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Pharmacotherapeutic Options in the Treatment of Comorbid Depression and Anxiety

Published online by Cambridge University Press:  07 November 2014


Although anxiety and mood disorders are listed as separate disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, they frequently coexist. They may be expressed phenotypically as comorbidities or as the provisional entity mixed anxiety-depressive disorder. Patients with both anxiety and depression are more symptomatic, use more health care resources, and have a worse prognosis than those with a single disorder. Recognizing and treating these patients are challenges for physicians because the symptoms of the two disorders often overlap. Administration of effective treatment, comprising both anxiolytic and antidepressant effects, can reduce patient distress and disability, as well as inappropriate utilization of medical services. Medications such as tricyclic antidepressants, selective serotonin reuptake inhibitors, nefazodone, venlafaxine XR (extended release) and mirtazapine, are highly effective in treating comorbid depression and anxiety. These newer agents now represent the pharmacotherapeutic treatments of choice for the comorbid conditions.

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1.Wetzler, S, Katz, MM. Problems with the differentiation of anxiety and depression. J Psychiatr Res. 1989;23:112.CrossRefGoogle ScholarPubMed
2.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Ed, Text Revision. Washington, DC: American Psychiatric Association; 2000:345-484, 780781.Google Scholar
3.Kessler, RC, McGonagle, KA, Zhao, S, et al.Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:819.CrossRefGoogle ScholarPubMed
4.Michels, R, Marzuk, PM. Progress in psychiatry (second of two parts). N Engl J Med. 1993;329:628638.CrossRefGoogle Scholar
5.Zajecka, JM, Ross, JS. Management of comorbid anxiety and depression. J Clin Psychiatry. 1995;56(suppl 2):1013.Google ScholarPubMed
6.Boulenger, J-P, Lavallee, Y-J. Mixed anxiety and depression: diagnostic issues. J Clin Psychiatry. 1993;54(suppl):38.Google ScholarPubMed
7.Boulenger, JP, Fournier, M, Rosales, D, et al.Mixed anxiety and depression: from theory to practice. J Clin Psychiatry. 1997;58(suppl 8):2734.Google ScholarPubMed
8.Zinbarg, RE, Barlow, DH, Liebowitz, M, et al.The DSM-IV field trial for mixed anxiety-depression. Am J Psychiatry. 1994;151:11531162.Google ScholarPubMed
9.Stein, MB, Kirk, P, Prabhu, V, et al.Mixed anxiety-depression in a primary-care clinic. J Affect Disord. 1995;34:7984.CrossRefGoogle Scholar
10.Kessler, RC, Nelson, CB, McGonagle, KA, et al.Comorbidity of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey. Br J Psychiatry. 1996;168(suppl 30):1730.Google Scholar
11.Katon, W, Roy-Byrne, PP. Mixed anxiety and depression. J Abnorm Psychol. 1991;100:337345.CrossRefGoogle ScholarPubMed
12.Fawcett, J. Predictors of early suicide: identification and appropriate intervention. J Clin Psychiatry. 1988;49(suppl):78.Google ScholarPubMed
13.Johnson, J, Weissman, MM, Klerman, GL. Panic disorder, comorbidity, and suicide attempts. Arch Gen Psychiatry. 1990;47:805808.CrossRefGoogle ScholarPubMed
14.Feighner, JP, Entsuah, AR, McPherson, MK. Efficacy of once-daily venlafaxine extended release (XR) for symptoms of anxiety in depressed outpatients. J Affect Disord. 1998;47:5562.CrossRefGoogle ScholarPubMed
15.Cohen, LJ. Rational drag use in the treatment of depression. Pharmacotherapy. 1997;17:4561.Google Scholar
