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Pharmacological management of treatment resistant depression: a clinical review

Published online by Cambridge University Press:  13 June 2014

Noel Kennedy
Affiliation:
Box 63, Institute of Psychiatry, London, England
Michael McDonough
Affiliation:
Maudsley Hospital, London, England

Abstract

Objectives: Treatment resistant depression (TRD), commonly encountered in clinical practice, leads to socioeconomic disability and therapeutic pessimism. This paper reviews evidence for pharmacological approaches used in TRD.

Method: Electronic literature searches were performed using Medline and Psychlit using broad search terms relating to TRD.

Results: Agents that potentiate both serotonin and noradrenaline may allow more patients to achieve full remission. Attention must be paid to dose titration and length of treatment courses in TRD. Augmentation with lithium and switching within antidepressant class or between classes can often improve symptoms but efficacy of other augmentation approaches remains uncertain. Antidepressant combinations and addition of atypical antipsychotics can be useful but combinations of predominantly serotonergic antidepressants should be avoided. Electroconvulsive therapy retains an important role in TRD but pharmacological treatments need to be continued concomitantly.

Conclusions: Good improvement is seen in TRD after vigorous antidepressant treatment but most patients continue to have lower grade symptomatology.

Type
Review
Copyright
Copyright © Cambridge University Press 2000

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References

1.Leonard, BE. Biochemical aspects of therapy-resistant depression. Br J Psychiatry 1988;152:453459.CrossRefGoogle ScholarPubMed
2.Nierenberg, AA, Amsterdam, D. Treatment resistant depression: definition and treatment approaches. J Clin Psychiatry 1990; 6 (Suppl.): 3947.Google Scholar
3.Fava, M, Davidson, KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am 1996; 19:179199.CrossRefGoogle ScholarPubMed
4.Nelson, JC. Overcoming treatment resistance in depression. J Clin Psychiatry 1998; 59 (Suppl. 16): 1319.Google ScholarPubMed
5.Fawcett, J, Kravitz, HM. Treatment refractory depression. In Schatzburg, AF, ed. Common Treatment Problems in Depression. Washington DC, American Psychiatric Press 1988: 213234.Google Scholar
6.Berndt, ERet al.Lost human capital from early-onset chronic depression. Am J Psychiatry 2000; 157: 940947.CrossRefGoogle ScholarPubMed
7.Hirschfeld, RMet al.Social functioning in depression: a review. J Clin Psychiatry 2000, 61:268275.CrossRefGoogle ScholarPubMed
8.Judd, LLet al.Psychosocial disability during the long-term course of unipolar major depressive disorder. Arch Gen Psychiatry 2000; 57: 375380.CrossRefGoogle ScholarPubMed
9.Goodman, WK, Charney, DS. Biological approaches to the treatment of refractory depression. Yale Psychiatric Quarterly 1984; 2: 523.Google Scholar
10.McGrath, PJet al.Treatment of refractory depression with a monoamine oxidase inhibitor anti-depressant. Psychopharmacol Bull 1987; 23: 169173.Google Scholar
11.Nelsen, MR, Dunner, DL. Treatment resistance in unipolar depression and other disorders. Psychiatr Clin North Am 1993; 16: 541566.CrossRefGoogle ScholarPubMed
12.Fink, M. Electroconvulsive therapy in medication-resistant depression. In Amsterdam, JD, Hornig, M, Nierenberg, AA. eds. Treatment-Resistant Mood Disorders. Cambridge University Press, Cambridge, United Kingdom 2001: 223238.CrossRefGoogle Scholar
13.Thase, ME, Rush, AJ. When at first you don't succeed: sequential strategies for antidepressant non-responders. J Clin Psychiatry 1997; 58 (Suppl. 13): 2329.Google Scholar
14.Souery, Det al.Treatment resistant depression: methodological overview and operational criteria. European Neuropsychopharmacol 1999; 9: 8391.CrossRefGoogle ScholarPubMed
15.Targum, SDet al.Thyroid hormone and the TRH stimulation test in refractory depression. J Clin Psychiatry 1984; 45: 345346.Google ScholarPubMed
