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Tardive dysphoria: antidepressant-induced chronic depression

Published online by Cambridge University Press:  13 June 2014

Rif S El-Mallakh
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Louisville School of Medicine, Louisville, Kentucky
R Jeannie Roberts
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Louisville School of Medicine, Louisville, Kentucky
Alan Swann
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Texas, Houston Health Science Centre, Houston, Texas
Pat R. Rutherford Jr.
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Texas, Houston Health Science Centre, Houston, Texas
Anton Surja*
Affiliation:
Department of Psychiatry and Behavioural Sciences, University of Louisville School of Medicine, Louisville, Kentucky, United States
*
*Correspondence Email: [email protected]

Abstract

Objectives: A significant number of depressed individuals experience inadequate benefit from long-term antidepressant use. This paper investigates the hypothesis that in some individuals persistent use of antidepressants may be prodepressant.

Methods: Literature regarding the effect of long-term use of antidepressants was reviewed by searching PubMed and Ovid data bases with terms: antidepressant tachyphylaxis, treatment-resistant depression, chronic depression and antidepressant tolerance.

Results: Antidepressant treatment-resistant patients frequently had a positive initial response to antidepressants. When resistance appeared, initial increases in dose or medication changes usually resulted in transient improvement. Eventually, the episodic course of the original depressive illness was replaced with a continuous, unresponsive depressive syndrome. We propose the term tardive dysphoria to describe this phenomenon.

Conclusions: The phenomenon of antidepressantinduced depression, or tardive dysphoria, needs to be experimentally examined in blinded, randomised antidepressant discontinuation studies.

