Major depressive disorder is the most prevalent mood disorder in the world. Also called clinical depression, or just depression, is when you’ve had symptoms of low mood or hopelessness for at least two weeks. Scientists still do not know the reason for this. But they know that treating it is complex and that people who suffer from it need more ways to feel better faster.
For nearly half a century, scientists have made great efforts to improve drugs that target a small group of neurotransmitters. These are chemicals in the brain — serotonin, norepinephrine, and dopamine in particular — that affect how neurons talk to each other, which then affects your mood.
Most people respond to standard antidepressants. But at least 30% of people who try two different types of these medications go on to develop symptoms of depression. This is called treatment-resistant depression.
Therefore, over the past two decades, scientists have changed the way they think about treating major depressive disorder as their understanding of the brain biology behind depression has changed.
The biggest change is that drug research has gone beyond targeting only certain neurotransmitters, says Gerard Sanakura, MD, PhD, director of the Yale Depression Research Program in New Haven, Connecticut. “We’ve opened up a whole new horizon for potential targets for new drugs.”
New Medicines, Faster Results
There is a long-standing idea that it takes weeks or months to treat depression. But Sanakura says the new, fast-acting therapies have “changed what we think is possible in this area.”
In 2019, the US Food and Drug Administration approved brexanolone (Zulresso). It is the first medication designated for postpartum depression, a type of major depression. Experts aren’t quite sure how it works. But it is a man-made version of a steroid that your body naturally makes. It affects your GABA receptors, which help regulate mood.
Brexanolone is not as easy to take as other antidepressants. You get it through a vein in your arm in a 60-hour health care facility. But it can work quickly. Symptoms of depression may begin to rise by the end of your treatment.
Another breakthrough drug appeared in the same year.
Esketamine is a prescription nasal spray. The low-dose psychedelic drug boosts glutamate activity in parts of your brain associated with mood. The function of glutamate is to excite cells in the brain and nervous system. Esketamine can stimulate new connections in your brain, too. You may begin to see improvements in your depression within hours or days of using it, says Sanacora.
Esketamine offers lifesaving hope for people who have had suicidal thoughts, and it also provides relief for people with treatment-resistant depression. But when used alone, symptom relief may only last up to two weeks. That’s why experts agree that you should take quick-released medications alongside conventional treatments.
For those with mild or moderate depression, Sanacora still suggests cognitive behavioral therapy first, followed by traditional antidepressants also known as selective serotonin reuptake inhibitors (SSRIs). Doctors need more information about the safety and long-term effects of new treatments for depression.
“Over the past 20 years, there has been a drastic change in the way we treat depression,” Sanakura says. “But we still have to make it easier to understand which patients these treatments are best for and when.”
Improvements in brain stimulation
Medications are not the only treatment for depression. ECT has been around for more than 70 years. It remains one of the most effective ways to manage major depressive disorder, especially if you don’t respond to other treatments. Although it’s not new, scientists have fine-tuned the procedure over the past decades.
Today, ECT uses less energy than in the past. The goal is to give you the same benefits but with less negative impact on your memory and thinking skills. “This has been a huge improvement,” says Susan Conroy, MD, a psychiatrist and neuroscientist at Indiana University School of Medicine.
Conroy also uses transcranial magnetic stimulation to treat depression, which has fewer side effects than ECT. It works by sending magnetic pulses around your skull.
Brain tissue translates these signals into electrical energy, Conroy says, which changes the way brain regions talk to each other. “By changing those circuits, we think this is how TMS makes people better at depressed people.”
These and other forms of brain stimulation are not suitable for everyone. But tell your doctor if other treatments don’t help and your depression prevents you from doing daily activities, not eating, and you have persistent suicidal thoughts.
“These are all signs that your treatment needs to step up and very quickly,” Conroy says.
future treatment
On the horizon are many other promising treatments for depression. Single deep brain stimulation. In this treatment, the surgeon implants electrodes into your brain. These nodes send out painless glides that alter the electrical activity that’s causing your symptoms.
You can think of this therapy as a pacemaker for your mood. While it hasn’t been approved for the general public, it may soon. “Technology is advancing very quickly,” says Conroy.
Researchers are also studying a drug called SAGE-217. Sanacora says there is interest in how it can help prevent serious relapse in people with a history of depression. The idea is that you’ll take it as soon as your symptoms return. “But you don’t wait until symptoms are complete,” he says.
There is also a lot of hype around drugs like psilocybin. Studies show that this “magic mushroom” can relieve depression as quickly as ketamine – what esketamine is made of – with effects that may last longer. But when it comes to psychedelics, Sanakura says, “We need more research before we can say anything with confidence.”
In his 25 years in the field, Sanacora says he’s never seen such excitement about treatments for depression. But that doesn’t mean researchers have all the answers or that major depressive disorder has a cure.
However, you can now take steps to relieve depression or protect against relapse. This may include medications, different types of talk therapy, regular exercise, a good social life, and a healthy sleep routine. You should do “all the things we know you can do to protect yourself as much as possible,” says Sanakura.
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