After discussing with the decision-maker various treatments’ risks and benefits, it might be useful to ask, for example, “If Mrs. B could have foreseen her behaviors 10 years ago, what do you think she would have wanted us to do? Some people might have been mortified by the thought of attacking other people, whereas other people would not mind this as much as the fear of being ‘overmedicated.’ Which end of the spectrum do you think she would have leaned toward?”
When medical research does not offer clear answers for the “right” next clinical step, clinicians can:
- acknowledge our own limits and those of human knowledge
- engage the caregiver (or, when appropriate, the patient) in shared decision-making, recognizing that some people will appreciate the opportunity for “equal partnership” whereas others will want us to decide based on our best clinical judgment.
Table 2
Pharmacologic alternatives to antipsychotics: What the evidence says
| Treatment | Evidence/results |
|---|---|
| Selective serotonin reuptake inhibitors | 2 positive studies with citalopram (more effective than placebo for agitation in 1 trial and equivalent to risperidone for psychosis and agitation with greater tolerability in the other); 2 negative trials with sertraline |
| Other antidepressants | 1 study showed trazodone was equivalent to haloperidol for agitation, with greater tolerability; another found trazodone was no different from placebo; other agents have only case reports or open-label trials |
| Anticonvulsants | 3 trials showed divalproex was equivalent to placebo; 2 positive trials for carbamazepine, but tolerability problems in both; other agents tried only in case reports or open-label trials |
| Benzodiazepines/anxiolytics | 3 trials showed oxazepam, alprazolam, diphenhydramine, and buspirone were equivalent to haloperidol in effects on agitation, but none used a placebo control; trials had problematic methodologies and indicated cognitive worsening with some agents (especially diphenhydramine) |
| Cognitive enhancers | Some evidence of modest benefit in mostly post-hoc data analyses in trials designed to assess cognitive variables and often among participants with overall mild psychiatric symptoms; prospective studies of rivastigmine and donepezil specifically designed to assess neuropsychiatric symptoms have found no difference compared with placebo |
| Miscellaneous drugs | Failed trial of transdermal estrogen in men; small study showed propranolol (average dose 106 mg/d) more effective than placebo |
| Source: References 5,21 | |
Table 3
How well do psychosocial/behavioral therapies manage
psychosis/agitation in dementia?*
| Treatment | Evidence/results |
|---|---|
| Caregiver psychoeducation/support | Several positive RCTs (evidence grade A) |
| Music therapy | 6 RCTs, generally positive in the short term (evidence grade B) |
| Cognitive stimulation therapy | Three-quarters of RCTs showed some benefit (evidence grade B) |
| Snoezelen therapy (controlled multisensory stimulation) | 3 RCTs with positive short-term benefits (evidence grade B) |
| Behavioral management therapies (by professionals) | Largest RCTs with some benefits (grade B) |
| Staff training/education | Several positive studies of fair-to-good methodologic quality (evidence grade B) |
| Reality orientation therapy | Best RCT showed no benefit (evidence grade D) |
| Teaching caregivers behavioral management techniques | Overall inconsistent results (evidence grade D) |
| Simulated presence therapy | Only 1 RCT which was negative (evidence grade D) |
| Validation therapy | 1-year RCT with mixed results (evidence grade D) |
| Reminiscence therapy | A few small studies with mixed methodologies (evidence grade D) |
| Therapeutic activity programs (such as exercise, puzzle play) | Varied methods and inconsistent results (evidence grade D) |
| Physical environmental stimulation (such as altered visual stimuli, mirrors, signs) | Generally poor methodology and inconsistent results; best results with obscuring exits to decrease exit-seeking (evidence grade D) |
| * Evidence grades from A (strongest) to D (weakest) were assigned in a review by Livingston G, Johnston K, Katona C, et al. Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia. Am J Psychiatry 2005;162:1996-2021 | |
| RCT: randomized controlled trial | |
| Source: Reference 22 | |
Duration of treatment
Limited evidence leaves psychiatrists largely on our own in regards to how long to continue pharmacotherapy with antipsychotics. Neuropsychiatric symptoms such as psychosis and agitation exhibit variable patterns. Symptoms may wax and wane for unclear reasons.
Given the tenuous nature of the risk-benefit profile for atypical antipsychotics in dementia, consider a gradual taper for persons with dementia who remain asymptomatic after 3 to 6 months of atypical antipsychotic treatment. Monitor them closely for symptom recurrence.5
Carefully consider the necessary duration of antipsychotic therapy in patients (such as Mrs. B) in whom you can identify possibly reversible precipitants of psychosis and aggression. Patients may have a delayed beneficial response to the correction of precipitating factors such as medical illness, physical discomfort, or medication side effects.
Mrs. B received risperidone, but evidence for efficacy and safety in dementia-related psychosis or agitation does not yet significantly distinguish among the atypical agents (except that data are limited for ziprasidone and clozapine). Usual starting and target doses are provided in Table 4.23