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neuro.restless-legs.v1PRODUCTION
neuro.restless-legs.v1

Restless Legs Syndrome / Willis–Ekbom Disease

neurologychronicadultpregnancygeriatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

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Detailed

Chronic urge-to-move-legs with a circadian rest/evening-night pattern partially/totally relieved by movement — clinical RLS/WED by the IRLSSG five essential criteria; classify primary/idiopathic vs secondary (iron deficiency / CKD-ESRD / pregnancy / drug-induced) (AASM 2025 PMID 39324694)

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All five IRLSSG essential criteria met (else re-route to mimic)

Patient inputs (18)

Prevalence rises with age; geriatric → dopamine-agonist ICD/sleep-attacks/falls + gabapentinoid sedation/fall risk (STOPP) — dose-reduce

Prior/current dopamine-agonist or levodopa exposure → screen for augmentation (the central long-term hazard) + impulse-control disorder (~17%; Cornelius 2010 PMID 20120624)

Pregnancy-associated RLS very common 3rd trimester, usually remits postpartum — iron/folate + non-pharm first; most drugs avoided; OB co-management (Silber 2021 PMID 34218864)

CKD/ESRD/dialysis = high-prevalence secondary RLS — IV iron preferred; gabapentinoid accumulates → marked renal dose-reduction; route neph.ckd.core.v1

Antihistamines, dopamine antagonists/antiemetics, most antidepressants (esp. mirtazapine/SSRI/SNRI), antipsychotics, alcohol, caffeine, nicotine worsen RLS — bupropion is RLS-neutral/beneficial (preferred in RLS + depression)

Relief by movement distinguishes RLS from neuropathy (NOT relieved), cramps (relieved by stretch not walking), and positional discomfort

RLS is a CLINICAL diagnosis — all five IRLSSG essential criteria must be met (urge±sensation, worse at rest, relieved by movement, evening/night, not solely a mimic); any absent → re-route to mimic (AASM 2025 PMID 39324694)

MANDATORY in ALL patients — brain iron deficiency is the central RLS pathophysiology; treat iron when ferritin ≤75 ng/mL (oral, if TSAT >20%) (IRLSSG iron consensus PMID 29425576)

MANDATORY with ferritin — treat iron when TSAT <20% (or ferritin ≤75); IV iron if ferritin ≤100 or oral inappropriate; ferritin is an acute-phase reactant so TSAT is load-bearing in inflammation/CKD (PMID 29425576)

Identify iron-deficiency anemia / microcytic pattern; route heme.iron-deficiency-anemia.core.v1 for source workup if overt IDA

eGFR (CKD-EPI 2021) — CKD secondary cause + drives renal-adjusted gabapentinoid dosing (gabapentin enacarbil avoid if CrCl <30; gabapentin/pregabalin renal-adjust)

On dopaminergic therapy: symptoms EARLIER in day / more intense / spreading / shorter rest-latency — especially after a dose increase = augmentation, NOT undertreatment; do NOT increase dose (Garcia-Borreguero 2016 PMID 27448465)

Pathological gambling/shopping/hypersexuality/binge-eating/punding on a dopamine agonist (~17% any ICD; Cornelius 2010 PMID 20120624) → discontinue/rotate agonist

Frequency + IRLS-band severity (intermittent vs chronic-persistent clinically significant ≥2-3×/wk + sleep/QoL impact) drives pharmacotherapy candidacy (calc.irls schema-blocked — encoded narratively)

Stocking-distribution sensory loss / burning NOT relieved by movement → peripheral neuropathy mimic + possible secondary cause → route neuro.peripheral-neuropathy.v1

Polysomnography ONLY if diagnosis unclear/atypical/refractory or OSA suspected — quantifies PLMS index (PLMD); not required for typical clinical RLS

RLS-depression/anxiety comorbidity common (bidirectional with sleep loss); avoid mirtazapine/SSRI/SNRI worsening — use bupropion; PHQ-9/GAD-7 screen

Hypothyroidism is a screenable secondary contributor; thyroid panel in the secondary-cause workup

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Severity triggers (9)

9 need judgement
  • informationalsevereaugmentation_on_dopaminergic_therapy
    Augmentation on dopaminergic therapy — RLS symptoms now occurring EARLIER in the day, MORE intense, SPREADING to other body parts, or shorter rest-latency, especially after a dose increase; the central long-term hazard of dopaminergic RLS therapy (Garcia-Borreguero 2016 PMID 27448465)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereimpulse_control_disorder_on_dopamine_agonist
    Impulse-control disorder on a dopamine agonist — pathological gambling, compulsive shopping, hypersexuality, binge-eating, or punding (~17% any ICD on dopaminergic RLS therapy; Cornelius 2010 PMID 20120624)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_refractory_rls_qol_collapse
    Severe refractory RLS with major sleep deprivation and quality-of-life collapse despite iron repletion + adequate alpha-2-delta (± dopamine-agonist rotation) — specialist + low-dose opioid pathway
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereaugmentation_deprescribing_trigger
    Augmentation-deprescribing trigger (quantified): on long-term short-acting dopaminergic therapy, augmentation accrues at ~5-8%/yr cumulatively (up to ~40-70% over years on levodopa/short-acting dopamine agonists; Garcia-Borreguero 2016 PMID 27448465) — once augmentation criteria are met, DEPRESCRIBE the dopaminergic (do NOT up-titrate). Switching pramipexole 0.5 mg → pregabalin reduced 40-52-wk augmentation from 7.7% to 2.1% (Allen NEJM 2014 PMID 24521108). Action: ensure ferritin/TSAT repleted (ferritin ≤75 / TSAT <20% per IRLSSG iron consensus PMID 29425576), cross-taper OFF the dopamine agonist over 1-2 wk, bridge to an alpha-2-delta ligand and/or low-dose prolonged-release oxycodone-naloxone (Trenkwalder 2013 PMID 24140442 — IRLS 31.7→15.1 vs placebo 31.6→22.1 at wk 12, n=304).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateiron_threshold_met
    Serum ferritin ≤75 ng/mL OR transferrin saturation <20% — iron-treatment threshold met (brain iron deficiency is the central RLS pathophysiology; IRLSSG iron consensus PMID 29425576)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatepregnancy_severe_rls
    Severe pregnancy-associated RLS (very common 3rd trimester) — non-pharm + iron/folate first; most drugs avoided; low-dose clonazepam or low-dose opioid or gabapentin only if severe and OB/specialist co-managed; usually remits postpartum (Silber 2021 PMID 34218864)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateckd_esrd_secondary_rls
    CKD/ESRD/dialysis-associated RLS — high prevalence; IV iron preferred; alpha-2-delta ligands accumulate in renal failure → marked dose-reduction; rotigotine an option
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderategeriatric_da_icd_and_fall_risk
    Geriatric RLS pharmacotherapy hazard (quantified): impulse-control disorder occurs in ~17% of patients on dopaminergic RLS therapy (9% compulsive shopping, 11% compulsive eating, 5% pathological gambling, 3% hypersexuality, 7% punding; Cornelius 2010 PMID 20120624 case-control). Gabapentinoids and dopamine agonists add sedation/orthostasis/sleep-attack fall risk (STOPP). In the elderly: dopamine agonists NOT first-line — use lowest effective alpha-2-delta dose (renal-adjusted), prefer rotigotine patch (stable plasma level → lower augmentation) over short-acting oral agonists if a dopaminergic is unavoidable, AVOID clonazepam (STOPP).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatepregnancy_rls_quantified_branch
    Pregnancy-associated RLS (quantified branch): prevalence peaks in the 3rd trimester (~2-3× the non-pregnant rate) and usually remits within days-weeks postpartum (Silber 2021 PMID 34218864). First-line is low-dose IRON (oral ferrous sulfate if ferritin ≤75 ng/mL & TSAT >20%; IV iron if oral inappropriate) + folate + non-pharm; AVOID dopamine agonists and gabapentinoids in pregnancy (insufficient/teratogenicity-uncertain data) — if severe and OB/sleep-specialist co-managed, a LOW-DOSE OPIOID (or low-dose clonazepam) only. Reassess postpartum and DEPRESCRIBE on remission.
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

