Introduction
Behavioral disturbances (BD) are common in patients with dementia and increase the risk of institutionalization, caregiver burden, and risk of elder abuse (Sourial et al., Reference Sourial2001; Cohen-Mansfield, Reference Cohen-Mansfield2008). BD also decrease the quality of life for both patient and caregiver. BD includes verbally aggressive behaviors (e.g. swearing, threats), verbally non-aggressive behaviors (e.g. repetitive vocalization, pleas for help), physically aggressive behaviors (e.g. hitting, biting, scratching, kicking, punching), and physically non-aggressive behaviors (e.g. pacing, wandering) (Sourial et al., Reference Sourial2001; Cohen-Mansfield, Reference Cohen-Mansfield2008).
Management of BD includes both pharmacological and non-pharmacological interventions. For patients with mild agitation, non-pharmacological interventions, such as decreasing environmental stimuli, may be effective (Sadowsky et al., Reference Sadowsky2012). However, if behaviors continue, pharmacological steps may be employed. Currently, no medication is FDA approved for the treatment of BD in dementia. Various medications have been utilized with only some shown to be effective compared to the placebo including citalopram (Prosteinsson et al., Reference Porsteinsson2014; Weintraub Reference Weintraub2015) and sertraline (Seitz, Reference Seitz2011). There were issues with citalopram in that it required nine weeks in order to be superior to placebo (Weintraub, Reference Weintraub2015) and also there were concerns that the effective dose of 30 mg is higher than recommended due to potential cardiac effects. Trials of trazodone did not show any superiority to placebo (Seitz, Reference Seitz2011). Of the mood stabilizers, carbamazepine has the best evidence for effectiveness, but it has issues with safety and tolerability (Yeh, Reference Yeh and Ouyand2012). Antipsychotics have also shown superiority over placebo, although they are associated with only low to moderate efficacy (Schneider et al., Reference Schneider1990). In addition, antipsychotics are often avoided or discontinued because of adverse effects, federal regulations, and black box warnings (Devanand, Reference Devanand2012).
Buspirone is a 5HT1A partial receptor agonist approved in 1986 for the treatment of generalized anxiety disorder. The use of buspirone in the treatment of agitation in dementia has been described, however, there are no placebo controlled trials (Smith et al., Reference Smith1992; Tariot, Reference Tariot1997; Colenda, Reference Colenda III1998; Cooper, Reference Cooper2003; Desai et al., Reference Desai2012). One small blinded study compared 17 nursing home patients on buspirone (15 mg/d) with 14 patients treated with haloperidol (1.5 mg/d) for ten weeks, and found that buspirone significantly decreased muscle tension and anxiety compared to haloperidol, and was well tolerated (Cantillon et al.,Reference Cantillon1996). Buspirone's safety profile and low potential for dependence makes it an attractive option for the treatment of agitation in patients with dementia. We present a retrospective study of the use of buspirone for the treatment of patients with dementia and BD.
Methods
A retrospective chart review of patients managed by our geriatric psychiatric outreach program to nursing home and assisted living facilities was conducted. Inclusion criteria included patients with a diagnosis of dementia, ages 65 years and over, treated with buspirone for BD, rather than anxiety. Of 2,311 patients, 179 met inclusion criteria. Data collected included age, gender, marital status, race, type of dementia, other psychiatric diagnosis, compliance with medications, dose and length of treatment of buspirone was used, response to buspirone as assessed using the Clinical Global Impression Scale (CGI) 0, (unchanged or worse) to 3 (marked or complete remission), any side effects noted, and other psychotropic medications if any. Data was entered into SPSS and the data was analyzed. Patients who were determined to respond by CGI to have responded (scores of 2 or 3, moderate to marked response) were compared to patients who did not respond. This included demographics (including gender, age) type of behavior, and dose, schedule and length of treatment of buspirone, correlations were analyzed between effectiveness of buspirone and demographic and clinical variables. Significance was assumed for p values of 0.05 or less. The study was approved by the institutional IRB.
Results
There were 60 males and 119 females, mean age 83.8 + 7 years. The majority were widowed (n = 97; 56.7%), with 49 married (28.7%), 17 single (9.9%), and 8 divorced (4.7%). Patients resided in nursing homes (n = 136; 76.8%) and in assisted living facilities (n = 38, 21.5%). Most patients had children (n = 126; 76.4%) and had a history of employment (n = 111/127; 87.4%). Mean education level was 13.0 + 3.3 years.
Alzheimer's dementia was the most common dementia (n = 61; 34.1%) followed by mixed-type dementia (Alzheimer and vascular) (n = 50, 27.9%), vascular type (n = 31; 17.3%), Parkinson's Dementia (n = 7, 3.9%) alcohol related dementia (n = 5, 2.8%), and frontotemporal dementia (n = 3,1.2%). The majority were also diagnosed with co-morbid depression (n = 129; 72.1%), with two diagnosed with bipolar disorder (1.1%) and two with schizophrenia (1.1%). Ten had co-morbid diagnoses of anxiety disorders (n = 10; 5.6%). Eighteen (10.1%) had a diagnosis of alcohol abuse/dependence and one carried a personality disorder diagnosis (0.6%). Twenty-three patients (12.8%) had a history of psychiatric hospitalization and only one patient (0.6%) had a history of attempted suicide. No patients had ever received ECT.