Type
Review
Copyright
Copyright © Cambridge University Press 2011

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References

1.Murray, C, Lopez, AD. The global burden of disease. Cambridge, Mass: Harvard University Press, 1996.Google ScholarPubMed
2.Keller, MB. Issues in Treatment-Resistant Depression. J Clin Psychiatry 2005; 66 (suppl 8): 512.Google ScholarPubMed
3.Kocsis, JH. Recurrent depression: patient characteristics, clinical course, and current recommendations for management. CNS Spectrums 2006; 11:12 (Suppl 15): 611.CrossRefGoogle ScholarPubMed
4.Crown, WH, Finkelstein, S, Berndt, ER, Ling, D, Poret, AW, Rush, AJ, Russell, JM. The impact of treatment resistant depression on health care utilization and costs. J Clin Psychiatry 2002; 63:963971.CrossRefGoogle ScholarPubMed
5.Angst, J. The course of affective disorders. Psychopathology 1986; 19 (suppl 2):4752.CrossRefGoogle ScholarPubMed
6.American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Fourth Edition. Washington, DC: American Psychiatric Press, 2000:339342.Google Scholar
7.Posternak, MA, Solomon, DA, Leon, AC, Mueller, TI, Shea, MT, Endicott, J, Keller, MB. The naturalistic course of unipolar major depression in the absence of somatic therapy. J Nerv Mental Dis 2006; 194:324329.CrossRefGoogle ScholarPubMed
8.Coryell, W, Endicott, J, Keller, M. Outcome of patients with chronic affective disorder: a five-year follow up. Am J Psych 1990; 147: 16271633.Google ScholarPubMed
9.Hirschfield, RMA. Guidelines for the long-term treatment of depression. J Clin Psychiatry 1994; 55(12 suppl): 6169.Google Scholar
10.Thase, M, Sullivan, L. Relapse and recurrence of depression: a practical approach for prevention. CNS Drugs 1995; 4(4): 261277.CrossRefGoogle Scholar
11.Solomon, DA, Keller, MB, Leon, AC, Mueller, TI, Lavori, PW, Shea, MT, Coryell, W, Warshaw, M, Turvey, C, Maser, JD, Endicott, J. Multiple recurrences of major depressive disorder. Am J Psychiatry 2000; 157:229233.CrossRefGoogle ScholarPubMed
12.Bockting, CL, Spinhoven, P, Koeter, MWJ, Wouters, LF, Schene, AH, Depression Evaluation Longitudinal Therapy Assessment Study Group. Prediction of recurrence on recurrent depression and the influence of consecutive episodes on vulnerability for depression: a 2-year prospective study. J Clin Psychiatry 2006; 67:747755.CrossRefGoogle Scholar
13.Reynolds, CF 3rd, Frank, E, Perel, JM, Imber, SD, Cornes, C, Miller, MD, Mazumdar, S, Houck, PR, Dew, MA, Stack, JA, Pollock, BG, Kupfer, DJ. Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years. JAMA 1999; 281: 3945.CrossRefGoogle ScholarPubMed
14.Keller, MB, Kocsis, JH, Thase, ME, Gelenberg, AJ, Rush, AJ, Koran, L, Schatzberg, A, Russell, J, Hirschfeld, R, Klein, D, McCullough, JP, Fawcett, JA, Kornstein, S, LaVange, L, Harrison, W. Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial. JAMA 1998; 280: 16651672.CrossRefGoogle ScholarPubMed
15.American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000; 157 (suppl 4): 145.Google Scholar
16.Prien, RF, Kupfer, DJ, Mansky, PA, Small, JG, Tuason, VB, Voss, CB, Johnson, WE. Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders: report of the NIMH collaborative study group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination. Arch Gen Psychiatry 1984; 41:1096–104CrossRefGoogle Scholar
17.Fava, M, Davidson, KG. Definition and epidemiology of treatment resistant depression. Psychiatr Clin North Am 1996; 19: 179200.CrossRefGoogle ScholarPubMed
18.Thase, ME, Rush, AJ. Treatment-resistant depression; in Bloom, RE, Kupfer, DJ (eds): Psychopharmacology: The Fourth Generation of Progress. New York, NY: Raven Press, Ltd, 1995: 10811097.Google Scholar
19.Shelton, RC, Tollefson, GD, Tohen, M, Stahl, S, Gannon, KS, Jacobs, TG, Buras, WR, Bymaster, FP, Zhang, W, Spencer, KA, Feldman, PD, Meltzer, HY. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry 2001; 158: 131134.CrossRefGoogle ScholarPubMed
20.Keitner, GI, Ryan, CE, Solomon, DA. Realistic expectations and a disease management model for depressed patients with persistent symptoms. J Clin Psychiatry 2006; 67:14121421.CrossRefGoogle Scholar
21.Burrows, GD, Norman, TR, Judd, FK. Definition and differential diagnosis of treatment-resistant depression. Int Clin Psychopharmacol 1994; 9 (Suppl 2): 510.CrossRefGoogle ScholarPubMed
22.Surja, AAS, El-Mallakh, RS. Fertility and childhood bipolar disorder. Med Hypotheses 2007; 69(3):587589.CrossRefGoogle ScholarPubMed
23.Hirschfeld, RM, Keller, MB, Panico, S, Arons, BS, Barlow, D, Davidoff, F, Endicott, J, Froom, J, Goldstein, M, Gorman, JM, Marek, RG, Maurer, TA, Meyer, R, Phillips, K, Ross, J, Schwenk, TL, Sharfstein, SS, Thase, ME, Wyatt, RJ. The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA 1997; 277: 333340.CrossRefGoogle ScholarPubMed
