What is the recommended protocol for switching from oral paliperidone (Invega) to oral aripiprazole (Abilify)?

From the Guidelines

When switching from oral paliperidone (Invega) to oral aripiprazole (Abilify), a cross-titration approach is recommended. Begin by adding aripiprazole at a starting dose of 5-10 mg daily while maintaining the current paliperidone dose for 1-2 weeks. This overlap period allows aripiprazole to reach therapeutic levels while maintaining symptom control. After this initial period, gradually reduce the paliperidone dose by 3 mg increments every 1-2 weeks while simultaneously increasing aripiprazole by 5 mg increments as needed, up to a target dose of 10-30 mg daily. Complete discontinuation of paliperidone should occur over 2-4 weeks depending on the initial dose. This gradual approach minimizes withdrawal effects and rebound symptoms. Monitor closely for side effects during the transition, particularly for extrapyramidal symptoms, akathisia, and changes in metabolic parameters. The cross-titration method is preferred because these medications work on different receptor profiles—paliperidone primarily blocks D2 and 5-HT2A receptors, while aripiprazole acts as a partial D2 agonist with different 5-HT receptor activity. This pharmacological difference necessitates a period of overlap to maintain clinical stability during the switch 1.

Some key considerations when switching between these medications include:

• The potential for withdrawal effects and rebound symptoms if the switch is done too quickly
• The importance of monitoring for side effects, particularly extrapyramidal symptoms and changes in metabolic parameters
• The need for a period of overlap to maintain clinical stability during the switch
• The potential benefits of using a cross-titration approach to minimize withdrawal effects and rebound symptoms

It's also important to note that antipsychotic polypharmacy, which involves the use of multiple antipsychotic medications simultaneously, may be necessary in some cases, but it should be used with caution and under close clinical monitoring 1. The use of antipsychotic polypharmacy has been associated with increased risks of adverse effects, including extrapyramidal symptoms, metabolic changes, and increased mortality 1. However, some studies have suggested that antipsychotic polypharmacy may be effective in reducing symptoms and improving treatment outcomes in certain patient populations 1.

In terms of specific guidelines, the World Health Organization recommends that antipsychotic treatment should be continued for at least 12 months after the beginning of remission, and that withdrawal may be considered in individuals who have been stable for several years on antipsychotic treatment, keeping in mind the increased risk of relapse and possible adverse effects of medicines 1.

Overall, the decision to switch from oral paliperidone to oral aripiprazole should be made on a case-by-case basis, taking into account the individual patient's needs and circumstances. Close clinical monitoring and careful consideration of the potential benefits and risks of the switch are essential to ensure the best possible outcome for the patient.

From the FDA Drug Label

Switching from Other Antipsychotics There are no systematically collected data to specifically address switching patients with schizophrenia from other antipsychotics to aripiprazole tablets or concerning concomitant administration with other antipsychotics While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

The recommended protocol for switching from oral paliperidone to oral aripiprazole is not explicitly stated in the FDA drug label. However, it is recommended that:

• The period of overlapping antipsychotic administration should be minimized.
• Immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients, but more gradual discontinuation may be most appropriate for others. It is essential to consider individual patient needs and medical history when switching antipsychotics, and consultation with a healthcare professional is necessary to determine the best course of action 2.

From the Research

Switching from Oral Paliperidone to Aripiprazole Oral

• The recommended protocol for switching from oral paliperidone (Invega) to oral aripiprazole (Abilify) is not directly stated in the provided studies, but several studies offer guidance on switching to aripiprazole from other antipsychotics 3, 4, 5, 6.
• A study from 2009 suggests that tapering off the previous antipsychotic over 4 or 6 weeks while initiating aripiprazole could be preferable to abrupt discontinuation to prevent early worsening of symptoms 3.
• Another study from 2003 found that any of the three strategies evaluated (immediate initiation of aripiprazole with simultaneous discontinuation of the current antipsychotic, immediate initiation of aripiprazole while tapering off the current antipsychotic over 2 weeks, or up-titrating aripiprazole while tapering off the current antipsychotic) can be used safely for switching patients to aripiprazole from antipsychotic monotherapy 4.
• A 2015 study provides guidance on initiating aripiprazole once-monthly, suggesting that tapering the prior oral antipsychotic while titrating up the oral aripiprazole dose over more than 1 to 4 weeks may be an effective strategy 5.
• A 2008 study compared two switching strategies to aripiprazole treatment in patients with schizophrenia and found that both strategies (add-on of aripiprazole on a current regimen, wait for 4 weeks, and then tapering of prior antipsychotics, and add-on of aripiprazole and simultaneous tapering of prior antipsychotics) were objectively safe and well tolerated 6.
• While these studies do not specifically address switching from oral paliperidone to aripiprazole, they provide general guidance on switching to aripiprazole from other antipsychotics, which may be applicable 3, 4, 5, 6.
• A 2024 study compared the safety and tolerability of starting aripiprazole lauroxil with aripiprazole lauroxil NanoCrystal Dispersion in 1 day followed by aripiprazole lauroxil every 2 months using paliperidone palmitate monthly as an active control in patients with schizophrenia, but does not provide direct guidance on switching from oral paliperidone to oral aripiprazole 7.