Treatment of BPSD: Pharmacological and Non-Pharmacological Interventions PDF

Absolutely! Here is the conversion of the document in the image to a markdown format: # Treatment / Management Management of BPSD involves choosing an appropriate setting, treating discomfort, implementing non-pharmacological interventions, and conducting systematic trials of evidence-based pharma...

Absolutely! Here is the conversion of the document in the image to a markdown format: # Treatment / Management Management of BPSD involves choosing an appropriate setting, treating discomfort, implementing non-pharmacological interventions, and conducting systematic trials of evidence-based pharmacological therapies if needed. Unless patients endanger themselves or others, interventions should begin only after establishing a baseline by identifying and quantifying target symptoms. ## Choose an Appropriate Setting The first step in management is to decide on the proper setting for treatment and address safety issues. Patients with delirium are best managed in a hospital to facilitate medical evaluation because parenteral medications may be required. Referral to a geropsychiatry unit is appropriate for medically stable patients who are endangering themselves or others (aggression with injury or capacity to cause injury, refusing fluids or basic hygiene, suicidal behavior), especially if pharmacotherapy is refused or is ineffective. Pending transfer, patients who are dangerous to themselves or others require monitoring with one-on-one observation, and treatment with antipsychotic medications will usually be necessary, following a risk or benefit discussion with their surrogates or guardians. ## Treat Discomfort Before any BPSD-specific interventions, all patients should be assessed and treated for causes of discomfort (eg, pain, constipation, urinary retention, room temperature), as described above and treated appropriately. ## Non-Pharmacological Interventions for BPSD The next step in management is implementing non-pharmacological interventions, which may be sufficient for mild BPSD and should always accompany pharmacotherapy. Geriatrics organizations and experts advocate the use of non-pharmacological interventions for BPSD. However, a meta- analysis of 10 randomized controlled trials in patients with moderate to severe dementia found no benefit, except for music therapy in reducing overall BPSD and massage therapy in reducing depression.[13] **Caregiver training:** This meta-analysis excluded interventions focused on caregiver training, effectively reducing a range age of BPSD and improving caregiver well-being. [14] Caregiver training focuses on understanding behavioral disturbances as responses to discomfort, unmet needs, or attempts to communicate, creative soothing environments with optimal levels of stimulation, and responding to patients in ways that de-escalate problematic behaviors (eg, distraction, giving patients clear instructions and simple choices, not rewarding the behaviors). The Alzheimer Association offers online educational modules and in-person training classes, providing professional and peer support for caregivers. For patients whose BPSD occurs primarily during personal care, a randomized, multi-site crossover study showed that training caregivers to deliver a protocol called Bathing without a Battle (available online) reduced agitation, bathing time, and antipsychotic use. [15] **Other non-pharmacological approaches:** While non-pharmacological interventions other than caregiver training and music therapy have not been consistently effective for BPSD in randomized, controlled trials, they may benefit individual patients and, unlike medications, rarely have adverse effects. These include aromatherapy, bright light therapy to reduce circadian disturbances, massage, multisensory stimulation, and reminiscence therapy, in which patients review their past via conversation, photographs, or music. [16] Some interventions with anecdotal effectiveness for agitation include giving patients simple tasks to perform, such as folding laundry or using busy quilts (lap quilts with exciting objects such as zippers, Velcro, beads, ties, etc) and weighted blankets (similar to those used to calm children with pervasive developmental disorders). A clinical trial (Clinical Trials.gov ID NCT03643991) is currently underway to evaluate the latter. In general, non-pharmacological approaches are well-tolerated, but rare cases of worsening agitation have occurred with music therapy. ## Pharmacologic Interventions for Agitation and Aggression Psychotropic medications are frequently used to treat BPSD, although the side effect burden is high, and the benefits are modest. Wandering and repetitive vocalizations rarely respond to pharmacotherapy and are best addressed with non-pharmacological measures. Pharmacological approaches will differ based on the nature and severity of the symptoms. The primary focus of clinical trials has been on symptoms of agitation, aggression, and psychosis since these are typically the most problematic and distressing manifestations. **Empiric treatment of pain:** Painful conditions are present in at least 49% of patients with dementia, but only 20% to 40% of patients with dementia receive analgesics, compared to 60% to 80% of similar patients without dementia. This relates to both under-reporting by patients and under- recognition by clinicians. [12] Since untreated pain has a strong relationship with (BPSD), an 8-week multicenter cluster randomized controlled trial examined the effect of a stepwise protocol for empiric treatment of pain in patients with dementia-related agitation. Patients were started on routine acetaminophen (3 g daily) if they were not receiving analgesics. If this was insufficient, they were stepped up to low-dose morphine (up to 20 mg daily), buprenorphine transdermal patch (up to 10 mcg hourly), or pregabalin (up to 300 mg daily). The primary outcome measure was a change in scores on the Cohen-Mansfield Agitation Inventory; cognitive and physical functioning changes were also assessed. After 8 weeks, agitation was reduced by 17% in the intervention group (an effect comparable to that seen with risperidone, the antipsychotic most commonly used for BPSD), without any adverse effects on cognition or physical functioning, suggesting that pain relief did not achieve benefit for BPSD simply by sedating patients.