Pregabalin

Epilepsy

Clinical experience with pregabalin when used as add-on therapy in 101 adult patients with refractory partial epilepsy followed for at least 1 year has been reviewed retrospectively [ ]. Adverse reactions required withdrawal in 15 patients and nine withdrew because of inefficacy and adverse events. The most common adverse events were weight gain (26%), dizziness/ataxia (20%), lower limb edema (9.9%), and blurred vision (3.9%).

Long-term persistence with pregabalin treatment has been retrospectively evaluated in 402 patients with epilepsy, of whom 15 stopped taking it within 1 week (all reported either adverse reactions or worsening of seizures) [ ]. At last follow-up, 168 patients (42%) continued to take pregabalin. Adverse reactions were reported by 220 patients, of whom 162 withdrew. The most frequent adverse reactions were nervous system-related, including lethargy, tiredness, headaches, blurred vision, double vision, unsteadiness, and ataxia, which were reported by 141 patients. Weight gain was reported by 48 patients (30 withdrew). Psychiatric adverse reactions were observed in 26 patients (12 reported depression, low mood, or mood swings, and 24 withdrew). Woman were more likely to report adverse reactions than men, but not more likely to report weight gain.

Pregabalin has been evaluated in an open 21-week study in 476 adults (mean age 40 years) with partial seizures inadequately controlled with one to three antiepileptic drugs; 7% discontinued for lack of efficacy and 12% because of adverse events [ ]. The three most common adverse reactions were dizziness (17%), somnolence (13%), and weight gain (13%).

Neuropathic pain

Pregabalin 75–300 mg bd has been evaluated in 111 Indian patients with peripheral neuropathic pain in a prospective, multicenter, non-comparative, open study for 3 weeks [ ]. Despite the short study duration, there was significant pain reduction. The most common adverse events were somnolence (n = 9), dizziness (n = 9), headache (n = 4), and edema (n = 3). In six patients unspecified adverse events required withdrawal of pregabalin.

A flexible-dose regimen of pregabalin has been assessed in 217 patients with diabetic peripheral neuropathy or post-herpetic neuralgia in an open study; 125 had at least one adverse event, including a psychotic disorder in one subject [ ]. The most frequent adverse reactions were dizziness (n = 33) and fatigue (n = 31). Increased weight and peripheral edema occurred in 18 and 11 subjects respectively. In all, 17 subjects withdrew because of adverse reactions.

In a prospective open pilot study, 16 patients with multiple sclerosis and painful paroxysmal symptoms were treated with pregabalin 75–300 mg/day for at least 3 months [ ]. Three dropped out of the study because of adverse reactions: one with dizziness, two with difficulty in concentration and general malaise.

In an open study, 30 children, who had been treated for solid tumors and leukemia and had developed a painful peripheral neuropathy, were given pregabalin 150–300 mg/day for 8 weeks [ ]. There was significant long-lasting pain relief in 25 them. There were mild or moderate adverse reactions (nausea and drowsiness in the titration phase) in four patients; drug withdrawal was not required.

Two different therapeutic strategies in the treatment of chronic neuropathic pain have been compared in an open, prospective, non-randomized study [ ]. The first strategy was to switch to monotherapy or add-on therapy with pregabalin. The second was to change the doses and combinations of pre-existing monotherapy or combination therapy without including pregabalin. After 4 weeks, patients in the pregabalin group (n = 85) achieved significantly greater pain reduction compared with the other group (n = 102). The number of patients who withdrew because of treatment-associated adverse reactions was 3.2% for pregabalin and 6.9% for the others. The most commonly reported treatment-associated adverse reactions were dizziness, vertigo, and somnolence; no serious adverse reactions were reported.

The effects of pregabalin have been investigated in patients with neuropathic pain who were either switched from gabapentin to pregabalin (32 gabapentin responders and 29 non-responders) or continued to take gabapentin (n = 40) [ ]. Both gabapentin responders and non-responders had additional pain relief from pregabalin after 6 and 12 months. More patients had adverse reactions to pregabalin among the gabapentin non-responders, who had also had more adverse reactions due to gabapentin than the gabapentin responders. The most common adverse reactions in the gabapentin responders, gabapentin non-responders, and those who continued to take gabapentin were: sedation (3, 15, and 10 respectively), dizziness (3, 6, and 3), peripheral edema (3, 3, and 6), fatigue (3, 8, and 7), and dry mouth (4, 4, and 2).

Postoperative pain

In a randomized study of the quality of analgesia in women undergoing day-case gynecological laparoscopic surgery, premedication with pregabalin 75 mg (n = 30) or 150 mg (n = 26) was compared with diazepam 5 mg (n = 28) [ ]. Analgesia was better after pregabalin 150 mg than diazepam 5 mg. Dizziness occurred in 64% of those treated with diazepam, 53% of those treated with pregabalin 75 mg, and 80% of those treated with 150 mg. Headache occurred in 32%, 27%, and 19% of patients respectively; blurred vision in 11%, 20%, and 27%; lack of concentration in 74%, 67% and 85%; and pruritus in 7%, 23%, and 19%.

