Objective:In dementia, disturbed behavior including delusional thinking, hallucinations, agitation and aggression is often noted and affects up to 80% of patients with Alzheimer’s disease. Many affected patients also demonstrate anxiety, restlessness, psychomotor disturbances, depression, apathy, and sleep-wake cycle perturbations as complications of dementia. The decision of a caregiver to seek institutional placement of an affected patient into a nursing home is often the consequence of untreated or inadequately treated behavioral changes. As a result, identification of effective therapies for dementia associated behavioral problems is of great practical importance. The serotonergic system appears to be involved in dementia with behavioral change; there are reports of the efficacy of citalopram and trazodone as therapies. Mirtazapine is a novel agent that blocks presynaptic alpha 2 adrenergic receptors and postsynaptic serotonin type 2 and type 3 receptors. It is an effective antidepressant and has antianxiety properties. As such, mirtazapine has the potential to be useful in the treatment of dementia-associated behavioral changes. The objective of this open label pilot study was to show that mirtazapine is safe and effective for the treatment of non-psychotic behavioral symptoms in dementia.
Design:Open label 12-week trial.
Materials and Methods:This was an open-label trial of mirtazapine over a 12-week period in ten patients with dementia and significant non-psychotic behavioral disturbances as established by using threshold cutoff scores for inclusion on the BEHAVE-AD and Neuropsychiatric Inventory (NPI). These scales were also the Primary efficacy measures. Outcome data, vital signs and adverse events were recorded at each monthly visit. Subjects were started on 15 mg/day of mirtazapine; if greater efficacy was desired, the daily dose could be increased by 15 mg per week until a maximum tolerated dose of 45 mg/day was achieved.
Results:To date, analyses of the data reveal that the mean change in symptom severity from baseline to study endpoint on the NPI was 5.8 (17% reduction in symptom severity). Changes in several NPI subscales were particularly notable (Depression, Agitation, Irritability and Anxiety subscales showed reductions of 50%, 40%, 89% and 89% respectively). Mean reduction on the Behave-AD was 5.8 (45% reduction in symptom severity). The mean dose of mirtazapine was 38 mg/day. Mirtazapine was well tolerated overall. Three study participants experienced adverse events, of these, only one, nocturnal myoclonus, appeared to be drug related.
Conclusion:This report of an open label trial of mirtazapine in dementia demonstrates that this agent appears effective and well-tolerated for the treatment of non-psychotic behavioral disturbances.
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