16.Gold, PW, Goodwin, FK, Chrrousos, GP. Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. Part II. NEJM 1988; 319: 413420.Google Scholar
17.Gruber, AJ, Hudson, Jl, Pope, HG. The management of treatment depression in disorders on the interface of psychiatry and medicine. Psychiatr Clin North Am 1996; 19:351361.CrossRefGoogle ScholarPubMed
18.Nelsen, MR, Dunner, DL. Clinical and differential diagnostic aspects of treatment-resistant depression. J Psychiatr Res 1995; 29: 4350.CrossRefGoogle ScholarPubMed
19.Pfohl, B, Stangl, D, Zimmerman, M. The implications of DSM-III personality disorders for patients with major depression. J Affect Disord 1984; 7: 309318.CrossRefGoogle ScholarPubMed
20.Scott, J, Eccleston, D, Boys, R. Can we predict the persistence of depression? Br J Psychiatry 1992; 161: 633637.CrossRefGoogle ScholarPubMed
21.O'Leary, Det al.Remission, onset and relapse in depression. An 18-month prospective study of course for 100 first admission patients. J Affect Disord. 2000; 57: 159171.Google ScholarPubMed
22.Anderson, IM. Lessons to be learnt from meta-analysis of newer versus older antidepressants. Advan Psychiatr Treat 1997; 3: 5863.CrossRefGoogle Scholar
23.Anderson, IM. Meta-analytical studies on new antidepressants. Br Med Bull 2001; 57:161178.CrossRefGoogle ScholarPubMed
24.Clerc, GE, Ruimy, P, Verdeau-Palles, J. A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group. Int Clin Psychopharmacol 1994; 9:139143.CrossRefGoogle ScholarPubMed
25.Dierick, Met al.A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. Prog in Neuropsychopharmacol Biol Psychiatry 1996; 20: 5771.CrossRefGoogle ScholarPubMed
26.Costa e Silva, J. Randomized double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression. J Clin Psychiatry 1998; 59: 352357.CrossRefGoogle ScholarPubMed
27.Methonen, OPet al.Randomized, double-blind comparison of venlafaxine and setraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group. J Clin Psychiatry 2000; 61: 95100.CrossRefGoogle Scholar
28.Nierenberg, AAet al.Venlafaxine for treatment-resistant unipolar depression. J Clin Psychopharmacol 1994; 14: 419423.CrossRefGoogle ScholarPubMed
29.de Montigny, Cet al.Venlafaxine in treatment-resistant major depression: a Canadian multicenter, open-labelled trial. J Clin Psychopharmacol 1999; 19: 401406.CrossRefGoogle Scholar
30.Poirier, MF, Boyer, P. (1999) Venlafaxine and paroxetine in treatment-resistant depression. Double-blind randomised comparison. Br J Psychiatry 1999; 175: 1216.CrossRefGoogle ScholarPubMed
31.Medical Research Council Clinical Trials Subcommittee. Clinical trial on the treatment of depressive illness. BMJ 1965; 2: 881886.Google Scholar
32.Quitkin, FMet al.Colombia atypical depression. A subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo. Br J Psychiatry 1983; 163 (Suppl. 21): 3034.CrossRefGoogle Scholar
33.Pande, ACet al.Fluoxetine versus phenelzine in atypical depression. Biol Psychiatry 1996; 40: 10171020.CrossRefGoogle ScholarPubMed
34.McGrath, PJet al.A placebo controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry 2000; 157: 344350.CrossRefGoogle ScholarPubMed
35.Keller, MBet al.Treatment received by depressed patients. JAMA 1982; 248:18481855.CrossRefGoogle ScholarPubMed
36.Scott, J. Are there different subtypes of chronic major depression? A preliminary report. Adv Affect Disord 1992; 7: 67.Google Scholar
37.Lehman, HE. Therapy-resistant depression: a clinical classification. Pharmacopsychiatrica 1974; 7:156163.CrossRefGoogle Scholar
38.Simpson, GMet al.Two doses of imipramine in hospitalized endogenous and neurotic depressives. Arch Gen Psychiatry 1976; 33:10931102.CrossRefGoogle Scholar
39.Kocsis, JH, Voss, C, Mann, JJ. Chronic depression: demographic and clinical characteristics. Psychopharmacol Bull 1986; 22:192195.Google ScholarPubMed
40.Guscott, R, Goff, P. The clinical meaning of refractory depression: a review for the clinician. Am J Psychiatry 1991; 148: 695704.Google ScholarPubMed
