Abstract: We included 13 small RCTs (479 participants) in this review (at least 274 participants were women, with 118 parturients after a lumbar puncture for regional anaesthesia). In the original version of this Cochrane review, only seven small RCTs (200 participants) were included. Pharmacological drugs assessed were oral and intravenous caffeine, subcutaneous sumatriptan, oral gabapentin, oral pregabalin, oral theophylline, intravenous hydrocortisone, intravenous cosyntropin and intramuscular adrenocorticotropic hormone (ACTH). Two RCTs reported data for PDPH persistence of any severity at follow-up (primary outcome). Caffeine reduced the number of participants with PDPH at one to two hours when compared to placebo. Treatment with caffeine also decreased the need for a conservative supplementary therapeutic option. Treatment with gabapentin resulted in better visual analogue scale (VAS) scores after one, two, three and four days when compared with placebo and also when compared with ergotamine plus caffeine at two, three and four days. Treatment with hydrocortisone plus conventional treatment showed better VAS scores at six, 24 and 48 hours when compared with conventional treatment alone and also when compared with placebo. Treatment with theophylline showed better VAS scores compared with acetaminophen at two, six and 12 hours and also compared with conservative treatment at eight, 16 and 24 hours. Theophylline also showed a lower mean "sum of pain" when compared with placebo. Sumatriptan and ACTH did not show any relevant effect for this outcome. Theophylline resulted in a higher proportion of participants reporting an improvement in pain scores when compared with conservative treatment. There were no clinically significant drug adverse events. The rest of the outcomes were not reported by the included RCTs or did not show any relevant effect. None of the new included studies have provided additional information to change the conclusions of the last published version of the original Cochrane review. Caffeine has shown effectiveness for treating PDPH, decreasing the proportion of participants with PDPH persistence and those requiring supplementary interventions, when compared with placebo. Gabapentin, hydrocortisone and theophylline have been shown to decrease pain severity scores. Theophylline has also been shown to increase the proportion of participants that report an improvement in pain scores when compared with conventional treatment. There is a lack of conclusive evidence for the other drugs assessed (sumatriptan, adrenocorticotropic hormone, pregabalin and cosyntropin). These conclusions should be interpreted with caution, due to the lack of information to allow correct appraisal of risk of bias, the small sample sizes of the studies and also their limited generalisability, as nearly half of the participants were postpartum women in their 30s.

Plain-language summary: This is an updated review, and we searched for new trials in July 2014. We included 13 small randomised clinical trials (RCTs), with a total of 479 participants. The trials assessed eight drugs: caffeine, sumatriptan, gabapentin, hydrocortisone, theophylline, adrenocorticotropic hormone, pregabalin and cosyntropin. Caffeine proved to be effective in decreasing the number of people with PDPH and those requiring extra drugs (2 or 3 in 10 with caffeine compared to 9 in 10 with placebo). Gabapentin, theophylline and hydrocortisone also proved to be effective, relieving pain better than placebo or conventional treatment alone. More people had better pain relief with theophylline (9 in 10 with theophylline compared to 4 in 10 with conventional treatment). No important side effects of these drugs were reported. The quality of the studies was difficult to assess due to the lack of information available. Conclusions should be interpreted with caution.