Efficacy of Expectancy Focused Exposure Therapy for Anxiety Disorders

NCT07753330 | Recruiting DMC

• 1 other identifier: Fondecyt #1251388 (ANID)
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial evaluates whether an optimized exposure-based treatment improves long-term outcomes for adults with anxiety disorders. Specifically, it examines whether Expectancy Focused Exposure (EFE), based on the inhibitory learning model, is more effective than Anxiety Focused Exposure (AFE) in reducing anxiety symptoms and preventing the return of fear over time. The study includes adults aged 18 years and older diagnosed with an anxiety disorder, including social anxiety disorder, specific phobia, generalized anxiety disorder, and panic disorder with or without agoraphobia. Anxiety disorders are highly prevalent and can significantly interfere with daily functioning, work performance, and interpersonal relationships. Exposure therapy is a central component of cognitive behavioral treatment for anxiety disorders. Traditional exposure approaches often focus on reducing anxiety during exposure sessions, but many individuals experience a return of fear after treatment. New theoretical models suggest that exposure may be more effective when designed to violate threat expectations and strengthen inhibitory learning. Participants will be recruited in sequential cohorts and randomly assigned to immediate treatment or a brief waitlist before treatment begins. Those assigned to the waitlist will start treatment at the next study step. When treatment begins, participants will receive either EFE or AFE. Both treatments consist of approximately 10 weekly individual psychotherapy sessions delivered by trained therapists. Participants will complete clinical assessments before treatment, during treatment, immediately after treatment, and at 6, 12, and 18 months after treatment completion. In AFE, exposure exercises are organized along an anxiety hierarchy and focus on reducing anxiety responses through repeated confrontation with feared stimuli. In EFE, exposure focuses on identifying and testing threat expectations, and exercises are designed to maximize expectancy violation and strengthen inhibitory learning. Potential risks include temporary emotional discomfort during exposure exercises. All sessions will be conducted by trained clinicians who monitor participant safety throughout the study. The results may help improve exposure-based treatments for anxiety disorders by identifying strategies that enhance long-term outcomes and reduce relapse.

Conditions

Anxiety Disorders; Panic Disorder; Social Anxiety Disorder (SAD); Generalised Anxiety Disorder; Specific Phobia

Keywords

Exposure Therapy; Randomized Controlled Trial; Expectancy Violation; Optimized Exposure; Inhibitory Retrieval Model; Extinction Learning; Anxiety Disorders; Associative Map; Fear Extinction; Relapse Prevention

Outcome Measures

Primary Outcomes (1)

• Change in standardized disorder-specific anxiety symptom severity

  Severity of the principal anxiety disorder will be assessed using one disorder-specific measure according to each participant's primary diagnosis: the Liebowitz Social Anxiety Scale for social anxiety disorder, the Severity Measure for Specific Phobia-Adult for specific phobia, the Generalized Anxiety Disorder 7-item Scale for generalized anxiety disorder, or the Panic and Agoraphobia Scale for panic disorder with or without agoraphobia. Each scale yields a total symptom severity score, with higher scores indicating greater anxiety severity. Score ranges are: Liebowitz Social Anxiety Scale, 0-72; Severity Measure for Specific Phobia-Adult, 0-40; Generalized Anxiety Disorder 7-item Scale, 0-21; and Panic and Agoraphobia Scale, 0-52. Raw total scores will be transformed into standardized z-scores before analysis. The reported outcome will be a single aggregated standardized z-score representing disorder-specific anxiety severity. Higher z-scores indicate greater symptom severity.

  Baseline; weekly during treatment through post-treatment assessment at session 10, up to 10 treatment sessions; and follow-up assessments at 6, 12, and 18 months after treatment completion.

Secondary Outcomes (4)

• Change in general anxiety symptoms

  Baseline; weekly during treatment through post-treatment assessment at session 10, up to 10 treatment sessions; and follow-up assessments at 6, 12, and 18 months after treatment completion.

• Change in general psychological distress

  Baseline; weekly during treatment through post-treatment assessment at session 10, up to 10 treatment sessions; and follow-up assessments at 6, 12, and 18 months after treatment completion.

• Clinically significant change in standardized disorder-specific anxiety symptom severity

  Baseline; weekly during treatment through post-treatment assessment at session 10, up to 10 treatment sessions; and follow-up assessments at 6, 12, and 18 months after treatment completion.

• Recurrence of anxiety symptoms during follow-up

  From post-treatment assessment through follow-up assessments at 6, 12, and 18 months after treatment completion.

Other Outcomes (7)

• Change in quality of life

  Quality of life will be measured at Baseline, defined as 1 week before treatment begins; and immediately after completion of the 10-week treatment period (week 10)

• Change in state anxiety

  State anxiety will be measured at Baseline, defined as 1 week before treatment begins; and immediately after completion of the 10-week treatment period (week 10)

• Change in trait anxiety

  Trait anxiety will be measured at Baseline, defined as 1 week before treatment begins; and immediately after completion of the 10-week treatment period (week 10)

Study Arms (3)

Expectancy Focused Exposure (EFE)

EXPERIMENTAL

Exposure-based treatment designed to maximize expectancy violation and strengthen inhibitory learning.

Behavioral: Expectancy Focused Exposure

Anxiety Focused Exposure (AFE)

ACTIVE COMPARATOR

Traditional exposure therapy focused on gradual reduction of anxiety responses through repeated exposure.

Behavioral: Anxiety Focused Exposure

Waitlist

NO INTERVENTION

Participants assigned to the waitlist will not receive treatment for 12 weeks before starting one of the active interventions.