41.Phillips, KA, Nierenberg, AA. The assessment and treatment of refractory depression. J Clin Psychiatry 1994; 55 (Suppl.): 2026.Google ScholarPubMed
42.Young, WPet al.Human monoaminoxidase: lack of brain and platelet correlation. Arch Gen Psychiatry 1986; 43: 604609.CrossRefGoogle Scholar
43.Mendels, Jet al.Efficacy and safety of b.i.d. doses of venlafaxine in a dose-response study. Psychopharmacol Bull 1993; 29:169174.Google Scholar
44.Rudolph, RLet al.A randomized placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry 1996; 59:116122.CrossRefGoogle Scholar
45.Kienke, AS, Rosenbaum, JF. Efficacy of venlafaxine in the treatment of severe depression. Depress Anxiety 2000; 12 (Suppl. 1): 5054.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
46.Cowen, PJ. Pharmacological management of treatment-resistant depression. Advan Psychiatr Treat 1998; 4: 320327.CrossRefGoogle Scholar
47.Schweizer, Eet al.What constitutes an adequate antidepressant trial of fluoxetine? J Clin Psychiatry 1990; 51:811.Google ScholarPubMed
48.Fava, Met al.Lithium and tricyclic augmentation of fluoxetine treatment for major depression: a double-blind controlled study. Am J Psychiatry 1994; 151:13721374.Google ScholarPubMed
49.Quitkin, FM. The importance of dosage in prescribed antidepressants. Br J Psychiatry 1985; 147: 593597.CrossRefGoogle Scholar
50.Greenhouse, JBet al.Analysis of time to stabilization in the treatment of depression: biological and clinical correlates. J Affect Disord 1987; 13: 259266.CrossRefGoogle ScholarPubMed
51.Georgotas, Aet al.Factors affecting the delay of antidepressant effect in responders to nortriptyline and phenelzine. Psychiatry Res 1989; 28: 19.CrossRefGoogle ScholarPubMed
52.Amsterdam, JD, Berwish, MJ. High dose tranylcypromine therapy for resistant depression. Pharmacopsychiatry 1989; 22: 2125.CrossRefGoogle Scholar
53.Posternak, MA, Zimmerman, M. Switching versus augmentation: a prospective, naturalistic comparison in depressed, treatment-resistant patients. J Clin Psychiatry 2001;62:135142.CrossRefGoogle ScholarPubMed
54.Joffe, RTet al.Response to an open trial of a second SSRI in major depression. J Clin Psychiatry 1996; 57:114115.Google Scholar
55.Zarate, CA Jret al.Does intolerance or lack of response with fluoxetine predict the same will happen with sertaline? J Clin Psychiatry 1996; 57: 6771.Google ScholarPubMed
56.Paselow, EDet al.The short- and long-term efficacy of paroxetine hcl: B. Data from a double-blind crossover study and from a year-long trial vs. imipramine and placebo. Psychopharmacol Bull 1989; 25: 272276.Google Scholar
57.Bauer, M, Dopfmer, S. Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. J Clin Psychopharmacol 2001; 19: 427434.CrossRefGoogle Scholar
58.Price, LH, Carpenter, LL, Rasmussen, LA. Drug combination strategies. In: Amsterdam, JD, Hornig, M, Nierenberg, AA. eds. Treatment-Resistant Mood Disorders. Cambridge University Press, Cambridge, United Kingdom 2001: 194222.CrossRefGoogle Scholar
59.de Montigny, Cet al.Lithium induced rapid relief of depression in tricyclic antidepressant drug non-responders. Br J Psychiatry 1981; 138: 252256.CrossRefGoogle ScholarPubMed
60.Thase, ME, Rush, AJTreatment-resistant depression. In Bloom, FE, Kupfer, DJ. eds. Psychopharmacology: The Fourth Generation of Progress. New York, Raven Press 1995:10811097.Google Scholar
61.Price, LH, Charney, DS, Heninger, GR. Variability of response to lithium augmentation in refractory depression. Am J Psychiatry 1986; 143: 13871392.Google ScholarPubMed
62.Katona, CLEet al.Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine. Br J Psychiatry 1995; 166: 8086.CrossRefGoogle ScholarPubMed
63.Dinan, TG, Barry, S. A comparison of electroconvulsive therapy with a combined lithium and tricyclic combination among depressed tricyclic nonresponders. Acta Psychiat Scand 1989; 80; 97100.CrossRefGoogle ScholarPubMed