24.Byrne, SE, Rothschild, AJ. Loss of antidepressant efficacy during maintance therapy: possible mechanisms and treatments. J Clin Psychiatry 1998; 59: 279288.CrossRefGoogle Scholar
25.Fava, GA. Can long-term treatments with antidepressant drugs worsen the course of depression? J Clin Psychiatry 2003; 64: 123133.CrossRefGoogle Scholar
26.Sharma, V. Treatment resistance in unipolar depression: Is it an iatrogenic phenomenon caused by antidepressant treatment of patients with a bipolar diathesis? Med Hypotheses 2006; 67: 11421145.CrossRefGoogle ScholarPubMed
27.Lieb, J, Balter, A. Antidepressant tachyphylaxis. Med Hypotheses 1984; 15:279291.CrossRefGoogle ScholarPubMed
28.Cohen, B, Baldessarini, R. Tolerance to therapeutic effects of antidepressants. Am J Psychiatry 1985; 142: 489490.Google ScholarPubMed
29.Nierenberg, AA, Alpert, JE. Depressive breakthrough. Psychiatr Clin North Am 2000; 23(4): 731742.CrossRefGoogle ScholarPubMed
30.Solomon, D, Leon, AC, Mueller, TI, Coryell, W, Teres, IJ, Posternak, MA, Judd, LL, Endicott, J, Keller, MB. Tachyphalaxis in unipolar major depressive disorder. J Clin Psychiatry 2005; 66: 283290.CrossRefGoogle Scholar
31.Posternak, MA, Zimmerman, M. Dual reuptake inhibitors incur lower rates of Tachyphylaxis than selective serotonin reuptake inhibitors: a retrospective study. J Clin Psychiatry 2005; 66: 705707.CrossRefGoogle ScholarPubMed
32.Goldberg, JF, Sacks, MH, Kocsis, JH. Attenuation of response to serotonin reuptake inhibitors (letter). Am J Psychiatry 1995; 152: 954.Google Scholar
33.Diamond, B, Hamner, M, Sunde, D. Possible tolerance to the antidepressant, anti-obsessive-compulsive, and analgesic effects of fluoxetine (abstract). Biol Psychiatry 1989; 25: 155A.CrossRefGoogle Scholar
34.Reimherr, FW, Amsterdam, JD,Quitkin, FM, Rosenbaum, JF, Fava, M, Zajecka, J, Beasley, CM Jr, Michelson, D, Roback, P, Sundell, K. Optimal length of continuation therapy in depression. Am J Psychiatry 1998; 155:12471253.CrossRefGoogle ScholarPubMed
35.Sharma, V. Loss of response to antidepressants and subsequent refractoriness: diagnostic issues in a retrospective case series. J Affect Disord 2001; 64:99106.CrossRefGoogle ScholarPubMed
36.Dunner, DL, Rush, AJ, Russell, JM, Burke, M, Woodard, S, Wingard, P, Allen, J. Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression. J Clin Psychiatry 2006; 67(5): 688695.CrossRefGoogle ScholarPubMed
37.Lieb, J. Antidepressant tachyphlaxis. J Clin Psychiatry 1990; 51:36.Google Scholar
38.Mann, JJ. Loss of antidepressant effect with long-term monoamine oxidase inhibitor treatment without loss of monoamine oxidase inhibition. J Clin Psychopharmacol 1983; 3:363366.CrossRefGoogle ScholarPubMed
39.Donaldson, S. Tolerance to Phenelzine and subsequent refractory depression: three cases. J Clin Psychiatry 1989; 50:3335.Google ScholarPubMed
40.Fava, GA. Do antidepressant and antianxiety drugs increase chronicity in affective disorders? Psychother Psychosom 1994; 61(3-4): 125131.CrossRefGoogle ScholarPubMed
41.El-Mallakh, RS, Waltrip, C, Peters, C. Can long-term antidepressant use be depressogenic? J Clin Psychiatry 1999; 60:263.CrossRefGoogle ScholarPubMed
42.Van Scheyen, JD. Recurrent vital depressions. Psychiatr Neurol Neurochir 1973; 76:93112.Google ScholarPubMed
43.Di Mascio, A, Meyer, RE, Stifler, L. Effect of imipramine in individuals varying in levels of depression. Am J Psychiatry 1968; 127 (Suppl): 5558.CrossRefGoogle Scholar
44.Aronson, TA. Treatment emergent depression with antidepressants in panic disorder. Compr Psychiatry 1989: 30:267271.CrossRefGoogle ScholarPubMed
45.Fux, M, Taub, M, Zohar, J. Emergence of depressive symptoms during treatment for panic disorder with specific 5-hydroxytryptophan reuptake inhibitors. Acta Psychiatr Scand 1993;88:235237.CrossRefGoogle ScholarPubMed
46.Fava, GA, Bernardi, M, Tomba, E, Rafanelli, C. Effects of gradual discontinuation of selective serotonin reuptake inhibitors in panic disorder with agoraphobia. Int J Neuropsychopharmacol 2007; 10: 835838.CrossRefGoogle ScholarPubMed
47.Healy, D. Emergence of antidepressant induced suicidality. Prim Care Psychiatry 2000; 6: 2328.CrossRefGoogle Scholar
48.El-Mallakh, RS, Karippot, A. Chronic depression in bipolar disorder. Am J Psychiatry 163: 11371341, 2006CrossRefGoogle ScholarPubMed
49.El-Mallakh, RS, Karippot, A. Antidepressant-associated chronic irritable dysphoria (ACID) in bipolar disorder: a case series. J Affect Disord 2005; 84: 267272.CrossRefGoogle Scholar
50.Akiskal, HS, Mallya, G. Criteria for the “soft” bipolar spectrum: treatment implications. Psychopharmacol Bull 1987; 23, 6873.Google ScholarPubMed
51.Fava, M, Rappe, SM, Pava, JA, Nierenberg, AA, Alpert, JE, Rosenbaum, JF. Relapse in patients on long-term fluoxetine treatment: response to increased fluoxetine dose. J Clin Psychiatry 1995; 56: 5255.Google ScholarPubMed
