A 6-Year Posttreatment Follow-up of Panic Disorder Patients: Treatment With Clonazepam Predicts Lower Recurrence Than Treatment With Paroxetine.

BACKGROUND: The aim of this study was to identify factors associated with relapse in panic disorder (PD). METHODS: This was an observational study conducted in the outpatient clinic of a psychiatric hospital in Rio de Janeiro, Brazil. In a previous study, 120 patients diagnosed as having PD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were randomized to receive clonazepam or paroxetine. After 3 years, treatment was discontinued in patients who had achieved remission. These subjects were included in the current study and were followed up for 6 years. The follow-up assessments were made at 1, 2, 3, 5, and 6 years after treatment discontinuation. Assessment included the number of panic attacks per month, Clinical Global Impression-Severity, and other measures. Patients who had initiated psychotherapy or pharmacological treatment because of PD symptoms or who had Clinical Global Impression-Severity scores greater than 1 or panic attacks in the month preceding the assessment were considered relapse cases. Data were collected from January 2003 to August 2012. RESULTS: Eighty-five patients completed the follow-up. Cumulative relapse rates were 50% (n = 33) at 1 year and 89.4% (n = 76) at 6 years. One-year relapse rates were lower in patients previously treated with clonazepam (P = 0.001) compared with those treated with paroxetine. Low 6-year relapse rates were associated with high Hamilton Anxiety Rating Scale scores before treatment (P = 0.016) and previous treatment with clonazepam. CONCLUSIONS: Relapse is a frequent problem in PD, and long-term treatment does not protect these patients in the long run. Treatment with clonazepam predicts lower relapse when compared with paroxetine.

Clonazepam for the treatment of panic disorder.

Clonazepam was initially licensed as an anti-epileptic agent, but its use in a wide variety of psychiatric conditions, including panic disorder (PD) has now been well established. This overview evaluates the current role of clonazepam alone or in combination with antidepressants and/or behavioral therapy in the treatment of PD. We review the data establishing the use of clonazepam in the treatment of PD as well as new information, particularly confirmation of longterm efficacy and safety. We also discuss a regimen for safely tapered withdrawal of clonazepam, the characteristics of the respiratory subtype of PD, and CO2-induced panic attacks as a diagnostic measure and predictor for therapeutic success. It has been shown that panic attacks can more readily be induced by CO2 in PD patients with the respiratory subtype than those with the non-respiratory subtype. More than 25 years after the first report of efficacy in PD in 1984, clonazepam, alone or combined with selective serotonin reuptake inhibitors (SSRIs) and/or behavioral therapy, remains an important therapeutic modality for the management of PD.

A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine.

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

Tapering clonazepam in patients with panic disorder after at least 3 years of treatment.

High-potency benzodiazepines, such as clonazepam, are frequently used in the treatment of panic disorder (PD) because of their rapid onset of action and good tolerability. However, there is concern about their potential to cause withdrawal symptoms. We aimed to develop a protocol for safely tapering off clonazepam in patients with PD who had been receiving treatment for at least 3 years. A specific scale for judging withdrawal was also developed, the Composite Benzodiazepine Discontinuation Symptom Scale. We selected 73 patients with PD who had been asymptomatic for at least 1 year and who wished to discontinue the medication. The trial consisted of a 4-month period of tapering and an 8-month follow-up period. The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached, followed by a decrease of 0.25 mg per week. The mean dosage at the start of tapering was 2.7 +/- 1.2 mg/d. In total, 51 (68.9%) of the patients were free of the medication after the 4 months of tapering according to the protocol, and 19 (26.0%) of the patients needed another 3 months to be free of medication. Clonazepam discontinuation symptoms were mostly mild and included mainly: anxiety, shaking/trembling/tremor, nausea/vomiting, insomnia/nightmares, excessive sweating, tachycardia/palpitations, headache, weakness, and muscle aches. The improvement in PD and general well-being was maintained during both the taper and follow-up phases. Clonazepam can be successfully discontinued without any major withdrawal symptoms if the dose is reduced gradually. We recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk.

Benzodiazepine prescribing to the Swiss adult population: results from a national survey of community pharmacies.

UNLABELLED: The purpose of the study was to assess prevalence of benzodiazepine use in the Swiss adult population and to assess on benzodiazepine prescription patterns of physicians in domiciliary practice. STUDY DESIGN: A retrospective, population-based cross-sectional study with 520 000 patients covering a 6-month period. METHODS: We estimated the prevalence, amount and duration of benzodiazepine use using a pharmacy dispensing database. RESULTS: Of all patients, 9.1% (n=45 309) received at least one benzodiazepine prescription in the 6-month period. Most persons receiving benzodiazepine prescriptions were women (67%), and half of all patients were aged 65 or older. Of 45 309 patients with benzodiazepine prescriptions, 44% (n=19 954) had one single prescription, mostly for a short period (<90 days) and in lower than the recommended dose range. Fifty-six percent (n=25 354) had repeated benzodiazepine prescriptions, mostly for a long time period (>90 days), and in lower than the recommended or within the recommended dose range. In patients with long-term use (n=25 354), however, 1.6% had benzodiazepine prescriptions in extremely high doses. The sample of patients with repeated prescriptions allowed an estimation of a benzodiazepine use of 43.3 daily defined doses per 1000 inhabitants in Switzerland. CONCLUSIONS: Benzodiazepine prescriptions were appropriate for most patients and thus were prescribed in therapeutic doses, as indicated in the treatment guidelines. On the other hand, our survey showed that 1.6% of the patients had prescriptions for long time periods at very high doses, indicating an abuse or dependence on benzodiazepines in this subgroup.