What are the most effective pharmacological treatments for insomnia in elderly patients with Parkinson's disease (PD)?

From the Guidelines

For geriatric patients with Parkinson's disease who have insomnia, immediate-release melatonin is the preferred medication due to its mild sedating effects and lower risk of adverse events, with a recommended starting dose of 3 mg and increasing by 3-mg increments to 15 mg as needed 1. When considering treatment options for insomnia in geriatric patients with Parkinson's disease, it is essential to prioritize medications with a favorable safety profile and minimal drug interactions.

• Melatonin is an attractive option for older patients (> 50 years old) and those with neurodegenerative disease, as it is only mildly sedating and has a lower risk of adverse events compared to other sleep medications 1.
• Clonazepam, although sometimes used in lower doses (starting at 0.25 mg) for patients with secondary RBD and DLB or PD, is often associated with significant side effects, including morning sedation, gait imbalance/falls, depression, and cognitive disturbances, making it a less desirable option for geriatric patients 1.
• Rivastigmine, an acetylcholinesterase inhibitor, may be considered for patients with RBD and cognitive impairment refractory to other treatments, but its use is not recommended as a first-line treatment for insomnia in geriatric patients with Parkinson's disease due to potential side effects such as excessive daytime sleepiness 1. Non-pharmacological approaches, including sleep hygiene, regular sleep schedules, and cognitive behavioral therapy for insomnia, should be implemented concurrently with medication management to optimize treatment outcomes.
• Cognitive behavioral therapy for insomnia (CBT-I) has been shown to be an effective treatment for chronic insomnia disorder in adults, including older adults, and should be considered as a first-line treatment option 1.

From the FDA Drug Label

Ramelteon reduced the average latency to persistent sleep at each of the time points when compared to placebo. The second study employing PSG was a three-period crossover trial performed in subjects aged 65 years and older with a history of chronic insomnia Subjects received ramelteon (4 mg or 8 mg) or placebo and underwent PSG assessment in a sleep laboratory for two consecutive nights in each of the three study periods. Both doses of ramelteon reduced latency to persistent sleep when compared to placebo.

The best medication for insomnia in geriatric patients with Parkinson's is not explicitly stated in the provided drug labels. However, ramelteon has been shown to be effective in reducing sleep latency in older adults (aged 65 years and older) with chronic insomnia.

• The recommended doses are 4 mg or 8 mg.
• The 8 mg dose has been evaluated for long-term efficacy and safety in adults with chronic insomnia.
• There is no direct information about the use of ramelteon in patients with Parkinson's disease 2, 2, 2.

From the Research

Medications for Insomnia in Geriatric Patients with Parkinson's

• The choice of a hypnotic agent in the elderly is symptom-based, and several medications can be used to treat insomnia in geriatric patients with Parkinson's, including ramelteon, short-acting Z-drugs, suvorexant, and low-dose doxepin 3.
• For sleep-onset insomnia, ramelteon or short-acting Z-drugs can be used, while suvorexant or low-dose doxepin can improve sleep maintenance 3.
• Eszopiclone or zolpidem extended release can be utilized for both sleep onset and sleep maintenance, and low-dose zolpidem sublingual tablets or zaleplon can alleviate middle-of-the-night awakenings 3.
• However, benzodiazepines should not be used routinely due to the risks associated with their use in older adults 3, 4, 5.
• Trazodone, a commonly used off-label drug for insomnia, can improve sleep quality and sleep continuity but carries significant risks, including the potential to induce parkinsonism 6.
• Non-FDA-approved hypnotic agents, such as melatonin, diphenhydramine, tryptophan, and valerian, are also used to treat insomnia in older adults, but their benefits and harms are not well established 3, 7.
• Dual orexin receptor antagonists, such as almorexant, lemborexant, and filorexant, have shown some improvement in sleep maintenance and sleep continuity in phase II studies 3.
• Piromelatine may also improve sleep maintenance, and histamine receptor inverse agonists, such as APD-125, eplivanserin, and LY2624803, can improve slow-wave sleep 3.

Considerations for Geriatric Patients with Parkinson's

• When treating insomnia in geriatric patients with Parkinson's, it is essential to consider the potential risks and benefits of each medication, as well as the patient's individual needs and medical history 5, 7.
• Cognitive behavioral therapy for insomnia is the gold standard for treatment of insomnia in older adults, and nonpharmacologic interventions should be considered as the first-line therapy 5, 7.
• Pharmacologic options, such as low-dose doxepin, melatonin, ramelteon, and dual orexin receptor antagonists, can be used as an alternative or add-on treatment, but their use requires close monitoring due to the potential for adverse events 5, 7.