Table 8.

Randomized Controlled trials on Efficacious Intravenous Drugs for Complex Regional Pain Syndrome

Study: CRPS Type I Criteria	Treatment	Results	Comments	Adverse Effects
Sigtermans et al; IASP criteria; P, R, DB	Ketamine, 4.2 day infusion, stepwise tailored dose, median (range dose) of 22 +/−2 mg/h/70 kg; 60 patients, 30 per group	Significantly better results with ketamine in terms of pain relief, no difference in secondary outcomes	Differences in pain relief maintained up to 11 weeks, gone at 12w	Nausea, vomiting, psychomimetic effects (drug high, hallucinations)
Scharztman et al; IASP criteria; P, R, DB, PC;	Ketamine infusion for 4h x 10d; 0.35 mg/kg/h not to exceed 25 mg/h (100 mg over 4h); 19 subjects, 9 had ketamine	Significantly better results with ketamine over placebo in many pain parameters	Study terminated early as interim analysis showed no improvement with placebo in any of the parameters. Also, additional experience showed 50 mg/h (200 mg over 4h) gave greater and longer relief	Nausea, tiredness, dysphoria, headache (midazolam and clonidine given during infusion)
Adami et al; Kozin criteria; P, R, DB	Alendronate, 7.6 mg in 250 mL saline vs saline infusion daily x 3d followed by an open-label treatment; 20 patients, 10 per group	Improvement in pain, tenderness, swelling were significantly better with alendronate	Patients in the placebo group later responded in the open-label study	Fever
Robinson et al; IASP criteria; P, R, DB	Pamidronate 60 mg as a single infusion vs placebo; 27 patients, 14 had pamidronate	Pain scores, global assessment, physical function (SF-36) were better in the pamidronate group	There was variability of response to pamidronate among the patients	Influenza-like symptoms, infusion site symptoms (erythema, discomfort)
Varenna et al; Kozin criteria; P, R, C, DB	Clodronate 300 mg daily x 10 consecutive days vs placebo; 32 patients, 15 had clodronate	Significantly better results in the clodronate group	Significantly better improvements in the placebo group when treated openly with clodronate	Polyarthralgia, fever
Varenna et al; Budapest criteria; P, R, C, DB	Neridronate, 100 mg given four times over 10 days vs placebo; 82 patients, 41 per group	Significantly better results (evoked pain, McGill pain Questionnaire, SF-36)	Better response in the placebo group during the open-label phase.	Duration less than 2 days: Fever, chills sweating, postural hypotension, nausea, vomiting, diarrhea, lethargy, anxiety, restlessness, sleep disturbance, headache. S/s of anaphylactoid reaction (nasal congestion, itch, wheeze, exanthema) none needing treatment.
Goebel et al; Budapest criteria; P, R, DB, C	IVIG, total dose of 0.5 g/kg (0.25 g.kg/day) vs placebo; 12 patients, 7 of 7 patients assigned to IVIG finished both phases while 5 of 6 patients initially given saline completed the crossover portion of the study	Significantly better results with IVIG in terms of pain scores, limb symptoms scale		None
Dirckx et al, IASP criteria, P, R, DB, PC	Infliximab, 5 mg/kg given at 0, 2, 6 weeks; 13 patients (6 had infliximab)	No significant difference between the 2 groups: McGill Pain Questionnaire, cytokine levels in blister fluid	Study terminated early since results attained statistical power	Headache, hypertension, dizziness, diplopia, nausea, malaise, flu-like symptoms

C: Crossover; DB: Double-blind; IASP: International Association for the Study of Pain; IVIG: Intravenous immunoglobulin; P: Prospective; R: Randomized