RLS/WED chronic management — iron repletion → alpha-2-delta first-line → dopamine agonist limited → low-dose opioid refractory (AASM 2025 PMID 39324694; IRLSSG iron PMID 29425576; Garcia-Borreguero 2016 PMID 27448465)
axis: rls_managementstep 1 - Step 1 — Iron repletion + non-pharm + remove aggravators (ferritin ≤75 ng/mL or TSAT <20%; IRLSSG iron consensus Allen 2018 PMID 29425576; AAN 2016 Level B PMID 27856776)
Selected step "Step 1 — Iron repletion + non-pharm + remove aggravators (ferritin ≤75 ng/mL or TSAT <20%; IRLSSG iron consensus Allen 2018 PMID 29425576; AAN 2016 Level B PMID 27856776)" — ALL patients — serum ferritin + TSAT mandatory; iron treatment when ferritin ≤75 ng/mL (oral if TSAT >20%) or TSAT <20%; remove RLS-aggravating drugs; non-pharm measures
  • ferrous sulfate
    first line
    oral_iron_salt
    325 mg (≈65 mg elemental iron) + vitamin C 100-200 mg, alternate-day single dose (maximises fractional absorption — cross-ref heme.iron-deficiency-anemia.core.v1) • PO • every other day
    triggers: ferritin_<=75_and_TSAT_>20
    IRLSSG iron consensus PMID 29425576 — oral iron when ferritin ≤75 ng/mL & TSAT >20%; AAN 2016 Level B (ferrous sulfate + vitamin C) PMID 27856776; alternate-day dosing blunts hepcidin (cross-ref heme.iron-deficiency-anemia.core.v1)
    rxcui 24947
  • ferric carboxymaltose
    first line
    IV_iron
    750-1000 mg IV (per weight/regimen); recheck ferritin/TSAT before re-dosing • IV • single/two-dose course
    triggers: oral_iron_ineffective_or_intolerant, malabsorption, rapid_response_needed, ckd_or_esrd, TSAT_<20_or_ferritin_<=100
    FCM RCT IRLS decrease 8.9 vs 4.0, CGI-I much/very-much improved 48.3% vs 14.3% (corroborated PMID 28643901); IRLSSG iron consensus PMID 29425576 — IV iron when oral inappropriate / ferritin ≤100; strong evidence; preferred in CKD
    rxcui 1433693
  • iron sucrose
    second line
    IV_iron
    200 mg IV per session, multiple sessions to target dose • IV • multiple sessions
    triggers: fcm_unavailable_or_contraindicated, ckd_dialysis_unit_protocol
    Alternative IV iron — IRLSSG iron consensus PMID 29425576; often the dialysis-unit formulary IV iron
    rxcui 24909
  • IV iron infusion procedure + premedication/monitoring
    first line
    procedure
    triggers: iv_iron_indicated
    Infusion-reaction monitoring; hypophosphataemia surveillance with repeated FCM (cross-ref heme.iron-deficiency-anemia.core.v1)
  • sleep hygiene + moderate exercise + avoid evening caffeine/alcohol/nicotine
    first line
    lifestyle
    triggers: all_rls_patients
    Foundational non-pharmacologic measures (AASM 2025 PMID 39324694; Silber 2021 PMID 34218864)
  • withdraw RLS-aggravating drugs
    first line
    deprescribing
    triggers: aggravating_drug_present
    Antihistamines, dopamine antagonists/antiemetics, mirtazapine/SSRI/SNRI, antipsychotics, alcohol/caffeine/nicotine worsen RLS; switch antidepressant to bupropion (RxCUI 42347; RLS-neutral/beneficial)
  • pneumatic compression device
    second line
    device
    triggers: non_pharmacologic_approach_desired
    AAN 2016 Level B (PMID 27856776) — consider when a non-pharmacologic approach is desired; NIRS / rTMS Level C

outpatient playbook — drug actions (4)

