Company: GHRS
Filing Date: 2025-02-27
Form Type: 20-F
Source: 0001140361-25-006175
Chunk: 16

Company: GH Research PLC
Filing Date: 2025-02-27
Form: 20-F
Item: Item 4
Chunk 16
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 including slow onset of response, poor therapy adherence rates and various side effects. For the most commonly used antidepressants the average time to remission in those who remit extends to about five to seven weeks, according to the STAR*D study. Adherence levels are low, with less than 50% of individuals in primary and psychiatric care not adhering to their prescribed antidepressant medication after three months.
 
There is limited evidence to effectively guide clinical decisions following non-response or partial response to first-line antidepressant medications. Recommended treatment approaches include optimizing the current antidepressant dose or switching to another antidepressant. Partial response or lack of response thereafter is recommended to be addressed by combining antidepressants from different pharmacological classes or augmenting with an alternative medication, primarily with atypical antipsychotics but also mood stabilizers, anticonvulsants, thyroid hormones and stimulants.
 
Antipsychotics, such as olanzapine, quetiapine and aripiprazole, are typically used as adjunctive therapies when there is a lack of notable efficacy with an antidepressant. Despite there being an approved combination of olanzapine and fluoxetine for TRD that is administered once daily, research shows that combining antidepressants and antipsychotics can have serious side effects, such as weight gain, other metabolic complications, sedation, extrapyramidal side effects, which are drug-induced movement disorders, and QTc prolongation, which means the ventricles of the heart take longer than usual to recharge between beats.
 

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Ketamine is an N-methyl-D-aspartate, or NMDA, receptor antagonist that has been used for several decades for sedation, anesthesia and chronic pain and is being used as an off-label treatment for TRD. The S-enantiomer of ketamine, esketamine, is administered via a nasal spray and was approved by the FDA in 2019 for the treatment of TRD (marketed as SPRAVATO® in the United States). While ketamine and esketamine treatments typically require frequent administration (for example, in the case of SPRAVATO®, a twice-weekly administration for 4 weeks, followed by weekly administration for 4 weeks, and then bi-weekly or frequent continuous administration, each in a controlled environment under medical supervision, with an estimated 40 administration visits per year), and while such administration is costly for payors and relatively burdensome for patients, recent improvements in patient access and the large unmet