We identified seven comparative randomised

The GRADE recommendations for tapentadol, other antiepileptics, capsaicin cream, topical clonidine, selective serotonin reuptake inhibitor antidepressants, NMDA antagonists, and combination therapy40, 41 and 42 are inconclusive mainly because of discrepant findings. However, the combination of pregabalin or gabapentin and duloxetine or tricyclic antidepressants might be an alternative option to increasing doses of monotherapy for patients unresponsive to moderate doses of monotherapy (see 2-MPMDQ for details).
Cannabinoids and valproate have weak recommendations against their use in neuropathic pain and levetiracetam and mexiletine have strong recommendations against their use because of generally negative trials or safety concerns, or both (see appendix for details).
In accordance with previous reports,23 results of our meta-analysis show that the efficacy of systemic drug treatments is generally not dependent on the cause of the underlying disorder (appendix). Side-effects might, however, to some degree depend on the cause—eg, drugs with CNS-related side-effects might be tolerated less well in patients with CNS lesions.43 Pain due to HIV-related painful polyneuropathy and radiculopathy seems more refractory than other types of pain in our meta-analysis. This difference might be due to large placebo responses in HIV-related neuropathy trials,44 a distinct clinical phenotype in subgroups of patients with radiculopathy,45 or psychological or psychosocial comorbidities, often neglected in large trials. Topical agents have no known relevance for use in central pain, and this is clearly stated in our recommendations.