Restless Legs Syndrome¶

DIAGNOSIS: Restless Legs Syndrome (Willis-Ekbom Disease) ICD-10: G25.81 (Restless legs syndrome) SCOPE: Diagnosis confirmation using IRLSSG criteria, workup for secondary causes, pharmacologic and non-pharmacologic management, and augmentation prevention/treatment. Primarily outpatient management with limited ED/HOSP coverage for severe refractory cases.

STATUS: Draft - Pending Review

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

IRLSSG Diagnostic Criteria (All 5 Required)¶

Urge to move the legs usually accompanied by uncomfortable sensations
Symptoms begin or worsen during rest or inactivity (lying, sitting)
Symptoms are partially or totally relieved by movement (walking, stretching)
Symptoms occur exclusively or predominantly in the evening or night (circadian pattern)
Symptoms are not solely accounted for by another condition (leg cramps, positional discomfort, myalgia, venous stasis, leg edema, arthritis, habitual foot tapping)

Supportive Features: Family history (40-60%); response to dopaminergic therapy; periodic limb movements during sleep (PLMS) on polysomnography

SECTION A: ACTION ITEMS¶

1. LABORATORY WORKUP¶

1A. Essential/Core Labs¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
Ferritin	Iron deficiency is most common treatable cause; target >75 ng/mL for RLS (higher than general population)	>75 ng/mL (ideally >100)	URGENT	ROUTINE	ROUTINE	-
Transferrin saturation (TSAT)	Iron availability; TSAT <20% suggests iron deficiency even with normal ferritin	>20%	URGENT	ROUTINE	ROUTINE	-
Serum iron	Complete iron panel assessment	Normal range	URGENT	ROUTINE	ROUTINE	-
TIBC	Iron binding capacity; elevated in iron deficiency	Normal	URGENT	ROUTINE	ROUTINE	-
CBC with differential	Anemia evaluation; MCV for iron vs B12 deficiency	Normal; MCV 80-100 fL	URGENT	ROUTINE	ROUTINE	-
BMP (Creatinine, BUN, electrolytes)	Renal function (uremia causes secondary RLS)	eGFR >60 mL/min	URGENT	ROUTINE	ROUTINE	-
TSH	Thyroid dysfunction can mimic or exacerbate RLS	0.4-4.0 mIU/L	-	ROUTINE	ROUTINE	-
HbA1c	Diabetes screening (diabetic neuropathy commonly coexists)	<5.7% (normal); <7% if diabetic	-	ROUTINE	ROUTINE	-
Fasting glucose	Diabetes screening	70-99 mg/dL	-	ROUTINE	ROUTINE	-

1B. Extended Workup (Second-line)¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
Vitamin B12	Deficiency causes neuropathy and may worsen RLS	>300 pg/mL	-	ROUTINE	ROUTINE	-
Folate	Deficiency associated with RLS; often low with B12	>3 ng/mL	-	ROUTINE	ROUTINE	-
Magnesium	Deficiency can cause leg cramps and muscle symptoms	1.8-2.4 mg/dL	-	ROUTINE	ROUTINE	-
CRP, ESR	Inflammatory markers; chronic inflammation affects iron metabolism	Normal	-	ROUTINE	ROUTINE	-
Comprehensive metabolic panel	Hepatic function; renal clearance	Normal	-	ROUTINE	ROUTINE	-
Pregnancy test (if applicable)	RLS common in pregnancy (up to 25%); affects treatment choices	Negative or positive (determines treatment)	-	ROUTINE	ROUTINE	-

1C. Rare/Specialized (Refractory or Atypical)¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
24-hour urine protein	Nephrotic syndrome workup if renal disease suspected	<150 mg/24hr	-	-	EXT	-
Parathyroid hormone	Hyperparathyroidism can cause RLS	Normal	-	-	EXT	-
Anti-GAD65 antibodies	Autoimmune etiology in atypical cases	Negative	-	-	EXT	-
Paraneoplastic panel	Occult malignancy with neurological symptoms	Negative	-	-	EXT	-
Hemoglobin electrophoresis	Thalassemia trait; chronic hemolytic conditions	Normal	-	-	EXT	-
Vitamin D	Deficiency associated with RLS in some studies	>30 ng/mL	-	-	ROUTINE	-

