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Thus, the degree of cholinergic activity likely determines the amount of catecholamines released into the synaptic cleft of SS neurons

doi: 10.1259/bjr.20130490 541 ZhuJSanidadKZSukamtohEZhangG

Options for managing tolerance include a brief dose reduction for 4 to 8 weeks ("drug holiday" at a lower dose, not complete cessation), lifestyle optimization to maximize the medication effect, evaluation for other contributing factors (thyroid function, cortisol, sleep quality, medication interactions), and consideration of adding a complementary compound to address specific aspects of the plateau

Cancer Cell 21 , 297308 (2012)

doi: 10.1016/j.ejphar.2014.07.036