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Many people know someone living with depression or have firsthand experience with its symptoms themselves. According to the World Health Organization, more than 280 million people worldwide live with depression, making it one of the most common psychiatric disorders and the leading cause of disability worldwide. Clinically known as major depressive disorder (MDD), depression is a serious mental illness that causes a persistent feeling of sadness and loss of interest in activities. Depression affects how people feel, think, and behave, and it can lead to significant emotional and physical disruptions. For example, the disorder is often accompanied by sleep disturbances such as insomnia or hypersomnia, as well as fatigue, an inability to experience pleasure—known as anhedonia—loss of appetite, personality changes, or avoidance of social interaction.
Recognizing and treating depression as what it is—a disorder of the brain—is a key step toward fully advancing research that will lead to improved treatment options and better outcomes. Continued advancements in neuroscience are beginning to provide researchers a better understanding of certain diseases within larger disorders, thereby helping the field move away from a one-size-fits-all approach and closer to a future where personalized treatment for depression and other brain conditions becomes the norm.
People Living with Depression Need More Options to Meet Their Needs
For those living with MDD, it is important to shift from a clinical response to functional wellbeing—the ability to perform the usual tasks of daily living—which can only be achieved by addressing underlying symptoms that alleviate the intensity of disease. First, there must be an adjustment from the status quo of depression treatment, where significant unmet need remains. Seven out of every ten patients with depression experience residual symptoms with first-line, standard-of-care treatments; residual symptoms can include anhedonia, sleep disturbance, impaired cognition, anxiety, or fatigue. These can be mediated by changes in distinct brain circuits, or even improved by targeting proteins expressed within these circuits. To optimize depression treatment in this way will require a shift to precision neuropsychiatry.
Precision medicine is a more targeted approach to understanding disease that aims to integrate clinical data with other patient information to reveal disease subtypes, ultimately improving the accuracy with which patients can be characterized and treated. Through innovative clinical trial programs designed to realize this precision future in neuropsychiatry, companies like Janssen Research & Development, LLC, one of the Pharmaceutical Companies of Johnson & Johnson, are developing differentiated therapies for depression in patient subtypes, where subtypes are characterized by those experiencing a specific set of residual symptoms despite treatment with standard of care.
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The Path Toward Individualized Treatment for Insomnia and Anhedonia Subtypes of Depression
Among the many residual symptoms experienced by people living with MDD, two of the most common are insomnia and anhedonia.
Approximately 70% of people with depression experience insomnia or sleep disturbances, indicating that current antidepressants do not fully address these symptoms, which can take a significant toll on quality of life, including inability to concentrate, exhaustion, and lethargy. Symptom persistence despite treatment is associated with treatment-resistant depression.
Insomnia symptoms can be understood on a molecular level by looking at orexin-producing neurons. Orexin is believed to regulate a variety of functions through its actions on specific proteins in brain regions that work together to control sleep and emotion. However, overly high or low levels of orexin in the body are thought to cause problems with sleep, such as the insomnia seen in patients with depression, as well as hyperarousal—when the body is in high alert—that commonly occurs in MDD. Preclinical and clinical studies have shown the potential to treat insomnia effectively without affecting normal sleep patterns. As one example, Janssen’s latest research is investigating how the sleep-wake system may interact with mood-regulating brain circuits to reduce symptoms of depression, as not all treatments for insomnia have been shown to reduce depression symptoms. With continued clinical studies, there is potential to broaden the path for precision in antidepressant therapy through the selection of patient subgroups based on an easily-identified, coexisting symptom, like insomnia.
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Additionally, researchers are investigating kappa-opioid receptor (KOR) antagonists, which are thought to be involved in reducing depressive symptoms, including anhedonia, a core feature of MDD—second in prevalence only to depressed mood within the context of a major depressive episode. Clinically, anhedonia can manifest as an inability to experience life’s daily pleasures, as well as deficiencies in approach-related motivated behavior or learning how to match expectations to the environment.
Advances in the biological and clinical understanding of disease categories is enabling researchers to develop targeted therapeutic interventions for depression subtypes. Similar to the way we now treat cancers by targeting subtypes of tumors, precision medicine has the potential to transform neuroscience, redefining outcomes for people living with depression and other central nervous system disorders. Janssen aims to lead the precision revolution in neuroscience by pushing the boundaries of what’s possible in pursuit of a future where researchers can predict and prevent nervous system disorders and eliminate the burden they place on patients around the world.