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Essential/First-line¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
Clinical examination and history	At evaluation	IRLSSG criteria met; no mimicking conditions	None	URGENT	ROUTINE	ROUTINE	-
IRLS Rating Scale (IRLS)	At diagnosis and follow-up	Score 0-40; mild <10, moderate 11-20, severe 21-30, very severe >30	None	-	ROUTINE	ROUTINE	-

2B. Extended¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
Polysomnography (PSG)	If sleep apnea suspected; PLMS quantification	PLMI <15/hr normal; RLS typically >15/hr	None	-	-	ROUTINE	-
EMG/Nerve conduction studies	If peripheral neuropathy suspected (numbness, weakness, areflexia)	Normal or peripheral neuropathy pattern	Pacemaker (relative)	-	-	ROUTINE	-
Actigraphy	Objective assessment of sleep and limb movements	Activity pattern consistent with RLS	None	-	-	EXT	-

2C. Rare/Specialized¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
MRI Brain	Atypical presentation; concern for structural lesion or secondary parkinsonism	Normal	MRI contraindications	-	-	EXT	-
MRI Lumbar spine	Radiculopathy suspected; nerve root compression symptoms	Normal or explains symptoms	MRI contraindications	-	-	EXT	-
Suggested immobilization test (SIT)	Research/specialized; objective RLS measurement	Increased leg movements during immobility	Time-intensive	-	-	EXT	-

3. TREATMENT¶

3A. Acute/Emergent (Severe Symptom Relief)¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Gabapentin	PO	Acute severe symptoms requiring immediate relief	300 mg; 600 mg :: PO :: :: 300-600 mg PO for immediate symptom relief; may repeat once in 4-6 hours	Severe renal impairment (adjust dose)	Sedation, dizziness	URGENT	URGENT	-	-
Pregabalin	PO	Acute severe symptoms; faster onset than gabapentin	75 mg; 150 mg :: PO :: :: 75-150 mg PO for immediate relief; onset 30-60 min	Severe renal impairment (adjust dose)	Sedation, dizziness	URGENT	URGENT	-	-
Oxycodone (severe refractory)	PO	Severe acute symptoms refractory to alpha-2-delta ligands	5 mg :: PO :: :: 5 mg PO once for severe refractory symptoms; short-term only	Respiratory depression; opioid use disorder; concurrent CNS depressants	Respiratory status, sedation	EXT	EXT	-	-

3B. First-line Treatments (Iron Therapy)¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Ferrous sulfate + Vitamin C	PO	First-line if ferritin <75 ng/mL; oral iron repletion	325 mg with 100 mg vitamin C daily; 325 mg with 200 mg vitamin C daily :: PO :: :: 325 mg ferrous sulfate (65 mg elemental iron) with 100-200 mg vitamin C on empty stomach every other day; evening dosing preferred; treat 3-4 months minimum	Hemochromatosis; iron overload; GI bleeding	Ferritin, TSAT at 3-4 months; GI tolerability	-	ROUTINE	ROUTINE	-
Ferrous gluconate	PO	Alternative oral iron if ferrous sulfate not tolerated	325 mg daily; 325 mg BID :: PO :: :: 325 mg (38 mg elemental iron) daily to BID; better GI tolerability; lower elemental iron	Same as above	Same as above	-	ROUTINE	ROUTINE	-
Iron sucrose	IV	Oral iron failure or intolerance; rapid repletion needed; ferritin <75	200 mg per infusion; 200 mg x 5 doses :: IV :: :: 200 mg IV over 15-30 min; give 1000 mg total in 5 divided doses over 2 weeks	Iron overload; hypersensitivity	Ferritin, TSAT at 4-8 weeks; infusion reaction monitoring	-	ROUTINE	ROUTINE	-
Ferric carboxymaltose (Injectafer)	IV	Rapid iron repletion; single or two-dose regimen preferred	750 mg x 2 doses; 1000 mg x 1 dose :: IV :: :: 750 mg IV, repeat in 1 week (max 1500 mg total); OR 1000 mg single dose if weight >50 kg	Hypersensitivity to IV iron	Hypophosphatemia (common); infusion reaction; ferritin at 4-8 weeks	-	ROUTINE	ROUTINE	-
Ferric derisomaltose (Monoferric)	IV	Single-dose IV iron repletion	1000 mg single dose :: IV :: :: 1000 mg IV over 20+ min as single dose; may repeat if needed after 4 weeks	Same as ferric carboxymaltose	Same; lower hypophosphatemia risk	-	ROUTINE	ROUTINE	-

