Clinical trial NCT02852577: Long Term Treatment of Panic Disorder With Clonazepam or Paroxetine
Official title: Long-term, Open, Naturalistic, Randomized Clinical Trial With Clonazepam and Paroxetine in Panic Disorder With or Without Agoraphobia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Panic Disorder
Agoraphobia
Keywords: panic disorder
agoraphobia
clonazepam
paroxetine
Lead sponsor: Universidade Federal do Rio de Janeiro
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2016-08-02
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Global Impression Severity scores at 8 weeks
timeFrame: 8 weeks
Secondary outcomes:
measure: Clinical Global Impression Severity scores at 36 months
timeFrame: 36 months
measure: Clinical Global Impression Severity scores at 4 years
timeFrame: 4 years
measure: Clinical Global Impression Severity scores at 9 years
timeFrame: 9 years
measure: Change from baseline of Clinical Global Impression Severity (CGI-S) scale scores at 8 weeks
timeFrame: Baseline, 8 weeks
measure: Change from baseline of Clinical Global Impression Severity (CGI-S) scale scores at 36 months
timeFrame: Baseline, 36 months
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro
Study officials:
affiliation: Universidade Federal do Rio de Janeiro
name: Rafael C Freire, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.