Cipralex® for Anxiety Disorders in Adolescents

Study Overview
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Brief Summary
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The primary objective is to examine whether Cipralex® is effective and safe in the treatment of anxiety disorders in youth. The secondary objective is to identify changes in arousal and stress response from pre- to post-treatment with Cipralex® in youth with anxiety disorders.

Detailed Description
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Anxiety disorders are the most common mental illnesses of adolescence, with an overall prevalence ranging from 5.0% to 10.8% (Costello et al, 1996; Ford et al, 2003; Fergusson et al, 1993; Shaffer et al, 1996; Verhulst et al., 1997). Six- to 12-month prevalence has been estimated to be 0.5-2.4% for separation anxiety disorder (SAD), 2.1-4.6% for overanxious disorder (OAD), the DSM-III antecedent of generalized anxiety disorder (GAD), 1.7-6.9% for social phobia (SP), and 0.3-1.2% for panic disorder (PD) (Bowen et al, 1990; Fergusson et al, 1993; Ford et al, 2003; Lewinsohn et al, 1993; Romano et al, 2001; Verhulst et al, 1997). In the US National Comorbidity Survey, the median age of onset for anxiety disorders was 11 years (range 6-21 years), which was much younger than for substance use disorders (20 years) and mood disorders (30 years) (Kessler, 2005). However, anxious youth often go undiagnosed and untreated, possibly because they tend to be compliant and nondisruptive (Esser et al, 1990). This is of concern since research suggests that youth with untreated anxiety disorders are more likely to develop significant problems later in life, such as continued anxiety, depression, substance abuse, suicide attempts, educational underachievement, and impaired psychosocial functioning (Pine et al, 1998; Woodward & Fergusson, 2001). The existing literature on pharmacological treatment of anxiety disorders in adolescents is limited, but suggests that the selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for pervasive and impairing anxiety disorders in youth (Reinblatt & Walkup, 2005). A few randomized controlled trials (RCT) provide support for the use of SSRIs such as fluvoxamine and fluoxetine for the treatment of SAD, GAD and SP. Cipralex® is a newer SSRI whose use for treatment of anxiety disorders in adolescents has been documented in only one previous open trial (Isolan et al., 2007). Results from this study and a few RCTs conducted in adults with anxiety disorders suggest that Cipralex® should be effective and safe for relieving symptoms of anxiety in adolescents. Primary objectives: (1) to assess the clinical and psychosocial changes associated with 16-week open-label treatment with Cipralex® (10 to 20 mg/day) in adolescents with SAD, SP, PD and/or GAD; (2) to assess the tolerance and safety of Cipralex® (10 to 20 mg/day for 16 weeks) in adolescents with SAD, SP, PD and/or GAD. Secondary objective: (1) to investigate changes in physiological measures of arousal and stress response (i.e., heart rate variability, salivary concentrations of cortisol and alpha-amylase, acoustic startle response,) using standardized laboratory stressors, before and after treatment with Cipralex® (10 to 20 mg/day for 16 weeks) in youth with anxiety disorders.

Official Title
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Cipralex® for Anxiety Disorders in Adolescents: Clinical and Physiological Changes Associated With Open Label, Flexible-dose Treatment

Conditions
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Anxiety Disorder

Intervention / Treatment
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* Drug: Cipralex®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary diagnosis of (1 or more) Social Phobia Generalized Anxiety Disorder Separation Anxiety Disorder Panic Disorder Comorbid depression allowed Exclusion Criteria: Unstable medical condition Substance use disorder Current diagnosis of OCD Lifetime diagnosis of developmental delay, pervasive developmental disorder, psychosis

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cipralex®|Based on a starting rate of 5 mg/day, increased by 5 mg every 2 weeks to a maximum of 20 mg/day for weeks 7-16, each participant will receive up to: 10 mg tablets: 28 20 mg tablets: 84 Total for 30 participants: 10 mg tablets: 840 20 mg tablets: 2520 Continuation study for participants who respond to Cipralex - Across 12 weeks, each participant will receive up to: *20 mg tablets: 84 Total for continuation study for all participants (assuming a 60% response rate, N=18): *20 mg tablets: 1512|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Efficacy | Measures used to assess treatment efficacy: The Anxiety Disorders Interview Schedule for DSM-IV, Research and Lifetime Version for Children and Parents (Silverman & Albano, 1996) Multidimensional Anxiety Scale for Children (March et al., 1997) Youth Quality of Life Scale (Topolski et al., 2001), Pediatric Anxiety Rating Scale (RUPP, 2002) Beck Depression Inventory-2 (Beck et al., 1996 Behavioral and Emotional Rating Scale-2 (Epstein & Sharma, 2004), Clinical Global Impression Scale-Severity and Improvement (Guy, W. & ECDEU, 1976) | At week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physiological response to stress | Trier Social Stress Task for Children (TSST-C)[Baseline and week 18] Salivary cortisol[For baseline, samples will be collected in the home upon awakening/8 am, +30, +60 min, at 4 pm, and at 8 pm on 2 consecutive weekdays. Cortisol will also be measured from samples collected before and after the TSST-C(-1, +10, +20, +30, +45, and +60 min)] Salivary alpha-amylase[Before (-1), and +1, +10, +20, and +30 min after the TSST-C] Heart rate variability[Baseline and during the TSST-C] Acoustic Startle Response[Baseline and in a fear-potentiated condition with an ASR system] Urine drug test | At week 18 - see below | 
| Suicide risk | At each treatment visit, the clinician will elicit AEs and SAEs, and complete the Columbia-Suicide Severity Rating Scale (C-SSRS) (Posner et al, 2007) | Each treatment visit (baseline then weeks 2, 4, 6, 8, 12, 16, 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescents, Anxiety Disorder, Cipralex, Social Phobia, Separation Anxiety Disorder, Panic Disorder, Generalized Anxiety Disorder, physiological arousal, stress response, salivary cortisol, salivary alpha-amylase, heart rate variability