16.Noble, S, Benfield, P. Citalopram: a review of its pharmacology, clinical efficacy and tolerability in the treatment of depression. CNS Drugs. 1997;8:410431.CrossRefGoogle Scholar
17.Rudolph, RL, Entsuah, R, Chitra, R. A meta-analysis of the effects of venlafaxine on anxiety associated with depression. J Clin Pharmacol. 1998;18:136144.Google ScholarPubMed
18.Fawcett, J, Barkin, RL. A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry. 1998;59:123127.CrossRefGoogle Scholar
19.Lepola, UM, Wade, AG, Leinonen, EV, et al.A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder. J Clin Psychiatry. 1998;59:528534.CrossRefGoogle ScholarPubMed
20.Fawcett, J, Marcus, RN, Anton, SF, et al.Response of anxiety and agitation symptoms during nefazodone treatment of major depression. J Clin Psychiatry. 1995;56(suppl 6):3742.Google ScholarPubMed
21.Noyes, R Jr, Burrows, GD, Reich, JH, et al.Diazepam versus alprazolam for the treatment of panic disorder. J Clin Psychiatry. 1996;57:349355.Google ScholarPubMed
22.Lydiard, RB, Laraia, MT, Ballenger, JC, et al.Emergence of depressive symptoms in patients receiving alprazolam for panic disorder. Am J Psychiatry. 1987;144:664665.Google ScholarPubMed
23.Shader, RI, Greenblatt, DJ. Use of benzodiazepines in anxiety disorders. N Engl J Med. 1993;328:13981405.Google ScholarPubMed
24.Central nervous system drugs. In: Drug Facts and Comparisons, 1999 Edition. 7th ed. St Louis, Mo: Facts and Comparisons; 1998:1603.Google Scholar
25.Rickels, K, Amsterdam, J, Clary, C, et al.Buspirone in depressed outpatients: a controlled study. Psychopharmacol Bull. 1990;26:163167.Google ScholarPubMed
26.Wells, BG, Mandos, LA. Depressive disorders. In: DiPiro, JT, Talbert, RL, Yee, GC, et al, eds. Pharmacotherapy: a Pathophysiologic Approach. 3rd ed. Stamford, Conn: Appleton & Lange; 1997:13951417.Google Scholar
27.Gorman, JM. Comorbid depression and anxiety spectrum disorders. Depress Anxiety. 1996;4:160168.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
28.Liebowitz, MR, Fryer, AJ, Gorman, JM, et al.Tricyclic therapy of the DSM-III anxiety disorders: a review with implications for further research. J Psychiatr Res. 1988;22 (suppl 1):731.CrossRefGoogle ScholarPubMed
29.Kuzel, RJ. Treating comorbid depression and anxiety. J Fam Pract. 1996;43(6 suppl):S45S53.Google ScholarPubMed
30.Baldessarini, RJ. Drags and the treatment of psychiatric disorders: depression and mania. In: Hardman, JG, Limbird, LE, Molinoff, PB, et al, eds. Goodman & Gillman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill; 1996:431459.Google Scholar
31.Montejo-Gonzalez, AL, Llorca, G, Izquierdo, JA, et al.SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997;23:179194.CrossRefGoogle Scholar
32.Honig, PK, Wortham, DC, Zamani, K, et al.Terfenadine-ketoconazole interaction: pharma-cokinetic and electrocardiographic consequences. JAMA. 1993;269:15131518.CrossRefGoogle Scholar
33.Goss, JE, Ramo, BW, Blake, K. Torsades de pointes associated with astemizole (Hismanal) therapy [letter]. Arch Intern Med. 1993;153:2705.CrossRefGoogle Scholar
34.Morton, WA, Sonne, SC, Verga, MA. Venlafaxine: a structurally unique and novel antidepressant. Ann Pharmacother. 1995;29:387395.CrossRefGoogle ScholarPubMed
35.Silverstone, PH, Ravindran, A, for the Venlafaxine XR 360 Study Group. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. J Clin Psychiatry. 1998;60:2228.CrossRefGoogle Scholar
36.Montgomery, SA. Rapid onset of action of venlafaxine. Int Clin Psychopharmacol. 1995;10(suppl 2):2127.CrossRefGoogle ScholarPubMed