  1. 1. ferrous sulfate 325 mg + vitamin C
    rxcui 24947
    325 mg + vitamin C 100-200 mg • PO • every other day
    trigger: Ferritin ≤75 ng/mL & TSAT >20%
    IRLSSG iron consensus PMID 29425576; AAN 2016 Level B PMID 27856776 — iron repletion FIRST in all patients
  2. 2. gabapentin enacarbil
    rxcui 1101333
    600 mg • PO • once daily ~5 pm
    trigger: Chronic-persistent clinically-significant RLS
    AASM 2025 STRONG first-line (PMID 39324694) — preferred over dopamine agonists (no augmentation)
  3. 3. gabapentin OR pregabalin (alternative alpha-2-delta)
    rxcui 25480
    Gabapentin 300 mg QHS titrate / pregabalin 150-300 mg QHS • PO • QHS
    trigger: Gabapentin enacarbil unavailable/intolerant; renal-adjust in CKD
    AASM 2025 conditional (PMID 39324694); Allen NEJM 2014 (PMID 24521108) — low augmentation
  4. 4. switch aggravating antidepressant to bupropion
    rxcui 42347
    Per depression protocol • PO • daily
    trigger: On mirtazapine/SSRI/SNRI with RLS + depression comorbidity
    Bupropion is RLS-neutral/beneficial — preferred antidepressant in RLS

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Urge to move the legs, usually with/caused by an uncomfortable or unpleasant leg sensation (IRLSSG essential criterion 1; AASM 2025 PMID 39324694); Symptoms begin or worsen during rest or inactivity (sitting, lying — criterion 2); Partial or total relief by movement (walking, stretching) at least as long as the activity continues (criterion 3).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Restless Legs Syndrome / Willis–Ekbom Disease** (neuro.restless-legs.v1).
Phenotype framing: Primary/idiopathic vs secondary (iron deficiency / CKD-ESRD / pregnancy / drug-induced); mimics — nocturnal leg cramps (relieved by stretch not walking), akathisia (drug-induced, no circadian, not relieved by movement — route off offender), peripheral neuropathy (sensory loss, not relieved by movement), positional discomfort, PAD/venous, arthritis, myelopathy, anxiety; PLMD/PLMS association
Scope: Chronic urge-to-move-legs with a circadian rest/evening-night pattern partially/totally relieved by movement — clinical RLS/WED by the IRLSSG five essential criteria; classify primary/idiopathic vs secondary (iron deficiency / CKD-ESRD / pregnancy / drug-induced) (AASM 2025 PMID 39324694)

No severity triggers fired against current inputs.

