Depression affects 450 million people worldwide and 15 million adults in the United States (U.S.) alone. Suicide is the 10th leading cause of death in the United States, claiming over 40,000 lives every year. We see these heartbreaking stories making headlines too often, and there are tens of thousands more we do not know about.

The scariest part? There is no end in sight.

Antidepressants are one of the three most commonly used therapeutic drug classes in the United States. Approximately 1 in 9 Americans of all ages reported taking at least one antidepressant medication — a number that was less than 1 in 50 just three decades ago. The recent suicides of Kate Spade and Anthony Bourdain highlighted the growing need for a comprehensive solution for depression rates in the United States. In response to the suicides, many turned to the FDA to develop new drugs.

So, why aren’t suicide rates dropping?

The reality is up to one third of patients suffering from depression do not respond to or cannot tolerate antidepressant medication. Today, there are a number of other treatments that have been proven to be effective in helping those with treatment-resistant depression achieve remission. These treatments can work in combination with each other and psychotherapy.

Deep transcranial magnetic stimulation (Deep TMS), the “helmet that treats depression”, is a non-invasive neurostimulation therapy that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression, typically used when other depression treatments have failed. Using an electromagnetic coil, the electromagnet delivers a magnetic pulse that stimulates the nerve cells in the region of the brain involved in mood control and depression, activating regions of the brain that have decreased activity.

With 20-minute daily treatments for approximately four weeks, the treatment does not impact a patient’s regular routine or ability to work. The treatment is a low-risk procedure with mild headaches or discomfort being the most common side effects. And Deep TMS is often covered by insurance.

Ketamine has been shown to be effective in treating depression, as well. Ketamine got its start as an anesthetic in the 1960s, and since then, it has been shown to have antidepressant effects. Intravenous (IV) ketamine is known to have short-term effectiveness for the treatment of nonpsychotic, treatment resistant unipolar and bipolar major depression. The treatment has shown impressive results with patients who are acutely suicidal, reducing suicidal thoughts within 24 hours of IV administration.

However, the side effects can be significant. At large doses, ketamine induces severe dissociation commonly referred to as a “K-hole”, where a patient experiences intense detachment from their reality, which could lead to hallucinations and psychosis. And while the effects of IV ketamine are rapid, the effects do not last very long. Consequently, a patient would need continuous treatment, costing anywhere between $5,000 to $10,000 per year, with no insurance coverage.

More invasive procedures include vagus nerve stimulation (VNS), deep brain stimulation (DBS) and electroconvulsive therapy (ECT). VNS and DBS are both types of brain surgery performed to stimulate different parts of the brain, under general anesthesia. With DBS, electrodes are implanted on certain areas of the brain. These electrodes produce electrical impulses that regulate abnormal impulses. The electrical impulses can also affect certain cells and chemicals within the brain.

VNS involves the implantation of a device that stimulates the vagus nerve with electrical pulses. When activated, the device sends electrical signals along the vagus nerve to the brainstem, which then sends signals to certain areas of the brain. While there are non-invasive VNS devices that do not require surgery, they are only approved for use in Europe and have not yet been approved in the United States.

ECT is a procedure done under general anesthesia in which small electric currents are passed through the brain to intentionally trigger a brief seizure. ECT appears to cause changes in brain chemistry that can reverse symptoms of certain mental illnesses. While a lot of the stigma around ECT is based off of early treatments in which high doses of electricity were administered leading to memory loss, fractured bones and other serious side effects, it is much safer today. Side effects may include confusion, memory loss, nausea, headache or medical complications. The treatment is covered by most insurance plans.

There are many more therapies that are currently undergoing clinical trials to treat depression that can serve as effective alternatives to medication. Reducing the national suicide rate is top of mind for clinicians in the healthcare space, and for the millions of Americans still suffering from treatment-resistant depression with no hope for relief, tapping into other proven treatment options is important to combat the rising rates of depression and suicide in the country.