3C. First-line Treatments (Alpha-2-Delta Ligands - Preferred)¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Gabapentin	PO	First-line pharmacotherapy; no augmentation risk; good for pain component	300 mg qHS; 300 mg BID; 600 mg qHS; 300 mg TID; 600 mg BID :: PO :: :: Start 300 mg qHS; titrate by 300 mg q3-7 days; target 600-1800 mg/day in 1-3 doses; max 2400 mg/day; give largest dose in evening	Severe renal impairment (dose adjust); respiratory depression with opioids	Sedation, dizziness, peripheral edema, weight gain; renal function	-	ROUTINE	ROUTINE	-
Gabapentin enacarbil (Horizant)	PO	FDA-approved for RLS; better bioavailability than immediate release gabapentin	600 mg daily :: PO :: :: 600 mg PO once daily at 5 PM with food; no titration needed; extended release formulation	Same as gabapentin; do NOT substitute mg-for-mg with regular gabapentin	Same as gabapentin	-	ROUTINE	ROUTINE	-
Pregabalin	PO	First-line; faster onset than gabapentin; helpful if comorbid anxiety or fibromyalgia	75 mg qHS; 150 mg qHS; 75 mg BID; 150 mg BID; 300 mg qHS :: PO :: :: Start 75 mg qHS; titrate by 75 mg q1wk; target 150-450 mg/day; max 300 mg in evening	Severe renal impairment (adjust dose); avoid abrupt discontinuation	Same as gabapentin; Schedule V controlled	-	ROUTINE	ROUTINE	-

3D. Second-line Treatments (Dopamine Agonists - Use with Caution)¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Pramipexole (Mirapex)	PO	Alpha-2-delta failure/intolerance; use LOWEST effective dose; augmentation risk ~7%/year	0.125 mg qHS; 0.25 mg qHS; 0.5 mg qHS :: PO :: :: Start 0.125 mg 2-3 hrs before symptoms; titrate by 0.125 mg q4-7 days; max 0.5 mg/day for RLS (lower than Parkinson's doses)	Warn patient about augmentation, ICDs	Severe renal impairment (reduce dose by 50% if CrCl <60); pathological gambling risk	AUGMENTATION (symptoms earlier, more intense, spread to arms); impulse control disorders; excessive daytime sleepiness; renal function	-	ROUTINE	ROUTINE	-
Ropinirole (Requip)	PO	Alpha-2-delta failure/intolerance; augmentation risk similar to pramipexole	0.25 mg qHS; 0.5 mg qHS; 1 mg qHS; 2 mg qHS :: PO :: :: Start 0.25 mg 1-3 hrs before symptoms; titrate by 0.25 mg q2-3 days; max 4 mg/day for RLS	Warn patient about augmentation, ICDs	Hepatic impairment; concurrent CYP1A2 inhibitors (adjust dose)	Same as pramipexole; nausea common initially	-	ROUTINE	ROUTINE	-
Rotigotine patch (Neupro)	Transdermal	Once-daily patch; less pulsatile dopaminergic stimulation; may reduce augmentation	1 mg/24hr; 2 mg/24hr; 3 mg/24hr :: Transdermal :: :: Start 1 mg/24hr patch; titrate by 1 mg/24hr weekly; max 3 mg/24hr for RLS	Warn patient about augmentation, ICDs	Sulfite sensitivity; MRI (remove patch - contains aluminum)	Site reactions; augmentation; impulse control disorders	-	-	ROUTINE	-

