A Practical Guide to Pharmacological Treatment

  • 1. Consider anti-dementia medication prior to non-pharmacological treatment. AChEI and memantine may specifically have some efficacy on agitation and aggression (please see Sect. “Anti-dementia Medication” for references). Patients with a diagnosis of AD, DLB, or Parkinson’s disease dementia should be started on one of these medications, regardless of whether agitation, aggression, irritability, or hyperactivity (or other BPSD) is present.
  • 2. Prescribe antidepressants when depression coexists with agitation, aggression, irritability, or hyperactivity. The evidence base is limited on the efficacy of antidepressants on BPSD in the absence of depression and should therefore primarily be reserved for BPSD when depression is present. However, it is generally recognized that a diagnosis of depression may be difficult to establish or rule out in patients with agitation, aggression, irritability, and hyperactivity, and this should be kept in mind.
  • 3. Reserve antipsychotics for instances of aggression and agitation that cause extreme distress for the patient or that put the patient or others at high risk. An atypical antipsychotic is recommended and risperidone appears to have the largest evidence base. Start low, go slow: a low start dosage with slow up-titration to therapeutic dose is recommended, though the urgency of instituting the therapy should be taken into consideration. Side effects may be severe and should be avoided by closely monitoring them and the therapeutic effects to ensure the lowest effective dose. Severe side effects should lead to immediate titrating down or discontinuation of medication.

Antipsychotics should be limited to a 3-month period since evidence for efficacy beyond 3 months is limited and because the risk of side effects with length of treatment increases. As a result, we recommend planned discontinuation at 3 months. Before discontinuation, non-pharmacological treatment should be instituted or alternative pharmacological treatment considered if further treatment is considered necessary. If continued treatment with antipsychotics is necessary, a frequent (e.g., every 4 weeks) review of treatment response and side effects should be carried out, and discontinuation should be attempted at regular intervals (e.g., every 3 months).

In some instances, formal and informal carers may exert considerable pressure to institute antipsychotics for agitation or aggression. Nevertheless, the physician should remain aware that institution of therapy should be based on patient symptoms and distress, except when others may be at severe risk.

  • 4. Consider antidepressants or mood stabilizers/anticonvulsants in some instances, even in the absence of overt depression. Carbamazepine or selective serotonin reuptake inhibitors (SSRIs) (e.g., citalopram) are an option for patients when anti-dementia medication and antipsychotics are not indicated (e.g., presence of contraindications) or where further pharmacological treatment is necessary in patients already treated with antipsychotics for 3 months (and where agitation does not lead to severe distress for the patient or aggression does not put the patient or others at extreme risk).
  • 5. Use anxiolytics sparingly, reserving them for acute treatment of severe agitation and aggression. There is no evidence on the efficacy of benzodiazepines on BPSD and serious concerns exist regarding side effects. Benzodiazepines should be considered rescue medication to be used in acute treatment only of severe agitation and aggression for a short period (days).

Pharmacological Treatment: Evidence

A multitude of systematic reviews and meta-analyses on pharmacological treatment have been published over the years, and a complete review of this literature is beyond the scope of this chapter: hence, we focus only on the largest studies, which have impacted practice the most. Since many pharmacological treatments are associated with severe side effects, we will also review these.

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