64.Howland, RH. Thyroid dysfunction in refractory depression: implications for pathophysiology and treatment. J Clin Psychiatry 1993; 54: 4754.Google ScholarPubMed
65.Joffe, RT, Singer, W. A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants. Psychiatry Res 1990; 32: 241251.CrossRefGoogle ScholarPubMed
66.Blier, P, Bergeron, R. The use of pindolol to potentiate antidepressant medication. J Clin Psychiatry 1998; 59:1623.Google ScholarPubMed
67.Bordet, R, Thomas, P, Dupuis, B. Effect of pindolol on onset of action of paroxetine in the treatment of major depression: intermediate analysis of a double-blind, placebo-contolled trial. Reseau de Recherche et d'Experimentation Psychopharmacologique. Am J Psychiatry 1998; 155: 13461351.CrossRefGoogle Scholar
68.McAskill, R, Mir, S, Taylor, D. Pindolol augmentation of antidepressant therapy. Br J Psychiatry 1998; 173: 203208.CrossRefGoogle ScholarPubMed
69.Moreno, FAet al.Pindolol augmentation of treatment-resistant patients. J Clin Psychiatry 1997; 58: 437439.CrossRefGoogle Scholar
70.Perez, Vet al.A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Arch Gen Psychiatry 1999; 56: 375379.CrossRefGoogle ScholarPubMed
71.Jacobsen, FW. Possible augmentation of antidepressant response by buspirone. J Clin Psychiatry 1991; 52: 217220.Google ScholarPubMed
72.Joffe, RT, Schuller, DR. An open study of buspirone augmentation of serotonin reuptake inhibitors in refractory depression. J Clin Psychiatry 1993; 54: 269271.Google ScholarPubMed
73.Landen, Met al.A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. J Clin Psychiatry 1998; 59: 664668.CrossRefGoogle ScholarPubMed
74.Appelberg, BGet al.Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study. J Clin Psychiatry 2001; 62: 448452.CrossRefGoogle ScholarPubMed
75.Nelson, JCThe use of antipsychotic drugs in the treatment of depression. In Zohar, J, Belmaker, RH. eds. Treating Resistant Depression. New York, PMA Publishing 1987: 131145.Google Scholar
76.Ostroff, RB, Nelson, JC. Risperidone augmentation of selective serotonin reuptake inhibitors in major depresssion. J Clin Psychiatry 1999; 60: 256259.CrossRefGoogle Scholar
77.Weisler, RHet al.Adjunctive use of olanzapine in mood disorders: five case reports. Ann Clin Psychiatry 1997; 9: 259262.CrossRefGoogle ScholarPubMed
78.Rothschild, AJet al.Olanzapine response in psychotic depression. J Clin Psychiatry 1999;60:116118.CrossRefGoogle ScholarPubMed
79.Ghaemi, SNet al.Does olanzapine have antidepressant properties? A retrospective preliminary study. Bipolar Disord 2000; 2: 196199.CrossRefGoogle ScholarPubMed
80.Shelton, RCet al.A novel augmentation strategy for treating major depression. Am J Psychiatry 2001; 158:131134.CrossRefGoogle Scholar
81.Weilburg, JBet al.Tricyclic augmentation of fluoxetine. Ann Clin Psychiatry 1991; 3:209213.CrossRefGoogle Scholar
82.Nierenberg, AAet al.Trazodone for antidepressant-associated insomnia. Am J Psychiatry 1994; 151: 10691072.Google ScholarPubMed
83.Young, JPR, Lader, MH, Hughes, WC. Controlled trial of trimipramine, monoamine oxidase inhibitors and combined treatment in depressed outpatients. BMJ 1979; 279: 13151317.CrossRefGoogle Scholar
84.Razani, Jet al.The safety and efficacy of combined amitriptyline and tranylcypramine antidepressant treatment. Arch Gen Psychiatry 1983; 40: 657661.CrossRefGoogle Scholar
85.O'Brien, S, McKeon, P, O'Regan, M. The efficacy and tolerability of combined antidepressant treatment in different depressive subgroups. Br J Psychiatry 1993; 162: 363368.CrossRefGoogle ScholarPubMed
86.Ebert, Det al.Combined SSRI-RIMA treatment in refractory depression. Safety data and efficacy. Psychopharmacol 1995; 119:342344.CrossRefGoogle ScholarPubMed
87.Kennedy, N, Paykel, ES. Treatment and response in refractory depression: results from a British specialist affective disorders unit. In Press 2002.Google Scholar
88.Prudic, JM, Sackeim, HA, Rifas, S. Medication resistance, response to ECT and prevention of relapse. Psychiatr Ann 1994; 24: 228231.CrossRefGoogle Scholar
