Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-14T05:40:51.719Z Has data issue: false hasContentIssue false
  • English
  • Français

Antidepressant augmentation and combination in unipolar depression: strong guidance, weak foundations

Published online by Cambridge University Press:  13 June 2014

Erik Kolshus ,
Leonard Douglas  and
Ross Dunne
Erik Kolshus*
Affiliation:
Trinity College Dublin andSt. Patrick's University Hospital, Dublin
Leonard Douglas
Affiliation:
CUH, Cork
Ross Dunne
Affiliation:
Department of Psychiatry, Trinity College Dublin, Ireland
*
*Correspondence E-mail: kolshue@tcd.ie
Get access Rights & Permissions [Opens in a new window]

Extract

Depression will be the second leading contributor to the global burden of disease by 2020. In Ireland, in 2009, 6061 people were hospitalised with depressive disorders. This represents a significant economic and social burden. There is growing awareness of the difficulty in treating depression with medications alone. The likelihood that a patient will achieve remission with the first antidepressant tried is around 30%, and the rates are similar for the second antidepressant tried. This falls to around 15% after three trials. Many patients are exposed to pharmacotherapy for extended periods of time with little beneficial effect, but often with side-effects. Patients are therefore in great need of clear information with regard to their chance of success. Clinicians are in need of clear guidance on prescribing strategies which have proven efficacy. However, this guidance often discusses treatment strategies based on varying levels of evidence. Guiding bodies may approach the problem from varying perspectives. The UK National Institute for Health and Clinical Excellence (NICE) has a clear government mandate with regard to provision of not only effective but cost-effective treatments. The British Association of Psychopharmacology (BAP) is an independent body of interested researchers and therefore may discuss prescribing options from the point of view of tertiary care institutions, and university centres. The South London and Maudsley NHS Foundation Trust publish the popular Maudsley guidelines. These are perhaps more pragmatic in nature, but include very low levels of evidence, including case series.

The American Psychiatric Association (APA) is an independent member association which also publishes guidelines. These are published in the American Journal of Psychiatry and the latest guidelines were published in October 2010.

All these bodies attempt to weigh their advice according to the level of evidence available and aim to provide clinical guidance in difficult situations. The burden on guiding organisations is to provide some direction and clarity in areas that are often unclear or controversial. Clinical guidelines are one method of providing support and guidance to busy clinicians. However, this clinician-centered approach has limitations. The onus is on the authors of the guidance to provide ever-more treatment options. This may mean that conclusions about the efficacy of medications is overstated or the limitations of the literature not fully explored in explanatory notes.

Type
CPD
Information
Irish Journal of Psychological Medicine , Volume 28 , Issue 4 , December 2011 , pp. i - ix
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Murray, CJL, Lopez, AD (1997). Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. The Lancet 349(9064): 1498–1504.CrossRefGoogle ScholarPubMed
2.Daly, A, Walsh, D. Activities of Irish Psychiatric Units and Hospitals 2009. HRB StatisticsGoogle Scholar
