Authors and Affiliations

  • Mehdi Zemestani

    • Department of Clinical Psychology, University of Kurdistan, Sanandaj, Iran

  • Negar Beheshti

    • Department of Clinical Psychology, University of Kurdistan, Sanandaj, Iran

  • Farzin Rezaei

    • Department of Psychiatry, Kurdistan University of Medical Sciences, Sanandaj, Iran

    • Neuroscience Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

  • Colin van der Heiden

    • Outpatient Treatment Centre PsyQ & Erasmus University, Rotterdam, Netherlands

  • Philip C. Kendall

    • Department of Psychology, Temple University, Philadelphia, Pennsylvania, USA

Corresponding Author

  • Mehdi Zemestani

    • Email: m.zemestani@uok.ac.ir

Publication Details

  • Received: 24 March 2021

  • Accepted: 6 August 2021

  • First Published Online: 1 September 2021

Abstract

  • Issue at Hand: High prevalence and adverse outcomes of Generalized Anxiety Disorder (GAD) necessitate effective treatments.

  • Objective: Compare effectiveness between cognitive behavior therapy targeting intolerance of uncertainty (CBT-IU) and selective serotonin reuptake inhibitors (SSRIs).

  • Participants: 30 Iranian patients with GAD (Mean age: 25.16 ± 6.73).

  • Methods: Participants randomized into CBT-IU (n=15) or SSRI (n=15) with treatment measures including SCID-5, PSWQ, WW-II, IUS, and NPOQ.

  • Results: CBT-IU showed significantly better treatment outcomes compared to SSRIs at post-treatment.

  • Conclusion: Supports the use of CBT-IU as a cross-culturally effective non-medication intervention for reducing GAD symptoms.

  • Keywords: CBT; GAD; intolerance of uncertainty; pharmacotherapy; SSRIs

Introduction

Definition and Prevalence of GAD

  • Generalized Anxiety Disorder (GAD) is characterized by excessive and persistent worry, impacting daily functioning. (American Psychiatric Association, 2013)

  • Epidemiology:

    • Lifetime prevalence of 3.7% globally (Ruscio et al., 2017).

    • 4.3% in the US population (Kessler et al., 2012).

    • Higher prevalence in females compared to males (McLean et al., 2011; Vesga-López et al., 2008).

    • Often chronic, with delayed treatment (6-12 years post onset) (Revicki et al., 2012).

  • Comorbidity: Commonly comorbid with major depression or other anxiety disorders (Kessler et al., 2012; Mennin et al., 2018; Wittchen & Jacobi, 2005).

Treatment Options

Pharmacological Treatments

  • SSRIs and SNRIs are common first choices.

  • Guidelines: SSRIs recommended as first-line treatments (Baldwin et al., 2017; Katzman et al., 2014).

  • Efficacy of SSRIs: Systematic reviews indicate SSRIs are superior to placebo for treating GAD (Baldwin et al., 2017; Slee et al., 2019).

    • However, full remission is rare (Mitte, 2005).

  • Side Effects: Patients may experience adverse effects including suicidality and sexual dysfunction (Baldwin et al., 2017; Schatzberg & DeBattista, 2015).

Psychological Interventions

  • Treatment guidelines recommend CBT, psychodynamic therapy, and applied relaxation (Bolognesi et al., 2014; Covin et al., 2008; Gonçalves & Byrne, 2012; Otte, 2011; Roemer & Orsillo, 2014).

  • CBT: Evidence-based first-line treatment for GAD shown superior to waitlist or treatment-as-usual in RCTs (Szkodny et al., 2014).

  • Effect Sizes: Medium to large effect sizes reported in meta-analyses (Carl et al., 2020; Chen et al., 2019).

  • Recovery Rates: Only 50% achieved criteria for recovery, declining in follow-up assessments (Borkovec et al., 2002).

  • Need for Improved Interventions: Limited recovery rates call for enhancements in treatment (Clark & Beck, 2011; Dugas et al., 2007; Waters & Craske, 2005).

Intolerance of Uncertainty (IU)

Definition

  • Intolerance of Uncertainty (IU): The inability to endure the negative emotional response triggered by uncertainty, leading to avoidance behaviors (Carleton, 2016).

  • Relevance to GAD: A core mechanism in anxiety disorders, particularly GAD (Carleton, 2016; Hebert & Dugas, 2018).

Cognitive Behavioral Therapy for IU (CBT-IU)

  • Purpose: Targets components of IU and its role in GAD.

