Nonsteroidal Anti-inflammatory Drugs, Acetaminophen, Barbiturates, and Combinations. First-line medications that are often trialed in patients where a conservative pathway is attempted are nonsteroidal anti-inflammatory drugs, acetaminophen, opioids such as oxycodone, or combination medications commonly prescribed for tension and migraine headaches, where barbiturates (butalbital), acetaminophen, and caffeine (discussed below) are added in a single formulation. Data on the efficacy of these medications are lacking, although they are often mentioned in conservative treatment pathways and are often used in control arms of other studies. 17–19 A survey of practitioner management regimens for PDPH performed by Baysinger et al20 reported that medications such as nonsteroidal antiinflammatory drugs and opioids were employed by 87% and 71% of respondents, respectively. The reported success rates to these treatments, however, were low, with over 60% of respondents reporting that these medications were successful less than 40% of the time, and 34% of respondents reporting a success rate of less than 20%.

Methylxanthines. Methylxanthines, namely caffeine and theophylline, are some of the most studied medications for relief of PDPH. These medications treat PDPH symptomatology by 2 mechanisms. First, these drugs interfere with calcium uptake by the sarcoplasmic reticulum, block phosphodiesterase, and antagonize adenosine, which all result in cerebral vasoconstriction. 21, 22 Second, methylxanthines increase CSF production by stimulating sodium-potassium pumps. 23 The data on caffeine are highly heterogeneous as both intravenous (IV) and oral formulations at varying dosages and intervals were utilized during the investigations. Most