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McDonagh M, Peterson K, Lee N, et al. Drug Class Review: Antiepileptic Drugs for Indications Other Than Epilepsy: Final Report Update 2 [Internet]. Portland (OR): Oregon Health & Science University; 2008 Oct.

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Drug Class Review: Antiepileptic Drugs for Indications Other Than Epilepsy: Final Report Update 2 [Internet].

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Appendix EMeta-analysis of specific adverse events associated with antiepileptic drugs in the treatment of bipolar disorder

The patient-level adverse event analysis included 14 trials and evaluated 8 specific adverse events (diarrhea, dizziness, headache, nausea, rash, somnolence, tremor, and weight gain). The results of our meta-analysis of specific adverse events at a patient level are shown in Tables 1 and 2 of this appendix. In Table 1, three antiepileptic drugs (carbamazepine, valproate, and lamotrigine) are assessed against lithium. Because the numbers of trials and patients are small, and the 95% confidence intervals are wide, the lack of statistically significant evidence for a specific adverse event cannot be taken to mean that an antiepileptic drug did not cause that adverse event. Lamotrigine (2 trials), but not valproate (1 trial), was significantly less likely than lithium to be associated with diarrhea. Lamotrigine (1 trial) and carbamazepine (2 trials), but not valproate (1 trial), were associated with a significantly lower odds of tremor than lithium.

Table 1

Table 1

Adverse event analysis at patient level, mood: Antiepileptic drug compared with lithium

Table 2

Table 2

Adverse events analysis at patient level, mood: Antiepileptic drug compared with placebo

Table 2 pools data comparing antiepileptic drugs (carbamazepine, valproate, gabapentin, and lamotrigine) with placebo. Again, the numbers of trials and patients are small, and the 95% confidence intervals are wide. In general, the same cautions as mentioned for Table 1 apply. Lamotrigine (4 trials), and not carbamazepine (1 trial) or gabapentin (1 trial), was more likely than placebo to be associated with headache. Carbamazepine (2 trials), and not valproate (1 trial) or lamotrigine (2 trials), was more likely than placebo to be associated with nausea. Lamotrigine (2 trials), and not carbamazepine (1 trial), was associated with significantly higher odds of rash relative to placebo. Carbamazepine (2 trials), and not gabapentin (1 trial) or lamotrigine (3 trials), was more likely than placebo to be associated with somnolence. Valproate (1 trial), and not lamotrigine (1 trial), was associated with significantly higher odds of tremor as compared with placebo. Only valproate was reported to cause weight gain as an adverse event.

The only consistent finding was a higher likelihood of tremor with valproate than lamotrigine, based on the data from lithium- and placebo-controlled trials. However, the 95% confidence intervals overlapped in both analyses (0.61 to 1.77 for valproate and 0.11 to 0.68 for lamotrigine, antiepileptic drug compared with lithium; and 2.38 to 10.26 for valproate and 0.33 to 3.79 for lamotrigine, antiepileptic drug compared with placebo). Therefore, we cannot conclude that there is a definite difference between valproate and lamotrigine in their association with tremor.

One limitation of the evaluation of specific adverse events and the pooled analyses of adverse events is inconsistency in the definition of common adverse events among trials. For example, trials may consider an adverse event to be common if it occurs in at least 5%, 8%, or 10% of patients. Variation in reporting of common adverse events may influence indirect comparisons between antiepileptic drugs.

Meta-analyses similar to the ones presented for bipolar disorder were done for neuropathic pain for the original version of this report. Although Update 2 does not include neuropathic pain, we present its adverse event analysis. The patient-level analysis of adverse events reported in neuropathic pain trials included 23 trials and evaluated 9 adverse events (diarrhea, dizziness, edema, headache, nausea, rash, somnolence, tremor, and weight gain). Table 3 presents the results of our pooled analyses of placebo-controlled trials. Gabapentin (7 trials) and pregabalin (4 trials), but not lamotrigine (1 trial), was associated with a significantly higher likelihood of dizziness compared with placebo. The 95% confidence intervals overlapped; therefore, we cannot conclude that the odds of dizziness were different for the 3 agents. Gabapentin and pregabalin were more likely than placebo to be associated with edema (2 and 4 trials for each drug, respectively) and somnolence (8 and 4 trials for each drug, respectively). Again, the 95% confidence intervals overlapped, and so we cannot conclude that the odds of each adverse event are different for the two agents.

Table 3

Table 3

Adverse events analysis at patient level, pain: Antiepileptic drug compared with placebo

Copyright © 2008, Oregon Health & Science University, Portland, Oregon.
Bookshelf ID: NBK10366

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