1. Introduction
Emotional disorders are common disorders that affect the quality of life and cause problems in people worldwide. One of these disorders is the Generalized Anxiety Disorder (GAD) that involves chronic and unpleasant tension and worrying over multiple events or activities and often lasts for at least 6 months and is difficult to control. Despite increasing research on anxiety disorders, GAD remains a less frequently studied disorder. According to multidimensionality and prevalence of GAD and its impact on all aspects of life as well as its complex psychopathology, and considering that most of these patients have more than one disorder and are less likely to respond to psychological therapies, GAD requires more comprehensive interventions and comprehensive treatment guidelines. This study aims to compare the effectiveness of integrated Cognitive-Behavioral Therapy (CBT) and transdiagnostic treatment method in reducing symptoms of patients with GAD comorbid with depression.
2. Materials and Methods
This is a single-case quays-experimental study. The study population consists of all people with GAD and depression referred to counseling centers in Isfahan, Iran in 2019, from whom 10 were selected using a purposive sampling method and randomly assigned into two groups of CBT (n=5) and transdiagnostic treatment (n=50). Subjects in both groups were assessed at baseline, 3rd, 4th, 8th, 10th sessions, and during a one-month follow-up period using the 7-item Generalized Anxiety Scale (GAD-7), the Beck Depression Inventory (BDI-II), and the Penn State Worry Questionnaire (PSWQ). 
After sampling, questionnaires were distributed among the subjects at baseline. Then, the interventions were performed individually. The transdiagnostic treatment was based on the Barlow protocol presented weekly at one-hour sessions. The subjects were re-evaluated  at 3rd, 4th, 8th, 10th sessions (end of treatment) and one month after treatment. To report the results, visual analysis of graphs and Reliable Change Index (RCI), improvement percentage and statistical and clinical significance were used.
3. Results
Visual analysis, percentage of improvement, and RCI value showed that both treatments produced clinically and statistically significant changes in symptoms of GAD, worry and depressive symptoms and whose therapeutic effects continued at the follow-up period. The percentage of improvement in the CBT group was higher in GAD, worry and depression. Regarding depression, CBT with post-intervention improvement percentage of 55.8% and follow-up improvement percentage of 51.8% was more effective compared to transdiagnostic treatment with post-intervention improvement percentage of 35.22% and follow-up improvement percentage of 40.26%. Regarding the symptoms of GAD (Table 1), CBT with post-intervention improvement percentage of 40.21% and follow-up improvement percentage of 40.66% was more effective than transdiagnostic treatment with post-intervention improvement of 32.56% and follow-up improvement of 32.7%.


regarding the variable of worry, CBT with post-intervention improvement of 40.95% and follow-up improvement of 41.81% was more effective than transdiagnostic treatment with post-intervention improvement of 31.40% and follow-up improvement of 34.13%. Therefore, the difference in the effectiveness of treatments is in favor of CBT.
4. Discussion
According to the results, CBT can be used by therapists and specialists along with other treatment models based on the conditions and needs of GAD patients. However, more studies are needed to determine the effectiveness of this method in anxious patients. 

Ethical Considerations
Compliance with ethical guidelines
This study was registered with the code IRCT20200918048749N1 in the Iranian clinical trial site. This article is taken from Farzad Ghaderi's doctoral dissertation with IR.UI code of ethics. REC.1398.013 is from the Department of Psychology, University of Isfahan. Ethical principles included full awareness of the participants about the research process and the confidentiality of their information.

Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors contributions
All authors contributed equally in preparing all parts of the research.

Conflicts of interest
The authors declared no conflict of interest.
