A Single-blind Trial of Risperidone vs. Paroxetine for Treatment of Panic Attacks

Rationale

Risperidone is an atypical antipsychotic drug that acts as an antagonist at 5-HT2A/2C and D2 receptors (Chouignard et al, 1993; Marder & Meibach, 1994). In its serotonergic activity, risperidone resembles both the atypical antidepressant and 5HT2-antagonist nefazodone (Bakish et al, 1993) and a 5HT2-antagonist ritanserine (Lima & Moncrieff, 2000; Preskorn 1995). Nefazodone treats anxiety symptoms and induces less agitation than other reuptake blockers (Fawcett et al, 1995) while ritanserin shows effectiveness in treatment of dysthymia in clinical trials. Moreover, risperidone increases release of dopamine and norepinephrine in the prefrontal cortex (Zhang et al, 2000), an activity that in other pharmacological agents is associated with their antidepressant, anxiolytic, and antipanic properties (Thase, 2002).

Therefore, risperidone has a potential to be effective for treatment of either Generalized Anxiety Disorder, or Panic Disorder, or Major Depressive Disorder with Panic Attacks (DSM-IV, 1994) as a single agent. Moreover, due to its D2 and 5-HT2A/2C antagonism and proven antipsychotic efficacy, the drug could be uniquely effective for severe panic attacks with psychotic features or para-psychotic features (Galynker et al, 1996). Consistent with this supposition, Marder et al (1997) reported that in patients with schizophrenia, risperidone produced significantly greater improvements than haloperidol in PANSS scores measuring anxiety and depression.

Our clinical experience with over 50 patients with panic attacks showed that low dose risperidone, similar to lorazepam, reduced or eliminated anxiety and panic, often after the first dose. Risperidone was most effective for patients experiencing obsessive, intrusive, anxiety-inducing thoughts. In contrast to lorazepam, risperidone treatment did not result in building of tolerance to the drug or disinhibition. We did not observe extrapyramidal side effects in patients treated with risperidone for panic attacks. Thus, our preliminary clinical data indicate that due to its efficacy, quick onset of action, absence of addictive potential, and lack of side effects, risperidone could be superior to both benzodiazepines and SSRIs for treatment of panic attacks, particularly for severe panic attacks. Moreover, risperidone has a potential to be the first line drug for treatment of these symptoms.

Consequently, at present, a clinical study of risperidone for treatment of panic attacks is indicated and is of great potential value. We are therefore proposing an exploratory open label single-blind trial of risperidone in vs. paroxetine for treatment of panic attacks.