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    Switching and Deprescribing

    Switching Between Serotonin-Dopamine Antagonists and Partial Agonists (SDA-PAs)

    October 22, 2025
    Switching Between Serotonin-Dopamine Antagonists and Partial Agonists (SDA-PAs)
    General Principles
    • Engage in shared decision making
      • Work with patients and their caregivers to identify treatment goals, values, and tolerability concerns
      • Identify patient preferences for pace and method of switching and align the switch plan with patient comfort and safety (e.g., some patients want a slower taper to avoid side effects; others prefer a faster transition)
      • Establish realistic expecations: no medication is perfect; balance "good enough" efficacy and tolerability and avoid unrealistic hopes (e.g., complete cure)
    • Assess clinical context before switching
      • Consider history of response, nature and acuity of psychiatric condition, target signs and symptoms, history of adherence, need for special monitoring, and patient preference
      • Weigh potential benefits of switching against risks of destabilization (e.g., are other interventions available to address tolerability)
    • Monitor and manage tolerability issues
      • Switching can trigger withdrawal, rebound, or new side effects
      • Consider supportive strategies (e.g., rescue sleep medications, tapering anticholinergics slowly)
    Pharmacodynamic (PD) and Pharmacokinetic (PK) Principles
    • Assess potential for rebound phenomena
      • Can occur when a previously-blocked receptor is no longer blocked, leading to increased stimulation by the endogenous neurotransmitter
      • Dopaminergic rebound: potential worsening of psychosis, mania, or agitation; potential hyperkinetic motor side effects
      • Histaminergic and cholinergic rebound: risk for agitation, insomnia, akathisia, dyskinesia, or Parkinsonism
      • Higher risk
        • Switching from an agent with more antagonism to one with less antagonism/partial agonism (PD)
        • Switching from an agent with a shorter half-life to one with a longer half-life (PK)
      • Lower risk/protective
        • Switching from an agent with less antagonism to one with more antagonism (PD)
        • Switching from an agent with a longer half-life to one with a shorter half-life (PK)
    • Take steps to mitigate risk
      • Delay or slow discontinuation of the previous medication
      • Consider short-term use of sedating co-medications during cross-titration
    Adapted from NEI Prescribe and from Correll CU. Strategies for switching between oral postsynaptic antidopaminergic antipsychotics in patients with schizophrenia: A systematic review. CNS Drugs 2025;39:913-35.

    Related Practice Resources
    Medication Tips and Pearls
    Dose Equivalence: D2 Antagonists and SDA-PAs
    Medication Tips and Pearls
    Binding Profiles of Serotonin-Dopamine Antagonists and Partial Agonists (SDA-PAs)
    Patient Education
    Medication Guides: SDA-PAs

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