Sulpiride and refractory panic disorder

Dear Editor, The use of antipsychotics in patients with anxiety in recent years has increased, with a recent study showing that over a 12-year period, antipsychotic prescriptions in visits for anxiety disorders increased from 10.6 to 21.3 %, with the biggest increase among panic disorder (PD) patients (from 8 to 21.3 %) (Comer et al. 2011). Reasons for this remain unclear, but possible explanations include changes in patient characteristics, including increasing severity of illnesses among outpatient clients; greater prevalence or recognition of comorbidities (Comer et al. 2011); greater physician emphasis on symptom reduction, with increased acceptance of off-label antipsychotic prescriptions; a possible extrapolation to anxiety subjects by psychiatrists from their clinical experience of treating depressed patients with antipsychotics (Berman et al. 2009); and the availability of new antipsychotics with better side effect profiles, leading to a trend of changing from typical to atypical antipsychotics (Crystal et al. 2009). Also, contributing to this scenario could have been the fact that even with well-established treatment options, nearly 20 % of PD patients will remain substantially ill despite the use of the usual antipanic medication (Holt and Lydiard 2007). Furthermore, there is increasing evidence for the role of dopamine in fear and anxiety, through its modulation as a cortical brake that themedial prefrontal cortex exerts on the anxiogenic output of the amygdala, influencing the trafficking of impulses between the basolateral and central nuclei of the amygdala (de la Mora et al. 2010). Sulpiride is an antipsychotic of the benzamide type, structurally similar to amisulpride, and is used to treat schizophrenia, as well as depressive symptoms (Ruther et al. 1999). Also, anxiolytic-like effects of this drug have been reported in the elevated plus-maze test (Rodgers et al. 1994) and stress-induced freezing behavior in rats (Cavazzuti et al. 1999), in punished drinking behavior (Pich and Samanin 1986), and the mouse hyperdefensiveness test (PuglisiAllegra and Cabib 1988), suggesting a probable role in treatment of anxiety disorders, even as monotherapy. It is an antagonist of D2/D3 receptors, with almost no affinity for other receptors (Miyamoto et al. 2005), representing a good option in studies targeting effects on dopaminergic transmission. The aim of this study was to investigate the effects of 8 weeks of treatment with sulpiride on anxiety symptoms in a population with refractory PD. An open label challenge with sulpiride was conducted with 19 subjects (8 males and 11 females), aged 22 to 58 (mean age, 37.4 years). All patients were recruited from the outpatient clinic of Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro, in its Panic and Respiration Laboratory after a structured clinical interview (The Mini International Neuropsychiatric Interview) (Sheehan et al. 1998) and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for PD with agoraphobia. The subjects had no other E. A. Nunes (*) : J. A. S. Crippa : J. E. C. Hallak Department of Neuroscience and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, National Institute for Translational Medicine (INCT-TM), Av. Bandeirantes, 3900, Monte Alegre S/N, Hospital das Clinicas 3o andar, Ribeirao Preto, SP, Brazil 14048-900 e-mail: emerson_arcoverde@yahoo.com.br