Vilazodone for Separation Anxiety Disorder

In this randomized clinical trial, 40 adults with a principal diagnosis of Adult Separation Anxiety Disorder (ASAD) and no major depression or substance abuse disorders will be randomized to 12 weeks of treatment with vilazodone (flexibly dosed) or matched pill placebo. Outcome will be assessed in respect to symptomatic improvement, quality of life, adverse events and safety.

• Vilazodone (Drug), also known as Viibryd (brand name): 10mg to 40mg per day for 12 weeks
• Placebo (Drug): One to two pills per day for 12 weeks

Primary outcomes

• Clinical Global Impression-Improvement Scale [Up to 12 weeks]: Clinical Global Impression-Improvement Scale rating at week 12 A quickly administered and widely used observer rating, with ratings from 1 (very much improved) to 7 (very much worse). "Responder" is a score of 1 or 2.

Secondary outcomes

• Change From Baseline Hamilton Rating Scale for Depression 17-item Total Score [Up to 12 weeks]: This standard scale will be used to assess severity of depression, looking at change in total score from baseline to week 12, rating severity of depression on a scale from 0 (least depression) to 50 (greatest depression).
• Change From Baseline in Attachment Style Questionnaire Score [Up to 12 weeks]: Measure Description: (15 min) Attachment Style Questionnaire (Feeney at al., 1994) 40 items relating to quality of adult relationships. Questionnaire includes questions concerning Confidence (8 items, minimum score=8, maximum score=48), Discomfort (10 items, minimum score=10, maximum score=60), Relationships as Secondary (7 items, minimum score=7, maximum score=42), Need for Approval (7 items, minimum score=7, maximum score =42), and Preoccupation with Relationships (8 items, minimum score = 8, maximum score=48), each self-rated on a six-point scale, each self-rated from 1 (totally disagree) to 6 (totally agree).
• Change From Baseline in Quality of Life Enjoyment & Satisfaction Questionnaire [Up to 12 weeks]: Measure Description: (10 min) Quality of Life Enjoyment \& Satisfaction Questionnaire (Q-LES-Q, Endicott et al, 1993): self-rated assessment of quality of life. 16 items related to life quality, each rated on a score of 1 (very poor) to 5 (very good), with a minimum total score of 16, and a maximum total score of 80.
• Change From Baseline on Structured Clinical Interview for Separation Anxiety Disorder [Baseline and week 12]: The Structured Clinical Interview for Separation Anxiety Disorder was modified for DSM-5. The eight separation anxiety disorder criteria are rated for both childhood (rated at baseline only) and past week time frames, scored as 0 (not at all), 1 (sometimes), 2 (often) or ? (don't recall). In keeping with the DSM-5 guidelines, endorsement of three or more of the eight criterion symptoms (symptoms rated as '2' or 'often') is used as a threshold to determine categorical (yes/no) diagnosis of separation anxiety disorder. Scores on each of the eight items are also summed to produce a continuous measure of separation anxiety symptoms experienced during childhood and adulthood (range for each scale=0-16).
• Change From Baseline on Adult Separation Anxiety - 27 Scale [Up to 12 weeks]: Measure Description: (15 min) Adult Separation Anxiety - 27 Scale 27 items pertaining to adult separation anxiety, each self-rated on a four-point scale, 0=best, 3=worse. Minimum Total Score=0 (better); Maximum Total Score = 81 (worse)

Sex: All, ages: 18 Years to 60 Years

Inclusion Criteria:

* Current primary (most clinically significant) diagnosis of DSM5 ASAD
* Able to give consent, fluent in English

Exclusion Criteria:

* Past or current DSM-IV diagnosis of any psychotic disorder; organic mental disorder or other cognitive disorder; bipolar disorder; or antisocial personality disorder. Current MDD of moderate or greater severity. Any other current primary Axis I disorder.
* Recent history (past 3 months) of substance or alcohol abuse or dependence (other than nicotine or caffeine)
* Suicidal ideation or behavior (in the past year) that poses a significant danger to the subject
* Medical illness that could significantly increase risk of vilazodone treatment or interfere with assessment of diagnosis or treatment response, including organic brain impairment from stroke, CNS tumor, or demyelinating disease; renal impairment; diabetes mellitus
* Current or past history of seizure disorder (except febrile seizure in childhood)
* History of non-response to ≥ 2 serotonergic reuptake inhibitor antidepressants (SSRIs and/or SNRIs) for the treatment of ASAD after adequate treatment trials (adequate treatment is defined as at least 8 weeks at an adequate dose\[s\] based on approved package insert recommendations)
* Currently taking medication which has been effective for patient's ASAD
* For patients taking any ineffective psychoactive drug or herbal remedy, inability to tolerate or unwillingness to accept a drug-free period prior to beginning the study of 2 weeks or 5 half-lives (whichever is longer) before beginning study treatment, or ever having been treated with a depot antipsychotic. Fluoxetine washout period will be at least 5 weeks.
* Requiring concomitant treatment with any prohibited medications, supplements, or herbal remedies, except for zolpidem, or zolpidem extended release for insomnia, which may be continued provided the medication has been used in a consistent manner for 4 weeks prior to randomization
* History of intolerance or hypersensitivity to vilazodone, SNRIs or SSRIs
* History of light therapy, electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, or any other experimental procedure for central nervous system disorders within 6 months of beginning this study
* Pregnancy, lactation; for women of childbearing potential, not using an effective birth control method (e.g., oral contraceptive or double barrier method) for the duration of the study
* Current formal psychotherapy initiated within 3 months of beginning this study. This includes: psychodynamic, cognitive-behavioral and interpersonal therapies

Participant flow

Outcome results

• Clinical Global Impression-Improvement Scale (Primary), Count of participants, Participants: Vilazodone 7; Placebo 4 (p .064)
• Change From Baseline Hamilton Rating Scale for Depression 17-item Total Score (Secondary), Mean, units on a scale: Vilazodone 3.7 +/- 3.2; Placebo 8.4 +/- 7.2 (p 0.11)
• Change From Baseline in Attachment Style Questionnaire Score (Secondary), Mean, units on a scale: Vilazodone 32.3 +/- 7.3; Placebo 26.9 +/- 10.3 (p 0.89)
• Change From Baseline in Quality of Life Enjoyment & Satisfaction Questionnaire (Secondary), Mean, units on a scale: Vilazodone 68.9 +/- 9.8; Placebo 47.8 +/- 31.0 (p 0.008)
• Change From Baseline on Structured Clinical Interview for Separation Anxiety Disorder (Secondary), Mean, units on a scale: Vilazodone 3.1 +/- 2.4; Placebo 5.0 +/- 3.5 (p 0.026)
• Change From Baseline on Adult Separation Anxiety - 27 Scale (Secondary), Mean, units on a scale: Vilazodone 14.4 +/- 12.6; Placebo 40.6 +/- 19.2 (p 0.01)

Adverse events

Time frame: Baseline to week 12

Other adverse events by term

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• Results publication: Schneier FR, Moskow DM, Choo TH, Galfalvy H, Campeas R, Sanchez-Lacay A. A randomized controlled pilot trial of vilazodone for adult separation anxiety disorder. Depress Anxiety. 2017 Dec;34(12):1085-1095. doi: 10.1002/da.22693. Epub 2017 Oct 25. PMID 29071764

• Statistical Analysis Plan (PDF, 2016-10-07)
• Informed Consent Form (PDF, 2016-09-30)
• Study Protocol (PDF, 2016-10-07)

• Franklin Schneier, MD, Principal investigator, NYSPI