  • Mechanism: Focuses on mediators of worry:

    1. Intolerance of uncertainty

    2. Cognitive avoidance

    3. Positive beliefs about worry

    4. Negative problem orientation

  • Empirical Support: CBT-IU has demonstrated effectiveness in some trials (Dugas et al., 2010; Hebert & Dugas, 2018; van der Heiden et al., 2012).

Study Methodology

Participants

  • Recruitment: Patients from outpatient psychiatric centers in Sanandaj, Iran.

  • Inclusion: Female, aged >18, meeting DSM-5 criteria for GAD.

  • Exclusion: Severe psychiatric disorders, substance abuse, active suicidal thoughts.

Procedure

  • Design: Pretest-posttest design; registered and ethically approved study.

  • Randomization: Computer-generated random numbers ensured unbiased assignment to CBT-IU or SSRI groups.

Treatments

Pharmacotherapy (SSRIs)

  • Continuous use of SSRIs at optimized doses (e.g., Citalopram, Sertraline, Fluoxetine).

  • Regular monitoring by psychiatrists.

Cognitive Behavior Therapy Targeting Intolerance of Uncertainty (CBT-IU)

  • Format: 12 individual weekly sessions (1 hour each) over 12 weeks

    • Sessions included homework reviews and cognitive-emotional exposure.

    • Focused on psychoeducation, exposure to uncertainty, and cognitive restructuring based on the CBT-IU treatment manual.

Measures

  1. SCID-5: Structured clinical interview for psychiatric disorders based on DSM-5 criteria (reliable and valid).

  2. PSWQ: 16-item measure for worry in GAD; high internal consistency.

  3. WW-II: 25-item self-report measure for positive beliefs about worry; high reliability.

  4. IUS: 27-item measure assessing reactions to uncertainty; good validity.

  5. NPOQ: 12-item scale evaluating dysfunctional attitudes towards problem-solving; high reliability.

Data Analysis

  • Procedure: Data analyzed using IBM SPSS Statistics 22.0 based on intention-to-treat principles.

  • Statistical Tests: 2 (Time) × 2 (Intervention) repeated measures ANOVA.

Results

  • General Findings: Symptoms improved over time with both treatments.

  • CBT-IU versus SSRI: Significant improvements in CBT-IU group for worry (PSWQ), IU (IUS), and negative problem orientation (NPOQ) compared to SSRI group.

  • Statistical Results:

    • For PSWQ: F = [12.59], p = .002, ηp² = .36.

    • For WW-II: F = [11.82], p < .002, ηp² = .35.

    • For IUS: F = [42.55], p < .0001, ηp² = 0.65.

    • For NPOQ: F = [9.83], p < .005, ηp² = .30.

Clinical Implications

  • Treatment Recommendations: Integrating components that tolerate uncertainty in treating GAD patients may enhance therapeutic outcomes.

  • Outcome: Novel CBT protocol targeting IU can effectively reduce GAD symptoms in fewer sessions.

Discussion

  • Significance of Findings: Consistent support for CBT-IU as effective treatment for GAD across cultures, implicating the importance of addressing IU in therapy.

  • Future Directions: Need for larger, more diverse studies to evaluate long-term effects and applicability in varied populations.

Limitations

  • Small sample size and lack of follow-up limit generalizability.

  • Further research necessary to confirm treatment efficacy across broader and more diverse context.

Authors' Contributions

  • MZ: Conceptualized, coordinated, and analyzed the research

  • NB: Data collection and analysis contributions

  • FR: Oversight on pharmacotherapy

  • PCK: Manuscript revisions

Acknowledgements

  • Thanks to participants and contributors to the study.

Funding

  • None reported

Declaration of Interest

  • No conflicts of interest declared.

Ethical Standards

  • Compliance with the Declaration of Helsinki ensuring participant confidentiality and voluntary participation.

Data Availability Statement

  • Data available upon reasonable request.

Symptoms and Characteristics of GAD

  • Excessive Worry: GAD is defined by persistent and chronic anxiety regarding various aspects of life that interferes with daily functioning.

  • Demographics: The disorder is more prevalent in females than males, with a global lifetime prevalence of approximately 3.7%3.7\%.

  • Course of Illness: It is often chronic, and many individuals wait between 6 to 12 years after the onset of symptoms before seeking professional help.

  • Comorbidity: High rates of association with major depression and other anxiety disorders exacerbate the clinical picture.

Biological and Genetic Factors

  • Pharmacological Evidence: The efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs) in treating GAD points toward neurobiological and chemical imbalances as significant biological factors in the maintenance of the disorder (Baldwin et al., 2017).