 

References

1. Koenigsberg, JZ. Anxiety disorders: Integrated psychotherapy approaches. London: Routledge; 2020. [DOI:10.4324/9780429023637]
2. Bower ES, Wetherell JL, Mon T, Lenze EJ. Treating anxiety disorders in older adults: Current treatments and future directions. Harvard Review of Psychiatry. 2015; 23(5):329-42. [DOI:10.1097/HRP.0000000000000064] [PMID]
3. Timulak L, McElvaney J. Emotion-focused therapy for generalized anxiety disorder: An overview of the model. Journal of Contemporary Psychotherapy. 2016; 46(1):41-52. https://link.springer.com/article/10.1007/s10879-015-9310-7#citeas
4. Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®). Washington, D.C: American Psychiatric Pub; 2013. https://books.google.com/books?id=-JivBAAAQBAJ&printsec=frontcover&dq=Diagnostic+and+statistical+manual+of+mental+disorders+(DSM-5%C2%AE).+2013&hl=en&sa=X&ved=2ahUKEwjYsrTpg9f1AhWSYMAKHcVfCGkQ6AF6BAgFEAI#v=onepage&q&f=false
5. Mohammadi MR, Pourdehghan P, Mostafavi SA, Hooshyari Z, Ahmadi N, Khaleghi A. Generalized anxiety disorder: Prevalence, predictors, and comorbidity in children and adolescents. Journal Anxiety Disord. 2020; 73:102234. [DOI:10.1016/j.janxdis.2020.102234] [PMID]
6. Kaplan BJ, Sadock VA, Ruiz P. Kaplan and sadock's synopsis of psychiatry. Behavioral sciences/clinical psychiatry. Tijdschrift Voor Psychiatrie. 2016; 58(1):78-9. https://www.tijdschriftvoorpsychiatrie.nl/issues/497/articles/10744
7. Shihata S, McEvoy PM, Mullan BA. Pathways from uncertainty to anxiety: An evaluation of a hierarchical model of trait and disorder-specific intolerance of uncertainty on anxiety disorder symptoms. Journal of Anxiety Disorders, 2017; 45:72-9. [DOI:10.1016/j.janxdis.2016.12.001] [PMID]
8. Sharifi V, Amin-Esmaeili M, Hajebi A, Motevalian A, Radgoodarzi R, Hefazi M, et al. Twelve-month prevalence and correlates of psychiatric disorders in Iran: The Iranian Mental Health Survey, 2011. Archives of Iranian Medicine. 2015; 18(2):76-84. [PMID]
9. Leahy RL, Holland SJ, McGinn LK. Treatment plans and interventions for depression and anxiety disorders. New York: Guilford Press; 2011. https://books.google.com/books?id=xZy2xJB-9YsC&printsec=frontcover&dq=Treatment+plans+and+interventions+for+depression+and+anxiety+disorders&hl=en&sa=X&ved=2ahUKEwjwztqyidf1AhVJQ0EAHROVB5sQ6AF6BAgKEAI#v=onepage&q=Treatment%20plans%20and%20interventions%20for%20depression%20and%20anxiety%20disorders&f=false
10. Sharpley CF, Bitsika V, Christie DR. Incidence and nature of anxiety-depression comorbidity in prostate cancer patients. Journal of Men's Health. 2010; 7(2):125-34. [DOI:10.1016/j.jomh.2010.03.003]
11. Saha S, Lim CCW, Cannon DL, Burton L, Bremner M, Cosgrove P, et al. Co-morbidity between mood and anxiety disorders: A systematic review and meta-analysis. Depression and Anxiety. 2021; 38(3):286-306. [DOI:10.1002/da.23113] [PMID] [PMCID]
12. Hobbs MJ, Mahoney AE, Andrews G. Integrating iCBT for generalized anxiety disorder into routine clinical care: Treatment effects across the adult lifespan. Journal of Anxiety Disorders. 2017; 51:47-54. [DOI:10.1016/j.janxdis.2017.09.003] [PMID]
13. Roberge P, Normand-Lauzière F, Raymond I, Luc M, Tanguay-Bernard MM, Duhoux A, et al. Generalized anxiety disorder in primary care: Mental health services use and treatment adequacy. BMC Family Practice. 2015; 16(1):146. [DOI:10.1186/s12875-015-0358-y] [PMID] [PMCID]
14. Rapgay L, Bystritsky A, Dafter RE, Spearman M. New strategies for combining mindfulness with integrative cognitive behavioral therapy for the treatment of generalized anxiety disorder. Journal of Rational-Emotive & Cognitive-Behavior Therapy. 2011; 29(2):92-119. [DOI:10.1007/s10942-009-0095-z] [PMID] [PMCID]
