Clinical trial NCT00438971: The Efficacy and Tolerability of Duloxetine for the Treatment of Panic Disorder
Official title: The Efficacy and Tolerability of Duloxetine for the Treatment of Panic Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Panic Disorder
Keywords: Panic Disorder
Anxiety Disorder
Duloxetine
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2007-02-22
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether duloxetine is effective in the treatment of panic disorder.

Detailed description: Panic Disorder is relatively common, with a lifetime prevalence of 3.5 % (Kessler, et al 1994) and characterized by a typically chronic course (Marzol \& Pollack, 2000). Affected individuals tend to be high utilizers of general health care services, frequently receiving extensive and unrevealing medical work-ups (Katon, 1997); while the panic disorder itself often goes unrecognized (Sartorious, et al 1993). Panic disorder has a significant negative impact on work, family, and social life (Rubin, et al 2000), and is associated with increased rates of negative life events and diminished overall quality of life (Cramer, et al 2005). Research indicates that the quality of life and well-being of patients with panic disorder is similarly or more impaired than that of patients with serious medical illnesses, such as type II diabetes (Rubin, et al 2000).

Treatment of panic disorder is focused on the reduction of panic attacks, avoidance behavior, and anticipatory anxiety, as well as the resolution of comorbid conditions. The overarching goal of panic disorder treatment is reduction in symptoms to allow improvement in overall quality of life (Pollack, 2005).

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that has greater initial noradrenergic effects than venlafaxine (Goldstein, et al 2004). Recent data from a placebo controlled fixed dose study, suggested that venlafaxine at 225 mg/d (a dose at which noradrenergic effects are likely to be relevant), was more efficacious on a number of measures of panic disorder than the SSRI, paroxetine (Pollack, et al 2003). This data, combined with our clinical experience with duloxetine to date, support the assertion that duloxetine is likely to prove an effective agent for panic disorder.

Thus, we propose to perform the first systematic examination of the efficacy of duloxetine for panic disorder in a study in which 15 patients with panic disorder will receive duloxetine flexibly dosed from 30 to 120 mg/d in open treatment for 8 weeks. Information learned in this study will help guide treatment selection for panic disorder by providing initial open efficacy data for duloxetine in panic disorder.

Eligibility criteria: Inclusion Criteria:

* Male and female outpatients, age 18-75.
* Diagnosis of Panic Disorder with or without Agoraphobia by DSM-IV criteria
* MGH Panic Clinical Global Impression of Severity score Score equal to or greater than 4
* Patients with current major depressive disorder will be allowed if the panic disorder is primary (as determined on interview by clinician and patient), and the baseline MADRS score is less than or equal to 20
* Willingness and ability to comply with the requirements of the study protocol.

Exclusion Criteria:

* Pregnant or lactating women or others not using acceptable means of birth control (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, implanted progesterone rods stabilized for at least 3 months).
* Patients with current or history of posttraumatic stress disorder, obsessive compulsive disorder, bipolar disorder, schizophrenia or other psychotic conditions.
* Patients on other psychoactive medication, including MAOIs, and those with the potential need to use an MAOI during the study or within 5 day of discontinuation of study drug will be excluded. Participants must have discontinued MAOI use at least 14 days prior study baseline. Patients must discontinue regular benzodiazepine or other non-MAOI antidepressant therapy at least one week (5 weeks for fluoxetine) prior to baseline. Concomitant beta-blockers are proscribed unless prescribed for a medical indication (e.g., hypertension, at a stable daily dose for \> 1 month).
* Patients with a history of alcohol or substance abuse or dependence within the last twelve months, significant alcohol dependence, or a positive toxicology screen consistent with abuse at baseline.
* Patients with significant or unstable neurological or medical disorders or instability for which hospitalization may be likely within the next year. In particular, patients with end-stage renal disease (requiring dialysis) or severe renal impairment, or hepatic insufficiency (defined as twice normal on LFTs as follows: SGPT \>110 u/L or SGOT \>80 u/L) will be excluded.
* Patients with uncontrolled narrow-angle glaucoma will be excluded.
* Seizure disorders with the exception of a history of febrile seizures if they occurred during childhood, were isolated, and did not recur in adulthood.
* Severe personality disorders likely to interfere with study participation.
* Ongoing psychotherapy directed toward the treatment of the panic disorder or agoraphobia. Prohibited psychotherapy includes cognitive behavioral therapy or psychodynamic therapy that focuses on exploring specific, dynamic causes of the panic or phobic symptoms and provides skills for their management, or any of the active ingredients of these psychotherapies. General supportive individual, couples, or family therapy greater than 2 months duration is acceptable.
* History of hypersensitivity or prior non-response or intolerance of duloxetine.
* Patients who have failed 4 or more medication trials of at least 4 weeks at adequate dose (e.g. paroxetine 20mg or equivalent). Treatment failure is here defined as clinician judgment based on assessment of patient history of prior treatment of minimal or no reduction in panic attacks, anticipatory anxiety or avoidance during a specific, medication trial.
* Patients with significant suicidal ideation (MADRS item 10 score \> 3) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.

