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When to increase dose Consider increasing if: Minimal response after 4-6 weeks at current dose No side effects at current dose Current dose below the higher end of recommended range Goals not being met with conservative approach Increase gradually, typically by 25-50% at a time

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Functional interactions often involve specific hydrogen bonds and, in some cases, salt bridges, whereas nonfunctional interactionslacking evolutionary selectionare primarily driven by hydrophobic effects 63

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