15. Fresco DM, Mennin DS, Heimberg RG, Ritter M. Emotion regulation therapy for generalized anxiety disorder. Cognitive and Behavioral Practice. 2013; 20(3):282-300. [DOI:10.1016/j.cbpra.2013.02.001] [PMID] [PMCID]
16. Hoyer J, Beesdo K, Gloster AT, Runge J, Höfler M, Becker ES. Worry exposure versus applied relaxation in the treatment of generalized anxiety disorder. Psychotherapy and Psychosomatics. 2009; 78(2):106-15. [DOI:10.1159/000201936] [PMID]
17. Edrisi F, Khanzadeh M, Bahrainian A. [Structural model of emotional regulation and symptoms of generalized anxiety disorder in students (Persian)]. Clinical Psychology Studies. 2015; 5(20):203-26. https://www.sid.ir/en/journal/ViewPaper.aspx?id=542968
18. Norton PJ, Barrera TL, Mathew AR, Chamberlain LD, Szafranski DD, Reddy R, et al., Effect of transdiagnostic CBT for anxiety disorders on comorbid diagnoses. Depression and Anxiety. 2013; 30(2):168-73. [DOI:10.1002/da.22018] [PMID]
19. Norton P. Transdiagnostic approaches to the understanding and treatment of anxiety and related disorders. Journal Anxiety Disord. 2017; 46:1-3. [DOI:10.1016/j.janxdis.2017.02.004] [PMID]
20. Norton PJ, Barrera TL. Transdiagnostic versus diagnosis-specific CBT for anxiety disorders: A preliminary randomized controlled noninferiority trial. Depression and Anxiety. 2012; 29(10):874-82. [DOI:10.1002/da.21974] [PMID] [PMCID]
21. Akbari M, Roshan R, Shabani A, Fata L, Shairi MR, Zarghami F. [The comparison of the efficacy of transdiagnostic therapy based on repetitive negative thoughts with unified transdiagnostic therapy in treatment of patients with co-occurrence anxiety and depressive disorders: A randomized clinical trial (Persian)]. Iranian Journal of Psychiatry and Clinical Psychology. 2015; 21(2):88-107. http://ijpcp.iums.ac.ir/article-1-2416-en.html
22. Clark DA, TaylorS. The transdiagnostic perspective on cognitive-behavioral therapy for anxiety and depression: new wine for old wineskins? Journal of Cognitive Psychotherapy. 2009; 23(1):60-6. https://connect.springerpub.com/content/sgrjcp/23/1/60
23. Barlow DH, Franchione TJ, Fairholme CP, Ellard KK, Biosseau CL, Allen LB, et al. Unified protocol for transdiagnostic treatment of emotional disorders: Therapist guide. Oxford: Oxford University Press; 2010. https://www.oxfordclinicalpsych.com/view/10.1093/med:psych/9780199772667.001.0001/med-9780199772667
24. Farchione TJ, Fairholme CP, Ellard KK, Boisseau CL, Thompson-Hollands J, Carl JR, et al. Unified protocol for transdiagnostic treatment of emotional disorders: A randomized controlled trial. Behavior Therapy. 2012. 43(3): 666-78. [DOI:10.1016/j.beth.2012.01.001] [PMID] [PMCID]
25. Boisseau CL, Farchione TJ, Fairholme CP, Ellard KK, Barlow DH. The development of the unified protocol for the transdiagnostic treatment of emotional disorders: A case study. Cognitive and Behavioral Practice. 2010; 17(1):102-13. [DOI:10.1016/j.cbpra.2009.09.003] [PMID] [PMCID]
26. Ellard KK, Fairholme CP, Boisseau CL, Farchione TJ, Barlow DH. Unified protocol for the transdiagnostic treatment of emotional disorders: Protocol development and initial outcome data. Cognitive and Behavioral Practice. 2010. 17(1):88-101. [DOI:10.1016/j.cbpra.2009.06.002] [PMID] [PMCID]
27. Newby JM, Mewton L, Andrews G. Transdiagnostic versus disorder-specific internet-delivered cognitive behaviour therapy for anxiety and depression in primary care. Journal of Anxiety Disorders. 2017; 46:25-34. [DOI:10.1016/j.janxdis.2016.06.002] [PMID]
28. Schaeuffele C, Schulz A, Knaevelsrud C, Renneberg B, Boettcher J. CBT at the crossroads: The rise of transdiagnostic treatments. International Journal of Cognitive Therapy. 2021; 14(1):86-113. https://link.springer.com/article/10.1007/s41811-020-00095-2#citeas
