Company: GHRS
Filing Date: 2025-07-29
Form Type: 20-F/A
Source: 0001140361-25-027850
Chunk: 160

Company: GH Research PLC
Filing Date: 2025-07-29
Form: 20-F/A
Chunk 160
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 MDD alone in the United States is estimated to be US $326 billion (2018 estimate), up from $236 billion in 2010, with 35% being attributable to the direct costs of treatment, 4% to suicide-related costs, and 61% to indirect workplace costs. Per patient, TRD has a greater economic and societal cost than non-TRD MDD. TRD patients are often unable to perform daily tasks, are less productive at work and have higher rates of unemployment. They are also more likely to receive disability or welfare benefits and are reported to have a higher rate of co-occurring conditions, including diabetes, anemia and hypertension. Research conducted in 2018 and published in the Journal of Affective Disorders suggests that the proportion of patients suffering with TRD attempting suicide at least once during their lifetime could be as high as 30%. 88 Table of Contents According to a report published in the Journal of Affective Disorders, direct medical costs are approximately two- to threefold higher for TRD patients compared to non-TRD MDD patients. TRD patients have higher prescriptions costs, require more doctor visits and experience increased rates of hospitalization. They also have, on average, twice the number of inpatient visits compared with non-TRD MDD patients and their hospital stays are approximately 36% longer on average, according to an article published in the Journal of Clinical Psychiatry. Existing Therapies for Depression Because depression has a diverse set of biological, social, psychological, environmental, genetic and stress-related determinants, many of which co-occur, treatment options are wide-ranging and often combined. Current pharmacological and non-pharmacological treatments are efficacious only for a subset of MDD patients, and many patients do not respond or experience relapses. Clinicians lack high-quality evidence of whether certain therapies are suitable for certain patients and often rely on a lengthy trial-and-error approach, course-correcting as patients experience relapses or difficult side effects. Pharmacotherapies There are five main categories of antidepressants available. These are:

| 1. | selective serotonin reuptake inhibitors, or SSRIs; |

| 2. | serotonin-norepinephrine reuptake inhibitors, or SNRIs; |

| 3. | atypical antidepressants; |

| 4. | monoamine oxidase inhibitors, or MAOIs; and |

| 5. | tricyclic antidepressants, or TCAs. |

Antidepressants are