Though antipsychotics are generally used for long-term treatment of psychiatric conditions, there are several instances where therapy may be stopped altogether. We outline several practice pearls and clinical considerations when determining if antipsychotic tapering is appropriate. Deprescribing antipsychotic therapy may be appropriate in a number of different situations as listed below.
Antipsychotic Tapering Candidates
- Have achieved remission
- Developed serious side effects (e.g. agranulocytosis)
- No longer have an indication for use or were prescribed antipsychotics inappropriately (e.g. treatment of insomnia)
- Request to stop current medication (i.e. patient preference)
Antipsychotic Tapering Risks
Discontinuation shouldn’t be taken lightly and poses several risks, including worsening of symptoms, the emergence of withdrawal symptoms, or relapse. Tapering is a strategy used to mitigate the risks associated with therapy discontinuation. Unfortunately, there are no clear guidelines regarding the appropriate tapering of antipsychotic medications and it remains highly variable. The length and intensity of a taper often depend on the primary condition, symptom emergence, patient comfortability, length of treatment, and reason for discontinuation. In general, the faster the taper, the greater the risk.
Timing Of The Taper
Dose reductions over 4 weeks are most commonly done in practice. For example, one strategy recommends reducing antipsychotic doses linearly by 25% every 1-2 weeks and then stopping. Though gradual, this taper is relatively rapid fast considering it occurs over a 4 week period. Studies suggest nearly half of patients relapse following a 3-10 week taper and even higher after abrupt discontinuation. To comprehend this phenomenon, it is crucial to understand that antipsychotic response and receptor binding is observed in a logarithmic curve. Repeated exposure to antipsychotics upregulates D2 receptors, causing overstimulation and withdrawal symptoms when removed. Knowing how neuroadaptation, receptor occupancy, and hypersensitivity play a role in relapse, longer, slow-paced tapers are suggested to lower risk and reduce the severity of adverse effects.
From a pharmacokinetic standpoint, hyperbolic dose reductions that correspond to linear reductions in D2 receptor occupancy would be optimal to mitigate adverse effects, though this is not always practical. Liquid formulations and pill cutters have been useful in achieving smaller doses if necessary. In reality, tapering by 10% or less each month over the course of several months to years may be the next best option as gradual dose reductions over an extended period of time allows the body to reacclimate to reduced receptor occupancy. This is especially important in patients who have been on antipsychotic therapy for years.
Of course, slow tapers are not always reasonable or appropriate. In instances where serious side effects develop (such as agranulocytosis), antipsychotic therapy should be withdrawn immediately. Depending upon the setting, a more aggressive taper may be employed in inpatient facilities where closer monitoring can be accomplished. When determining how to taper an antipsychotic, here are a few key considerations (also see table below):
- Primary condition
- Status of condition & risk for relapse
- Current antipsychotic & dose
- Length of treatment
- Treatment response
- Treatment setting
- Patient comfortability
- Reason for discontinuation
Antipsychotic Tapering Timing Considerations – Table
|Primary Condition||Labeled indication||Off-label use|
|Condition Status/Risk for Relapse||Poorly controlled, high risk (e.g. multiple episodes, hospitalization)||Well-controlled, low risk (e.g. 1 episode)|
|Current Antipsychotic||Short half-life (e.g. clozapine, quetiapine)||Long half-life (e.g. aripiprazole, brexpiprazole)|
|Current Dose||High dose||Low dose|
|Length of Treatment||Less than 1 year||Greater than 1 year|
|Adverse Effects||Moderate or emerge during taper||Mild|
|Patient Preference||If worried or anxious, consider a slower taper||Consider faster taper if the patient is ready and willing|
Needless to say, gradual dose reductions over several months or years have had the greatest success in reducing side effects and preventing relapse. Regardless of the taper, though, monitoring is critical in managing psychiatric conditions and antipsychotic withdrawal. If symptoms start to develop, the rate of dose reduction is too fast. If symptoms are severe enough, a dose increase may be warranted before attempting to reduce it again. In any circumstance, emphasis should be placed on non-pharmacological approaches (e.g. behavioral, environmental) to manage or aid in the management of symptoms. The risk versus benefit of treatment should always be taken into consideration. In some, discontinuation may not be appropriate, particularly in those who require lifelong treatment (i.e. repeated episodes/relapse). Restarting therapy, reducing the dose to the lowest effective dose, or switching agents may be more appropriate in this population.
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Want more information? Check out these resources on antipsychotic tapering:
- Bjerre LM, Farrell B, Hogel M, Graham L, Lemay G, McCarthy L, et al. Deprescribing antipsychotics for behavioural and psychological symptoms of dementia and insomnia: Evidence-based clinical practice guideline. Can Fam Physician 2018;64:17-27 (Eng), e1-e12 (Fr).
- Horowitz, M.A., Jauhar, S., Natesan, S., Murray, R. M., & Taylor, D. (2021). A method for tapering antipsychotic treatment that may minimize the risk of relapse. Schizophrenia bulletin, 47(4), 1116-1129.
- Keks, N., Schwartz, D., & Hope, J. (2019). Stopping and switching antipsychotic drugs. Australian prescriber, 42(5), 152–157. https://doi.org/10.18773/austprescr.2019.052
- Keks, N., Schwartz, D., & Hope, J. (2019). Antipsychotic switching tool. Australian prescriber, 42(5), 156. https://doi.org/10.18773/austprescr.2019.056
- Moncrieff, J., Gupta, S., & Horowitz, M. A. (2020). Barriers to stopping neuroleptic (antipsychotic) treatment in people with schizophrenia, psychosis or bipolar disorder. Therapeutic advances in psychopharmacology, 10, 2045125320937910.