29. Leichsenring F, Steinert C. Towards an evidence-based unified psychodynamic protocol for emotional disorders. Journal of Affective Disorders. 2018; 232: 400-16. [DOI:10.1016/j.jad.2017.11.036] [PMID]
30. Fernandez KC, Jazaieri H, Gross JJ. Emotion regulation: A transdiagnostic perspective on a new RDoC domain. Cognitive therapy and research. 2016; 40(3):426-40. [DOI:10.1007/s10608-016-9772-2] [PMID] [PMCID]
31. Dear BF, Staples LG, Terides MD, Karin E, Zou J, Johnston L, et al., Transdiagnostic versus disorder-specific and clinician-guided versus self-guided internet-delivered treatment for generalized anxiety disorder and comorbid disorders: A randomized controlled trial. Journal of Anxiety Disorders. 2015; 36:63-77. [DOI:10.1016/j.janxdis.2015.09.003] [PMID]
32. Leichsenring F, Abbass A, Hilsenroth MJ, Luyten P, Munder T, Rabung S, et al. "Gold standards," plurality and monocultures: The need for diversity in psychotherapy. Frontiers in Psychiatry. 2018; 9:159. [DOI:10.3389/fpsyt.2018.00159] [PMID] [PMCID]
33. Hirsch CR, Beale S, Grey N, Liness S. Approaching cognitive behavior therapy for generalized anxiety disorder from a cognitive process perspective. Frontiers in Psychiatry. 2019; 10:796. [DOI:10.3389/fpsyt.2019.00796] [PMID] [PMCID]
34. Olatunji BO, Cisler JM, Deacon BJ. Efficacy of cognitive behavioral therapy for anxiety disorders: A review of meta-analytic findings. Psychiatric Clinics of North America. 2010; 33(3):557-77. [DOI:10.1016/j.psc.2010.04.002] [PMID]
35. Alladin A. Integrative CBT for anxiety disorders: An evidence-based approach to enhancing cognitive behavioural therapy with mindfulness and hypnotherapy. New Jersey: John Wiley & Sons; 2015. https://onlinelibrary.wiley.com/doi/book/10.1002/9781118509869
36. Ghaderi F, Akrami N, Namdari K, Abedi A. [Developing an integrated psychotherapy model of generalized anxiety disorder comorbid with emotional disorders; A qualitative approach (Persian)]. Iranian Journal of Rehabilitation Research In Nursing. 2020; 6(4):70-82. https://www.sid.ir/en/journal/ViewPaper.aspx?id=809335
37. Khodayarifard M, Mansori A, Besharat MA, Gholamali Lavasani M. [Religiously and spiritually integrated treatments and generalized anxiety disorder (Persian)]. Journal of Research in Behavioural Sciences. 2017; 15(1):126-34. https://rbs.mui.ac.ir/article-1-524-en.html
38. Daitch C. Cognitive behavioral therapy, mindfulness, and hypnosis as treatment methods for generalized anxiety disorder. American Journal of Clinical Hypnosis. 2018; 61(1):57-69. [DOI:10.1080/00029157.2018.1458594] [PMID]
39. Zolfaghari A, Bahrami H, Ganji K. [Effect of an Integrated Cognitive-Behavioral, Acceptance, and Commitment Intervention on Generalized Anxiety Disorder among University Students (Persian)]. Journal of Education and Community Health. 2018; 4(4):32-38. https://jech.umsha.ac.ir/Article/A-10-458-1
40. Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: The GAD-7. Archives of Internal Medicine. 2006; 166(10):1092-7. [DOI:10.1001/archinte.166.10.1092] [PMID]
41. Naeinian MR, Shaeiri MR, Sharifi M, Hadian M. [To study reliability and validity for a brief measure for assessing generalized anxiety disorder (GAD-7) (Persian)]. Clinical Psychology & Personality. 2011; 9(1):41-50. http://cpap.shahed.ac.ir/article_2647.html?lang=en
42. Davey GC, Wells A. Worry and its psychological disorders: Theory, assessment and treatment. New Jersey: John Wiley & Sons; 2006. https://onlinelibrary.wiley.com/doi/book/10.1002/9780470713143
43. Dehshiri G, Golzari M, Borjali A, Sohrabi F. [Psychometrics particularity of farsi version of pennsylvania state worry questionnaire for college students (Persian)]. Journal of Clinical Psycology. 2009; 1(4):67-75.[DOI:10.22075/jcp.2017.1988]