Primary outcomes:
measure: Panic Disorder Severity Scale (PDSS)
timeFrame: 8 weeks
Secondary outcomes:
measure: Clinical Global Impression of Severity Scale (CGI-S)
timeFrame: 8 weeks
measure: Panic Attack Scale (PAS)
timeFrame: 8 weeks
Other outcomes:
measure: Montgomery Asberg Depression Rating Scale (MADRS)
timeFrame: 8 weeks
measure: Beck Anxiety Inventory (BAI)
timeFrame: 8 weeks
measure: Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
timeFrame: 8 weeks
measure: Sheehan Disability Scale (SDS)
timeFrame: 8 weeks
measure: Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)
timeFrame: 8 weeks
Locations:
city: Boston
country: United States
facility: The Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Mark H Pollack, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Marzol PC, Pollack MH. New developments in panic disorder. Curr Psychiatry Rep. 2000 Aug;2(4):353-7. doi: 10.1007/s11920-000-0081-8.
citation: Katon W, Hart R, Montano B. The effect of panic disorder in the managed care setting. Manag Care Interface. 1997 Nov;10(11):88-94, 98.
citation: Sartorius N, Ustun TB, Costa e Silva JA, Goldberg D, Lecrubier Y, Ormel J, Von Korff M, Wittchen HU. An international study of psychological problems in primary care. Preliminary report from the World Health Organization Collaborative Project on 'Psychological Problems in General Health Care'. Arch Gen Psychiatry. 1993 Oct;50(10):819-24. doi: 10.1001/archpsyc.1993.01820220075008.
citation: Rubin HC, Rapaport MH, Levine B, Gladsjo JK, Rabin A, Auerbach M, Judd LL, Kaplan R. Quality of well being in panic disorder: the assessment of psychiatric and general disability. J Affect Disord. 2000 Jan-Mar;57(1-3):217-21. doi: 10.1016/s0165-0327(99)00030-0.
citation: Cramer V, Torgersen S, Kringlen E. Quality of life and anxiety disorders: a population study. J Nerv Ment Dis. 2005 Mar;193(3):196-202. doi: 10.1097/01.nmd.0000154836.22687.13.
citation: Pollack MH. The pharmacotherapy of panic disorder. J Clin Psychiatry. 2005;66 Suppl 4:23-7.
citation: Pollack MH, Meoni P, Otto MW, Simon N, Hackett D. Predictors of outcome following venlafaxine extended-release treatment of DSM-IV generalized anxiety disorder: a pooled analysis of short- and long-term studies. J Clin Psychopharmacol. 2003 Jun;23(3):250-9. doi: 10.1097/01.jcp.0000084025.22282.84.
citation: Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, Demitrack MA. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004 Aug;24(4):389-99. doi: 10.1097/01.jcp.0000132448.65972.d9.
citation: Simon NM, Kaufman RE, Hoge EA, Worthington JJ, Herlands NN, Owens ME, Pollack MH. Open-label support for duloxetine for the treatment of panic disorder. CNS Neurosci Ther. 2009 Winter;15(1):19-23. doi: 10.1111/j.1755-5949.2008.00076.x.