Company: GHRS
Filing Date: 2025-02-27
Form Type: 20-F
Source: 0001140361-25-006175
Chunk: 18

Company: GH Research PLC
Filing Date: 2025-02-27
Form: 20-F
Item: Item 4
Chunk 18
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 unmet need.
 
Bipolar Disorder (BD)
 
BD is a recurrent chronic affective disorder characterized by fluctuations in mood state and energy, affecting more than 10 million people in the United States and Europe, based on estimates of the National Institute of Mental Health and an article published in European Neuropsychopharmacology. The main characteristic separating BD from other affective disorders is the presence of recurring manic or hypomanic episodes that may alternate with depressive episodes. Although the symptoms come and go, BD usually requires lifelong treatment.
 
Bipolar I disorder, or BDI, is defined by the presence of overt manic episodes with a range of manifestations, including overconfidence, grandiosity, talkativeness, extreme disinhibition, irritability, decreased need for sleep, and highly elevated mood. Bipolar II disorder, or BDII, is characterized mainly by episodes of depression, but alternating with hypomania, a milder form of the overt mania in BDI. As defined by the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the lifetime presence of at least one manic episode is needed for the diagnosis of BDI and of at least one hypomanic episode and one major depressive episode is needed for the diagnosis of BDII.
 

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Whereas hypomania is a milder form of mania, BDII is not generally perceived to be a milder form of BDI. Studies published in Archives of General Psychiatry on the natural course of BD found that BDII patients were symptomatic during 53.9% of follow-up weeks, with depressive symptoms present during 50.3% of follow-up weeks, while BDI patients were symptomatic during 47.3% of follow-up weeks with depressive symptoms present during 31.9% of follow-up weeks. It is evident that depressive symptoms dominate the symptomatic status in both types of BD, but most notably so in BDII. Evidence also suggests that a significant proportion of patients suffering from BD attempt suicide, with highest risk in phases with depressive symptoms and in patients with BDII.
 
Despite the disease burden of depressive symptoms in BDII, few studies have focused on the treatment of depression in BDII and only two drugs are specifically approved by the FDA for this indication, lumateperone and quetiapine. However, these treatments can be associated with significant side effects, such as somnolence, dizziness and dry mouth, they often exhibit delayed onset of response,