Gradual structural changes occur in the dopaminergic system with age and increase the propensity for antipsychotic adverse effects. The number of dopaminergic neurons and D2 receptors decreases approximately 10% per decade. In order to avoid the development of adverse effects related to extrapyramidal symptoms, approximately 20% of receptors need to be free. FGAs tend to block approximately 90% of D2 receptors, whereas SGAs block less than 70% to 80% and dissociate more rapidly from D2 receptors.13 FGAs should therefore be avoided, as they have been associated with numerous adverse effects, including parkinsonism, tardive dyskinesia, akathisia, sedation, peripheral and central anticholinergic effects, postural hypotension, cardiac conduction defects, and falls. As noted above, they have been linked to a greater risk of mortality (Figure14 ).
When the decision to use an antipsychotic agent is made for a person with dementia, SGAs appear to be a better choice. There appear to be modest differences within the class of SGAs in terms of effectiveness, tolerability, and adverse effect profile. Although the association between the dose of an antipsychotic and the risk of mortality or stroke remains undefined, other common adverse effects, such as sedation, extrapyramidal symptoms, and risk of falls, can be reduced by starting at the lowest dose possible and titrating slowly.
Dosing considerations
When beginning treatment with an antipsychotic, the starting dose should be as low as possible. This is particularly important for patients who are older, frail, cognitively impaired, or who carry a specific, significant risk that the antipsychotic may increase, such as a risk for falling. The starting dose can be divided or scheduled according to the behavior. For example, a lunchtime dose may be appropriate for patients exhibiting increased agitation towards the end of the day (“sundowning”). A good rule of thumb is to administer a dose approximately 2 hours before the behaviors typically occur. While there is no formal evidence from clinical trials to support this type of dosing schedule, clinical experience has shown it to have merit.
Dose increments should be modest and, in a nonemergent setting, may be adjusted at weekly intervals depending on response. Prior to starting a treatment trial, it is advisable to estimate what will constitute a worthwhile clinical response, the duration of treatment, and the maximum dose. Avoid high doses or prolonged use of antipsychotics that have not significantly improved the target behavior.
When the decision to use a SGA is made, choosing the initial starting dose is challenging given that none of these medications has an indication for use in this population. We propose doses that have been used in completed randomized trials that reflect the best information available about the dose likely to maximize benefit and minimize risk. On the basis of those trials, reasonable starting doses would be15-22:
- quetiapine 25 to 50 mg/d
- risperidone 0.5 to 1 mg/d
- aripiprazole 2 to 10 mg/d
- olanzapine 2.5 to 5 mg/d
- ziprasidone 20 mg/d
Continued to: The highest doses tested...