Five next-gen depression treatments that could revolutionize the field

Medications and psychotherapy can work wonders for people dealing with depression. But as scientists argue in a new special issue of the Harvard Review of Psychiatry, an “unacceptably high proportion” of people with depression experience little to no benefit from standard treatments. And even when they work, one meta-analysis of standard psychotherapy for depression suggests any improvement can be short-lived.

For those who have had no luck treating their depression, five areas of research that harness novel technologies and tackle the condition from new angles could offer a roadmap to treatments that actually work.

By analyzing hundreds of clinical trials, the special issue offers a glimpse into an unusual future of depression treatments — one in which more people may get the help they desperately need.

Here, in no order, are the five areas of most promise.

5: Depression’s gender gap

One paper highlights the gender skew in depression diagnoses. Roughly twice as many women over the age of 12 are diagnosed with depression as their male counterparts, according to a 2017 analysis.

This striking gender imbalance underscores the need for individualized treatments. It also prompts the need for further study on what exactly happens during adolescence and beyond to tip the scale towards depression in women.

To dig into the factors driving the gender gap, researchers combed past research and utilized the ABC model. The model focuses on affective, biological, and cognitive vulnerabilities that can make it harder for people to handle and bounce back from stress. If someone has a vulnerability, such as heightened body consciousness or troublesome hormonal changes, it may make it more challenging to encounter and recover from a negative life event, like a sexual trauma or death in the family.

The researchers also describe sociocultural factors like structural inequality — i.e. the wage gap — and objectification in the media that might be at play. They call for a more comprehensive approach to researching — and treating — depression in women, one that accounts for the myriad of complex factors that may make women more at-risk than men.

4: Depression’s gut connection

The review also illuminates a mind-body connection that’s garnering growing attention: the gut microbiome. This vast array of microorganisms contains the most neurons in the human body after the brain. The gut ecosystem is highly dynamic, “undergoing constant change over time,” from factors like exercise, age, and diet, the authors say.

Over the past few years, research has revealed the gut microbiome is in communication with the brain, through the gut–brain axis, according to the paper. This could affect how and when someone develops depression, and how severe their condition becomes. It isn’t a one way street — evidence suggests depression can affect the microbiome, too.

Future treatments might focus on building healthy gut microbiota through supplements, like vitamin B-12. The supplement has shown promise in improving depression symptoms, according to the paper. Other strategies may involve reducing stress, or adopting inflammation-reducing diets, like the Mediterranean diet.

Eventually, people might use “psychobiotics,” pre- or probiotics designed to improve mental health.

A more drastic treatment might involve a microbiome transplant, but research supporting this technique is in its very early stages.

3: Opioid signals and depression

Current depression treatments are only moderately effective: studies estimate that 30 to 40 percent of individuals fail to respond to available antidepressant medications. To reach these people, researchers propose targeting their opioid receptors — mu, kappa, delta,, and the nociceptin/ orphanin FQ receptor — using medications like ketamine that may lead to faster improvements in depression.

A fast-acting depression medication could change the game. Currently, people typically have to wait about two to three weeks before seeing positive results from “traditional” depression medications, the authors write. The novel treatments, which influence opioid signaling, may stimulate cellular processes and neural circuitry involve in stress and resilience.

Like the rest of potential treatments on this list, many more randomized controlled trials are needed before these treatments transition from the lab to the clinic.

2: Changing your behavior

One of the hallmarks of depression is anhedonia, or the loss of pleasure or motivation.

Now, researchers suggest targeting the human brain’s reward pathways, through an approach called “positive affect treatment.” Instead of dwelling on negative symptoms, the treatment focuses on achieving rewards, setting goals, and shifting behavior in a positive direction. The first randomized clinical trial shows promising results: six months after the treatment, participants showed reduced depression symptoms, suicidal ideation, and stress.

If the positive affect treatment continues to improve some of the distressing symptoms that come along with depression, the technique may also have applications for other psychiatric disorders, like post-traumatic stress disorder and schizophrenia.

1: Mental health tech for depression

Emerging technologies like wearables and GPS devices may also help researchers capture depression symptoms, and potentially inform diagnosis and treatment, according to one paper in the issue.

Sleep trackers may document how much rest a depressed person is getting — a lifestyle factor that can impact their condition. GPS data can reveal if a person is staying at home a lot — a sign they may be drifting apart from family or friends.

Depression manifests differently in each individual, the researchers argue, and tech might help health professionals better diagnose patients. Currently, diagnosis relies on nine criteria: depressed mood, loss of interest or pleasure, appetite or weight disturbance, sleep disturbance, psychomotor changes, loss of energy, feelings of worthlessness/guilt, decreased concentration, and suicidal ideation.

Each person with depression has a mix of these criteria, but some factors, like loneliness, helplessness, and grief, aren’t incorporated in the standard diagnostic criteria. New technologies might better measure the nuances in these criteria, and help people access appropriate treatment. Apps tracking symptoms might also help identify people in acute need, facilitating helpful short-term interventions.

But developing trust and transparency around apps and technology isn’t easy, and could present huge stumbling blocks to putting them into practice.

What’s the future of depression treatment?

Harnessing technology, digging into the gender gap, focusing on positive behavior change, and targeting opioid signaling are promising areas of research for future pursuit, scientists say.

Whether these leads will indeed transform care for depression patients remains to be seen. But, for the millions of people with depression who may be frustrated by their current options, emerging research may offer novel therapies that could actually help. The future of depression treatment may look nothing like it does today.