Plan

Regimen axis: **RLS/WED chronic management — iron repletion → alpha-2-delta first-line → dopamine agonist limited → low-dose opioid refractory (AASM 2025 PMID 39324694; IRLSSG iron PMID 29425576; Garcia-Borreguero 2016 PMID 27448465)** — step "Step 1 — Iron repletion + non-pharm + remove aggravators (ferritin ≤75 ng/mL or TSAT <20%; IRLSSG iron consensus Allen 2018 PMID 29425576; AAN 2016 Level B PMID 27856776)".
1. ferrous sulfate 325 mg (≈65 mg elemental iron) + vitamin C 100-200 mg, alternate-day single dose (maximises fractional absorption — cross-ref heme.iron-deficiency-anemia.core.v1) PO every other day (oral_iron_salt, first line) — IRLSSG iron consensus PMID 29425576 — oral iron when ferritin ≤75 ng/mL & TSAT >20%; AAN 2016 Level B (ferrous sulfate + vitamin C) PMID 27856776; alternate-day dosing blunts hepcidin (cross-ref heme.iron-deficiency-anemia.core.v1)
2. ferric carboxymaltose 750-1000 mg IV (per weight/regimen); recheck ferritin/TSAT before re-dosing IV single/two-dose course (IV_iron, first line) — FCM RCT IRLS decrease 8.9 vs 4.0, CGI-I much/very-much improved 48.3% vs 14.3% (corroborated PMID 28643901); IRLSSG iron consensus PMID 29425576 — IV iron when oral inappropriate / ferritin ≤100; strong evidence; preferred in CKD
3. iron sucrose 200 mg IV per session, multiple sessions to target dose IV multiple sessions (IV_iron, second line) — Alternative IV iron — IRLSSG iron consensus PMID 29425576; often the dialysis-unit formulary IV iron
4. IV iron infusion procedure + premedication/monitoring (procedure, first line) — Infusion-reaction monitoring; hypophosphataemia surveillance with repeated FCM (cross-ref heme.iron-deficiency-anemia.core.v1)
5. sleep hygiene + moderate exercise + avoid evening caffeine/alcohol/nicotine (lifestyle, first line) — Foundational non-pharmacologic measures (AASM 2025 PMID 39324694; Silber 2021 PMID 34218864)
6. withdraw RLS-aggravating drugs (deprescribing, first line) — Antihistamines, dopamine antagonists/antiemetics, mirtazapine/SSRI/SNRI, antipsychotics, alcohol/caffeine/nicotine worsen RLS; switch antidepressant to bupropion (RxCUI 42347; RLS-neutral/beneficial)
7. pneumatic compression device (device, second line) — AAN 2016 Level B (PMID 27856776) — consider when a non-pharmacologic approach is desired; NIRS / rTMS Level C

Setting playbook (outpatient) — Primary-care diagnosis (IRLSSG 5 criteria), MANDATORY ferritin + TSAT, iron repletion, remove aggravators, non-pharm, and initiate alpha-2-delta first-line pharmacotherapy for chronic-persistent clinically-significant RLS
8. ferrous sulfate 325 mg + vitamin C 325 mg + vitamin C 100-200 mg PO every other day — Ferritin ≤75 ng/mL & TSAT >20% (IRLSSG iron consensus PMID 29425576; AAN 2016 Level B PMID 27856776 — iron repletion FIRST in all patients)
9. gabapentin enacarbil 600 mg PO once daily ~5 pm — Chronic-persistent clinically-significant RLS (AASM 2025 STRONG first-line (PMID 39324694) — preferred over dopamine agonists (no augmentation))
10. gabapentin OR pregabalin (alternative alpha-2-delta) Gabapentin 300 mg QHS titrate / pregabalin 150-300 mg QHS PO QHS — Gabapentin enacarbil unavailable/intolerant; renal-adjust in CKD (AASM 2025 conditional (PMID 39324694); Allen NEJM 2014 (PMID 24521108) — low augmentation)
11. switch aggravating antidepressant to bupropion Per depression protocol PO daily — On mirtazapine/SSRI/SNRI with RLS + depression comorbidity (Bupropion is RLS-neutral/beneficial — preferred antidepressant in RLS)

Non-pharmacologic actions:
- Sleep hygiene, moderate exercise, avoid evening caffeine/alcohol/nicotine
- Withdraw RLS-aggravating drugs where feasible
- Pneumatic compression if non-pharmacologic approach desired (AAN 2016 Level B)
- Patient education: augmentation warning signs if dopaminergic ever started; symptom diary