3E. Third-line/Refractory Treatments¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Tramadol	PO	Refractory RLS; failed alpha-2-delta and dopamine agonists	50 mg qHS; 50 mg BID; 100 mg qHS :: PO :: :: Start 50 mg qHS; max 100 mg BID; use lowest effective dose	Seizure history; concurrent MAOIs/SSRIs (serotonin syndrome); opioid use disorder	Constipation, sedation, nausea; seizure risk; dependence	-	ROUTINE	ROUTINE	-
Oxycodone (low-dose)	PO	Severe refractory RLS; augmentation from dopamine agonists	5 mg qHS; 5 mg BID; 10 mg qHS :: PO :: :: Start 5 mg qHS; max 5-10 mg BID; lowest effective dose; long-term monitoring required	Opioid use disorder; severe respiratory disease; concurrent CNS depressants	Constipation, sedation, dependence; respiratory depression; prescribe conservatively	-	EXT	ROUTINE	-
Oxycodone/naloxone (Targiniq ER)	PO	Refractory RLS with constipation concern	5/2.5 mg BID; 10/5 mg BID :: PO :: :: Start 5/2.5 mg BID; max 20/10 mg BID; naloxone reduces constipation	Same as oxycodone	Same; monitor bowel function	-	-	EXT	-
Methadone	PO	Severe refractory RLS failing other opioids	5 mg qHS; 5 mg BID :: PO :: :: 5 mg qHS to BID; requires experienced prescriber; ECG monitoring for QTc	QTc prolongation; opioid use disorder; respiratory disease	QTc interval; respiratory status; requires DEA registration	-	-	EXT	-
Clonazepam	PO	Adjunct for sleep; helps with PLMS-related arousals	0.25 mg qHS; 0.5 mg qHS; 1 mg qHS :: PO :: :: Start 0.25 mg qHS; max 2 mg qHS; use short-term or intermittently	Fall risk in elderly; respiratory depression; substance use history	Sedation, dependence, falls, cognitive effects; avoid long-term in elderly	-	ROUTINE	ROUTINE	-
Clonidine	PO	Alternative for mild symptoms; alpha-2 agonist	0.1 mg qHS; 0.2 mg qHS :: PO :: :: Start 0.1 mg qHS; max 0.3 mg qHS	Hypotension; bradycardia	BP, HR; rebound hypertension if stopped abruptly	-	-	ROUTINE	-
Buprenorphine patch	Transdermal	Severe refractory RLS; concern for opioid misuse	5 mcg/hr; 10 mcg/hr :: Transdermal :: :: Start 5 mcg/hr weekly patch; titrate slowly	Same as other opioids	Same; requires REMS prescriber certification (changing)	-	-	EXT	-
Dipyridamole	PO	Limited evidence; adenosine modulation	100 mg qHS; 200 mg qHS :: PO :: :: 100-200 mg qHS; off-label; variable response	Hypotension; bleeding disorders	Headache, hypotension	-	-	EXT	-

3F. Augmentation Management¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Dopamine agonist taper	PO	Augmentation from dopamine agonist; must taper slowly	10-25% dose reduction q1-2wk :: PO :: :: Reduce dopamine agonist by 10-25% every 1-2 weeks; expect 1-2 weeks worsening ("washout"); bridge with alpha-2-delta or opioid	Do NOT stop abruptly (dopamine agonist withdrawal syndrome)	Worsening symptoms during taper (expected); DAWS symptoms	-	-	ROUTINE	-
Alpha-2-delta ligand bridge	PO	Cover augmentation symptoms during dopamine agonist taper	Per gabapentin or pregabalin dosing :: PO :: :: Start alpha-2-delta at therapeutic dose before or during dopamine agonist taper; provides symptom coverage	Per individual drug	Sedation; adjust as dopamine agonist tapers	-	-	ROUTINE	-
Low-dose opioid bridge	PO	Severe augmentation; alpha-2-delta insufficient	Per tramadol or oxycodone dosing :: PO :: :: Short-term opioid coverage during dopamine agonist washout; plan transition to non-dopaminergic maintenance	History of opioid use disorder	Dependence; use short-term	-	-	ROUTINE	-