[17] This study supports the empiric treatment of known or potential pain as a first step in addressing BPSD. An excellent first step is initiating routine acetaminophen, with a maximum recommended dose of 3 g/day in the elderly. Topical therapies such as transdermal lidocaine, diclofenac gel, or methyl salicylate cream are safe. They can be effective if a localized source of pain is suspected. Duloxetine, Gabapentin, or Pregabalin can be helpful if there is a concern for neuropathic pain, although they are associated with an increase in falls. Clinicians should generally avoid using muscle relaxants, chronic NSAIDs, and tricyclic antidepressants. Although opioids can also contribute to falls and fractures, Tramadol has a stronger association than most other opioids. Transdermal Buprenorphine may be the safest alternative and does not worsen renal insufficiency, which is common in older adults. [18] **Antipsychotics:** Second-generation antipsychotics (primarily risperidone, olanzapine, quetiapine, and aripiprazole) are the mainstay of treatment for agitation and aggression, although, in a systematic review of 16 meta-analyses of randomized, controlled trials, the effect sizes (differences between treatment and placebo) were typically quite small for Risperidone, Olanzapine, and Aripiprazole, ranging between 0.15 to 0.30 in most studies, and Quetiapine generally did not differ from placebo. Adverse effects, including extrapyramidal symptoms, cerebrovascular events, somnolence, urinary tract symptoms, and death, were higher in the antipsychotic group, and worsening confusion was common with Quetiapine and Olanzapine. [19] In the United States, the Food and Drug Administration (FDA) has issued a black box warning about the increased risk for death among elderly patients with dementia who receive treatment with antipsychotics for (BPSD) (3.5% vs. 2.3%, mainly due to cerebrovascular disease and infections). For this reason, antipsychotic medications should only be an option when non-pharmacological interventions and pharmacological interventions, such as pain control and selective serotonin reuptake inhibitors (SSRIs), have been ineffective or if the patient is a harm to themselves or others. Starting maximum doses of antipsychotics for BPSD are as follows: Aripiprazole 2 mg daily and 15 mg daily, respectively; Olanzapine 2.5 mg daily and 10 mg daily; Quetiapine 12.5 mg twice daily and 100 mg twice daily; and Risperidone 0.25 mg twice daily and 1 mg twice daily. Doses can be increased in small increments every 2 weeks after insufficient improvement, based on prospective ratings from caregivers. Due to their potential to worsen motor symptoms, clinicians should avoid using antipsychotics other than Quetiapine, Pimavanserin, and Clozapine in Lewy body dementia and dementia associated with Parkinson disease. Clozapine requires special monitoring and reporting when prescribed. In the United States, Pimavanserin is approved by the Food and Drug Association for the treatment of psychosis related to Parkinson disease. However, it carries the same black box warning as other antipsychotics. [20] The starting and target dose of pimvanserine is the same (34 mg). Like other antipsychotics, it prolongs the QT interval and carries a black box warning about the increased risk of death in geriatric patients with dementia. Patients receiving antipsychotic medications require monitoring for adverse motor effects, and periodic (every 3 to 6 months) attempts to taper and discontinue the medication are necessary. Although the quality of evidence is low, antipsychotic discontinuation does not result in the worsening of BPSD, as evidenced by one longitudinal study in which about 80% of patients on long-term antipsychotics were successfully discontinued without increased BPSD or use of as-needed medication. [21] Discontinuation may be less successful for patients who have had severe symptoms. **Selective serotonin reuptake inhibitors (SSRIs):** Due to the adverse effects associated with antipsychotics, other medications have undergone research for the treatment of agitation and aggression. A 2011 meta-analysis demonstrated that the SSRI antidepressants Citalopram and Sertraline were associated with improvement in these symptoms, with a rate of adverse effects similar to placebo, although Trazodone was ineffective. [22] A subsequent multicenter randomized controlled trial of Citalopram 30 mg daily versus placebo showed a number needed to treat for moderate to marked overall benefit in BPSD of 7. Still, no difference in agitation scores was seen, and patients had an average increase in corrected QT interval of 18 ms. [23] Antidepressant dosing strategies used in the studies were the same as for depression, and researchers observed common SSRI adverse effects such as nausea and hyponatremia. It is wise to heed the geropsychiatry maxim "start low, go slow, but go as high as you need to go" when treating mild to moderate BPSD with SSRIs because too-rapid titration can worsen agitation. Citalopram should be started at 10 mg daily and Sertraline at 25 mg daily. Target symptoms and their baseline frequency or severity should undergo an assessment before starting the medication, and patients should be followed for 2 to 3 weeks for response and tolerability. If no benefit exists but also no adverse effects, Citalopram dosing should increase to 20 mg and Sertraline to 50 mg. Sertraline may be further increased to a maximum dose of 200 mg daily. The maximum recommended dose of Citalopram is 20 mg daily due to QTc prolongation at higher doses. **Other pharmacotherapies:** The combination of Dextromethorphan and Quinidine, which has approval in the U.S. and Europe for the pseudobulbar effect, was studied in a single randomized trial, with modest benefit for agitation but significant adverse effects, especially falls. [24] Prazosin (average dose of about 6 mg daily) was beneficial for BPSD without adverse effects on blood pressure in a study with 22 participants. [25] Medications that have no clinically meaningful efficacy for agitation or aggression include Cholinesterase inhibitors, Memantine, Valproate, and benzodiazepines.[26] [27][28][29][30] An exception to the negative findings regarding cholinesterase inhibitors in the dementia population as a whole is the possible benefit