“Necessary clinical adjustments,” as noted in Chapter 1, come with the pharmacological territory for most patients with complex psychiatric disorders – partly because symptoms often can be protean and nonstatic, partly because illness severity can wax and wane, partly because of the impact of cotherapies, and partly from other factors such as pharmacokinetic interactions, treatment nonadherence, loss of efficacy, or other events in the natural evolution of illness. The mechanics and logistics of changing from one pharmacotherapy to another, or deciding when and how to deprescribe an ineffective or otherwise unhelpful medication, are seldom discussed in textbooks or practice guidelines. From an evidence-based perspective, there are few controlled trials designed to compare tolerability and outcomes across various methods and timeframes for stopping and starting or cross-tapering one drug in exchange for another.