Long Term Treatment of Panic Disorder With Clonazepam or Paroxetine (LTTPANIC)

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

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.

Study Overview

• Status: Completed
• Conditions: Panic Disorder; Agoraphobia
• Intervention / Treatment: Drug: Clonazepam; Drug: Paroxetine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 22290140
    • Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clonazepam; Treatment with clonazepam	Drug: Clonazepam; 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.
Active Comparator: Paroxetine; Treatment with paroxetine	Drug: Paroxetine; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Universidade Federal do Rio de Janeiro
• Collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Investigators: Principal Investigator: Rafael C Freire, MD, PhD, Universidade Federal do Rio de Janeiro

Publications and helpful links

General Publications

• Nardi AE, Valenca AM, Freire RC, Mochcovitch MD, Amrein R, Sardinha A, Levitan MN, Nascimento I, de-Melo-Neto VL, King AL, de O E Silva AC, Veras AB, Dias GP, Soares-Filho GL, da Costa RT, Mezzasalma MA, de Carvalho MR, de Cerqueira AC, Hallak JE, Crippa JA, Versiani M. Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine. Braz J Med Biol Res. 2011 Apr;44(4):366-73. doi: 10.1590/s0100-879x2011007500020. Epub 2011 Feb 18.
• Nardi AE, Valenca AM, Freire RC, Amrein R, Sardinha A, Levitan MN, Nascimento I, de-Melo-Neto VL, King AL, de O e Silva AC, Veras AB, Dias GP, Soares-Filho GL, da Costa RT, Mezzasalma MA, de Carvalho MR, de Cerqueira AC, Hallak JE, Crippa JA, Versiani M. Randomized, open naturalistic, acute treatment of panic disorder with clonazepam or paroxetine. J Clin Psychopharmacol. 2011 Apr;31(2):259-61. doi: 10.1097/JCP.0b013e318210b4ee. No abstract available.
• Nardi AE, Freire RC, Mochcovitch MD, Amrein R, Levitan MN, King AL, Valenca AM, Veras AB, Paes F, Sardinha A, Nascimento I, de-Melo-Neto VL, Dias GP, E Silva AC, Soares-Filho GL, da Costa RT, Mezzasalma MA, de Carvalho MR, de Cerqueira AC, Hallak JE, Crippa JA, Versiani M. A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine. J Clin Psychopharmacol. 2012 Feb;32(1):120-6. doi: 10.1097/JCP.0b013e31823fe4bd. Erratum In: J Clin Psychopharmacol. 2012 Apr;32(2):206.

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: July 21, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimate): August 2, 2016

Study Record Updates

• Last Update Posted (Estimate): August 2, 2016
• Last Update Submitted That Met QC Criteria: July 28, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: paroxetine; panic disorder; agoraphobia; clonazepam
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Anxiety Disorders; Disease; Panic Disorder; Agoraphobia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; GABA Modulators; GABA Agents; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine; Clonazepam
• Other Study ID Numbers: 0003.0.249.000-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No