3.Menza, M. STAR*D: the results begin to roll in. Am J Psychiatry. 2006. Jul;163(7):1123CrossRefGoogle ScholarPubMed
4.Phillips, Bet al.Oxford Centre for Evidence-based Medicine Levels of Evidence (March 2009). www.cebm.net/?o=1116)Google Scholar
5.Horgan, D, Dodd, S, Berk, M. A survey of combination antidepressant use in Australia. Australas Psychiatry 2007; 15: 26–29.CrossRefGoogle ScholarPubMed
6.Valenstein, M, McCarthy, JF, Austin, KL, Greden, JF, Young, EA, Blow, FC. What happened to lithium? Antidepressant augmentation in clinical settings. Am J Psychiatry. 2006 Jul;163(7):1219–25CrossRefGoogle ScholarPubMed
7.The UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. The Lancet. 2003 March;361(9360):799–808CrossRefGoogle Scholar
8.Cuijpers, P, Dekker, J, Hollon, SD, Andersson, G. Adding psychotherapy to pharmacotherapy in the treatment of depressive disorders in adults: a meta-analysis. J Clin Psychiatry. 2009 Sep;70(9):1219–29.CrossRefGoogle ScholarPubMed
9.Cuijpers, P, Geraedts, AS, van Oppen, P, Andersson, G, Markowitz, JC, van Straten, A. Interpersonal psychotherapy for depression: a meta-analysis. Am J Psychiatry. 2011 Jun;(168(6):652CrossRefGoogle ScholarPubMed
10.NICE (2010) The treatment and management of depression in adults (updated edition). National Clinical Practice Guideline 90. London: NICEGoogle Scholar
11.Souery, D, Papakostas, GIet al. (2006). Treatment-resistant depression. J Clin Psychiatry 67 Suppl 6: 16–22Google ScholarPubMed
12.Fekadu, A, Wooderson, SC, Markopoulo, K, Donaldson, C, Papadopoulos, A, Cleare, AJ. What happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies. J Affect Disord 2009 Jul;116(1-2):4–11.CrossRefGoogle ScholarPubMed
13.Fava, M. Diagnosis and definition of treatment-resistant depression. Biological Psychiatry. 2003 April;53(8):649–659CrossRefGoogle ScholarPubMed
14.Rush, AJ, Trivedi, MH, Wisniewski, SR, Nierenberg, AA, Stewart, JW, Warden, D, Niederehe, G, Thase, ME, Lavori, PW, Lebowitz, BD, McGrath, PJ, Rosenbaum, JF, Sackeim, HA, Kupfer, DJ, Luther, J, Fava, M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006 Nov;163(11):1905–17.CrossRefGoogle ScholarPubMed
15.Keks, NA, Burrows, GD, Copolov, DL, Newton, R, Paoletti, N, Schweitzer, I, Tiller, J. Beyond the evidence: is there a place for antidepressant combinations in the pharmacotherapy of depression? MJA 2007; 186 (3): 142–144Google Scholar
16.Ezquiaga, E, Garcia, A, Bravo, F, Pallarés, T. Factors associated with outcome in major depression: a 6-month prospective study. Social Psychiatry and Psychiatric Epidemiology. 1998;33(11):552–7.CrossRefGoogle ScholarPubMed
17.Nunes, E, Deliyannides, MD, Donovan, S, McGrath, PJ. The management of treatment resistance in depressed patients with substance use disorders. Psy Cli North America. 1996 19(2); 311–327CrossRefGoogle ScholarPubMed
18.Kornstein, SG, Schneider, RK. Clinical features of treatment-resistant depression. The Journal of clinical psychiatry. 2001 62 Suppl 16, 18–25.Google ScholarPubMed
19.Broly, F, Gaedigk, A, Heim, M, et al.Debrisoquine/sparteine hydroxylation genotype and phenotype: analysis of common mutations and alleles of CYP2D6 in a European population. DNA Cell Biol 1991; 10: 545–558.CrossRefGoogle ScholarPubMed
20.Uhr, M, Tontsch, A, Namendorf, C, Ripke, S, Lucae, S, Ising, M, et al.Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008 Jan 24;57(2):203–9.CrossRefGoogle ScholarPubMed
21.Graziottin, A, Serafini, A. Depression and the menopause: why antidepressants are not enough? Menopause Int. 2009 Jun;15(2):76–81CrossRefGoogle ScholarPubMed