Dysautonomia

In 15 patients with familial dysautonomia, pregabalin up to a dose of 6 mg/kg/day gave good results in the treatment of nausea and dysautonomic crises [ ]. Adverse reactions included peripheral edema in one patient who stopped taking pregabalin, weight gain in four, and worsened balance in seven.

Carbamazepine versus pregabalin

In a double-blind, crossover, randomized trial, the effects of carbamazepine and pregabalin on eye movements and posture control have been compared in 12 healthy volunteers who took single doses of pregabalin 75 mg and slow-release carbamazepine 400 mg [ ]. Carbamazepine caused more slowing of the peak horizontal saccade (27%) than pregabalin (14%). For other parameters there were no statistically significant changes compared with baseline or between the two drugs. Both drugs impaired posture control but the effects were not statistically significant.

Celecoxib versus pregabalin

As optimal pain relief after surgery is difficult to achieve with the use of a single drug, many pain experts advocate the use of two or more classes of medications, in order to reduce the adverse reactions to any one drug. The analgesic efficacy of perioperative celecoxib, pregabalin, or both has been assessed after spinal fusion surgery in 80 patients scheduled to undergo elective decompressive lumbar laminectomy with posterior spinal fusion [ ]. They were randomized to oral placebo 1 hour before and 12 hours after surgery, celecoxib 400 mg 1 hour before and 200 mg 12 hours after surgery, pregabalin 150 mg 1 hour before and 12 hours after surgery, or pregabalin + celecoxib 400 mg/150 mg 1 hour before and 200 mg/150 mg 12 hours after surgery. Those who used pregabalin + celecoxib consumed the least patient-controlled morphine. Celecoxib alone or pregabalin alone also reduced opioid use compared with placebo, but not as much as when combined. Pregabalin + celecoxib was the most effective treatment for reducing pain, both at rest and with movement over the 24 hours after surgery. Fewer patients had nausea after pregabalin + celecoxib than after placebo. The most common adverse event was nausea in 6/20 with pregabalin compared with 10/20 in the placebo group. Fewer patients on pregabalin reported excessive sedation than those who received placebo (5 versus 7). However, this work has been retracted since publication because it contained fabricated data.

Pregabalin and celecoxib, alone and in combination, have been evaluated in the treatment of chronic low-back pain in 36 patients in a 12-week, randomized, crossover study [ ]. The combination was more effective than either monotherapy. Adverse reactions were recorded in 16 patients and four patients withdrew as a result. Five patients reported nausea or dizziness during treatment with pregabalin and seven had similar symptoms during treatment with celecoxib + pregabalin.

Gabapentin versus pregabalin

The effects of gabapentin and pregabalin in the treatment of fibromyalgia have been compared in a systematic review and meta-analysis [ ]. The authors concluded that adverse events such as dizziness, somnolence, dry mouth, weight gain, and peripheral edema could lead one out of four patients to stop taking treatment (NNT _H = 6).

Lidocaine versus pregabalin

Pregabalin and 5% lidocaine in a medicated plaster have been compared in a randomized, open, multicenter, non-inferiority study in 96 patients with post-herpetic neuralgia and 204 with painful diabetic polyneuropathy [ ]. Overall, 66% of those who used the lidocaine plaster and 62% of those who used pregabalin were considered to have responded. There were fewer adverse reactions from lidocaine than pregabalin (5.8% versus 41%).

Oxycodone versus pregabalin

In an open study 409 patients with neuropathic pain were given pregabalin + controlled-release oxycodone (n = 169) or monotherapy with either oxycodone (n = 106) or pregabalin (n = 134) [ ]. The combination of controlled-release oxycodone + pregabalin and controlled-release oxycodone monotherapy were both more effective in alleviating neuropathic pain than pregabalin monotherapy. Combination therapy had a better safety profile than monotherapy with either drug, with a dropout rate due to adverse events of 5.9% compared with 10% and 19% respectively. The most frequently reported adverse events with pregabalin were somnolence and peripheral edema. Combination therapy was most often associated with constipation. Overall, the combination of controlled-release oxycodone and pregabalin resulted in an improved adverse events profile compared with pregabalin monotherapy.

Prazepam versus pregabalin

In 48 healthy women who were randomized to either oral pregabalin 150 mg 12-hourly or prazepam 10 mg 12-hourly at induction of epidural analgesia (ropivacaine 0.1% with sufentanil 0.25 micrograms/ml) in the late termination of pregnancy procedure, retained placenta occurred in three of those who were given prazepam and four of those who were given pregabalin [ ]. One patient who was given pregabalin reported blurred vision and none complained of excessive sedation, vertigo, or dizziness.