Can Anticonvulsants Help Patients With Anxiety Disorders?

Despite numerous open studies and reports, most publications have sever­al methodological limitations, includ­ing inadequate sample size; lack of pla­ce­­bo control; use of outcome measures, such as the clinical global impression scales; and lack of controlling for patient variables, such as comorbidity, diagnostic subtype, and concom­i­tant medications.^9-11 These factors may help explain why anti­­con­vul­sants have yielded inconsistent results in the treatment of anxiety disorders.

Generalized anxiety disorder
The strongest evidence is for pregabalin(Drug information on pregabalin) in patients with GAD with and without comorbidity (Table 2). Pregabalin has been shown to be effective at high dosages (300 to 600 mg/d) in a number of controlled studies compared with benzodiazepines and venlafaxine.^11,12 Recent data support the efficacy of pregabalin in the long-term treatment and in the amelioration of comorbid depressive symptoms.^13,14

Regarding other anticonvulsant drugs, tiagabine(Drug information on tiagabine) is the only other compound being investigated for GAD. This agent has shown promise in an open study. However, controlled data from 260 patients showed no significant difference from placebo in responder rates measured with the Hamilton Anxiety Scale.¹⁵

Social anxiety disorder
Controlled studies show interesting results for pregabalin (600 mg/d) and gabapentin(Drug information on gabapentin) (900 to 3600 mg/d).^16,17 Both drugs share the same mechanisms of action, namely the modulation of N- and P/Q-type voltage-dependent calcium channels.⁴

Among other anticonvulsant drugs, valproate(Drug information on valproate) and topiramate have been shown to ameliorate phobic symptoms in small open studies involving 17 and 23 patients, respectively.^9-11 Further controlled studies are warranted to reach definitive conclusions.

Data on levetiracetam(Drug information on levetiracetam) are not conclusive either. An open-label, flexible-dose study in 20 patients showed a clinically significant reduction in anxiety and phobic symptoms.¹⁸ However, results of a controlled study comprising 16 subjects were clearly negative, although some methodological limitations such as the small sample size make it impossible to get definitive evidence about this anticonvulsant for social phobia.¹⁹ Further investigations are needed.

Panic disorder
Although a number of anticonvul­sant drugs have been used for panic disorder, conclusive data are not avail­able. The majority of studies have been uncontrolled and have had small sample sizes. The results for gabapentin have been somewhat mixed, although post hoc analyses of a controlled study suggest that gabapentin (600 to 3600 mg/d) may be useful in patients with moderate to severe panic disorder.²⁰

There are no more than anecdotal reports for vigabatrin(Drug information on vigabatrin), tiagabine, and oxcarbazepine. The literature is inconclusive for carbamazepine(Drug information on carbamazepine). Although an open study suggested a possible antipanic effect, the only controlled study conducted in a limited sample of 14 patients showed no effect.²¹ Theoretically, data on valproate may be more interesting and promising, although currently they are still limited to open studies.^9-11