22.NICE (2010). The treatment and management of depression in adults (updated edition). National Clinical Practice Guideline 90. London: NICEGoogle Scholar
23.McPherson, S, Cairns, P, Carlyle, J, Shapiro, DA, Richardson, P, Taylor, D. The effectiveness of psychological treatments for treatment-resistant depression: a systematic review. Acta Psychiatr Scand 2005; 111:331–340CrossRefGoogle ScholarPubMed
24.Thase, Met al.Cognitive Therapy Versus Medication in Augmentation and Switch Strategies as Second-Step Treatments: A STAR*D Report. Am J Psychiatry 2007;164:739–752.CrossRefGoogle ScholarPubMed
25.de la Gándara, J., Rojo, J. E., Ros, S., Agiiera, L. and de Pedro, J. M., Neuropharmacological basis of combining antidepressants. Acta Psychiatrica Scandinavica, 2005 112: 11–13.CrossRefGoogle Scholar
26.Lam, RW, Wan, DD, Cohen, NL, Kennedy, SH. Combining antidepressants for treatment-resistant depression: a review. J Clin Psychiatry. 2002 Aug;63(8):685–93CrossRefGoogle ScholarPubMed
27.Blier, P, Ward, HE, Tremblay, P, Laberge, L, Hebert, C, Bergeron, R. Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Am J Psychiatry. 2010; 167(3):281–8.CrossRefGoogle ScholarPubMed
28.Cowen, PJ. New drugs, old problems: Revisiting the pharmacological management of treatment-resistant depression. Adv Psychiatr Treat 2005 11: 19–27CrossRefGoogle Scholar
29.NICE (2010) The treatment and management of depression in adults (updated edition). National Clinical Practice Guideline 90. London: NICEGoogle Scholar
30.Joffe, RT, Levitt, AJ. Antidepressant failure: augmentation or substitution? J Psychiatry Neurosci. 1995 Jan;20(1):7–9.Google ScholarPubMed
31.McGrath, PJ, Stewart, JW, Fava, M, Trivedi, MH, Wisniewski, SR, Nierenberg, AA, et al.Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1531–41CrossRefGoogle ScholarPubMed
32.Landén, M, Eriksson, E, Agren, H, Fahlén, T. Effect of buspirone on sexual dysfunction in depressed patients treated with selective serotonin reuptake inhibitors. J Clin Psychopharmacol. 1999 Jun;19(3):268–71.CrossRefGoogle ScholarPubMed
33.Hatcher, S. (2008). The STAR*D trial: the 300lb gorilla is in the room, but does it block all the light? Evid Based Ment Health 11(4): 97–99.CrossRefGoogle Scholar
34.Rush, Jet al.STAR*D: Revising conventional wisdom. CNS Drugs. 2009 Aug;23(8):627–647Google ScholarPubMed
35.Kornstein, SG, Schneider, RK. Clinical features of treatment-resistant depression.Google Scholar
36.Taylor, D, Paton, C, Kapur, S (2009). Maudsley prescribing guidelines-10th ed. Informa HealthcareCrossRefGoogle Scholar
37.Shaldubina, A, Agam, G, Belmaker, RH. The mechanism of lithium action: state of the art, ten years later. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2001;25(4):855–66.CrossRefGoogle ScholarPubMed
38.Beaulieu, J-Met al.Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(14):5099–104.CrossRefGoogle ScholarPubMed
39.Crossley, NA, Bauer, M. Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized, placebo-controlled trials. J Clin Psychiatry. 2007 Jun;68(6):935–40.CrossRefGoogle ScholarPubMed
40.Crossley, NA, Bauer, M. Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized, placebo-controlled trials. J Clin Psychiatry. 2007 Jun;68(6):935–40.CrossRefGoogle ScholarPubMed
41.Schweitzer, I, Tuckwell, V. Risk of adverse events with the use of augmentation therapy for the treatment of resistant depression. Drug Saf 1998; 19 (6): 455–64CrossRefGoogle ScholarPubMed
42.Baumann, P, Nil, R, Souche, A, et al.A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical pharmacokinetic, and pharmacogenetic investigation. J Clin Psychopharmacol 1996; 16: 307–14CrossRefGoogle ScholarPubMed
