What is the best approach to treating insomnia in a patient with comorbid Restless Leg Syndrome (RLS) and depression, considering medications like Belsomra (suvorexant) and Dayvigo (lemborexant)?

From the Guidelines

For patients with comorbid insomnia, Restless Leg Syndrome (RLS), and depression, a dual-targeted approach is recommended, prioritizing orexin receptor antagonists like Dayvigo (lemborexant, 5-10 mg) or Belsomra (suvorexant, 10-20 mg) for insomnia, as they do not worsen RLS symptoms and have fewer interactions with antidepressants 1.

When considering the treatment of insomnia in patients with comorbid RLS and depression, it's essential to address each condition while minimizing the risk of medication interactions or symptom exacerbation. The American Academy of Sleep Medicine (AASM) clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults provides a framework for selecting appropriate pharmacotherapy 1.

Key considerations include:

• The choice of a specific pharmacological agent should be directed by symptom pattern, treatment goals, past treatment responses, patient preference, cost, availability of other treatments, comorbid conditions, contraindications, concurrent medication interactions, and side effects 1.
• Orexin receptor antagonists are preferred for insomnia due to their mechanism of action, which promotes sleep by blocking wake-promoting signals rather than through sedation, making them suitable for patients with RLS and depression.
• For RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status, and suggests against the standard use of levodopa, pramipexole, ropinirole, and other dopamine agonists due to the risk of augmentation and other adverse effects 1.
• For depression management, an SSRI like sertraline (50-200 mg daily) or an SNRI like duloxetine (30-60 mg daily) can be effective, though it's crucial to be aware of potential interactions with other medications and the possibility that some antidepressants may worsen RLS symptoms.

The most effective approach is to use Dayvigo (lemborexant) or Belsomra (suvorexant) for insomnia, given their favorable profile in patients with comorbid RLS and depression, and to manage RLS and depression with therapies that have the least potential for adverse interactions 1.

In terms of specific treatment strategies:

• Dayvigo (lemborexant, 5-10 mg) or Belsomra (suvorexant, 10-20 mg) can be used to address insomnia, as they are less likely to exacerbate RLS symptoms and have a more favorable interaction profile with antidepressants.
• For RLS, iron supplementation with ferrous sulfate is recommended for patients with appropriate iron status, and other treatments like dipyridamole or gabapentin may be considered based on individual patient factors and the presence of comorbidities like end-stage renal disease 1.
• Depression can be managed with SSRIs or SNRIs, taking into account potential interactions with other medications and the need to monitor for worsening RLS symptoms.

Overall, a comprehensive approach that addresses insomnia, RLS, and depression, while considering the potential interactions and side effects of various medications, is crucial for optimizing outcomes in patients with these comorbid conditions.

From the FDA Drug Label

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use BELSOMRA safely and effectively. See full prescribing information for BELSOMRA. BELSOMRA is an orexin receptor antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance (1). Worsening of Depression/Suicidal Ideation: Worsening of depression or suicidal thinking may occur. Risk increases with dose. Immediately evaluate any new behavioral changes (5.2). Need to Evaluate for Co-morbid Diagnoses: Reevaluate if insomnia persists after 7 to 10 days of treatment (5. 6).

The best approach to treating insomnia in a patient with comorbid Restless Leg Syndrome (RLS) and depression is not explicitly stated in the provided drug label for Belsomra. However, it is crucial to consider the following key points:

• Belsomra is indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.
• The drug label warns about the worsening of depression/suicidal ideation, which is a critical consideration in patients with comorbid depression.
• It is essential to reevaluate the patient if insomnia persists after 7 to 10 days of treatment, considering co-morbid diagnoses like RLS and depression. Given the lack of direct information on the use of Belsomra in patients with RLS and depression, a conservative clinical decision would be to approach treatment with caution and closely monitor the patient's response to therapy, while also considering the management of their comorbid conditions 2.

From the Research

Treatment Approach for Insomnia with Comorbid Restless Leg Syndrome (RLS) and Depression

The treatment of insomnia in patients with comorbid Restless Leg Syndrome (RLS) and depression requires a comprehensive approach, considering the complex interplay between these conditions.

• Medications like Belsomra (suvorexant) and Dayvigo (lemborexant): While these medications are approved for the treatment of insomnia, their effectiveness in patients with comorbid RLS and depression is not well-established 3, 4.
• Cognitive Behavioral Therapy for Insomnia (CBT-I): CBT-I has been shown to be an effective treatment for insomnia in patients with comorbid mental disorders, including depression 5. It may also be beneficial for patients with RLS, although more research is needed to confirm its efficacy in this population.
• Treatment of RLS: The treatment of RLS typically involves the use of dopamine agonists, such as ropinirole, or gabapentin 3, 6. However, these medications may have varying degrees of effectiveness in patients with comorbid depression.
• Antidepressant Medications: Some antidepressant medications, such as bupropion, may be effective in treating depression in patients with RLS, although they may exacerbate RLS symptoms in some cases 3, 7.

Considerations for Treatment

When treating insomnia in patients with comorbid RLS and depression, it is essential to consider the potential interactions between medications and the impact of treatment on each condition.

• Differential Diagnosis: RLS can masquerade as chronic insomnia, highlighting the importance of careful diagnosis and differential diagnosis 4.
• Comorbidities: The presence of comorbidities, such as anxiety or mood disorders, can impact treatment outcomes and should be considered when developing a treatment plan 6, 7.
• Individualized Treatment: Treatment should be individualized to address the unique needs and circumstances of each patient, taking into account the complex interplay between insomnia, RLS, and depression.