44. Behar E, Alcaine O, Zuellig AR, Borkovec TD. Screening for generalized anxiety disorder using the Penn State Worry Questionnaire: A receiver operating characteristic analysis. Journal of Behavior Therapy and Experimental Psychiatry. 2003; 34(1): 25-43. [DOI:10.1016/S0005-7916(03)00004-1] [PMID]
45. Ghassemzadeh H, Mojtabai R, Karamghadiri N, Ebrahimkhani N. Psychometric properties of a Persian-language version of the Beck Depression Inventory-Second edition: BDI-II-PERSIAN. Depression and Anxiety. 2005; 21(4):185-92. [DOI:10.1002/da.20070] [PMID]
46. Behirooz A, Haghayegh SA. [Comparison of suicidal thoughts and stress levels among depressed students with morning and evening types (Persian)]. Shenakht Journal of Psychology and Psychiatry. 2019; 6(1):64-74. [DOI:10.29252/shenakht.6.1.64]
47. Hamidpour H, Dolatshai B, Shahbaz AP, Dadkhah A. The efficacy of schema therapy in treating women's generalized anxiety disorder. Iranian Journal of Psychiatry and Clinical Psychology. 2011; 16(4):420-31. https://psycnet.apa.org/record/2011-26327-008
48. Ingram RE, Hayes A, Scott W. Empirically supported treatments: A critical analysis. In: Snyder CR, Ingram RE, editors. Handbook of psychological change: Psychotherapy processes & practices for the 21st century. New Jersey: John Wiley & Sons; 2000. pp. 40-60. https://psycnet.apa.org/record/2001-00353-003
49. Otani A. Hypnosis and mindfulness: The Twain finally meet. American Journal of Clinical Hypnosis. 2016; 58(4):383-98. [DOI:10.1080/00029157.2015.1085364] [PMID]
50. Newby JM, McKinnon A, Kuyken W, Gilbody S, Dalgleish T. Systematic review and meta-analysis of transdiagnostic psychological treatments for anxiety and depressive disorders in adulthood. Clinical Psychology Review. 2015; 40:91-110. [DOI:10.1016/j.cpr.2015.06.002] [PMID]
51. Abasi F, Kimiyae A, Safarian Tosi MR, Abedi MR. [The fourth wave of behavior therapy: The process of formation of behavior Treatments and its challenges (Persian)]. Journal of Rooyesh-e-Ravanshenasi. 2018; 7(1):223-36. http://frooyesh.ir/article-1-965-en.html
52. Bakhshipour A, Vojodi B, Mahmood Alilo M, Abdi R. The effectiveness of integrated Transdiagnostic Treatment in reducing the symptoms of major depressive disorder. Thoughts and Behavior in Clinical Psychology. 2016; 11(41):67-76.
53. Hooman F, Mehrabizadeh Honarmand M, Zargar Y, Davodi I. [The effectiveness of transdiagnostic therapy on anxiety, depression, cognitive strategies of emotional regulation, and general performance in women with comorbid anxiety and depression (Persian)]. Journal of Fasa University of Medical Sciences. 2016; 5(4):551-63. http://jabs.fums.ac.ir/article-1-798-en.html
54. Mansell W, Harvey A, Watkins ED, Shafran R. Conceptual foundations of the transdiagnostic approach to CBT. Journal of Cognitive Psychotherapy. 2009; 23(1):6-19. https://connect.springerpub.com/content/sgrjcp/23/1/6
55. Wilamowska ZA, Thompson-Hollands J, Fairholme CP, Ellard KK, Farchione TJ, Barlow DH. Conceptual background, development, and preliminary data from the unified protocol for transdiagnostic treatment of emotional disorders. Depression and Anxiety. 2010; 27(10): 882-90. [DOI:10.1002/da.20735] [PMID]
56. Fairholme CP, Boisseau CL, Ellard KK, Ehrenreich JT, Barlow DH. Emotions, emotion regulation, and psychological treatment: A unified perspective. In: Kring AM, Sloan DM, editors. Emotion regulation and psychopathology: A transdiagnostic approach to etiology and treatment. New York: The Guilford Press; 2010. pp. 283-309. https://psycnet.apa.org/record/2009-21674-012
57. Hofmann SG, Hayes SC. The future of intervention science: Process-based therapy. Clinical Psychological Science. 2019; 7(1):37-50. [DOI:10.1177/2167702618772296] [PMID] [PMCID]