43.Nierenberg, AA, Fava, Met al.A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006 Sep;163(9):1519–30CrossRefGoogle Scholar
44.Joffe, RT. Is the thyroid still important in major depression? J Psychiatry Neurosci 2006;31(6):367–8Google ScholarPubMed
45.Nierenberg, AA, Fava, Met al.A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006 Sep;163(9):1519–30CrossRefGoogle Scholar
46.Aronson, R, Offman, HJ, Joffe, RTet al.Triiodothyronine augmentation in the treatment of refractory depression: a meta-analysis. Arch Gen Psychiatry 1996; 53:842–8CrossRefGoogle ScholarPubMed
47.Cooper-Kazaz, R, Lerer, B. Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors. Int J Neuropsychopharmacol. 2008 Aug;11(5):685–99.CrossRefGoogle ScholarPubMed
48.Papakostas, GI, Cooper-Kazaz, Ret al. (2009). Simultaneous initiation (coinitiation) of pharmacotherapy with triiodothyronine and a selective serotonin reuptake inhibitor for major depressive disorder: a quantitative synthesis of double-blind studies. Int Clin Psychopharmacol 24(1): 19–25.CrossRefGoogle Scholar
49.Lojko, D, Rybakowski, JK. L-thyroxine augmentation of serotonergic antidepressants in female patients with refractory depression. J Affect Disord. 2007 Nov;103(1-3):253–6.CrossRefGoogle ScholarPubMed
50.Kelly, TF, Lieberman, DZ. Long term augmentation with T3 in refractory major depression. J Affect Disord. 2009 May;115(1-2):230–3CrossRefGoogle ScholarPubMed
51.Celada, P, Puig, MVet al.The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci. 2004 July; 29(4): 252–265.Google ScholarPubMed
52.Nelson, JC, Papakostas, GI. Atypical antipsychoic augmentation in major depressive disorder: A meta-analysis of placebo-controlled randomized trials. Am J Psychiatry 2009;166:980–991CrossRefGoogle ScholarPubMed
53.Bauer, M, El-Khalili, N, Datto, C, Szamosi, J, Eriksson, H. A pooled analysis of two randomised, placebo-controlled studies of extended release quetiapine fumarate adjunctive to antidepressant therapy in patients with major depressive disorder. J Affect Disord. 2010;127(1-3):19–30.CrossRefGoogle ScholarPubMed
54.Keitner, GI. Adding atypical antipsychotics to antidepressants increases response in treatment-resistant major depression but increases discontinuation as a result of adverse events. Evid Based Med 2010; 15(1): 19–20.CrossRefGoogle ScholarPubMed
55.Schindler, F, Anghelescu, IG. Lithium versus lamotrigine augmentation in treatment resistant unipolar depression: a randomized, open-label study. Int Clin Psychopharmacol. 2007 May;22(3):179–82.CrossRefGoogle ScholarPubMed
56.Barbosa, L, Berk, M, Vorster, M. A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. J Clin Psychiatry 2003; 64(4):403–407.CrossRefGoogle ScholarPubMed
57.Santos, MA, Rocha, FLet al.Efficacy and safety of antidepressant augmentation with lamotrigine in patients with treatment-resistant depression: a randomized, placebo-controlled, double-blind study. Prim Care Companion J Clin Psychiatry 2008 10(3): 187–190.CrossRefGoogle ScholarPubMed
58.Artigas, F, Romero, L, de Montigny, C, Blier, P. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci. 1996;19:378–383.CrossRefGoogle ScholarPubMed
59.Geretsegger, C., Bitterlich, W., Stelzig, R., Stuppaeck, C., Bondy, B., Aichhorn, W.Paroxetine with pindolol augmentation: A double-blind, randomized, placebo-controlled study in depressed in-patients. European Neuropsychopharmacology, 2008 Volume 18, Issue 2, Pages 141–146CrossRefGoogle ScholarPubMed
