Moving toward a more personalized approach to treating depression

One of the reasons is that depression is what we call a “syndromic diagnosis,” meaning it’s identified based on patterns of symptoms and patient-reported experiences rather than a specific biological test. Unlike conditions such as high blood pressure or diabetes, there’s no test result or biomarker that can confirm a diagnosis of MDD.

MDD is also a complex, heterogeneous disorder with as many as 256 possible symptom combinations. We don’t believe these 256 classifications all have one identical cause—however, they all get the same diagnosis. Finding the right treatment for each patient is something of a trial-and-error process because the symptoms and underlying biology can vary widely.

For instance, some people with MDD experience increased appetite and sleep, while others lose interest in food and suffer from insomnia. Some feel slowed down and fatigued; others feel restless or agitated. Those are just two examples. Every patient has some sort of unique mix of symptoms.

Even with available therapies, many people continue to experience unresolved symptoms. Understanding why these differences occur and how to address them effectively remains one of the field’s greatest challenges. What’s more, a number of the current treatments have side effects that people don’t find acceptable and that leads to discontinuation of treatment. Given all the challenges, there is a significant unmet need for effective treatments.

One major challenge is the high rate of nonresponse or inadequate response to existing medications. Nearly a third of people with MDD have what’s known as treatment-resistant depression, which means they are considered to have tried at least two first-line treatments without success. Another third find that antidepressants are initially effective but become less effective or stop working altogether after a while.

Of the patients who do respond to standard antidepressant treatments like selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), two in three patients continue to experience residual symptoms, such as insomnia or anxiety, while on treatment. So while these patients feel better, they’re not fully better.

On top of that, it typically takes about four to six weeks of treatment with standard antidepressants before patients start to notice meaningful symptom improvement. If they experience partial or no symptom relief, a healthcare provider may increase the dose of their current antidepressant or switch them to a different treatment altogether. Unfortunately, this means patients continue to struggle with symptoms while they wait to see if a treatment will offer them significant relief.

For patients who don’t achieve full response with an SSRI or SNRI alone, adjunctive therapies are often added, highlighting the need for additional add-on options that may help better address the full complexity of MDD.

In 2019, Johnson & Johnson introduced a new medication—the first new mechanism of action for depression in more than 30 years—that targets a specific pathway in the brain. We know that depression acts on the brain’s neural circuits, which you can think of as “wires” in the brain made of cells that send electrical and chemical signals to each other to help you think, feel, learn, move and more. The brain cells in these circuits communicate with each other using neurotransmitters; certain antidepressants work on specific neurotransmitters. For example, SSRIs work by increasing serotonin in one of the neural circuits impacted by depression.

The medication Johnson & Johnson developed works on the neurotransmitter glutamate to treat the symptoms of MDD. One of the biggest upsides of this drug is that it works quickly—some patients experience symptom improvement within 24 hours. And while this medication was initially used in combination with an antidepressant, we’ve found that using it on its own as a monotherapy is very effective.

Our approach to MDD reflects the complexity of the condition. We’re advancing a pipeline of mechanistically distinct therapies aimed at addressing the biological drivers of MDD, including the residual symptoms that standard antidepressants often leave unresolved. One example is an already approved therapy for other neuropsychiatric disorders that works differently than other antidepressants, and it was recently approved by the U.S. Food and Drug Administration.

We’re also studying an investigational medication that targets a different neural circuit in the brain, which we think may be overactive in some patients with MDD. Early research suggests it may be particularly helpful for people who have depression with insomnia symptoms, when it’s added onto their oral antidepressant.

We are going to see more targeted treatments that have a rapid onset of action, so we’re not asking patients to wait for weeks to feel relief. With high rates of inadequate response with standard antidepressants and many patients cycling through multiple therapies to treat their depression, it’s crucial we continue to bring options that deliver relief more quickly and more durably.

We’re also highly invested in precision approaches that aren’t just about new mechanisms of action, but also about matching the right mechanism to the right patient through more precise patient selection. For example, there are emerging technologies, such as linguistic analysis and facial analysis, that can predict MDD patients who might be at risk of suicide. I’m hopeful that we’ll continue to see new biomarker-driven strategies and digital tools that will help us identify more specifically the right medicine at the right time for the right patient. Johnson & Johnson is committed to staying the course until we do.