Table 2.
Nondopaminergic drugs for the treatment of RLS.
| - | Longest Study Period (N) |
Effective
Daily Dose |
Adverse Effects | Clinical Benefits | Mechanism of Action |
|---|---|---|---|---|---|
| α2δ Ligands | Well tolerated | Regulates Ca2+ influx and reduces excitatory neurotransmitter levels [51, 52] | |||
| Gabapentin enacarbil | 24 weeks (N=327) [44] |
600 or 1200 mg [8] | Somnolence, dizziness [44-47] |
Improves nighttime RLS symptoms and subjective nighttime sleep; reduces pain [44-47] | - |
| Gabapentin | 6 weeks (N=24) [50] |
800 mg; uremic RLS: 200 mg [8] | Somnolence, dizziness, peripheral edema [6, 48-50] | Improves nighttime RLS symptoms and subjective nighttime sleep; reduces pain [6, 48-50] | - |
| Pregabalin | 52 weeks (N=719) [13] |
150–450 mg [8] | Somnolence, dizziness, fatigue, headache [13-15] | Improves nighttime RLS symptoms and subjective nighttime sleep; reduces pain [13-15] | - |
| Opioids | Well tolerated but side effects should be monitored | Stimulates dopamine release [57] | |||
| Oxycodone–naloxone | 12 weeks plus 1 year open trial (N=306) [16] |
Mean dose, 21.9 mg [8] | Addictive tendency, possible respiratory problems [16] | Improves nighttime RLS symptoms and subjective nighttime sleep; reduces pain [16] | - |
| Methadone | 92 weeks N=27 [53] |
Mean dose, 15.6 mg [8] | Addictive tendency, possible respiratory problems [53] | Improves nighttime RLS symptoms and subjective nighttime sleep; reduces pain [53] | - |
| Oxycodone | 2 weeks (N=11)[54] |
Likely efficacious Mean dose:15.9 mg [8] |
Addictive tendency, possible respiratory problems [54] | Improves nighttime RLS symptoms and subjective nighttime sleep; reduces pain [54] | - |
| Iron supplementation | |||||
| Intravenous ferric carboxymaltose |
12 weeks (N=110) [58] |
Likely efficacious [8] | Nausea, headache; requires more time to stabilize RLS; lack of pain and subjective nighttime sleep assessments [58] | Improves nighttime RLS symptoms; well tolerated [58] | Regulates dopaminergic system; controls central nervous system hypoxia pathways; regulates adenosine A1 receptors [28, 29, 41, 62] |
| Glutamatergic therapy | |||||
| Perampanel | 8 weeks (N=20) [63] |
Likely efficacious Mean dose: 3.8 mg [63] |
Somnolence, dizziness, headache, irritability; lack of pain assessment [63] | Improves nighttime RLS symptoms and subjective nighttime sleep; well tolerated [63] | Inhibits glutamate release [63] |
| Adenosine therapy | Regulates hypoadenosinergic state [64] | ||||
| Dipyridamole | 8 weeks (N=13) [64] |
Likely efficacious Mean dose: 281.8 mg [64] |
Abdominal cramps, diarrhea, dizziness, flushing; lack of pain assessment [64] | Improves nighttime RLS symptoms and subjective nighttime sleep; well tolerated [64] | - |