Depression is often misunderstood as temporary feelings of distress or sadness. Phrases such as “I’m feeling stressed” or “I’m having a rough week” — while not to be dismissed — are not typical descriptions of how depression feels.
Instead, those who have depression describe a feeling of darkness and hopelessness, like being at the bottom of a well and seeing no way out. Those feelings can quickly escalate and affect your ability to work, hold relationships and even stay alive.
This mental health condition is relatively common — affecting an estimated 10% of Americans each year. But depression can be difficult to treat because it involves complex workings of the brain. What’s effective for one person may not work for another. In recent years, researchers have tested a number of new treatments that show promise for improving depression when other treatments aren’t working.
Limitations of standard treatments
Currently, two classes of drugs — selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) — are typically recommended as a first treatment for depression in adults. They are often paired with cognitive behavioral therapy, a form of therapy in which people learn skills to manage symptoms of depression.
SSRIs and SNRIs impact neurotransmitters — chemical messengers used to communicate between brain cells. In particular, these drugs affect neurotransmitters that regulate mood. SSRIs and SNRIs control and manage the symptoms of depression for many people, especially when paired with therapy sessions and lifestyle strategies.
However, these medications come with significant drawbacks, including:
Some people don’t see much relief after taking these drugs. As many as one-third to one-half of people with severe depression — also called major depressive disorder — don’t get relief from SSRIs or SNRIs. If they do not see symptom improvements after trying two different medications over several weeks, they’re considered to have treatment-resistant depression.
The drugs don’t reach full effectiveness until a month or longer after taking the first dose. That means people having a psychological crisis have to find other ways to manage until the drugs start working.
Antidepressants can cause side effects including nausea, headaches and sleep problems. In the long term, sexual dysfunction, including loss of libido, is fairly common.
Newer approaches, faster results
Treatments that aim to improve upon those drug shortcomings have been recently approved. The most promising new antidepressant treatments come from a class of drugs called N-methyl-d-aspartate (NMDA) receptor antagonists. The effect they have in the brain is different from that of other antidepressants.
For instance, SSRIs work by increasing the availability of serotonin — a neurotransmitter connected to mood. Drugs in the NMDA class, on the other hand, act on a pathway in the brain that affects glutamate. Glutamate is a neurotransmitter important for processing information People with depression often don’t have as many connections, called synapses, between brain cells, which may contribute to an increase in depression symptoms. These drugs create more of those connections, which may ease symptoms. Here’s a look at two newer options.
Esketamine (Spravato) is a fast-acting antidepressant that was approved by the Food and Drug Administration (FDA) in 2019 for people with treatment-resistant depression. It’s given as a nasal spray, so it enters the bloodstream and reaches the brain much faster than an oral medication does. That swift delivery can ease depression symptoms within several hours, and many people report significant relief within one day. However, that effect appears to wear off rather quickly, with some studies showing a dose loses effectiveness within a week. The drug is to be taken in conjunction with an oral antidepressant.
Another drawback to esketamine is that, at this time, it can only be given in a clinical setting under the supervision of a healthcare professional. That’s primarily because of potential side effects, including prolonged sedation and distortion of perceptions such as time and space. Also, research still is needed to determine how long a person can take esketamine safely.
Right now, standard dosing involves taking the medication twice a week for about four weeks, then switching to once a week for another four weeks, and then tapering further as the care team recommends.
Esketamine’s long-term effectiveness is not clear, and long-term side effects are not yet well understood. Potential short-term side effects include blurred vision, dizziness, drowsiness, nausea, vomiting and higher blood pressure.
The combination drug dextromethorphan-bupropion (Auvelity) was approved by the FDA for major depressive disorder in 2022. Dextromethorphan is a common cough suppressant with some effectiveness against depression, while bupropion is a common antidepressant. It’s a tablet taken twice a day. Like esketamine, dextromethorphan-bupropion reduces symptoms of depression quickly, within 1 to 2 weeks, and reaches maximum effectiveness in 4 to 6 weeks. Unlike esketamine, the prescription drug can be taken at home, without direct supervision from a medical professional.
In clinical trials, the most common side effects of the drug included dizziness, nausea, diarrhea, headache, drowsiness and dry mouth. About 2 in 3 people reported side effects, which is about the same as for SSRIs and SNRIs.
Nondrug treatment options
A procedure called repetitive transcranial magnetic stimulation (rTMS) was approved by the FDA in 2008 to treat depression. It was later approved to treat headache- related pain and, in 2018, obsessive- compulsive disorder (OCD).
The treatment uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression. An electromagnetic coil is placed against the scalp near the forehead. The magnet creates electric currents that stimulate nerve cells in the region of the brain involved in mood control and depression. Treatment is typically delivered in rapid bursts during 30-minute sessions, often over the course of several weeks.
The benefits of rTMS for depression do not appear to be as strong as those of some other therapies. However, rTMS does ease symptoms to some extent. Some studies have suggested that the benefit lasts at least a year in about half of the people who receive it.
This therapy causes few or no serious side effects in most people. It’s also seen as a promising treatment for older adults, who are more likely to be taking medications that can interact with antidepressants.