Augmentation strategies in mood and psychosis

Meet the patient

A 52-year-old teacher is referred with "treatment-resistant depression". She has been on a therapeutic dose of venlafaxine for four months, and her PHQ-9 fell from the severe band to the moderate band and then stopped moving.^[2][20]

Two details are buried on page three of the letter. She stopped the tablets for three weeks in month two when she ran out of repeats, and she has been drinking most nights since her father died.^[1][8]

The examiner is not asking which drug you would add. The examiner is asking whether this patient has actually had one adequate trial yet — and that is the question this whole topic exists to answer.^[2][8]

Augmentation is high-yield precisely because it tests decision architecture rather than brand names: re-diagnose, define an adequate trial, choose between switch, augment, combination and neuromodulation, name doses and monitoring, and stop a failed add-on on a measured outcome. Examiners punish premature polypharmacy and years of incomplete trials with equal enthusiasm, because both let suicide risk and metabolic harm accumulate.^[1][8][9]

References20ShowHide

1. [1]Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report Am J Psychiatry, 2006.PMID 17074942
2. [2]Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice Am J Psychiatry, 2006.PMID 16390886
3. [3]Nierenberg AA, Fava M, Trivedi MH, Wisniewski SR, Thase ME, McGrath PJ, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report Am J Psychiatry, 2006.PMID 16946176
4. [4]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.PMID 16946177
5. [5]Nelson JC, Papakostas GI Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials Am J Psychiatry, 2009.PMID 19687129
6. [6]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.PMID 17592920
7. [7]Mohamed S, Johnson GR, Chen P, Hicks PB, Davis LL, Yoon J, et al. Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial JAMA, 2017.PMID 28697253
8. [8]Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments Can J Psychiatry, 2016.PMID 27486148
9. [9]Malhi GS, Bell E, Bassett D, Boyce P, Bryant R, Hazell P, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders Aust N Z J Psychiatry, 2021.PMID 33353391
10. [10]Petrides G, Malur C, Braga RJ, et al. Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study Am J Psychiatry, 2015.PMID 25157964
11. [11]Wagner E, Löhrs L, Siskind D, et al. Clozapine augmentation strategies - a systematic meta-review of available evidence. Treatment options for clozapine resistance J Psychopharmacol, 2019.PMID 30696332
12. [12]Howes OD, McCutcheon R, Agid O, et al. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology Am J Psychiatry, 2017.PMID 27919182
13. [13]Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Am J Psychiatry, 2019.PMID 31109201
14. [14]Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression N Engl J Med, 2006.PMID 16554525
15. [15]UK ECT Review Group Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis Lancet, 2003.PMID 12642045
16. [16]O'Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial Biol Psychiatry, 2007.PMID 17573044
17. [17]Kane J, Honigfeld G, Singer J, et al. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry, 1988.PMID 3046553
18. [18]Kane JM, Agid O, Baldwin ML, et al. Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia J Clin Psychiatry, 2019.PMID 30840788
19. [19]Galletly C, Castle D, Dark F, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders Aust N Z J Psychiatry, 2016.PMID 27106681
20. [20]Kroenke K, Spitzer RL, Williams JB The PHQ-9: validity of a brief depression severity measure J Gen Intern Med, 2001.PMID 11556941