Does amitriptyline (Elavil) cause Restless Legs Syndrome (RLS)?

From the Guidelines

Amitriptyline can potentially worsen restless leg syndrome (RLS) rather than cause it, as it is known to block dopamine receptors in the brain, which can exacerbate RLS symptoms in some individuals 1. If you're taking amitriptyline and experiencing new or worsening RLS symptoms, you should discuss this with your healthcare provider. They may consider adjusting your dose, switching to a different medication, or adding treatments specifically for RLS.

Some key points to consider:

• Other medications that can worsen RLS include many antidepressants, antihistamines, and certain antipsychotics.
• For those with both depression and RLS, medications like bupropion or certain dopamine agonists might be better alternatives as they're less likely to worsen RLS symptoms.
• It's essential not to stop amitriptyline suddenly, as this can cause withdrawal symptoms; any medication changes should be supervised by a healthcare provider.
• The American Academy of Sleep Medicine suggests various treatments for RLS, including ferrous sulfate, dipyridamole, extended-release oxycodone, and bilateral high-frequency peroneal nerve stimulation, among others 1.
• Iron treatment is an important addition to the treatment of RLS, particularly for those with iron deficiency, and IV ferric carboxymaltose receives a strong recommendation 1.

Overall, the management of RLS should be individualized, taking into account the patient's specific needs and medical history, and any changes to medication should be made under the guidance of a healthcare provider.

From the FDA Drug Label

1. Adverse Reactions ... CNS and Neuromuscular: ... restlessness

The FDA drug label mentions restlessness as a possible adverse reaction, but it does not specifically mention Restless Legs Syndrome (RLS).

• Restlessness is not the same as Restless Legs Syndrome (RLS), which is a distinct medical condition.
• The label does not provide enough information to determine if amitriptyline causes Restless Legs Syndrome (RLS) 2.

From the Research

Amitriptyline and Restless Legs Syndrome

• The relationship between amitriptyline (Elavil) and Restless Legs Syndrome (RLS) is complex, with some studies suggesting that antidepressants like amitriptyline may induce or worsen RLS symptoms 3.
• However, a systematic review of prospective studies found that amitriptyline appears to increase periodic limb movements, but these movements do not disrupt sleep and are thus unlikely to be clinically significant 3.
• Another study found that sedating antidepressants, including amitriptyline, do not seem to aggravate periodic limb movements 3.
• In contrast, a case study reported that amitriptyline was effective in ameliorating RLS symptoms in a patient with Parkinson's disease, suggesting a potential therapeutic effect of amitriptyline on RLS 4.
• It is worth noting that the current evidence is limited by poor study design, inadequate use of standardized questionnaires, and heterogeneous populations studied for variable lengths of time 3.

Comparison with Other Antidepressants

• Other antidepressants, such as mirtazapine, may be associated with higher rates of RLS and periodic limb movements 3, 5.
• Venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, may also be associated with an increase in RLS symptoms and periodic limb movements 3, 5.
• In contrast, bupropion may reduce RLS symptoms, at least in the short term 3.

Clinical Implications

• The available evidence suggests that amitriptyline is unlikely to cause significant RLS symptoms, but may increase periodic limb movements that do not disrupt sleep 3.
• However, the relationship between amitriptyline and RLS is complex, and more research is needed to fully understand the potential effects of amitriptyline on RLS symptoms 3, 5.