Evidence-based Approaches to Gradual Dose Reductions of Antipsychotic Drugs

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The use of antipsychotic drugs for the management of the Behavioral and Psychological Symptoms of Dementia (BPSD) is not an FDA-approved indication, is controversial, and yet continues to be utilized at high rates despite significant risks for patient harm, survey citation, and lawsuits directed at SNF providers and facilities.

The off-label use of these drugs in nursing facility residents may be considered a chemical restraint.  Regulatory guidance requires that nursing facilities ensure that residents prescribed these drugs for BPSD receive gradual dose reductions (GDR) and behavioral intervention, unless clinically contraindicated, in an effort to discontinue their use.

However, the abrupt discontinuation or significant dose reduction of these medications, especially when the patient receives a high dose for long duration, can cause physiological withdrawal symptoms including dyskinesias, insomnia, nausea, restlessness, and disruptive behaviors.  Unfortunately, these symptoms are often very similar to the indication for drug initiation and can lead providers and caregivers to assume that the GDR was a failure and that the patient “requires” the drug and the prior dose indefinitely.

Successful dose reduction and discontinuation of antipsychotic drugs require that clinicians recognize the potential for withdrawal symptoms and structure GDRs to minimize any negative clinical outcomes for the patient (and caregivers).  One approach is to structure the amount of each dose reduction and the intervals between dose reductions based on drug kinetics, including half-life and time to steady state.  Tjia and colleges developed a two-stage approach of 50% dosage reductions that included adjusting half-life by 1.5 for patients aged 65-89 and by 2.0 for those over 90.

In addition to age, dose reduction intervals may also be adjusted based on the duration of therapy.  If the drug has been used for only a few days or weeks, tapering may not be necessary, while long duration of use may require a more extended tapering plan.  The estimated tapering schedule ranges from 4 weeks to 4 months for second generation antipsychotics, and at least 4-8 weeks for first generation drugs (i.e. haloperidol).  See the table below for recommended intervals between dose reductions and estimated time to discontinuation.

 

Table 1

Generic/Brand Dose Reduction Interval Time to Discontinuation
Aripiprazole (Abilfy) 2 months 4 months
Olanzapine (Zyprexa) 2-4 weeks 4-8 weeks
Quetiapine (Seroquel) 2 weeks 4 weeks
Risperidone (Risperdal) 2-3 weeks 4-6 weeks
Ziprasidone (Geodon) 2 weeks 4 weeks
Haloperidol (Haldol) 2 weeks 4 weeks

 

 

Finally, if the drug is being used to treat an approved indication such as schizophrenia or bipolar disorder, gradual dose reduction may not be appropriate and in fact may be clinically contraindicated.  GDRs may also be contraindicated for patients who have a prior history of being a danger to self or others or if two prior taper attempts have failed.

 

Reference: Tjia et al Approaches to Gradual Dose Reduction of Chronic Off-Label Antipsychotics Used for Behavioral and Psychological Symptoms of Dementia The Consultant Pharmacist Vol. 30, No. 10 October 2015

This article was originally published in our monthly issue of From the Front Lines – a monthly publication that shares best practices and medication-related challenges faced by “front line” staff in long-term care and post-acute (LTCPAC) facilities.

>>> From the Front Lines – November 2015 <<<