4. OTHER RECOMMENDATIONS¶

4A. Referrals & Consults¶

Recommendation	ED	HOSP	OPD	ICU
Sleep medicine referral for polysomnography if sleep apnea suspected or PLMS quantification needed	-	-	ROUTINE	-
Neurology/movement disorders consultation for refractory RLS or diagnostic uncertainty	-	ROUTINE	ROUTINE	-
Hematology referral for IV iron infusion coordination or complex iron deficiency management	-	-	ROUTINE	-
Pain management consultation for severe refractory cases requiring opioid therapy	-	-	ROUTINE	-
Nephrology referral if chronic kidney disease contributing to secondary RLS	-	ROUTINE	ROUTINE	-
Psychiatry consultation if impulse control disorders develop on dopamine agonist therapy	-	-	ROUTINE	-
OB/GYN coordination for RLS management during pregnancy (common; limits treatment options)	-	ROUTINE	ROUTINE	-

4B. Patient Instructions¶

Recommendation	ED	HOSP	OPD
Take iron supplements on an empty stomach every other day (better absorption) with vitamin C; avoid taking with calcium, coffee, or tea	-	ROUTINE	ROUTINE
Take evening medications 2-3 hours before typical symptom onset for best effect	-	ROUTINE	ROUTINE
Report symptoms spreading to arms, occurring earlier in day, or becoming more intense (signs of augmentation)	-	ROUTINE	ROUTINE
Report new gambling urges, compulsive shopping, or hypersexuality if taking dopamine agonists (impulse control disorders)	-	ROUTINE	ROUTINE
Avoid antihistamines (diphenhydramine, Benadryl) which significantly worsen RLS - use alternatives for allergies or sleep	-	ROUTINE	ROUTINE
Inform prescribers about RLS before starting new medications as many can worsen symptoms	-	ROUTINE	ROUTINE
Keep a symptom diary tracking severity, timing, and potential triggers to optimize treatment	-	-	ROUTINE
Return if symptoms become severe enough to affect sleep, daytime function, or quality of life	ROUTINE	ROUTINE	ROUTINE

4C. Lifestyle & Prevention¶

Recommendation	ED	HOSP	OPD
Avoid caffeine especially in afternoon and evening as it worsens RLS symptoms	-	ROUTINE	ROUTINE
Limit or avoid alcohol which disrupts sleep architecture and can worsen RLS	-	ROUTINE	ROUTINE
Avoid nicotine/smoking which can exacerbate symptoms through vasoconstriction and sleep disruption	-	ROUTINE	ROUTINE
Regular moderate exercise (walking, swimming, yoga) earlier in day reduces symptoms; avoid vigorous exercise near bedtime	-	ROUTINE	ROUTINE
Maintain regular sleep schedule with consistent bed and wake times (sleep hygiene)	-	ROUTINE	ROUTINE
Leg massage, warm baths, or heating pads in the evening may provide temporary symptomatic relief	-	ROUTINE	ROUTINE
Cooling measures (cold compresses, leg wraps) may help some patients	-	-	ROUTINE
Mental distraction activities (engaging video games, puzzles) can reduce symptom awareness	-	ROUTINE	ROUTINE
Compression stockings or pneumatic compression may provide relief in some patients	-	-	ROUTINE
Review all current medications with provider to identify and eliminate RLS-exacerbating drugs	-	ROUTINE	ROUTINE

Medications to AVOID in RLS¶

Medication Class	Examples	Effect on RLS
Antihistamines (first-generation)	Diphenhydramine (Benadryl), hydroxyzine, promethazine, chlorpheniramine	Significantly worsen RLS; block dopamine
Antidopaminergic antiemetics	Metoclopramide (Reglan), prochlorperazine (Compazine)	Strong RLS exacerbation; block dopamine
Typical antipsychotics	Haloperidol, chlorpromazine	Severe RLS worsening; dopamine blockade
Atypical antipsychotics	Olanzapine, quetiapine, risperidone	Can worsen RLS; less than typicals
SSRIs	Sertraline, fluoxetine, paroxetine, citalopram	May worsen RLS in 10-20% of patients
SNRIs	Venlafaxine, duloxetine	Similar to SSRIs; variable effect
TCAs	Amitriptyline, nortriptyline	Can worsen RLS; antihistaminic effects
Lithium	Lithium carbonate	May exacerbate RLS
Sedating antihistamines in OTC sleep aids	ZzzQuil, Tylenol PM, Advil PM	Major RLS trigger