52.Schmidt, ME, Fava, M, Zhang, S, Gonzales, J, Raute, NJ, Judge, R. Treatment approaches to major depressive disorder relapse, part I: Dose increase. Psychother Psychosom 2002; 71: 190194.CrossRefGoogle ScholarPubMed
53.Poirier, MF, Boyer, P. Venlafaxine and paroxetine in treatment-resistant depression: double-blind, randomized comparison. Br J Psychiatry 1999; 175: 1216.CrossRefGoogle Scholar
54.Thase, ME, Blomgren, SL, Birkett, MA, Apter, JT, Tepner, RG. Fluoxetine treatment of patients with major depressive disorder who failed initial treatment with sertraline. J Clin Psychiatry 1997; 58: 1621.CrossRefGoogle ScholarPubMed
55.Maes, M, Vandoolaeghe, E, Densnyder, R. Efficacy of treatment with trazadone in combination with pindolol or fluoxetine in major depression. J Affect Disord 1996; 41: 201210.Google ScholarPubMed
56.Heils, A, Teufel, A, Petri, S, Seemann, M, Bengel, D, Balling, U, Riederer, P, Lesch, KP. Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. J Neural Transm 1995; 102: 247254.CrossRefGoogle ScholarPubMed
57.Heils, A, Teufel, A, Petri, S, Stober, G, Riederer, P, Bengel, D, Lesch, KP. Allelic variation of human serotonin trasporter gene expression. J Neurochem 1996; 66: 26212624.CrossRefGoogle Scholar
58.Lesch, KP, Bengel, D, Heils, A, sabol, SZ, Greenberg, BD, Petri, S, Benjamin, J, M_ller, CR, Hamer, DH, Murphy, DL. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 15271531.CrossRefGoogle ScholarPubMed
59.Caspi, A, Sugden, K, Moffitt, TE, Taylor, A, Craig, IW, Harrington, H, McClay, J, Mill, J, Martin, J, Braithwaite, A, Poulton, R. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003; 301: 386389.CrossRefGoogle ScholarPubMed
60.Wilhelm, K, Mitchell, PB, Niven, H, Finch, A, Wedgwood, L, Scimone, A, Blair, IP, Parker, G, Schofield, PR. Life events, first depression onset and the serotonin transporter gene. Br J Psychiatry. 2006; 188: 210215.CrossRefGoogle ScholarPubMed
61.Jacobs, N, Kenis, G, Peeters, F, Deron, C, Vlietinck, R, van Os, J. Stress-related negative affectivity and genetically altered serotonin transporter function: Evidence of synergism in shaping risk of depression. Arch Gen Psychiatry 2006; 63: 989996.CrossRefGoogle ScholarPubMed
62.Murphy, GM, Hollander, SB, Rodrigues, HE, Kremer, C, Schatzberg, AF. Effects of the serotonin trasporter gene promoter polymorphism on mirtrazapine and paroxetine efficacy and adverse events in geriatric major depression. Arch Gen Psychiatry 2004: 61: 11631169.CrossRefGoogle Scholar
63.Durham, LK, Webb, SM, Milos, PM, Clary, CM, Seymour, AB. The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology (Berl) 2004; 174(4): 525529.CrossRefGoogle Scholar
64.Yu, YW, Tsai, SJ, Chen, TJ, Lin, CH, Hong, CJ. Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol Psychiatry 2002; 7: 11151119.CrossRefGoogle ScholarPubMed
65.Pollock, BG, Ferrell, RE, Mulsant, BH, Mazundar, S, Miller, M, Sweet, RA, Davis, S, Kirshner, MA, Houck, PR, Stack, JA, Reynolds, CF III, Kupfer, DJ. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 2000; 23: 587590.CrossRefGoogle ScholarPubMed
66.El-Mallakh, RS, Peters, C, Waltrip, C. Antidepressant treatment and neural plasticity. J Child Adoles Psychopharmacol 2000; 10: 287294.CrossRefGoogle ScholarPubMed
67.Baker, MW, Croll, RP. Modulation of in vivo neuronal sprouting by serotonin in adult CNS of the snail. Cell Molec Neurobiol 1996; 16: 561576.CrossRefGoogle ScholarPubMed
68.Lira, A, Zhou, M, Castanon, N, Ansorge, MS, Gordon, JA, Francis, JH, Bradley-Moore, M, Lira, J, Underwood, MD, Arango, V, Kung, HF, Hofer, MA, Hen, R, Gingrich, JA. Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice. Biol Psychiatry 2003; 54(10): 960971.CrossRefGoogle ScholarPubMed
69.Ansorge, MS, Zhou, M, Lira, A, Hen, R, Gingrich, JA. Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 2004; 306: 879881.CrossRefGoogle ScholarPubMed
70.Voineskos, AN, Wilson, AA, Boovariwala, A, Sagrati, S, Houle, S, Rusjan, P, Sokolov, S, Spencer, EP, Ginovart, N, Meyer, JH. Serotonin transporter occupancy of high-dose selective serotonin reuptake inhibitors during major depressive disorder measured with [11C]DASB positron emission tomography. Psychopharmacology (Berl) 2007; 193(4): 539545.CrossRefGoogle ScholarPubMed
71.Meyer, JH, Wilson, AA, Sagrati, S, Hussey, D, Carella, A, Potter, WZ, Ginovart, N, Spencer, EP, Cheok, A, Houle, S. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11 C]DASB positron emission tomography study. Am J Psychiatry 2004; 161(5): 826835.CrossRefGoogle ScholarPubMed
72.Gaspar, P, Cases, O, Maroteaux, L. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 2003; 4(12): 10021012.CrossRefGoogle ScholarPubMed