  • Heritability: Research suggests that GAD involves a genetic predisposition, typically interacting with environmental stressors to manifest as clinical anxiety (Note: You may supplement with studies like Hettema et al., 2001, which estimate heritability at roughly 30%30\%).

Non-Genetic and Environmental Factors

  • Intolerance of Uncertainty (IU): A psychological mechanism described as the inability to endure the negative psychological response triggered by an uncertain situation. This leads to profound avoidance behaviors and chronic worry (Carleton, 2016).

  • Cognitive Mediators: Environmental factors and learned cognitive styles contribute to GAD maintenance through:

    1. Positive Beliefs About Worry: The misconception that worrying helps avoid catastrophe.

    2. Negative Problem Orientation: Viewing problems as threats rather than challenges.

    3. Cognitive Avoidance: Avoiding uncomfortable thoughts or images.

Effective Treatments for GAD
1. Selective Serotonin Reuptake Inhibitors (SSRIs)

  • Efficacy: Citations such as Baldwin et al. (2017) and Slee et al. (2019) establish SSRIs as a primary first-line treatment superior to placebos.

  • Functioning: While helpful for symptom reduction, SSRIs may involve side effects like sexual dysfunction or increased suicidality, and full remission is rarely achieved through medication alone (Mitte, 2005).

2. Cognitive Behavioral Therapy for Intolerance of Uncertainty (CBT-IU)

  • The Study: Zemestani et al. (2021) conducted a randomized clinical trial comparing CBT-IU to SSRIs in Iranian patients.

  • Mechanism: A 12-session protocol focusing on psychoeducation and exposure to uncertainty.

  • Outcomes: CBT-IU was found to be significantly more effective than SSRIs in several metrics:

    • Worry (PSWQ): F=12.59F = 12.59, p=.002p = .002

    • Intolerance of Uncertainty (IUS): F=42.55F = 42.55, p < .0001

    • Negative Problem Orientation (NPOQ): F=9.83F = 9.83, p < .005

  • Conclusion: CBT-IU is a robust, non-medication alternative that effectively targets the core cognitive mechanisms of GAD.

Discussion and Faith Integration

  • Practical Support: Suggestions for support should focus on helping the individual tolerate the "unknowns" of life and restructuring their beliefs about the utility of worry.

  • Faith Perspectives: Anxiety can challenge faith by causing feelings of fear or lack of trust in God's plan. Conversely, it can strengthen faith by encouraging a deeper reliance on divine support and prayer.

  • Scripture Integration: Consider using Philippians 4:6-7 ("Do not be anxious about anything…") or 1 Peter 5:7 ("Cast all your anxiety on him because he cares for you") to support a theological perspective on coping.

Environmental and Cognitive Mechanisms

  • Intolerance of Uncertainty (IU): Recognized as a pivotal psychological mechanism in the development and maintenance of GAD. Carleton (2016) defines IU as an individual's inability to tolerate the negative emotional response triggered by the perceived lack of vital or sufficient information, sustained by the perception of uncertainty. This mechanism often leads to profound avoidance behaviors and chronic worry as a maladaptive coping strategy.

  • Cognitive Mediators of Worry: Research by Dugas et al. (2007, 2010) identifies four key environmental and cognitive factors that influence the maintenance of GAD symptoms:

    1. Positive Beliefs about Worry: The cognitive distortion that worrying serves a protective function, such as preventing negative outcomes or aiding in problem-solving.

    2. Negative Problem Orientation: A dysfunctional cognitive set where individuals view problems as significant threats to their well-being, doubting their ability to solve them and becoming frustrated when encountering them.

    3. Cognitive Avoidance: The process of using worry to avoid more distressing mental imagery or underlying emotional conflicts. By focusing on abstract worries, the individual avoids processing the core emotional physiological responses associated with the threat.

    4. The Role of Learned Experience: While not explicitly detailed as "trauma," these models suggest that these cognitive styles are often learned through environmental interactions and reinforcement over time, contributing to the $3.7\%$ global prevalence rate for the disorder.

  • Intervention Research Support: Zemestani et al. (2021) suggests that targeting these non-genetic factors—specifically IU—leads to superior treatment outcomes compared to pharmacological interventions. This supports the theory that environmental and cognitive mechanisms are central to the disorder's persistence, as evidenced by significant reductions in worry scores (F=12.59F = 12.59, p=.002p = .002) and negative problem orientation (F=9.83F = 9.83, p < .005) when these specific cognitive styles are addressed in therapy.