60.Whale, R, Terao, T, Cowen, P, Freemantle, N, Geddes, J. Pindolol augmentation of serotonin reuptake inhibitors for the treatment of depressive disorder: a systematic review. J Psychopharmacol April 2010; 24(4): 513–520CrossRefGoogle ScholarPubMed
61.Rush, AJ, Trivedi, MH, Wisniewski, SR, Nierenberg, AA, Stewart, JW, Warden, D, Niederehe, G, Thase, ME, Lavori, PW, Lebowitz, BD, McGrath, PJ, Rosenbaum, JF, Sackeim, HA, Kupfer, DJ, Luther, J, Fava, M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905–17.CrossRefGoogle ScholarPubMed
62.Stahl, S. Essential Psychopharmacology. Cambridge University Press, 2000.Google Scholar
63.Ozmenler, NK, Karlidere, Tet al.Mirtazapine augmentation in depressed patients with sexual dysfunction due to SSRIs. Hum Psychopharmacol 2008 Jun; 23(4): 321–6.CrossRefGoogle Scholar
64.Meagher, D, Hannan, N, Leonard, M. Duloxetine-mirtazapine combination in depressive illness: The case for Limerick ‘rocket fuel’. Ir J Psych Med 2006; 23(3)Google ScholarPubMed
65.Carpenter, L, Yasmin, LSet al. (2002). A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry 51(2): 183–188.CrossRefGoogle ScholarPubMed
66.Blier, P, Ward, HEet al. (2010). Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomised study. Am J Psychiatry 167(3): 281–288.CrossRefGoogle Scholar
67.Matthew, J. Taylor, Lisa Rudkin, Hawton, Keith. Strategies for managing antidepressant-induced sexual dysfunction: Systematic review of randomised controlled trials. Journal of Affective Disorders - November 2005 (Vol. 88, Issue 3, Pages 241–254)Google Scholar
68.NICE (2010) The treatment and management of depression in adults (updated edition). National Clinical Practice Guideline 90. London: NICEGoogle Scholar
69.APA (2010) Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd Edition.Google Scholar
70.Joffe, RT, Schuller, DR. An open study of buspirone augmentation of serotonin reuptake inhibitors in refractory depression: Journal of Clinical Psychiatry 1993 Jul;54(7):269–271Google Scholar
71.Landen, M, Bjorling, G, Agren, H, Fahlen, T. A randomised, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. J Clin Psychiatry 1998 Dec;59(12):664–8CrossRefGoogle ScholarPubMed
72.Appelberg, BG, Syvälahti, EKet 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 Jun; 62(6):448–52.CrossRefGoogle ScholarPubMed
73.Lam, RW, Wan, DD, Cohen, NL, Kennedy, SH. Combining antidepressants for treatment-resistant depression: a review. J Clin Psychiatry 2002 Aug; 63(8):685–93.CrossRefGoogle ScholarPubMed
74.P K, Gillman, Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 2007 July; 151(6): 737–748.Google Scholar
75.Fava, Met al.Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and non-responders to fluoxetine. J Clin Psychopharmacology 2002 Aug;22(4): 379–87CrossRefGoogle ScholarPubMed
76.Hemeryck, A, Belpaire, FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions:an update. Curr Drug Metab. 2002 Feb;3(1):13–37CrossRefGoogle ScholarPubMed
77.Anderson, IMet al.Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2008 Jun;22(4):343–96.CrossRefGoogle ScholarPubMed
78.Taylor, MJ, Carney, SM, Goodwin, GM, Geddes, JR. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. J Psychopharmacol. 2004 Jun;18(2):251–6.CrossRefGoogle ScholarPubMed
79.Roberts, SHet al.Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial. BMC Psychiatry 2007 Nov 15;7:65.CrossRefGoogle ScholarPubMed
80.APA (2010) Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd Edition.Google Scholar
81.Taylor, D, Paton, C, Kapur, S (2009). Maudsley prescribing guidelines-10th ed. Informa HealthcareCrossRefGoogle Scholar