Post Hoc Analyses of Anxiety Measures in Adult Patients With Generalized Anxiety Disorder Treated With Vilazodone

Arif Khan, Suresh Durgam, Xiongwen Tang, Adam Ruth, Maju Mathews, Carl P Gommoll, Arif Khan, Suresh Durgam, Xiongwen Tang, Adam Ruth, Maju Mathews, Carl P Gommoll

Abstract

Objective: To investigate vilazodone, currently approved for major depressive disorder in adults, for generalized anxiety disorder (GAD).

Method: Three randomized, double-blind, placebo-controlled studies showing positive results for vilazodone (2,040 mg/d) in adult patients with GAD (DSM-IV-TR) were pooled for analyses; data were collected from June 2012 to March 2014. Post hoc outcomes in the pooled intent-to-treat population (n = 1,462) included mean change from baseline to week 8 in Hamilton Anxiety Rating Scale (HARS) total score, psychic and somatic anxiety subscale scores, and individual item scores; HARS response (≥ 50% total score improvement) and remission (total score ≤ 7) at week 8; and category shifts, defined as HARS item score ≥ 2 at baseline (moderate to very severe symptoms) and score of 0 at week 8 (no symptoms).

Results: The least squares mean difference was statistically significant for vilazodone versus placebo in change from baseline to week 8 in HARS total score (-1.83, P < .0001) and in psychic anxiety (-1.21, P < .0001) and somatic anxiety (-0.63, P < .01) subscale scores; differences from placebo were significant on 11 of 14 HARS items (P < .05). Response rates were higher with vilazodone than placebo (48% vs 39%, P < .001), as were remission rates (27% vs 21%, P < .01). The percentage of patients who shifted to no symptoms was significant for vilazodone on several items: anxious mood, tension, intellectual, depressed mood, somatic-muscular, somatic-sensory, cardiovascular, respiratory, and autonomic symptoms (P < .05).

Conclusions: Treatment with vilazodone versus placebo was effective in adult GAD patients, with significant differences between treatment groups found on both psychic and somatic HARS items.

Trial registration: ClinicalTrials.gov identifiers: NCT01629966, NCT01766401, NCT01844115.