AVOID / contraindication checks:
- Serum_ferritin_AND_TSAT_mandatory_in_ALL_patients (brain iron deficiency is central; IRLSSG iron consensus PMID 29425576)
- Iron_repletion_FIRST_when_ferritin_<=75_or_TSAT_<20; IV_FCM_if_oral_inappropriate_or_ferritin_<=100_or_CKD (PMID 29425576; AAN 2016 PMID 27856776)
- Alpha_2_delta_ligand_FIRST_LINE_over_dopamine_agonist_due_to_augmentation (AASM 2025 PMID 39324694; Garcia Borreguero 2016 PMID 27448465)
- AVOID_levodopa_for_daily_therapy_highest_augmentation_intermittent_PRN_only (Garcia Borreguero 2016 PMID 27448465)
- Dopamine_agonist_augmentation_recognition_do_NOT_increase_dose_rotate_off_ensure_iron_repleted_switch_alpha2delta_or_opioid (PMID 27448465; AASM 2025 PMID 39324694)
- Screen_impulse_control_disorder_on_dopamine_agonist_~17%_any_ICD_discontinue_if_present (Cornelius 2010 PMID 20120624)
- Dopamine_agonist_sleep_attacks_counsel_driving (AASM 2025 PMID 39324694)
- Gabapentinoid_renal_dose_adjust_avoid_gabapentin_enacarbil_if_CrCl_<30_marked_reduction_in_CKD_dialysis (accumulation)
- Gabapentinoid_and_dopamine_agonist_sedation_fall_risk_in_elderly_STOPP_dose_reduce (route symptom.falls.v1)
- Avoid_RLS_aggravating_drugs_antihistamines_dopamine_antagonists_mirtazapine_SSRI_SNRI_antipsychotics_alcohol_caffeine_nicotine; use_bupropion_in_RLS_plus_depression
- Opioid_stewardship_treatment_agreement_QT_respiratory_dependence_monitoring; tramadol_can_itself_cause_augmentation (PMID 27448465)
- Pregnancy_RLS_iron_folate_and_non_pharm_first_most_drugs_avoided_OB_co_management_usually_remits_postpartum (Silber 2021 PMID 34218864)
- CKD_ESRD_dialysis_IV_iron_preferred_renal_adjusted_gabapentinoid (route neph.ckd.core.v1)

Monitoring

Regimen monitoring:
- Serum ferritin + TSAT response; recheck 8-12 wk after repletion and before any repeat IV iron dose
- AUGMENTATION surveillance at EVERY visit on any dopaminergic agent (earlier onset / greater intensity / anatomic spread / shorter rest-latency — especially post-dose-increase)
- Impulse-control-disorder screen at every visit on a dopamine agonist (gambling/shopping/hypersexuality/binge-eating/punding)
- Renal-adjusted gabapentinoid dose review when eGFR changes; CKD/dialysis dose-reduction
- Sedation / fall risk surveillance in elderly on gabapentinoid or dopamine agonist (STOPP — symptom.falls.v1)
- Symptom-diary / IRLS-band re-grade for treatment response (calc.irls schema-blocked — narrative)
- Hypophosphataemia surveillance with repeated ferric carboxymaltose
- Opioid stewardship review (dose, function, misuse) if on opioid
- Pregnancy: re-evaluate postpartum for remission and de-prescribing

Setting (outpatient) monitoring:
- Ferritin/TSAT recheck 8-12 wk after repletion
- Symptom-diary / IRLS-band re-grade at follow-up
- Renal function for gabapentinoid dose; sedation/fall risk in elderly (STOPP)

Follow-up plan: Iron recheck 8-12 wk after repletion (and before re-dosing IV iron); titrate alpha-2-delta to effect; pregnancy RLS usually remits postpartum (de-prescribe); periodic aggravator review; long-term opioid stewardship; re-evaluate diagnosis if refractory despite repletion + adequate first-line therapy
- Close-out criterion: Response documented; de-prescribing / escalation / re-evaluation routed

