The Heavy Depressive Disorder
Major depressive disorder is the most prevalent mood disorder worldwide. It is also known as clinical depression, and occurs when you have symptoms of low mood or hopelessness for at least two weeks. Scientists still do not know what causes it, but they do know that the treatment is complex and that people affected need more options to feel better faster.
For about half a century, scientists have made great efforts to improve medications that target a small group of neurotransmitters: chemicals in the brain, specifically serotonin, norepinephrine, and dopamine, which affect how your nerve cells communicate and consequently impact your mood.
While most people respond to standard antidepressants, at least 30% of individuals who take two different types of these medications continue to exhibit symptoms of depression, a condition known as treatment-resistant depression.
As a result of changes in the understanding of the brain biology behind depression, scientists have altered their approach to treating severe depressive disorders in the last two decades.
According to Gerard Sanacora, MD, PhD, Director of the Yale Depression Research Program in New Haven, CT, the most significant change is that medication research no longer targets specific neurotransmitters. „We have opened up a completely new perspective on potential targets for new medications,“ he says.
New Medications and Faster Results
There is a long-standing belief that it takes weeks or months for a depression to disappear, but new fast-acting treatments have „changed what we thought was possible in this field,“ says Sanacora.
In 2019, the FDA approved Brexanolon (Zulresso), the first drug specifically for postpartum depression, a form of severe depression. Experts are not entirely sure how it works, but it is a synthetic version of a steroid that your body naturally produces, affecting your GABA receptors, which help regulate mood.
Brexanolon is not as simple to administer as other antidepressants. It is delivered over a 60-hour period in a healthcare facility through an IV, but it may produce quick results, improving your depressive symptoms by the end of the treatment.
Esketamine and Potential Treatments
Esketamine is a prescription nasal spray. The low-dose psychedelic medication enhances the activity of glutamate in parts of your brain related to mood. Its task is to stimulate cells in the brain and nervous system. Esketamine can also trigger new connections in your brain, with improvement of depression symptoms observed within hours or days of administration, according to Sanacora.
Esketamine provides life-saving hope for people with suicidal thoughts and relief for those with treatment-resistant depression. However, its symptom relief may only last a few weeks when used alone, which is why experts recommend combining it with conventional treatments.
For people with mild or moderate depression, Sanacora still recommends cognitive behavioral therapy followed by conventional antidepressants, also known as selective serotonin reuptake inhibitors (SSRI). More information is needed on the safety and long-term effects of newer depression treatment methods, he says.
Advancements in Brain Stimulation
Medication is not the only treatment for depression. Electroconvulsive therapy (ECT) has been around for over 70 years and remains one of the most effective methods for treating severe depressive disorder, particularly in non-responders to other treatments. Although not new, scientists have refined the procedure in the last decades. ECT now consumes less energy and aims to provide the same benefits with fewer negative effects on memory and cognitive abilities, says Dr. Susan Conroy, psychiatrist and neuroscientist at the Indiana University School of Medicine.
Conroy also uses transcranial magnetic stimulation (TMS) for depression treatment, which has fewer side effects compared to ECT. It sends magnetic pulses around your skull, converting these signals into electrical energy within your brain tissue and thus changing the way different areas of your brain communicate, potentially leading to recovery from depression. These and other forms of brain stimulation are not suitable for everyone, but it is important to inform your doctor if other treatments are ineffective and your depression is affecting your daily activities.
Many promising treatment options for depression are on the horizon. One of them is deep brain stimulation, where a surgeon implants electrodes in your brain. These nodes emit painless pulses that alter the electrical activity causing your symptoms.
Researchers are also investigating a drug called SAGE-217, which could help prevent a severe relapse in people with a history of depression. The idea is to take it when symptoms reappear, even before they become fully pronounced, says Sanacora. Psilocybin, often referred to as „magic mushrooms,“ is also being studied for its ability to rapidly alleviate depression similarly to ketamine, but more research is needed before any definitive conclusions can be drawn, he adds.
Sanacora notes that in his 25 years in this field, he has never seen such enthusiasm for treating depression. However, he emphasizes that there is still much to learn and no cure for severe depressive disorder. Nonetheless, there are steps you can take now to alleviate or prevent a relapse with depression, including medication, different types of talk therapy, regular exercise, a healthy social life, and good sleep habits.