Safer alternatives when possible: - For allergies: Non-sedating antihistamines (cetirizine, loratadine, fexofenadine) - For nausea: Ondansetron, ginger - For depression: Bupropion (least likely to worsen), mirtazapine may be neutral - For sleep: Trazodone, melatonin, alpha-2-delta ligands

SECTION B: REFERENCE¶

5. DIFFERENTIAL DIAGNOSIS¶

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Nocturnal leg cramps	Painful muscle contraction; visible/palpable muscle tightness; no urge to move	Clinical history; no relief with movement
Peripheral neuropathy	Numbness, tingling, burning in stocking-glove distribution; not circadian	EMG/NCS; exam findings (reflexes, sensation)
Akathisia	Inner restlessness; not limited to legs; associated with antipsychotic use	Medication history; generalized restlessness
Positional discomfort	Relieved by position change; no urge to move specifically	Clinical history
Periodic limb movement disorder (PLMD)	PLMS without RLS symptoms; bed partner may report jerking	PSG shows PLMS; no waking leg discomfort
Venous insufficiency	Aching worse with standing; varicosities visible; edema	Doppler ultrasound; worse during day
Arthritis (hip, knee, ankle)	Joint pain; stiffness; localized to joints	X-ray; rheumatologic workup
Radiculopathy/sciatica	Dermatomal pattern; worsened by spine movement; back pain	MRI spine; positive straight leg raise
Growing pains (pediatric)	Children; bilateral leg pain; no urge to move	Clinical history; self-limited
Fibromyalgia	Widespread pain; tender points; fatigue	Clinical criteria; no specific test
Anxiety/stress-related symptoms	Generalized restlessness; racing thoughts; no circadian pattern	Psychiatric evaluation
Drug-induced restlessness	Temporal relationship with offending medication	Medication review; trial withdrawal

6. MONITORING PARAMETERS¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
IRLS severity scale	Each visit	Score reduction >50% from baseline	Titrate medication; consider alternative agent	-	ROUTINE	ROUTINE	-
Sleep quality (subjective and actigraphy if available)	Each visit	Improved sleep; reduced awakenings	Assess compliance; consider adjuncts	-	ROUTINE	ROUTINE	-
Ferritin level	Every 3-4 months during repletion; annually when stable	>75 ng/mL (target >100)	Continue or restart iron supplementation	-	ROUTINE	ROUTINE	-
Transferrin saturation	With ferritin	>20%	Continue iron therapy	-	ROUTINE	ROUTINE	-
Augmentation assessment	Each visit if on dopamine agonist	No symptoms earlier in day; no spread to arms; no dose escalation need	Taper dopamine agonist; switch to non-dopaminergic	-	ROUTINE	ROUTINE	-
Impulse control disorders (ICDs)	Each visit if on dopamine agonist	No gambling, hypersexuality, compulsive shopping, binge eating	Stop or reduce dopamine agonist	-	ROUTINE	ROUTINE	-
Daytime somnolence	Each visit	ESS <10	Reduce dose; evaluate for sleep apnea	-	ROUTINE	ROUTINE	-
Renal function (if on gabapentin/pregabalin)	Annually or with changes	eGFR-appropriate dosing	Dose adjust per renal function	-	ROUTINE	ROUTINE	-
Weight, edema (if on gabapentin/pregabalin)	Each visit	Stable or acceptable	Dose reduction; switch agent	-	ROUTINE	ROUTINE	-
QTc (if on methadone)	Baseline, 2-4 weeks, annually	<500 msec	Reduce dose; consider alternative	-	-	ROUTINE	-

7. DISPOSITION CRITERIA¶

Disposition	Criteria
Discharge home with outpatient follow-up	Typical RLS diagnosis; initial workup ordered; treatment started or planned; follow-up arranged
Outpatient management (primary)	All patients with RLS; return 2-4 weeks for medication titration; then q3-6 months when stable
Admit to hospital (rare)	Severe refractory RLS preventing all sleep (unusual); IV iron infusion coordination if outpatient not available; acute decompensation with comorbidities
ED evaluation	Rarely needed; may see for severe acute symptoms or secondary cause evaluation