Interventions

Expectancy Focused Exposure BEHAVIORAL

Expectancy Focused Exposure is an exposure-based psychological treatment grounded in the inhibitory learning model of exposure therapy (Craske, 2022). The intervention emphasizes the identification and testing of explicit threat expectations associated with feared stimuli or situations. Exposure exercises are designed to maximize expectancy violation by confronting situations that strongly predict feared outcomes and by systematically testing whether these outcomes occur. The goal of the intervention is to strengthen inhibitory learning by disconfirming threat predictions rather than by reducing anxiety during exposure. Clinically, this approach guides how exposure exercises are designed and implemented. Therapists construct a comprehensive associative map of the feared situation in order to plan exposures that maximally challenge the patient's threat expectations. This associative map includes the feared element (conditioned stimulus; CS), the expected consequence (unconditioned stimu

Also known as: EFE

Expectancy Focused Exposure (EFE)

Anxiety Focused Exposure BEHAVIORAL

Anxiety Focused Exposure is a traditional exposure-based cognitive behavioral therapy approach in which exposure exercises are organized according to a graduated hierarchy of feared situations or stimuli. The primary goal of the intervention is to reduce anxiety responses through repeated confrontation with anxiety-provoking stimuli. Exposure sessions focus on gradual increases in exposure intensity while monitoring anxiety levels across repeated exposures. In this approach, the therapist and the participant collaboratively construct an exposure hierarchy that organizes feared situations from least to most anxiety-provoking. This hierarchy allows participants to approach feared situations progressively, beginning with stimuli that evoke lower levels of anxiety and gradually advancing toward more challenging situations. Exposure exercises are conducted following this hierarchical structure, with the aim of promoting reductions in anxiety as individuals repeatedly confront feared situati

Also known as: AFE

Anxiety Focused Exposure (AFE)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Participants must meet all of the following criteria:
• Age between 18 and 70 years.
• Seeking treatment for anxiety-related difficulties.
• Meet DSM-5 diagnostic criteria for a principal anxiety disorder, including:
• social anxiety disorder, specific phobia, generalized anxiety disorder, panic disorder with or without agoraphobia.
• Diagnosis will be established using the ADIS-5 structured clinical interview.
• For participants with generalized anxiety disorder, treatment will focus on the principal anxiety problem identified during assessment.
• Present clinically significant anxiety symptoms associated with the principal diagnosis.
• If currently taking anxiolytic medication, the dosage must have remained stable for at least three months before the start of treatment and should be maintained during the treatment phase whenever possible.
• Willingness and ability to participate in weekly psychotherapy sessions and complete all study assessments.
• Provide informed consent.
• Participants will be excluded if any of the following conditions are present:
• Current psychotic disorder.
• Current manic or hypomanic episode, consistent with bipolar disorder.
• High suicide risk requiring immediate clinical intervention.

Sponsors & Collaborators

• University of Chile: lead
• Universidad de los Andes, Chile: collaborator

Study Sites (1)

Facultad de Ciencias Sociales, Universidad de Chile

Santiago, Santiago Metropolitan, 7800284, Chile

RECRUITING

Related Publications (3)

• Treanor M, Zbozinek TD, Rosenberg BM, Sewart A, Sandman CF, Ruiz J, Craske MG. A randomized controlled trial comparing two processes of exposure therapy: Extinction learning and habituation. J Consult Clin Psychol. 2025 Oct;93(10):705-717. doi: 10.1037/ccp0000970.

  PMID: 41129370 BACKGROUND

• Pittig A, Heinig I, Goerigk S, Thiel F, Hummel K, Scholl L, Deckert J, Pauli P, Domschke K, Lueken U, Fydrich T, Fehm L, Plag J, Strohle A, Kircher T, Straube B, Rief W, Koelkebeck K, Arolt V, Dannlowski U, Margraf J, Totzeck C, Schneider S, Neudeck P, Craske MG, Hollandt M, Richter J, Hamm A, Wittchen HU. Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial. Depress Anxiety. 2021 Nov;38(11):1169-1181. doi: 10.1002/da.23204. Epub 2021 Jul 22.

  PMID: 34293223 BACKGROUND

• Craske, M. (2015). Optimizing Exposure Therapy for Anxiety Disorders: An Inhibitory Learning and Inhibitory Regulation Approach. Verhaltenstherapie, 25(2), 134-143. https://doi.org/10.1159/000381574

  BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Panic Disorder; Phobia, Social; Generalized Anxiety Disorder; Phobia, Specific

Condition Hierarchy (Ancestors)

Mental Disorders; Phobic Disorders

Study Officials

• Vanetza E Quezada-Scholz, PhD

  University of Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanetza E Quezada-Scholz, PhD

CONTACT

+56977361470; qvanetza@u.uchile.cl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessor are blinded to treatment allocation. Therapists are aware of the intervention delivered but are not informed of the study hypothesis regarding the relative effectiveness of the treatments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be enrolled in successive cohorts over time using an open-cohort stepped-wedge design with sequential recruitment. The study includes two active treatment conditions, Expectancy Focused Exposure (EFE) and Anxiety Focused Exposure (AFE), and a brief waitlist condition used as a delayed-start control in selected steps. In Step 1, participants will be randomly assigned to one of three conditions: waitlist, EFE, or AFE. In Step 2, no new waitlist condition will be opened due to the institutional recess and to maintain a uniform waiting period; participants will be assigned only to the two active treatment arms, EFE or AFE, while participants from the Step 1 waitlist will begin treatment. The same structure will be repeated in Steps 3 and 4: in Step 3, participants will again be assigned to waitlist, EFE, or AFE; in Step 4, no new waitlist condition will be opened, and participants will be assigned only to EFE or AFE, while participants from the Step 3 waitlist will begin

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: August 7, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: August 7, 2026

Record last verified: 2026-05

Locations

CL (1)