Long Term Treatment of Panic Disorder With Clonazepam or Paroxetine

Study Overview
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Brief Summary
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The purpose of this study was to determine whether clonazepam and paroxetine are effective in the treatment of panic disorder. Efficacy was evaluated in short-term, long-term and post-treatment.

Detailed Description
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The current study consisted of three steps. The first step was a naturalistic, prospective, randomized, open clinical trial with clonazepam and paroxetine. Subjects received either flexible dose clonazepam (0.5 - 2 mg/day) or paroxetine (10 - 40 mg/day), in monotherapy for eight weeks. In the second step, those who responded to monotherapy in the short-term study continued with the same drug and dose. Partial responders or non-responders were invited to receive combined pharmacological treatment with clonazepam and paroxetine. Patients received the maximum tolerated doses of clonazepam and paroxetine. The doses were flexible, ranging from 0.5 to 2 mg/day for clonazepam and from 10 to 40 mg/day of paroxetine. All patients were treated for 34 months in the second step. Patients who completed the second step and were in remission were included in the third step. For a period of four months all medications were tapered off. These patients were followed for 6 years with evaluations once a year. Those who relapsed were treated on a naturalistic basis, with drugs or psychotherapy. This study was conducted in accordance with the ethical principles established by the Declaration of Helsinki and the Brazilian National Ethics Committee (Conselho Nacional de Ética em Pesquisa - CONEP) guidelines. The local Ethics Committee approved the study protocol. Written informed consent was obtained from all patients.

Official Title
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Long-term, Open, Naturalistic, Randomized Clinical Trial With Clonazepam and Paroxetine in Panic Disorder With or Without Agoraphobia

Conditions
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Panic Disorder, Agoraphobia

Intervention / Treatment
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* Drug: Clonazepam
* Drug: Paroxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of panic disorder, with or without agoraphobia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision (DSM-IV-TR) criteria, as determined by a structured clinical interview. At least two panic attacks in the week preceding their inclusion in the study. Exclusion Criteria: Patients unable or unwilling to provide written informed consent. Did not complete all the evaluations before study initiation. Had comorbidities that could affect clinical evaluation including drug abuse, neurological disorders, or severe personality disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clonazepam<br>Treatment with clonazepam | Drug: Clonazepam<br>* Administration of clonazepam once a day, flexible dose (0.5 - 2 mg/day), for 36 months. If no remission after 8 weeks augmentation with paroxetine once a day, flexible dose (10 - 40 mg/day), for 34 months.<br>|
| Active Comparator: Paroxetine<br>Treatment with paroxetine | Drug: Paroxetine<br>* Administration of paroxetine once a day, flexible dose (10 - 40 mg/day), for 36 months. If no remission after 8 weeks augmentation with clonazepam once a day, flexible dose (0.5 - 2 mg/day), for 34 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression Severity scores at 8 weeks |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression Severity scores at 36 months |  | 36 months | 
| Clinical Global Impression Severity scores at 4 years |  | 4 years | 
| Clinical Global Impression Severity scores at 9 years |  | 9 years | 
| Change from baseline of Clinical Global Impression Severity (CGI-S) scale scores at 8 weeks |  | Baseline, 8 weeks | 
| Change from baseline of Clinical Global Impression Severity (CGI-S) scale scores at 36 months |  | Baseline, 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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panic disorder, agoraphobia, clonazepam, paroxetine