37.Pollack, MH, Worthington, JJ III, Otto, MW, et al.Venlalaxine for panic disorder: results from a double-blind, placebo-controlled study. Psychopharmacol Bull. 1996;32:667670.Google ScholarPubMed
38.Khan, A, Upton, GV, Rudolph, RL, et al.The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. J Clin Psychopharmacol. 1998;18:1925.CrossRefGoogle ScholarPubMed
39.Hackett, D, Parks, V, Salinas, E. A 6 month evaluation of 3 dose levels of venlafaxine extended-release in non-depressed outpatients with generalized anxiety disorder. Poster presented at: 19th Annual Conference of the Anxiety Disorders Association of America; March 25-28, 1999; San Diego, Calif.Google Scholar
40.Haskins, T, Rudolph, R, Aguiar, L, for the Venlafaxine XR 210 Study Group. Double-blind, placebo-controlled study of once daily venlafaxine XR in outpatients with generalized anxiety disorder. Poster presented at: Association of European Psychiatrists Congress; September 1998; Copenhagen, Denmark.Google Scholar
41.Davidson, JRT, DuPont, RL, Hedges, D, et al.Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry. 1999;60:528535.CrossRefGoogle ScholarPubMed
42.Haskins, JT, Rudolph, R, Aguiar, L, et al, for the Venlafaxine XR 218 Study Group. Venlafaxine XR is an efficacious short- and long-term treatment for generalized anxiety disorder. Poster presented at: European College of Neuropsychopharmacology Congress; October 1998; Paris, France.Google Scholar
43.Rudolph, RL, Derivan, AT. The safety and tolerability of venlafaxine hydrochloride: analysis of the clinical trials database. J Clin Psychopharmacol. 1996;16(3 suppl 2):54S61S.CrossRefGoogle ScholarPubMed
44.Amchin, J, Zarycranski, W, Taylor, KP, et al.Effect of venlafaxine on the pharmacokinetics of alprazolam. Psychopharmacol Bull. 1998;34:211219.Google ScholarPubMed
45.Ereshefsky, L, Riesenman, C, Lam, YWF. Antidepressant drug interactions and the cytochrome P450 system: the role of cytochrome P450 2D6. Clin Pharmacokinet. 1995; 29(suppl 1):1019.CrossRefGoogle ScholarPubMed
46.Ereshefsky, L. Drag-drag interactions involving antidepressants: focus on venlafaxine. J Clin Psychopharmacol. 1996;16(3 suppl 2):37S53S.CrossRefGoogle ScholarPubMed
47.Davis, R, Whittington, R, Bryson, HM. Nefazodone: a review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997;53:608636.CrossRefGoogle ScholarPubMed
48.Feiger, AD, Bielski, RJ, Bremner, J, et al.Doubleblind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression. Int Clin Psychopharmacol. 1999;14:1928.CrossRefGoogle Scholar
49.DeMartinis, NA, Schweizer, E, Rickels, K. An open-label trial of nefazodone in high comorbidity panic disorder. J Clin Psychiatry. 1996;57:245248.Google ScholarPubMed
50.Hedges, DW, Reimherr, FW, Strong, RE, et al.An open trial of nefazodone in adult patients with generalized anxiety disorder. Psychopharmacol Bull. 1996;32:671676.Google ScholarPubMed
51.Nelson, EC. An open-label study of nefazodone in the treatment of depression with and without comorbid obsessive compulsive disorder. Ann Clin Psychiatry. 1994;6:249253.CrossRefGoogle ScholarPubMed
52.Greene, DS, Barbhaiya, RH. Clinical pharmacokinetics of nefazodone. Clin Pharmacokinet. 1997;33:260275.CrossRefGoogle ScholarPubMed
53.Goodnick, PJ, Puig, A, DeVane, CL, et al.Mirtazapine in major depression with comorbid generalized anxiety disorder. J Clin Psychiatry. 1999;60:446448.CrossRefGoogle ScholarPubMed
54.Preskorn, SH. Selection of an antidepressant: mirtazapine. J Clin Psychiatry. 1997;58(suppl 6):38.Google ScholarPubMed

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