89.Brandon, Set al.Electroconvulsive therapy: results in depressive illness from the Leicestershire trial. BMJ 1984; 288: 2225.CrossRefGoogle ScholarPubMed
90.Prudic, Jet al. (1996) Resistance to antidepressant medications and short-term clinical response to ECT. Am J Psychiatry 1996; 153: 985992.Google ScholarPubMed
91.Devanand, DP, Sackeim, HA, Prudic, J. Electroconvulsive therapy in the treatment-resistant patient. Psychiatr Clin North Am 1991; 14:905923.CrossRefGoogle ScholarPubMed
92.Sackeim, HAet al.Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA 2001; 285: 12991307.CrossRefGoogle ScholarPubMed
93.Bridges, PKet al.Psychosurgery: Stereotactic Subcaudate Tractotomy. An indispensable treatment. Br J Psychiatry 1994; 599611.CrossRefGoogle ScholarPubMed
94.Malhi, GS, Bartlett, JR. Depression: a role for neurosurgery? Br J Neurosurg 2000; 14:415–23.Google ScholarPubMed
95.Ballantine, HT Jr, et al.Treatment of psychiatric illness by stereotactic cingulotomy. Biol Psychiatry 1987; 22: 807–19.CrossRefGoogle ScholarPubMed
96.Murphy, BEP. Antiglucocortoid therapies in major depression: a review. Psychoneuroendocrinol 1997; 22 (Suppl.): 125132.Google ScholarPubMed
97.Dinan, TG, Levelle, E, Cooney, J, et al.Dexamethasone augmentation augmentation in treatment-resistant depression. Acta Psychiat Scand 1997; 95: 5861.CrossRefGoogle ScholarPubMed
98.Wells, BG, Marken, PA. Bromocriptine in the treatment of depression. Ann Pharmacotherapy 1989; 23:106111.Google ScholarPubMed
99.Levine, J, Barak, Y, Gonzalves, M, et al.Double-blind, controlled trial of inositol treatment of depression. Am J Psychiatry 1993; 152: 792794.Google Scholar
100.Barbee, JG, Jamhour, NJ. Lamotrigine as an augmentation agent in treatment-resistant depression. J Clin Psychiatry 2002; 63: 737741.CrossRefGoogle ScholarPubMed
101.Vuckovic, A, Cohen, BM, Zubenko, BS. The use of captopril in treatment-resistant depression: an open trial. J Clin Psychopharmacol 1991; 11: 395396.CrossRefGoogle ScholarPubMed
102.Puri, BK, Counsell, SJ, Hamilton, G, et al.Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover. Int J Clin Praot 2001; 55: 560563.CrossRefGoogle ScholarPubMed
103.Sackeim, HA, Rush, AJ, George, MS, et al.Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects and predictors of outcome. Neuropsychopharmacol 2001; 25: 713728.CrossRefGoogle ScholarPubMed
104.Marangell, LB, Rush, AJ, George, MS, et al.Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes. Biol Psychiatry 2002; 51: 280287.CrossRefGoogle ScholarPubMed
105.O'Keane, V. Transcranial magnetic stimulation: an alternative physical treatment in depression. IrJ Psych Med 2001; 18: 7981.CrossRefGoogle ScholarPubMed
106.Keller, MBet al.Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. Arch Gen Psychiatry 1992; 49:809816.CrossRefGoogle ScholarPubMed
107.Mueller, TIet al.Recovery after 5 years of unremitting major depressive disorder. Arch Gen Psychiatry 1996; 53: 794799.CrossRefGoogle ScholarPubMed
108.Fava, GAet al.Cognitive behavioral treatment of residual symptoms in primary major depressive disorder. Am J Psychiatry 1994; 151:12951299.Google ScholarPubMed
109.Fava, GAet al.Prevention of recurrent depression with cognitive behavioral therapy: preliminary findings. Arch Gen Psychiatry 1998; 55: 816820.CrossRefGoogle ScholarPubMed
110.Paykel, ESet al.Prevention of relapse in residual depression by cognitive therapy. A controlled trial. Arch Gen Psychiatry 1999; 56: 829835.CrossRefGoogle ScholarPubMed
111.Reynolds, CF 3rdet al.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
112.Scott, Jet al.Effects of cognitive therapy on psychological symptoms and social functioning in residual depression. Br J Psychiatry 2000; 177: 440446.CrossRefGoogle ScholarPubMed
113.Jarrett, RBet al.Preventing recurrent depression using cognitive therapy with and without a continuation phase: a randomized clinical trial. Arch Gen Psychiatry 2001; 58:381388.CrossRefGoogle ScholarPubMed