Although progress has been made in our understanding of the underlying pathophysiology of major depressive and bipolar disorders, there is still a large unmet need for the development of new effective treatment options. A new study analysed real-world evidence to identify potential mechanisms of action, or new treatments for bipolar disorders, that could inform future development opportunities for novel treatment options.
Major depressive and bipolar disorders
Major depressive and bipolar disorders are mood disorders characterised by pathological alterations in the patient’s emotional state, cognition, motivation, psychomotor activity, energy, sleep and feeding behaviour. Both of these disorders are associated with impaired quality of life, high economic burden and premature mortality.
While progress has been made in our understanding of the underlying pathophysiology and development of pharmacological treatments for these disorders, there still is a large unmet need for finding effective treatment options. Around 30-40% of those with depression fail to respond to first line antidepressants, and a proportion of those patients go on to be diagnosed with treatment resistant depression. Furthermore, between 40% and 60% of patients with bipolar disorder who are treated with mood stabilisers relapse within 1-2 years. Therefore, understanding potential mechanisms of action or treatment pathways that may be effective in preventing or treating both depression and bipolar disorder at the onset could help address the unmet need for effective treatment options.
Using real-world evidence to identify new treatments for bipolar disorders
Over the past decade, large-scale, standardised electronic health data has become widely available, creating a valuable tool to inform drug development, identify novel pathways and aid in drug repositioning. The researchers behind this study worked to identify potential mechanisms of action or new treatment targets for depressive and bipolar disorders by using real world data to examine associations between these disorders and prescription medications approved in the US. They conducted a self-controlled cohort design in which subjects served as their own controls. The researchers chose this method as it has been shown to produce less biased estimates and has a higher predictive accuracy than other comparative study designs when investigating associations between drug exposures and health outcomes.
Presence or first depressive or bipolar disorder incidences were captured for each patient exposed to the drug or drug class under investigation. The researchers required patients to have at least 2 incidents of depressive disorder, or at least 3 incidences of bipolar disorder, occurring within 12 months of each other, and have at least 180 days of continuous enrolment prior to initial diagnosis.
Findings using real-world data to identify new treatments for bipolar disorders
This study included a total of 125,075,697 individuals, 1,933 medications and 464 drug classes. A total of 47 medications and 19 drug classes were identified as leading to a ≥50 % reduction in risk for both depressive and bipolar disorders. However, 39 of these medications and 14 of the drug classes were excluded from further analysis as the majority were already approved treatments for the conditions of interest.
Overall, seven drug classes and eight medications met the researcher evaluation criteria of at least a 50% reduction in risk for both depressive and bipolar disorders. These medications fell into 3 major groups:
- Drugs used to treat substance use disorders.
- Drugs that affect the cholinergic system.
- Drugs for cardiovascular-related conditions.
These medications can be investigated further to provide insights into potential mechanisms of actions or treatment targets that could aid research and discovery of novel treatments for depressive and bipolar disorders. For example, various sources suggest that cerebrovascular disease plays a major role in the pathogenesis of late-onset major depression. Therefore, it is believed that by reducing the incidence of new thromboembolic events in patients with cerebrovascular disease or other vascular conditions, it may reduce or delay the incidence of late onset depression.
Summary
This study utilised a self-controlled cohort study accessing administrative health care data on patients in the US to assess the associations between all marketed medications and the incidences of major depressive and bipolar disorders. The researchers were able to identify eight medications and seven drug classes that reduced the incidences of major depressive and bipolar disorders that could aid further research and discovery into new treatments for bipolar disorders.
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