The Efficacy and Tolerability of Duloxetine for the Treatment of Panic Disorder

Panic Disorder Clinical Trial

Official title:

The Efficacy and Tolerability of Duloxetine for the Treatment of Panic Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00438971
• Other study ID #: 2006-P-000263
• Status: Completed
• Phase: Phase 4
• First received: February 20, 2007
• Last updated: October 29, 2013
• Start date: August 2006
• Est. completion date: January 2009

Study information

• Verified date: October 2013
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disease
• Panic Disorder

Intervention

Drug:
• Duloxetine
Treatment will be initiated at 30mg/day in the first week (week 0), and then increased to 60mg/day at week 1, with the option to increase to 90mg at week 4, and 120mg at week 6.

Locations

Country	Name	City	State
United States	The Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View 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. — View 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. — View Citation

Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994 Jan;51(1):8-19. — View Citation

Marzol PC, Pollack MH. New developments in panic disorder. Curr Psychiatry Rep. 2000 Aug;2(4):353-7. Review. — View 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. Erratum in: J Clin Psychopharmacol. 2004 Feb;24(1):112. — View Citation

Pollack MH. The pharmacotherapy of panic disorder. J Clin Psychiatry. 2005;66 Suppl 4:23-7. — View 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. — View Citation

Sartorius N, Ustün 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Montgomery Asberg Depression Rating Scale (MADRS)	The MADRS is a 10-item clinician rating of depressive symptoms. Scores range from 0 to 60, with higher scores reflecting greater symptom severity.	8 weeks	No
Other	Beck Anxiety Inventory (BAI)	The BAI is a 21-item self-report measure of anxiety with a focus on somatic symptoms. Total scores range from 0 to 63, with higher scores reflecting greater symptom severity.	8 weeks	No
Other	Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)	The Q-LES-Q is a self-report measure of the degree of enjoyment and satisfaction experienced by subjects in various areas of daily functioning. Only the first 14 items are included in scoring, which ranges from 14 to 70, with higher scores reflecting greater enjoyment and satisfaction. The last two items are not included in the total score but are standalone items.	8 weeks	No
Other	Sheehan Disability Scale (SDS)	The SDS is a 3-item measure with each item rated on a 10-point scale. The SDS measures the extent to which work/school, social life, and home life or family responsibilities are impaired by symptoms. Total scores range from 0 to 30, with higher scores reflecting greater impairment.	8 weeks	No
Other	Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)	The LIFE-RIFT is a brief measure of psychosocial functioning in work, interpersonal relations, satisfaction, and recreation. Scores on the LIFE-RIFT can range from 4, indicating very good functioning (no impairment) in all of the 4 component areas, to 20, indicating very poor functioning (severe impairment) in all of the 4 areas.	8 weeks	No
Primary	Panic Disorder Severity Scale (PDSS)	The PDSS contains seven items assessing multiple dimensions of panic disorder severity, including (a) frequency of panic attacks, (b) distress during panic attacks, (c) anticipatory anxiety, (d) agoraphobic fear and avoidance, (e) interoceptive fear and avoidance, (f) impairment of work functioning, and (g) impairment of social functioning. The PDSS ranges from 0 to 28, with higher ratings reflecting greater degrees of symptom severity.	8 weeks	No
Secondary	Clinical Global Impression of Severity Scale (CGI-S)	The CGI-S is a clinician-rated instrument used to assess global severity of symptoms. The CGI-S ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill). Remission was defined strictly as a CGI-S score of 1 or 2 (not at all ill or borderline ill) and zero panic attacks at endpoint.	8 weeks	No
Secondary	Panic Attack Scale (PAS)	The PAS is a measure that assesses participants' total number of panic attacks (situational and unexpected with full and limited symptoms), as well as anticipatory anxiety, since last visit. There is no total score.	8 weeks	No

External Links

•   The Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital