Summary
Symptoms of anxiety and depression often appear together in patients, either as 2 discrete disorders, such as major depressive disorder and panic disorder, or as a combination of symptoms not meeting criteria for specific disorders. The social, economic, occupational and medical costs of such comorbid anxiety and depression can be enormous, affecting both the individual and society.
The clinician must be creative when treating patients with mixed anxiety and depressive symptoms; psychopharmacological treatment can involve the use of a variety of mono- and polytherapies. Benzodiazepines can be effective in treating anxiety symptoms, but unwanted adverse effects limit their use to the short term. Tricyclic antidepressants, although proven to be effective in treating both anxiety and depressive symptoms, have numerous adverse effects, making them a second-choice therapy. Traditional monoamine oxidase inhibitors have proven efficacy in atypical depression, and the newer reversible and selective inhibitors of monoamine oxidase-A may prove to be very effective in treating both sets of symptoms. Of particular importance in the treatment of patients with anxiety and depressive symptoms are the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, nefazodone and the azapirones (including buspirone).
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References
Robins LN, Locke BZ, Regier DA. An overview of psychiatric disorders in America. In: Robins LN, Regier DA, editors. Psychiatric disorders in America: the Epidemiologic Catchment Area Study. New York: Free Press, 1991: 328–66
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; 168Suppl. 30: 17–30
Angst J, Merikangas KR, Scheidegger P, et al. Recurrent brief depression: a new subtype of affective disorder. J Affect Disord 1990; 19: 87–98
Angst J, Vollrath M, Merikangas KR, et al. Comorbidity of anxiety and depression in the Zurich Cohort Study of young adults. In: Maser JD, Cloninger CR, editors. Comorbidity of mood and anxiety disorders. Washington, DC: American Psychiatric Press, 1990: 123–37
Ball SG, Buchwald AM, Waddell MT, et al. Depression and generalized anxiety symptoms in panic disorder: implications for comorbidity. J Nerv Ment Dis 1995; 183: 304–8
Blazer D, Schwartz M, Woodbury M, et al. Depressive symptoms and depressive diagnoses in a community population: use of a new procedure for analysis of psychiatric comorbidity. Arch Gen Psychiatry 1988; 45: 1078–84
Breslau N, Davis GC. DSM-III generalized anxiety disorder: an empirical investigation of more stringent criteria. Psychiatr Res 1985; 14: 231–8
Breslau N, Davis GC. Further evidence on the doubtful validity of generalized anxiety disorder [letter]. Psychiatr Res 1985; 16: 177–9
Cassano GB, Michelini S. Pharmacological treatment of depression and comorbid anxiety disorders. Adv Biochem Psychopharmacol 1995; 49: 113–25
Katon W, Roy-Byrne PP. Mixed anxiety and depression. J Abnorm Psychol 1991; 100: 337–45
Barrett JE, Barrett JA, Oxman TE, et al. The prevalence of psychiatric disorders in a primary care practice. Arch Gen Psychiatry 1988; 45: 1100–6
Liebowitz MR. Treating the patient with depression and associated anxiety. In: Serotonin —Reshaping the Treatment of Depression. MEDICINE Publishing Foundation Symposium Series, 32. Toronto: The Medicine Group (Canada) Ltd., 1992: 31–41
Boulenger J-P, Lavallée Y-J. Mixed anxiety and depression: diagnostic issues. J Clin Psychiatry 1993; 54Suppl. 1: 3–8
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. rev. Washington, DC: American Psychiatric Association, 1987
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994
Hamilton M. Frequency of symptoms in melancholia (depressive illness). Br J Psychiatry 1989; 154: 201–6
Fava GA, Grandi S, Zielezny M, et al. Cognitive behavioral treatment of residual symptoms in primary major depressive disorder. Am J Psychiatry 1994; 151: 1295–9
Stahl SM. Mixed anxiety and depression: clinical implications. J Clin Psychiatry 1993; 54Suppl. 1: 33–8
World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and guidelines. Geneva: WHO, 1992
Wittchen HU, Essau CA. Comorbidity and mixed anxiety-depressive disorders: is there epidemiologic evidence? J Clin Psychiatry 1993; 54Suppl. 1: 9–15
Thase ME, Simons AD, McGreary J, et al. Relapse after cognitive behavioral therapy of depression: potential implications for longer course of treatment. Am J Psychiatry 1992; 149: 1046–52
Keller MB, Hanks DL. Anxiety symptom relief in depression treatment outcomes. J Clin Psychiatry 1995; 56Suppl. 6: 22–9
Zajecka JM, Ross JS. Management of comorbid anxiety and depression. J Clin Psychiatry 1995; 56 Suppl. 2: 10–3
Kahn RJ, McMair DM, Lipman RS, et al. Imipramine and chlordiazepoxide in depressive and anxiety disorders. II. Efficacy in anxious outpatients. Arch Gen Psychiatry 1986; 43: 79–85
Hoehn-Saric R, McLeod DR, Zimmerli WD. Differential effects of alprazolam and imipramine in generalized anxiety disorder: somatic versus psychic symptoms. J Clin Psychiatry 1988; 49: 293–301
Johnstone EC, Cunningham Owens DG, Frith CD, et al. Neurotic illness and its response to anxiolytic and antidepressant treatment. Psychological Med 1980; 10: 321–8
Rickels K, Cdanalosi I, Chung HR, et al. Amitriptyline in anxious-depressed outpatients: a controlled study. Am J Psychiatry 1974; 131(1): 25–30
Rickels K, Schweizer E. The treatment of generalized anxiety disorder in patients with depressive symptomatology. J Clin Psychiatry 1993; 54 Suppl.: 20–3
Liebowitz MR, Quitkin FM, Stewart JW, et al. Antidepressant specificity in atypical depression. Arch Gen Psychiatry 1988; 45: 129–37
Quitkin FM, Stewart JW, McGrath PJ, et al. Phenelzine versus imipramine in the treatment of probable atypical depression: defining syndrome boundaries of selective MAOI responders. Am J Psychiatry 1988; 145: 306–11
Versiani M, Mundim FD, Nardi AE, et al. Tranylcypromine in social phobia. J Clin Psychopharmacol 1988; 8: 279–83
Liebowitz MR, Quitkin FM, Stewart JW, et al. Effect of panic attacks on the treatment of atypical depressives. Psychopharmacol Bull 1985; 21(3): 558–61
Lydiard RB. Co-existing depression and anxiety: special diagnostic and treatment issues. J Clin Psychiatry 1991; 52Suppl. 6: 48–54
Angst J, Stabl M. Efficacy of moclobemide in different patient groups: a meta-analysis of studies. Psychopharmacology 1992; 106 Suppl.: 109–3
Fitton A, Faulds D, Goa KL. Moclobemide: a review of its pharmacological properties and therapeutic use in depressive illness. Drugs 1992; 43(4): 561–96
Bakish D, Saxena BM, Bowen R, et al. Reversible monoamine oxidase A inhibitors in panic disorder. Clin Neuropharmacology 1993; 16(2 Suppl.): 77S–82S
Johnson MR, Lydiard RB, Ballenger JC. MAOIs in panic disorder and agoraphobia. In: Kennedy SH, editor. Clinical advances in monoamine oxidase inhibitor therapies. Washington, DC: American Psychiatric Press, Inc., 1994: 205–24
Versiani M, Nardi AE, Mundim FD, et al. Pharmacotherapy of social phobia: a controlled study with moclobemide and phenelzine. Br J Psychiatry 1992; 161: 353–60
Bakish D. The use of the reversible monoamine oxidase-A inhibitor brofaromine in social phobia complicated by panic disorder with or without agoraphobia. J Clin Psychopharmacol 1994; 14(1): 74–5
Wakelin J. Differential effects of fluvoxamine, imipramine and placebo on anxiety in depression [abstract]. 16th Congress Collequium Internationale Neuropsycho-pharmacologicum: 1988; Munich
Dunbar GC, Fuell DL. The anti-anxiety and anti-agitation effects of paroxetine in depressed patients. Int Clin Psychopharmacol 1992; 6Suppl. 4: 81–90
den Boer JA, Westenberg GM. Effect of a serotonin and noradrenaline uptake inhibitor in panic disorder: a double-blind comparative study with fluvoxamine and maprotiline. Int Clin Psychopharmacol 1988; 3: 59–74
Roy-Byrne P, Wingerson D, Cowley D, et al. Psychopharmacologic treatment of panic, generalized anxiety disorder, and social phobia. Psychiatr Clin North Am 1993; 16(4): 719–35
Montgomery S, McIntrye M, Osterheide R, et al. A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder. Eur Neuropsychopharmacol 1993; 3(2): 143–52
McDougle CJ, Goodman WK, Leckman JF, et al. The psychopharmacology of obsessive compulsive disorder: implications for treatment and pathogenesis. Psychiatr Clin North Am 1993; 16(4): 749–66
Louie AK, Lewis TB, Lannon RA. Use of low-dose fluoxetine in major depression and panic disorder. J Clin Psychiatry 1993; 54: 435–8
Sternbach H. Fluoxetine treatment of social phobia. J Clin Psychopharmacol 1990; 10(3): 230–1
DeWilde J, Spiers R, Mertens C, et al. A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients. Acta Psychiatr Scand 1993; 87: 141–5
Laws D, Ashford JJ, Anstee JA. A multicentre double-blind comparative trial of fluvoxamine versus lorazepam in mixed anxiety and depression treated in general practice. Acta Psychiatr Scand 1990; 81: 185–9
Houck C, Stankovic S. An open-label study of fluvoxamine in outpatients with mixed anxiety-depressive disorder [poster no. 118]. 37th Annual meeting of the New Clinical Drug Evaluation Unit (NCDEU) program: 1997 May 27–30; Boca Raton
Carrasco JL, Diaz-Marsa M, Saiz J. Sertraline in the treatment of mixed anxiety and depression disorder [in Spanish]. Actas Luso Esp Neurol Psiquiatr Cienc Afines 1997; 25(3): 141–5
Boyer WF, Feighner JP. Side effects of the selective serotonin re-uptake inhibitors. In: Feighner JP, Boyer WF, editors. Selective serotonin re-uptake inhibitors. Chichester: John Wiley & Sons, 1991: 109–17
Bakish D, Hooper CL, Filteau M-J, et al. A double-blind placebo-controlled trial comparing fluvoxamine and imipramine in the treatment of panic disorder with or without agoraphobia. Psychopharmacol Bull 1996; 32(1): 135–41
Schneier F, Campeas R, Fallon B, et al. Buspirone in social phobia [abstract no. O-12-7-8]. Presented at the 17th Congress of Collegium Internationale Neuro-Psychpharmacologium: 1991 Sep 10–14, Kyoto
Schwiezer EE, Amsterdam J, Rickels K, et al. Open trial of buspirone in the treatment of major depressive disorder. Psychopharmacol Bull 1986; 22: 183–5
Fabre LF. Buspirone in the management of major depression: a placebo-controlled comparison. J Clin Psychiatry 1990; 51Suppl. 9: 55–61
Sramek JJ, Tansman M, Suri A, et al. Efficacy of buspirone in generalized anxiety disorder with coexisting mild depressive symptoms. J Clin Psychiatry 1996; 57: 287–91
Sussman N. How to manage anxious patients who are depressed. J Clin Psychiatry 1993; 54(5 Suppl.): 8–16
Rickels K, Robinson DS, Schweizer E, et al. Nefazodone: aspects of efficacy. J Clin Psychiatry 1995; 56Suppl. 6: 43–6
Robinson DS, Roberts DL, Smith JM, et al. The safety profile of nefazodone. J Clin Psychiatry 1996; 57Suppl. 2: 31–8
Fawcett J, Marcus RN, Anton SF, et al. Response of anxiety and agitation symptoms during nefazodone treatment of major depression. J Clin Psychiatry 1995; 56Suppl. 6: 37–42
Zajecka JM. The effect of nefazodone on comorbid anxiety symptoms associated with depression: experience in family practice and psychiatric outpatient settings. J Clin Psychiatry 1996; 57: 10–5
DeMartinis NA, Schweizer E, Rickels K. An open-label trial of nefazodone in high comorbidity panic disorder. J Clin Psychiatry 1996; 57: 245–8
Stewart JW, Quitkin FM, McGrath PJ. Nefazodone may relieve anxiety within two weeks in anxious-depressives [poster 119]. 37th Annual meeting of the New Clinical Drug Evaluation Unit (NCDEU) program: 1997 May 27–30; Boca Raton
Lydiard RB, Laraia MT, Ballenger JC, et al. Emergence of depressive symptoms in patients receiving alprazolam for panic disorder. Am J Psychiatry 1987; 144: 664–5
Marks J. The benzodiazepines. Lancaster: MTP Press Limited, 1985: 100–5
Lecrubier Y, Bourin M, Moon CAL, et al. Efficacy of venlafaxine in depressive illness in general practice. Acta Psychiatr Scand 1997; 95: 485–93
Khan A, Upton V, 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: 19–25
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: 55–62
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Bakish, D., Habib, R. & Hooper, C.L. Mixed Anxiety and Depression. Mol Diag Ther 9, 271–280 (1998). https://doi.org/10.2165/00023210-199809040-00003
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DOI: https://doi.org/10.2165/00023210-199809040-00003