Switching antipsychotics

Galletly 2016Early Psychosis Guidelines Writing Group, EPPIC National Support Program 2016

The advice in this topic is intended to support the practical implementation of the antipsychotic recommendations for adults and young people with bipolar disorder or psychotic disorders.

A switch of antipsychotic may be required because of poor treatment response, adverse effects or patient request.

If a switch is being considered because of poor treatment response, first check whether the poor response can be explained by other factors (see Key questions to assess nonresponse to an antipsychotic for psychotic disorders, Key questions to assess nonresponse to pharmacotherapy for acute mania for acute mania, Key questions to assess nonresponse to pharmacotherapy for bipolar depression for bipolar depression and Key questions to assess nonresponse to pharmacotherapy for prophylaxis of bipolar disorder for prophylaxis of bipolar disorder). If nonadherence is identified as the cause of poor treatment response, determine barriers to adherence (eg antipsychotic adverse effects, impaired insight, cognitive impairment, lack of community or family support, psychosocial factors including financial, inadequate community treatment and lack of patient or caregiver education). These barriers may be the focus of treatment (eg addressing factors contributing to nonadherence) or guide the subsequent antipsychotic selection. If negative symptoms of psychosis are inadequately treated, see the management advice here before switching antipsychotics.

If treatment response is adequate but the patient is experiencing adverse effects, see here for management options to consider before switching antipsychotics.

Before switching antipsychotics, discuss the potential harms (eg relapse, temporary exacerbation of adverse effects) and benefits (eg improved symptom control, eventual reduction in adverse effects) of a switch with the patient and, if the patient consents, their family, carers or significant others.

If the decision is made to switch antipsychoticsTakeuchi 2018:

  • the switch should ideally occur in collaboration with the patient’s psychiatrist, mental health team or a practitioner experienced in switching
  • preferably switch to an antipsychotic with a different dopaminergic receptor occupancy profile (for which adverse effect profile is a surrogate) if the switch is because of poor treatment response or adverse effects; discuss with the patient which adverse effects are acceptable and how they are monitored for, prevented and addressed (see Overview of antipsychotic adverse effects)
  • decide whether a switch from oral to long-acting injectable antipsychotic would be preferable
  • plan the switch and decide the outcomes that will determine whether to continue or stop the switch (eg response, adverse effects)
  • choose a therapeutically equivalent dose to avoid relapse
  • monitor for, prevent and address adverse effects that arise because of the switch; see Approximate relative frequency of common adverse effects of antipsychotics for adverse effects seen when starting an antipsychotic and Common adverse effects of stopping or reducing the dose of an antipsychotic for problems seen when stopping an antipsychotic. An activation syndrome of restless overactivity, insomnia, nausea and vomiting can occur when switching from a sedating antipsychotic to a less-sedating antipsychotic; treat the syndrome with a short course of diazepam or lorazepam
  • monitor for early signs and symptoms of relapse, and educate the patient and their family, carers or significant others about characteristic early signs and symptoms of relapse.

The speed of a switch between oral antipsychotics depends on the pharmacokinetics of the antipsychotics (check a drug information resource for guidance), whether the patient is acutely unwell or stable, and the setting in which the switch is undertaken (eg hospital, community). For example:

  • for patients who are acutely unwell in hospital, a fast switch may be used; however, this increases the risk of adverse effects from antipsychotic drug withdrawal and drug interactions
  • for patients who are stable in the community, slowly reducing the dose of the first antipsychotic while simultaneously increasing the dose of the second antipsychotic reduces the risk of adverse effects or relapse.

For information about switching from an oral to a long-acting injectable antipsychotic formulation, see here for psychotic disorders and here for bipolar disorder.

When switching from a long-acting injectable to an oral antipsychotic formulation, stop the long-acting injectable and start a low dose of the oral antipsychotic on the date the next injection was due. Gradually increase the dose of the oral formulation—concentrations of long-acting injectable antipsychotics remain elevated for weeks to months depending on their pharmacokinetics (check a drug information resource). The exception to this approach is long-acting injectable risperidone; start the replacement oral antipsychotic early enough to achieve a therapeutically equivalent dose 3 weeks after the last risperidone injection (which is when the risperidone concentration is expected to rapidly drop). Adverse effects arising during the switch may be caused by the long-acting formulation (either an interaction with the new antipsychotic or withdrawal adverse effects) or the oral antipsychotic. If symptoms return after the long-acting injectable formulation drops to clinically insignificant concentrations (usually 2 to 5 months after the last dose, depending on pharmacokinetics), this can indicate the oral antipsychotic is inadequately dosed; also consider other factors for nonresponse.