.

In cases where depression is resistant to standard treatments, electroconvulsive therapy (ECT) can be used. ECT has become more precise and safer, with fewer side effects. It is typically reserved for individuals with severe, drug-resistant depression who exhibit bipolar characteristics.

Two newer treatment options that show promise for treating major depression are ketamine therapy and psychedelic drugs. Ketamine therapy, which involves resetting brain nodes and network connectivity, has provided long-lasting relief for some patients. While it is not the first choice due to its profound effects on the brain, it is being considered as an option for severe treatment-resistant depression, with ongoing discussions about its use earlier in treatment.

There is building evidence for the use of psychedelics like psilocybin (from mushrooms) and LSD (lysergic acid diethylamide) in treating major depression. Microdoses or millidoses of these drugs, either alone or in combination with antidepressants, have been shown to be effective in improving symptoms and function. However, the use of psychedelics is still stigmatised and regulated, and finding the right microdose and schedule requires skilled clinical expertise.

Transcranial Magnetic Stimulation (TMS) is another promising treatment option. By passing a weak magnetic current through the skull, TMS can alter the brain's electrical activity and reduce depression symptoms. Repetitive TMS has shown significant effectiveness in certain forms of treatment-resistant depression, often with rapid and durable responses. It can be used alone or in combination with psychotherapy or drug treatment, although its effects may diminish over time.

Deep Brain Stimulation (DBS), a newer and emerging treatment, involves implanting electrodes in specific brain areas to regulate symptoms of depression. Advances in the field, supported by the BRAIN Initiative, an NIH programme aimed at revolutionising our understanding of the human brain have led to a better understanding of how to precisely target the brain, potentially yielding better results. DBS has shown promise in resetting network activities in the brain, leading to long-lasting effects and significant improvements in patients' outlook and quality of life. However, DBS carries risks, including infection, haemorrhage, and misplacement of electrodes, and insurance coverage can be inconsistent.

Looking ahead, minimal or non-invasive DBS is seen as the future of treatment. Exciting advancements are being explored, such as the nonsurgical implantation of electrodes via small transmitters and stimulators that can be delivered through the bloodstream, inhaled, or swallowed. Minimally invasive approaches, involving fluid electrodes inserted through a small hole in the scalp and guided electromagnetically to the brain, are also being investigated. These developments hold the potential to revolutionise depression treatment in the next 5–10 years.

In summary, over the last two decades, significant strides have been made in the treatment of major depressive disorder. Advances in drug therapy, combined with psychotherapy, have improved outcomes. Newer treatments like ketamine therapy, psychedelics, TMS, and DBS offer hope for individuals with treatment-resistant depression. Further research and development are needed to optimise these treatments and pave the way for future innovations in depression care.