8. EVIDENCE & REFERENCES¶

Recommendation	Evidence Level	Source
Alpha-2-delta ligands (gabapentin, pregabalin) first-line for RLS	Class I, Level A	Silber et al. Mayo Clin Proc 2021
Gabapentin enacarbil FDA-approved for RLS	Class I, Level A	Kushida et al. Neurology 2009
Pregabalin effective for RLS	Class I, Level A	Allen et al. Sleep Med 2014
Iron supplementation if ferritin <75 ng/mL	Class I, Level A	Allen et al. Sleep Med 2018
IV iron effective for RLS with iron deficiency	Class I, Level B	Trotti et al. J Clin Sleep Med 2012
Dopamine agonist augmentation risk	Class II, Level B	Garcia-Borreguero et al. Sleep Med 2016
Low-dose opioids for refractory RLS	Class II, Level B	Trenkwalder et al. Lancet Neurol 2013
IRLSSG diagnostic criteria	Consensus, Level A	Allen et al. Sleep Med 2014
Dopamine agonists effective but augmentation concern	Class I, Level A	Silber et al. Mayo Clin Proc 2013
Pregnancy-associated RLS prevalence up to 25%	Class II, Level B	Manconi et al. Neurology 2004
Medications that worsen RLS	Class II-III, Level B-C	Mackie & Winkelman. Drugs 2015
Long-term management recommendations	Consensus, Level C	Garcia-Borreguero et al. Sleep Med Rev 2013

CHANGE LOG¶

v1.0 (January 27, 2026) - Initial template creation - Comprehensive iron therapy section with oral and IV options - Alpha-2-delta ligands emphasized as first-line (lower augmentation risk than dopamine agonists) - Detailed augmentation management section - Medications to avoid table - IRLSSG diagnostic criteria included - Structured dosing format for order sentence generation - Outpatient-focused with limited ED/HOSP coverage for severe cases

APPENDIX A: Augmentation Recognition and Management Algorithm¶

Signs of Augmentation (EURLSSG Criteria): 1. Symptoms occur 2+ hours earlier than before treatment 2. Symptoms are more intense than before treatment started 3. Symptoms spread to previously unaffected body parts (arms, trunk) 4. Shorter latency to symptoms at rest 5. Shorter duration of medication effect 6. Periodic limb movements worsen during wakefulness

Management Steps: 1. Confirm augmentation (not tolerance, progression, or noncompliance) 2. Check and optimize iron stores (ferritin >100 ng/mL) 3. Reduce dopamine agonist dose by 25-50% 4. If augmentation persists: taper and discontinue dopamine agonist over 2-4 weeks 5. Bridge with alpha-2-delta ligand or low-dose opioid 6. Expect 1-2 weeks of symptom worsening during washout 7. Transition to non-dopaminergic maintenance (alpha-2-delta preferred) 8. If severe: may need temporary opioid bridge during transition

Prevention: - Use lowest effective dopamine agonist dose - Prefer alpha-2-delta ligands as first-line - Monitor iron status and supplement to keep ferritin >75-100 - Avoid early dose escalation of dopamine agonists

APPENDIX B: RLS in Special Populations¶

Pregnancy¶

RLS affects up to 25% of pregnant women, especially 3rd trimester
Usually resolves within weeks postpartum
Treatment options limited:
First-line: Iron supplementation (safe in pregnancy)
Non-pharmacologic measures
Clonazepam (pregnancy category D - avoid if possible)
Alpha-2-delta ligands not well-studied in pregnancy
Dopamine agonists: limited data, generally avoided

Chronic Kidney Disease¶

RLS prevalence 20-40% in dialysis patients
Iron deficiency common; IV iron often needed
Dose adjust gabapentin/pregabalin for renal function
Dopamine agonists can be used (less augmentation concern in this population)
May improve after renal transplant

Pediatric RLS¶

Often misdiagnosed as "growing pains" or ADHD
Strong genetic component; family history important
Iron deficiency common; check ferritin (target >50)
Non-pharmacologic first; limited pediatric drug data
Gabapentin most commonly used off-label

Parkinson's Disease Coexistence¶

RLS can coexist with Parkinson's disease
May be difficult to distinguish from Parkinson's symptoms
Parkinson's medications may treat or worsen RLS
DaTscan can help differentiate if unclear