BD were mainly verbal aggression (n = 125; 69.8%), and physical aggression (n = 116; 64.8%). Patient were aggressive during care (n = 80, 54.1%) or were hitting without provocation (n = 52; 35.1%). Pacing behavior was found in 61 out of 150 patients (40.7%). These aggressive behaviors were found to happen throughout the day in 49 out of 101(48.5%), three patients were aggressive only during the morning (3%), 30 were aggressive only in the afternoon and evening (29.7%), and seven patient only at night time (6.9%). Twelve patients (11.9%) demonstrated aggression only during care.
Current use of psychotropic medications other than buspirone revealed 41 patients (23%) were taking an SSRI, 85 patients (47.5%) an SNRI, six patients (3.4%) were on bupropion, one patient (0.6%) was on a MAOI, 22 patients (12.3%) on mirtazapine, and 38 patients (21.2%) on trazodone. Seven patients (3.9%) were on a typical antipsychotic and 117 patients (65.4%) were on an atypical antipsychotic. 27 patients (15.2%) were taking benzodiazepines, and 18 patients (10.1%) were on a mood stabilizer. Only 15 patients (8.5%) were taking sleep medications. Thirty-eight (21.2%) patients were on buspirone monotherapy. Eleven additional patients had their other psychiatric meds reduced or stopped after successful buspirone therapy.
Table 1 summarizes the changes in behavior as ranked by the Clinical Global Impression scale while the patient was on buspirone. When patients improved, improvement was noted as early as one week after beginning buspirone but could take up to four weeks on a particular dose, with a mean improvement occurring at 14.2 + 5.2 days. The length of time non-responders were on buspirone was 12.3 + 4.2 weeks (generally with increasing dosages every four weeks or so).
Clinical global impression scale – behavioral change while on buspirone
When buspirone was ineffective, 77 patients (66.4%) were placed on an antipsychotic, nine patients (7.8%) tried an antidepressant (SSRI/SNRI), two patients (1.7%) were placed on a benzodiazepine, and four patients (3.4%) tried a mood stabilizer, other medications were tried in 24 patients. Some patients had more than one additional medication trial. These medications were found to be ultimately effective in 72 patients (71.3%) but there were 29 patients (28.7%) that did not respond to any medications.
Our study did not find any correlation between age, type of aggression/behavior, gender, presence of anxiety, dose, and effectiveness of buspirone.
The mean total dose of buspirone prescribed was 25.7 + 12.5 mg. Buspirone was scheduled twice a day in 76 patients (42.4%) and three times a day in 95 patients (53.7%). Four patients (2.3%) received once a day and four patients (2.3%) four times a day. Buspirone was used for less than four weeks in 14 patients (7.8%), 44 patients (24.6%) used it between 1 and 6 months, and 48 patients (27.4%) between 6 and 12 months. 29 patients (16.2%) used buspirone for more than one year, 38 patients (21.2%) for more than two years, and six patients (3.4%) for more than five years. Reasons for stopping included no longer needed due to progression of dementia or patient death, or lack of efficacy. No patient was noted to have adverse effects from buspirone as a reason for discontinuation. Due to positive response to buspirone, the physician was able to reduce or stop other medications on 11 patients.
Discussion
Our sample of elderly dementia patients had high rates of BD with 69.8% verbal aggression and 64.8% physical aggression. Other types of aggression such as throwing objects occurred in 26.7% of patients. Behaviors were common, occurring daily on average, and typically more than once per day. Our study did not find any gender differences related to the type or frequency of aggression.
The results show that 68.6% of patients responded to buspirone, with 41.8% being moderately to be markedly improved. The mean dose of buspirone was 25.7 mg ± 12.50. This shows that buspirone can be effective across a wide dosage range, with even low doses being effective in some cases. In patients in which buspirone was ineffective, other drugs, such as antipsychotics and mood stabilizers, were tried. We found that about a third of these patients still exhibited BD, even after the use of other treatment options.
This study adds to the literature of the use and effectiveness of buspirone for agitation in elderly patients with dementia. This study has the largest sample size of dementia patients treated with buspirone for BD. Our study has a number of limitations due to the retrospective design and that there was no control group. As well, the patients were on multiple psychoactive medications which make the effect of buspirone more difficult to discern. As well polypharmacy is also an issue in this population and makes it more difficult to determine the cause of improvement. Finally, as no particular adverse effects were noted in our patients, a prospective study would likely be better at assessing potential side effects of buspirone. Despite these limitations, the results suggest that buspirone may be an effective and safe treatment option for patients with dementia and BD. Given the FDA warning for antipsychotic drugs in this population, and the potential serious side effects with other drugs such as carbamazepine and valproic acid, buspirone is an attractive choice due to low risk of side effects. Prospective, double blind placebo controlled studies examining the tolerability and effectiveness of buspirone in this patient population are needed to confirm these results.
Conflict of interest
None
Description of authors’ roles
Maria R. Santa Cruz MD – Formulation of research question, literature review, data collection, data analysis, writing, and editing of manuscript; Priscilla Hidalgo MD – Formulation of research question, data collection, data analysis, and editing of manuscript; Meredith Lee DO – Formulation of research question, data collection, data analysis, and editing of manuscript; Cornelius Thomas MD – Formulation of research question, literature review, and editing of manuscript; Suzanne Holroyd MD – Formulation of research question, data analysis, writing, and editing of manuscript.
Acknowledgments
None.
