Abstract: We included 10 pharmacological (modafinil, intravenous immunoglobulin (IVIg), pyridostigmine, lamotrigine, amantadine, prednisone) and three non-pharmacological (muscle strengthening, rehabilitation in a warm climate (that is temperature ± 25°C, dry and sunny) and a cold climate (that is temperature ± 0°C, rainy or snowy), static magnetic fields) studies with a total of 675 participants with PPS in this review. None of the included studies were completely free from any risk of bias, the most prevalent risk of bias being lack of blinding. There was moderate- and low-quality evidence that IVIg has no beneficial effect on activity limitations in the short term and long term, respectively, and inconsistency in the evidence for effectiveness on muscle strength. IVIg caused minor adverse events in a substantial proportion of the participants. Results of one trial provided very low-quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations without generating adverse events. Data from two single trials suggested that muscle strengthening of thumb muscles (very low-quality evidence) and static magnetic fields (moderate-quality evidence) are safe and beneficial for improving muscle strength and pain, respectively, with unknown effects on activity limitations. Finally, there was evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS. Due to insufficient good-quality data and lack of randomised studies, it was impossible to draw definite conclusions about the effectiveness of interventions for PPS. Results indicated that IVIg, lamotrigine, muscle strengthening exercises and static magnetic fields may be beneficial but need further investigation to clarify whether any real and meaningful effect exists.

Plain-language summary: We searched scientific databases to find all studies on treatments for PPS up to July 2014. We found 13 studies involving a total of 675 participants that were of sufficient quality to include in this review. Ten studies evaluated the effects of drugs (modafinil, intravenous immunoglobulin (IVIg), pyridostigmine, lamotrigine, amantadine, prednisone), and three studies evaluated other treatments (muscle strengthening, rehabilitation in a warm climate (that is temperature ± 25°C, dry and sunny) and a cold climate (that is temperature ± 0°C, rainy or snowy), static magnetic fields). IVIg is a treatment in which antibodies that have been purified from donated blood are given as an infusion into a vein over a period of time. There was moderate- and low-quality evidence that IVIg has no beneficial effect on activity limitations in the short term and long term, respectively. Evidence for effectiveness on muscle strength was inconsistent, as results differed across studies. IVIg caused minor side effects in a substantial proportion of the participants. Lamotrigine is a drug used to help control certain kinds of epilepsy and to treat bipolar psychiatric disorder. Results of one trial provided very low-quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations, and in this study it was well-tolerated. We based these conclusions on results of only one small trial with important limitations in study design. There was very low-quality evidence that muscle strengthening of thumb muscles is safe and beneficial for improving muscle strength. Again, we based these conclusions on results of only one small trial with important limitations in study design, and they are applicable only to thumb muscles. Static magnetic fields is a therapy in which electrical currents are applied to the skin with the intention of reducing pain. There was moderate-quality evidence that static magnetic fields are safe and beneficial for reducing pain directly after treatment, although functional effects on activity limitations and long-term effects are unknown. Finally, there was evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS.