Patients with CrCl 60 mL/min and those that had abused alcohol or illicit drugs within the past 2 years were excluded. Patients were randomized to placebo (n = 65), ﬂexible- dose PGB (150–600 mg/day; n = 141), or ﬁxed-dose PGB (600 mg/day; n = 132). Patients randomized to the ﬂexible- dose group received weekly escalating doses (150, 300, 450, and 600 mg/day) of PGB based on response and toler- ability. These patients were permitted a single downward dose titration during the ﬁrst 4 weeks; if this occurred, the patient would remain on that dosage for the study duration. The ﬂexible-dosing schedule was thought to more closely mimic actual clinical practice. Mean age of the patients was between 61 and 62 years of age, slightly younger than the other 3 trials. The mean duration of PHN was between 35 and 39 months. As was the case with the previous 3 trials, patients were required to have a score of 40 mm on a 100 mm VAS at baseline and at randomization. Primary outcome measure was the endpoint mean pain score from the last 7 days of the patients’ daily pain diaries according to the 11-point numerical pain scale discussed previously. This study assessed related sleep interference due to pain as a secondary outcome using a sleep interference diary similar to the other trials discussed. Flexible-dose PGB signiﬁcantly reduced mean endpoint pain scores versus placebo by Week 2 (p = 0.021) and throughout the study (p 0.013); ﬁxed dose PGB signiﬁcantly reduced mean endpoint pain scores versus placebo by the end of Week 1 (p = 0.007) and subsequently throughout the rest of the trial (p 0.001). The magnitude in reduction of pain symptoms was similar in patients with either PHN or DPN. Moreover, signiﬁcantly more patients in the PGB-treated groups demonstrated a 50% reduc- tion in pain from baseline than those on placebo (48.2% in the ﬂexible-dose PGB group, 52.3% in the ﬁxed-dose PGB group, and 24.2% in the placebo group; p 0.001 for each PGB group versus placebo). The NNT based on those with 50% reduction in pain from baseline for all PGB-treated patients combined was 3.8. Sleep interference scores improved signiﬁcantly at endpoint over placebo for patients in each PGB treatment group (p 0.001 for each group versus placebo; exact values not given).25 Adverse effects/tolerability The most common adverse effects with PGB treatment noted in PHN trials were dizziness, somnolence, and peripheral edema.7,14,18,25 Other notable side effects commonly reported with PGB use include dry mouth, blurred vision, weight gain, ataxia, headache, “thinking abnormal,” and nausea. Dizziness and somnolence were the most common adverse effects Clinical Interventions in Aging 2009:4 Pregabalin for postherpetic neuralgia leading to study withdrawal.20 Dizziness and somnolence occurred more frequently at higher doses and began shortly after starting PGB.20,21 Symptoms including insomnia, nausea, headache, and diarrhea were reported by some patients following abrupt withdrawal of PGB. Therefore, PGB should be tapered gradually over a minimum of 1 week rather than discontinued abruptly. Weight gain noted in clinical trials of PGB was not limited to patients with peripheral edema. Even though weight gain was related to dose and duration of exposure to PGB, it did not appear to be associated with gender, age, or baseline BMI. A higher incidence of weight gain and peripheral edema were noted in patients taking both PGB and a thiazolidinedione, compared with patients taking either agent alone. Hence, care should be taken when co-administering PGB and one of these agents.20,21 The package insert cautions about the use of PGB in heart failure patients with NYHA Class III or IV cardiac status,20 and there have been reports of heart failure decompensation in patients using PGB for neuropathic pain.27 Place in therapy As discussed previously, PGB and gabapentin share several advantages such as a lack of pharmacokinetic drug interactions and similar mechanism of action and efﬁcacy. It is unclear if PGB has any clinical advantage over gabapentin, though, as there have been no direct comparisons done in clinical trials between the two drugs.24 Unlike gabapentin, PGB exhibits linear pharmacokinetics following oral administration with low intersubject variability, which results in a more predictable dose-response relationship, since plasma concentrations increase linearly with increasing dose. Additionally, because of the pharmacokinetic advantages PGB has over gabapentin, patients can be initiated and titrated up to a target dose more rapidly. A dose-response relationship was demonstrated in two of the PGB trials discussed.7,18 Based on clinical trial data presented here and recommendations in PGB product labeling, patients may see more improvements at higher doses and should be titrated up to 600 mg/day if they do not experience adequate relief at lower doses and can tolerate the higher PGB doses.7,18,20 Gabapentin has a cost advantage over PGB since gabapentin has a lower cost generic available, but the monthly cost of PGB is similar to generic gabapentin at the highest target doses of gabapentin.24,28 The long-term economic impact of PGB in treating PHN is unclear.24 A recently-updated meta-analysis on treatments for all types of neuropathic pain provides an evidence-based treatment algorithm for peripheral neuropathic pain. PGB/gabapentin and 21