Management of restless legs syndrome in primary care

• RLS-UK/Ekbom Syndrome Association •

Diagnostic criteria

• Diagnosis of restless legs syndrome (RLS) can be made if all of the following four criteria are met:
  • a need to move the legs, usually accompanied or caused by uncomfortable, unpleasant sensations in the legs
  • symptoms are:
    • exclusively present or worsen during periods of inactivity/rest
    • partially or totally relieved by movement such as walking or stretching at least as long as the activity continues
    • generally worse or exclusively occur in the evening or during the night

Associated features

• Clinical course is usually progressive. Adults of all ages can be affected but the prevalence increases with age; most commonly RLS affects middle-aged individuals
• RLS is commonly accompanied by sleep disturbances

Differential diagnosis

• Nocturnal leg cramps
• Akathisia
• Peripheral neuropathy
• Vascular disease (e.g. varicose veins or deep vein thrombosis)
• Painful legs/toes
• Intermittent claudication
• Attention-deficit hyperactivity disorder in children
• Anxiety/generalised anxiety disorder

Aetiology

• The majority of cases are primary with unknown origin
• Genetic predisposition and a chemical imbalance in the brain may play a role in some patients
• The three major reversible secondary causes of RLS – pregnancy, iron-deficiency anaemia and end-stage renal disease
  • are related to depleted iron stores
• Other secondary causes include:
  • vitamin B12/folate deficiency
  • peripheral neuropathy
  • Parkinson's disease
  • fibromyalgia
  • rheumatoid arthritis
  • spinocerebellar ataxia
  • Charcot-Marie-Tooth disease (type 2)

Investigations

• Physical examination is often normal, important examinations include:
• neurological – particularly of the peripheral nervous system
• vascular – to exclude vascular causes
• Required blood tests include:
  • full blood count
  • iron studies
  • serum ferritin
  • serum vitamin B12/folate
  • serum glucose
  • urea and electrolytes
  • thyroid function tests
• Patients with severe RLS and insomnia may require sleep studies such as polysomnography or immobilisation tests

General principles

• Treatment depends on the severity and frequency of symptoms
• Mild RLS may be managed with reassurance and lifestyle changes
• Severe cases may require drug therapy
• Secondary causes and exacerbating factors should be identified and corrected
  • iron supplementation for anaemia and other cases of deficiency
  • switching concomitant treatment (RLS can be worsened by anti-depressants, calcium channel blockers, anti-nausea drugs and some anti-allergy medications)
  • limiting other triggers (e.g. avoiding a high intake of caffeine or alcohol consumed during the evening)
• Mineral supplementation (magnesium, potassium and calcium) may prove useful

Non-pharmacological intervention

• Good sleep hygiene and habits are helpful; advise patients to:
  • sleep in a quiet, comfortable and cool environment
  • go to bed and wake at a regular hour (advise going to bed late and waking late)
  • avoid taking diuretics or caffeine before bedtime
• During an attack, patients may find benefit from:
  • walking and stretching
  • bathing in hot or cold water
  • relaxation exercises (biofeedback or yoga)
  • distracting the mind
  • massaging affected limbs

Pharmacological treatment

• Please see individual drug information prior to prescribing
• Patient age should be taken into account
• Use medication cautiously in pregnancy, RLS normally improves after parturition
• A step-by-step approach to drug therapy may be useful
• Start with a dopamine agonist (e.g. pramipexole, ropinirole) administered as a single, evening dose
  • if intolerant to one agent, try an alternative dopamine agonist
  • alleviates symptoms in at least 70% of patients
• Levodopa, taken at bedtime, may be used if patients are intolerant to dopamine agonists
  • up to 80% of patients treated will experience augmentation or rebound; therefore long-term use is limited
  • useful for intermittent RLS
• Levodopa and dopamine agonists:
  • use with caution in patients with angle-closure glaucoma, a history of malignant melanoma, cardiac disease or peptic ulcer disease
• Levodopa is associated with gastrointestinal adverse events such as anorexia, nausea and vomiting
• Re-introduce dopamine agonists for patients in whom symptoms persist or begin to appear in the early morning (rebound phenomenon) or in the evening/daytime with spread to the upper limb (augmentation)
• Anti-epileptic drugs such as carbamazepine or gabapentin may be useful for refractory cases
  • these drugs work by inhibiting hyperactivity in the nervous system that may be related to the symptoms
  • gabapentin is particularly useful for haemodialysis patients and for cases of painful RLS
• Severe unremitting painful RLS may require treatment with strong painkillers such as codeine, tramadol or oxycodone
  • treatment with such drugs should be given under specialist guidance only
• For patients with severe insomnia, bedtime sedatives such as clonazepam or zopliclone may be useful
  • these drugs reduce nervous activity and promote muscle relaxation

When to refer

• Most cases of RLS can be managed by primary care, however, referral may be considered for the following reasons:
  • diagnostic uncertainty
  • treatment failure
• Refer patients with severe, refractory RLS to specialist centres for hospitalisation and treatment with subcutaneous apomorphine