Anticonvulsant and antipsychotic medications in the pharmacotherapy of panic disorder: a structured review

BACKGROUND: As the remission rate of panic disorder (PD) achieved with conventional pharmacotherapy ranges between 20% and 50%, alternative psychopharmacological strategies are needed. We aimed to firstly review data regarding use of antipsychotic and non-benzodiazepine anticonvulsant medication in PD patients with or without comorbidities; secondly, to review data concerning reduction of panic symptoms during treatment of another psychiatric disorder with the same medications; and thirdly, to examine reports of anticonvulsant- or antipsychotic-induced new-onset panic symptomatology. METHODS: We performed a PubMed search (last day: 28 April 2020) of English-language studies only, combining psychopathological terms (e.g. ‘panic disorder’) and terms referring either to categories of psychotropic medications (e.g. ‘anticonvulsants’) or to specific drugs (e.g. ‘carbamazepine’). All duplications were eliminated. All studies included in the review met certain inclusion/exclusion criteria. The level of evidence for the efficacy of each drug was defined according to widely accepted criteria. RESULTS: In treatment-resistant PD, beneficial effects have been reported after treatment (mostly augmentation therapy) with a range of anticonvulsant (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbamazepine, valproate, vigabatrin, tiagabine) and antipsychotic (aripiprazole, olanzapine, risperidone, sulpiride) medications: overall, most medications appear generally well tolerated. Additionally, bipolar patients receiving valproate or quetiapine-XR (but not risperidone or ziprasidone) demonstrated reductions of comorbid panic-related symptoms. There are case reports of new-onset panic symptoms associated with clozapine, haloperidol, olanzapine and topiramate, in patients with conditions other than PD. The small-to-modest sample size, the lack of control groups and the open-label and short-term nature of most of the reviewed studies hinder definitive conclusions regarding either the short-term and long-term efficacy of antipsychotic and anticonvulsant medications or their potential long-term side effects. CONCLUSION: Some atypical antipsychotic and anticonvulsant medications may have a role in the treatment of some PD patients, mostly when more conventional approaches have not been successful, but the quality of supporting evidence is limited.