Figures

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References

    1. Fricchione G. Clinical practice. generalized anxiety disorder. N Engl J Med. 2004;351(7):675–682.
    1. Mendlowicz MV, Stein MB. Quality of life in indivssiduals with anxiety disorders. Am J Psychiatry. 2000;157(5):669–682.
    1. Bandelow B. Defining response and remission in anxiety disorders: toward an integrated approach. CNS Spectr. 2006;11(suppl 12):21–28.
    1. Scholten WD, Batelaan NM, van Balkom AJ, et al. Recurrence of anxiety disorders and its predictors. J Affect Disord. 2013;147(1–3):180–185.
    1. Davidson JR, Feltner DE, Dugar A. Management of generalized anxiety disorder in primary care: identifying the challenges and unmet needs. Prim Care Companion J Clin Psychiatry. 2010;12(2) PCC.09r00772.
    1. Wang PS, Lane M, Olfson M, et al. Twelve-month use of mental health services in the United States: results from the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):629–640.
    1. Wittchen HU, Jacobi F. Size and burden of mental disorders in Europe—a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol. 2005;15(4):357–376.
    1. Grant BF, Hasin DS, Stinson FS, et al. Co-occurrence of 12-month mood and anxiety disorders and personality disorders in the US: results from the national epidemiologic survey on alcohol and related conditions. J Psychiatr Res. 2005;39(1):1–9.
    1. Kessler RC, Aguilar-Gaxiola S, Alonso J, et al. The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol Psichiatr Soc. 2009;18(1):23–33.
    1. Hoffman DL, Dukes EM, Wittchen HU. Human and economic burden of generalized anxiety disorder. Depress Anxiety. 2008;25(1):72–90.
    1. Revicki DA, Travers K, Wyrwich KW, et al. Humanistic and economic burden of generalized anxiety disorder in North America and Europe. J Affect Disord. 2012;140(2):103–112.
    1. Baldwin DS, Waldman S, Allgulander C. Evidence-based pharmacological treatment of generalized anxiety disorder. Int J Neuropsychopharmacol. 2011;14(5):697–710.
    1. Bandelow B, Sher L, Bunevicius R, et al. WFSBP Task Force on Anxiety Disorders, OCD and PTSD. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract. 2012;16(2):77–84.
    1. Lydiard RB, Rickels K, Herman B, et al. Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. Int J Neuropsychopharmacol. 2010;13(2):229–241.
    1. Croft HA, Pomara N, Gommoll C, et al. Efficacy and safety of vilazodone in major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2014;75(11):e1291–e1298.
    1. Khan A, Cutler AJ, Kajdasz DK, et al. A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. J Clin Psychiatry. 2011;72(4):441–447.
    1. Rickels K, Athanasiou M, Robinson DS, et al. Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2009;70(3):326–333.
    1. Mathews M, Gommoll C, Chen D, et al. Efficacy and safety of vilazodone 20 and 40 mg in major depressive disorder: a randomized, double-blind, placebo-controlled trial. Int Clin Psychopharmacol. 2015;30(2):67–74.
    1. Thase ME, Chen D, Edwards J, et al. Efficacy of vilazodone on anxiety symptoms in patients with major depressive disorder. Int Clin Psychopharmacol. 2014;29(6):351–356.
    1. Gommoll C, Durgam S, Mathews M, et al. A double-blind, randomized, placebo-controlled, fixed-dose phase III study of vilazodone in patients with generalized anxiety disorder. Depress Anxiety. 2015;32(6):451–459.
    1. Gommoll C, Forero G, Mathews M, et al. Vilazodone in patients with generalized anxiety disorder: a double-blind, randomized, placebo-controlled, flexible-dose study. Int Clin Psychopharmacol. 2015;30(6):297–306.
    1. Durgam S, Gommoll C, Forero G, et al. Efficacy and safety of vilazodone in patients with generalized anxiety disorder: a randomized, double-blind, placebo-controlled, flexible-dose trial. J Clin Psychiatry. In Press.
    1. Newman MG, Llera SJ, Erickson TM, et al. Worry and generalized anxiety disorder: a review and theoretical synthesis of evidence on nature, etiology, mechanisms, and treatment. Annu Rev Clin Psychol. 2013;9(1):275–297.
    1. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50–55.
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
    1. Guy W. The Clinician Global Severity and Impression scales. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: National Institute of Mental Health; 218–222. DHEW Publication No 76–338. 1976.
    1. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62.
    1. Hidalgo RB, Tupler LA, Davidson JR. An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol. 2007;21(8):864–872.
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
    1. Culpepper L. Generalized anxiety disorder and medical illness. J Clin Psychiatry. 2009;70(suppl 2):20–24.
    1. Rickels K, Weisman K, Norstad N, et al. Buspirone and diazepam in anxiety: a controlled study. J Clin Psychiatry. 1982;43(12 pt 2):81–86.
    1. Rickels K, Zaninelli R, McCafferty J, et al. Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo-controlled study. Am J Psychiatry. 2003;160(4):749–756.
    1. Feighner JP, Cohn JB. Analysis of individual symptoms in generalized anxiety—a pooled, multistudy, double-blind evaluation of buspirone. Neuropsychobiology. 1989;21(3):124–130.
    1. Katz IR, Reynolds CF, 3rd, Alexopoulos GS, et al. Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials. J Am Geriatr Soc. 2002;50(1):18–25.
    1. Meoni P, Hackett D, Lader M. Pooled analysis of venlafaxine XR efficacy on somatic and psychic symptoms of anxiety in patients with generalized anxiety disorder. Depress Anxiety. 2004;19(2):127–132.
    1. Pollack MH, Zaninelli R, Goddard A, et al. Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry. 2001;62(5):350–357.
    1. Rickels K, Pollack MH, Sheehan DV, et al. Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry. 2000;157(6):968–974.
    1. Wittchen HU, Kessler RC, Beesdo K, et al. Generalized anxiety and depression in primary care: prevalence, recognition, and management. J Clin Psychiatry. 2002;63(suppl 8):24–34.
    1. Kessler RC, Keller MB, Wittchen HU. The epidemiology of generalized anxiety disorder. Psychiatr Clin North Am. 2001;24(1):19–39.
    1. Brawman-Mintzer O, Lydiard RB, Crawford MM, et al. Somatic symptoms in generalized anxiety disorder with and without comorbid psychiatric disorders. Am J Psychiatry. 1994;151(6):930–932.
    1. Yonkers KA, Bruce SE, Dyck IR, et al. Chronicity, relapse, and illness—course of panic disorder, social phobia, and generalized anxiety disorder: findings in men and women from 8 years of follow-up. Depress Anxiety. 2003;17(3):173–179.
    1. Bruce SE, Yonkers KA, Otto MW, et al. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Am J Psychiatry. 2005;162(6):1179–1187.
    1. Angst J, Gamma A, Baldwin DS, et al. The generalized anxiety spectrum: prevalence, onset, course and outcome. Eur Arch Psychiatry Clin Neurosci. 2009;259(1):37–45.
    1. Rodriguez BF, Weisberg RB, Pagano ME, et al. Characteristics and predictors of full and partial recovery from generalized anxiety disorder in primary care patients. J Nerv Ment Dis. 2006;194(2):91–97.
    1. Fava GA. Subclinical symptoms in mood disorders: pathophysiological and therapeutic implications. Psychol Med. 1999;29(1):47–61.
    1. Paykel ES. Remission and residual symptomatology in major depression. Psychopathology. 1998;31(1):5–14.
    1. Lecrubier Y, Dolberg OT, Andersen HF, et al. Qualitative changes in symptomatology as an effect of treatment with escitalopram in generalized anxiety disorder and major depressive disorder. Eur Arch Psychiatry Clin Neurosci. 2008;258(3):171–178.
    1. Pollack MH, Meoni P, Otto MW, et al. Predictors of outcome following venlafaxine extended-release treatment of DSM-IV generalized anxiety disorder: a pooled analysis of short- and long-term studies. J Clin Psychopharmacol. 2003;23(3):250–259.
    1. Simon NM, Zalta AK, Worthington JJ, 3rd, et al. Preliminary support for gender differences in response to fluoxetine for generalized anxiety disorder. Depress Anxiety. 2006;23(6):373–376.

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