Table 2.
RCTs with pharmacological interventions
| Intervention | N. of participants (N. of arms, control) | Dose, period (weeks) | Primary measurement (subscale) | Statistical significance |
|---|---|---|---|---|
| Psychiatric drugs | ||||
| (-)-OSU6162 [16] | 62 (2, placebo) | 30 mg, 60 mg/day, 2 | MFS, CGI | Not significant |
| Duloxetine [17] | 60 (2, placebo) | 60–120 mg/day, 12 | MFI (general fatigue) | Not significant |
| Clonidine-hydrochloride [18] | 188 (3, placebo, HC) | 50 μg or 100 μg/day, 9 | Number of steps per day | Not significant |
| Methylphenidate [19] | 60 (crossover, placebo) | 10 mg/day, 4 | CIS (fatigue, concentration) VAS (fatigue, concentration) | CIS (fatigue): P < 0.01, VAS: P < 0.01 |
| Galantamine hydrobromide [20] | 434 (5, placebo) | 7.5–30 mg/day, 16 | CGI | Not significant |
| Moclobemide [21] | 90 (2, placebo) | 450–600 mg/day, 6 | Globally improved cases, KPS, POMS | Not significant |
| Fluoxetine [22] | 96 (2, placebo) | 20 mg/day, 8 | CIS (fatigue)a | Not significant |
| Galantamine hydrobromide [23] | 49 (2, placebo) | 30 mg/day, 8 | VAS (fatigue) | Not significant |
| Immunomodulators | ||||
| BioBran MGN-3 [24] | 71 (2, placebo) | 6 g/day, 8 | Chalder scale(physical) | Not significant |
| Staphypan Berna [25] | 100 (2, placebo) | 0.1–1.0 ml/week and 1.0 ml/4 weeks, 24 | CGI, CPRS | CGI: P < 0.001, CPRS: P < 0.01 |
| Gamma globulin [26] | 71 (2, placebo) | 1 gm/kg 3 times/month, 8 | Mean functional score | P < 0.05 (6 month) |
| Poly(I):poly(C12U) [27] | 92 (2, placebo) | 400–800 mg/week, 24 | KPSa | P < 0.05 |
| Cortisol | ||||
| Hydrocortisone + 9-alfa-fludrocortisone [28] | 80 (crossover, placebo) | 5 mg + 50 μg/day, 12 | VAS (fatigue) | Not significant |
| Fludrocortisone acetate [29] | 100 (2, placebo) | 0.1 mg/day, 9 | Global wellness score | Not significant |
| Hydrocortisone [30] | 32 (crossover, placebo) | 5 or 10 mg/day, 4 | Chalder scale, CGI | Chalder scale: P < 0.01 |
| Hydrocortisone [31] | 70 (2, placebo) | 16 mg/m2/day, 12 | Global wellness score | Not significant |
| Fludrocortisone acetate [32] | 25 (crossover, placebo) | 0.1–0.2 mg/day, 6 | VAS, SF-36a | Not significant |
| Mitochondrial modulators | ||||
| KPAX002 [33] | 128 (2, placebo) | 12 mg/day, 12 | CIS (total score) | Not significant |
| CoQ10 + NADH [34] | 73 (2, placebo) | 200 mg + 20 mg/day, 8 | FIS-40 (total score) | P < 0.05 |
| NADH [35] | 26 (crossover, placebo) | 10 mg/day, 4 | Self-developed subject symptom scoring system | Not significant |
| Nutrients | ||||
| Acclydine [36] | 57 (2, placebo) | 1000–125 mg/day, 14 | CIS (fatigue), SIP-8 | Not significant |
| Polynutrient supplement [37] | 63 (2, placebo) | 125 ml/day, 10 | CIS (fatigue), N of CDC symptoms, SIP-8 | Not significant |
| Others | ||||
| Anakinra [38] | 50 (2, placebo) | 100 mg/day, 4 | CIS (fatigue) | Not significant |
| Ondansetron [39] | 67 (2, placebo) | 16 mg/day, 10 | CIS (fatigue), SIP-8 | Not significant |
| Homeopathic treatment [40] | 103 (2, placebo) | Not fixed, 24 | MFI | Not significant |
MFS Mental Fatigue Scale, CGI Clinical Global Impression, MFI Multidimensional Fatigue Inventory, CIS Checklist Individual Strength, VAS Visual Analogue Scale, KPS Karnofsky Performance Score, POMS Profile of Mood States, CPRS Comprehensive Psychopathological Rating Scale, SF-36 36-item Short Form health survey, FIS-40 Fatigue Impact Scale-40, SIP-8 Sickness Impact Profile-8
aIn cases of no mention for primary measurements or main outcomes in original articles with ≥ 4 measurements, the most fatigue-related measurements were selected by the authors of this review study