Table 4.

Levels of recommendation for the pharmacological treatment of primary headaches

Level I	Drugs with high efficacy supported by statistically significant data (evidence of at least two controlled, randomized studies versus placebo or versus active drugs of proven efficacy) or very high clinical benefit for patients (clinical effectiveness +++) and with no severe adverse events
Level II	Drugs whose value of efficacy is statistically of lower significance compared to drugs of group I and with a less significant clinical benefit for patients (clinical effectiveness ++) and no severe adverse events
Level III	Drugs showing efficacy from a statistical point of view but not from a clinical point of view (contrasting results or evidence is not conclusive). The drugs belonging to this group were further subdivided into two subgroups: (a) Drugs with no severe adverse events (b) Unsafe drugs or with complex indications for use (e.g. special diets) or important pharmacological interactions
Level IV	Drugs of proven efficacy but with frequent and severe adverse events or drugs whose efficacy has not been proven from a clinical or statistical point of view (no difference with respect to placebo). Drugs with unknown clinical patient benefit or statistical significance of efficacy (data unavailable or insufficient)