Monitoring phase: Ferritin/TSAT response + recheck; AUGMENTATION surveillance at every visit on any dopaminergic agent; ICD screening on dopamine agonists; renal-adjusted gabapentinoid dose + sedation/fall surveillance (elderly STOPP — route symptom.falls.v1); symptom-diary / IRLS-band re-grade; opioid stewardship if on opioid

Disposition

Current setting: outpatient — Primary-care diagnosis (IRLSSG 5 criteria), MANDATORY ferritin + TSAT, iron repletion, remove aggravators, non-pharm, and initiate alpha-2-delta first-line pharmacotherapy for chronic-persistent clinically-significant RLS

Disposition criteria:
- Stable on iron repletion ± alpha-2-delta with adequate control → continue primary-care management with periodic review
- Refractory / augmentation-complicated / ICD / severe pregnancy / ESRD → refer to specialist (transition handoff)

Escalation triggers (move to higher acuity):
- Refractory despite iron repletion + adequate alpha-2-delta → sleep-medicine/neurology referral
- Augmentation on any dopaminergic agent → specialist
- Impulse-control disorder on dopamine agonist → discontinue + specialist
- Severe pregnancy RLS → OB co-management + specialist
- CKD/ESRD secondary RLS → nephrology (neph.ckd.core.v1)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [SEVERE] Augmentation on dopaminergic therapy — RLS symptoms now occurring EARLIER in the day, MORE intense, SPREADING to other body parts, or shorter rest-latency, especially after a dose increase; the central long-term hazard of dopaminergic RLS therapy (Garcia-Borreguero 2016 PMID 27448465)
- [SEVERE] Impulse-control disorder on a dopamine agonist — pathological gambling, compulsive shopping, hypersexuality, binge-eating, or punding (~17% any ICD on dopaminergic RLS therapy; Cornelius 2010 PMID 20120624)
- [SEVERE] Severe refractory RLS with major sleep deprivation and quality-of-life collapse despite iron repletion + adequate alpha-2-delta (± dopamine-agonist rotation) — specialist + low-dose opioid pathway

Citations

- 2025 AASM Clinical Practice Guideline — Treatment of RLS and PLMD (Winkelman, JCSM 2025; NEWEST — primary floor) + AASM 2025 systematic review/meta-analysis/GRADE + AAN 2016 practice guideline + IRLSSG iron-treatment consensus (Allen 2018) + IRLSSG/EURLSSG/RLS-F first-line + augmentation guideline (Garcia-Borreguero 2016) + Silber Mayo updated algorithm 2021 [PMID:39324694](https://pubmed.ncbi.nlm.nih.gov/39324694/)
- Cited evidence (PMID 39324664) [PMID:39324664](https://pubmed.ncbi.nlm.nih.gov/39324664/)
- Cited evidence (PMID 27856776) [PMID:27856776](https://pubmed.ncbi.nlm.nih.gov/27856776/)
- Cited evidence (PMID 29425576) [PMID:29425576](https://pubmed.ncbi.nlm.nih.gov/29425576/)
- Cited evidence (PMID 27448465) [PMID:27448465](https://pubmed.ncbi.nlm.nih.gov/27448465/)

Last reconciled with current guidelines: 2026-05-26.
References
  • 2025 AASM Clinical Practice Guideline — Treatment of RLS and PLMD (Winkelman, JCSM 2025; NEWEST — primary floor) + AASM 2025 systematic review/meta-analysis/GRADE + AAN 2016 practice guideline + IRLSSG iron-treatment consensus (Allen 2018) + IRLSSG/EURLSSG/RLS-F first-line + augmentation guideline (Garcia-Borreguero 2016) + Silber Mayo updated algorithm 2021 — PMID:39324694
  • Cited evidence (PMID 39324664) — PMID:39324664
  • Cited evidence (PMID 27856776) — PMID:27856776
  • Cited evidence (PMID 29425576) — PMID:29425576
  • Cited evidence (PMID 27448465) — PMID:27448465