Can Anticonvulsants Help Patients With Anxiety Disorders?
What Does the Evidence Show?
By Marco Mula, MD, PhD |
February 1, 2009
Dr Mula is research associate and consultant in neurology and neuropsychiatry in the department of clinical and experimental medicine, section of neurology, The Neuropsychiatry Research Group at the Amedeo Avogadro University in Novara, Italy. Although he received no financial support for the preparation of this article, Dr Mula reports that through the years he has received travel support and speakers fees from various pharmaceutical companies who are involved in the manufacture of antiepilectic drugs, including Novartis, Pfizer, UCB-Pharma, Janssen-Cilag, and Sanofi-Aventis.
Posttraumatic stress disorder
At present, controlled studies of anticonvulsants involve lamotrigine(Drug information on lamotrigine) and valproate(Drug information on valproate).22,23 In one study, lamotrigine was associated with a significant diminution in the re-experiencing and avoidance/numbing symptoms relative to placebo.22 Unfortunately, only 10 patients in that study were followed and the dosage range was quite large (25 to 500 mg).22 These factors make any useful measure of effect size impossible.
Open studies of valproate for the treatment of posttraumatic stress disorder (PTSD) were initially promising, but a randomized, double-blind, placebo-controlled trial showed that the response to valproate monotherapy in 85 older male combat veterans was no different from that with placebo.9-11 Further studies are needed to determine the efficacy of monotherapy in women and the possible effectiveness of valproate as augmentation therapy.
Among other anticonvulsants, data are limited to open studies, which suggest some improvement in hyperarousal symptoms with carbamazepine(Drug information on carbamazepine), phenytoin, topiramate, and levetiracetam(Drug information on levetiracetam).9-11 Nonetheless, these are uncontrolled data that may deserve further investigations without any clear indication at the moment.
Among all anticonvulsant drugs, data on topiramate(Drug information on topiramate), from open studies, are the most compelling.9-11 Lamotrigine has been shown to be ineffective, while information on carbamazepine is limited to case reports.9-11
Who can benefit?
We are still far from straightforward guidelines on the use of anticonvulsants in patients with anxiety disorders. Apart from the direct comparison between pregabalin(Drug information on pregabalin) and venlafaxine for GAD, there are no head-to-head comparisons with first-line agents (ie, antidepressant drugs) for the long-term treatment of anxiety symptoms.12 Furthermore, there are no data about which clinical subgroups may preferentially respond to these drugs. Recent data on pregabalin suggest some utility in GAD with comorbid depression.14
We can speculate that patients with comorbid bipolar disorders may benefit from a mood stabilizer with anxiolytic properties. In this setting, lamotrigine and valproate may represent valuable options, although evidence on these 2 compounds in treating anxiety disorders per se is weak. Gabapentin(Drug information on gabapentin) has not been shown to have strong mood-stabilizing properties and there are no data for pregabalin.24 Their use in patients with bipolar disorders and comorbid anxiety disorders seems premature.
Patients with anxiety disorders, obesity, and comorbid eating disorders (eg, binge-eating disorder, bulimia) may benefit from treatment with topiramate, although promising results are still confined to obsessive- compulsive disorder and PTSD.25
The rationale for the use of anticonvulsants in anxiety disorders is supported by neurobiological underpinnings that make these compounds a likely alternative for short-term treatment in patients who do not respond to benzodiazepines or who have a contraindication (an addiction disorder, respiratory problems, or who are at risk for falls). However, data are limited, and current criteria for levels of evidence and lines of treatment recommendations suggest strong evidence only for pregabalin in patients with GAD with or without comorbidity (Table 2).
Pregabalin and gabapentin have been shown to be promising in social phobia. Data about gabapentin in panic disorder are somewhat mixed; they suggest a possible role only in patients who are moderately to severely affected. In any case, these compounds must still be considered second- or even third-line treatment.
Further studies are needed on the neurobiology of anxiety disorders and neuropharmacology of anticonvulsant drugs to develop pharmacological treatment strategies that target symptom patterns and patients’ needs.
Drugs Mentioned in This Article
Carbamazepine (Carbatrol, Tegretol, others)
Valproate/valproic acid (Depakote, others)
Also in this Special Report
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