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Metoclopramide usual dose (0.3-1 and 0.2 mg/kg) with canada drugs free shipping coupon or without a second medication (analgesic; acetaminophen, 0.05-0.06 mg/kg) (Tables 7 and 8). Table 7. Acute treatment of panic disorder with clozapine (Celexa®) compared standard doses of atypical antipsychotics: A total 659 patients treated with clozapine in an open-label manner (n=874). Drug: Mean (median) daily doses (mg) cumulative number of treatment days (days) No. (%)a Drug(s) Used, % Clozapine 0.4 (0.1)c Diazepam Tramadol 0.6 (0.2) 0.7 (0.3)c Diazepam-related withdrawal 3 (1.8) 8 (11) Open in a separate window Table 8. Acute treatment of panic disorder with clozapine compared standard doses of atypical antipsychotics: A total 476 patients treated with clozapine in a clinical trial (n=814) with atypical antipsychotics other than clozapine and a second medication (analgesic; acetaminophen, 0.05-0.06 mg/kg) (Tables 9 and 10). Drug: Mean (median) daily doses (mg) cumulative number of treatment days (day) No. (%)a Drug(s) Used, % Clozapine 0.1 Diazepam 0.2 Tramadol 0.3 0.4 Diazepam-related withdrawal Clozapine - Antispasmodics other than (citalopram, sertraline, risperidone) 0.4 No. of patients 0.8 7.8 Open in a separate window For patients not responding to clozapine treatment, a second antipsychotic should be considered.
RECOMMENDATION AND IMPLEMENTATION The recommendations in this review were based on the largest and most thorough study to date of the use second-line antipsychotics for treatment of panic disorder. Although clozapine is associated with the higher risk of discontinuation and mortality, all its other risks are associated with the use of clozapine and its metabolites, both of which are associated with a lower rate of discontinuation and mortality than other antipsychotics. In addition, these risks are similar to, or much lower than, those associated with atypical antipsychotic use. This review also underscores the high cost of these interventions: from $7,300 how much is metoclopramide cost in 2011 to $13,500 2003 (in 1999 values converted) for a first-line trial dose of clozapine. The cost second-line therapy for patients receiving clozapine may be $13,500 in 2011 dollars and an additional $4,200 if a second antipsychotic is used. The relative cost of atypical versus clozapine therapy is currently not known. In the future, use of clozapine in panic disorder may require its withdrawal. The risk of withdrawal (withdrawal anxiety or insomnia) among patients treated in an open-label study with clozapine was 4%, or 1 additional patient to every 4 receiving clozapine therapy. The risk of withdrawal, however, was significantly reduced in an observational study (n=30) of first-line clozapine (50 mg/day) therapy conducted in Australia.2 The withdrawal process, most significant barrier to treatment success among patients treated with clozapine, could be addressed a pharmacological approach with first-line agent, clozapine, given a longer duration in the treatment. However, because most effective antipsychotic agents for patients with panic disorder are second-line agents, such a pharmacological approach will be challenging. Furthermore, it may not be possible to obtain an adequate safety response, indication for an atypical agent. These factors make the use of second-line agents in addition to clozapine an attractive option. Although patients may have difficulty achieving adequate withdrawal or sleeping patterns due to the severity of panic disorder, these symptoms can be alleviated with an atypical antipsychotic. The safety profile of second-line agents should continue to be monitored closely and, thus, second-line agents may only be considered in patients who have significant side effects when using clozapine.