Rethinking the medication management of major depression

References

• World Health Organization. Depression and other common mental disorders: global health estimates. Geneva: World Health Organization; 2017.
   Google Scholar
• Ventriglio A, Bhugra D, Sampogna G, et al. From dysthymia to treatment-resistant depression: evolution of a psychopathological construct. Int Rev Psychiatry. 2020 Aug-Sep;32(5–6):471–476.
   PubMed Web of Science ®Google Scholar
• Fornaro M, De Berardis D, Anastasia A, et al. Novel psychopharmacology for depressive disorders. Adv Exp Med Biol. 2021;1305:449–461.
   PubMed Web of Science ®Google Scholar
• Tomasetti C, Montemitro C, Fiengo ALC, et al. Novel pathways in the treatment of major depression: focus on the glutamatergic system. Curr Pharm Des. 2019;25(4):381–387.
   PubMed Web of Science ®Google Scholar
• Hasin DS, Sarvet AL, Meyers JL, et al. Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA Psychiatry. 2018 Apr 1;75(4):336–346.
   PubMed Web of Science ®Google Scholar
• Kessler RC. The costs of depression. Psychiatr Clin North Am. 2012 Mar;35(1):1–14.
   PubMed Web of Science ®Google Scholar
• Keller MB, Lavori PW, Mueller TI, et 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 Oct;49(10):809–816.
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Florea I, Tonnoir B, et al. Efficacy of vortioxetine on cognitive functioning in working patients with major depressive disorder. J Clin Psychiatry. 2017 Jan;78(1):115–121.
   PubMed Web of Science ®Google Scholar
• Mann JJ, Michel CA, Auerbach RP. Improving suicide prevention through evidence-based strategies: a systematic review. Am J Psychiatry. 2021 Feb 18;178(7):611–624.
   PubMedGoogle Scholar
• Harman JS, Edlund MJ, Fortney JC. Disparities in the adequacy of depression treatment in the United States. Psychiatr Serv. 2004 Dec;55(12):1379–1385.
   PubMedGoogle Scholar
• Cipriani A, Geddes JR, Furukawa TA, et al. Metareview on short-term effectiveness and safety of antidepressants for depression: an evidence-based approach to inform clinical practice. Can J Psychiatry. 2007 Sep;52(9):553–562.
   PubMed Web of Science ®Google Scholar
• Cuffel BJ, Azocar F, Tomlin M, et al. Remission, residual symptoms, and nonresponse in the usual treatment of major depression in managed clinical practice. J Clin Psychiatry. 2003 Apr;64(4):397–402.
   PubMedGoogle Scholar
• Rush AJ. STAR*D: what have we learned? Am J Psychiatry. 2007 Feb;164(2):201–204.
   PubMed Web of Science ®Google Scholar
• Sinyor M, Schaffer A, Levitt A. The sequenced treatment alternatives to relieve depression (STAR*D) trial: a review. Can J Psychiatry. 2010 Mar;55(3):126–135.
   PubMed Web of Science ®Google Scholar
• American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder 2010 [2021 Dec 04]; 3rd:[ Available from: http://psychiatryonline.org/guidelines.aspx
   Google Scholar
• Lewis G, Marston L, Duffy L, et al. Maintenance or discontinuation of antidepressants in primary care. N Engl J Med. 2021 Sep 30;385(14):1257–1267.
   PubMedGoogle Scholar
• Zimmerman M, Posternak M, Friedman M, et al. Which factors influence psychiatrists’ selection of antidepressants? Am J Psychiatry. 2004 Jul;161(7):1285–1289.
   PubMed Web of Science ®Google Scholar
• Himmerich H, Wranik DW. Choice of treatment with antidepressants: influencing factors. Curr Pharm Des. 2012;18(36):5958–5975.
   PubMed Web of Science ®Google Scholar
• Mann JJ. The medical management of depression. N Engl J Med. 2005 Oct 27;353(17):1819–1834.
   PubMed Web of Science ®Google Scholar
• Dunlop BW, Kelley ME, Aponte-Rivera V, et al. Effects of patient preferences on outcomes in the predictors of remission in depression to individual and combined treatments (PReDICT) study. Am J Psychiatry. 2017 Jun 1;174(6):546–556.
   PubMed Web of Science ®Google Scholar
• Saveanu R, Etkin A, Duchemin AM, et al. The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment. J Psychiatr Res. 2015 Feb;61:1–12.
   PubMedGoogle Scholar
• Keller MB, McCullough JP, Klein DN, et al. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med. 2000 May 18;342(20):1462–1470.
   PubMed Web of Science ®Google Scholar
• Steffen A, Nubel J, Jacobi F, et al. Mental and somatic comorbidity of depression: a comprehensive cross-sectional analysis of 202 diagnosis groups using German nationwide ambulatory claims data. BMC Psychiatry. 2020 Mar 30;20(1):142.
   PubMed Web of Science ®Google Scholar
• Quitkin FM, McGrath PJ, Stewart JW, et al. Chronological milestones to guide drug change. When should clinicians switch antidepressants? Arch Gen Psychiatry. 1996 Sep;53(9):785–792.
   PubMed Web of Science ®Google Scholar
• Szegedi A, Jansen WT, van Willigenburg AP, et al. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry. 2009 Mar;70(3):344–353.
   PubMed Web of Science ®Google Scholar
• Kudlow PA, Cha DS, McIntyre RS. Predicting treatment response in major depressive disorder: the impact of early symptomatic improvement. Can J Psychiatry. 2012 Dec;57(12):782–788.
   PubMed Web of Science ®Google Scholar
• Lam RW. Onset, time course and trajectories of improvement with antidepressants. Eur Neuropsychopharmacol. 2012 Jan 01;22(Suppl 3):S492–8.
   PubMed Web of Science ®Google Scholar
• Sheline YI, Sanghavi M, Mintun MA, et al. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci. 1999 Jun 15;19(12):5034–5043.
   PubMed Web of Science ®Google Scholar
• Fava GA. May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance. Ther Adv Psychopharmacol. 2020;10:2045125320970325.
   Google Scholar
• Moylan S, Maes M, Wray NR, et al. The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications. Mol Psychiatry. 2013 May;18(5):595–606.
   PubMed Web of Science ®Google Scholar
• Ghio L, Gotelli S, Marcenaro M, et al. Duration of untreated illness and outcomes in unipolar depression: a systematic review and meta-analysis. J Affect Disord. 2014 Jan;152-154:45–51.
   PubMed Web of Science ®Google Scholar
• Oquendo MA, Perez-Rodriguez MM, Poh E, et al. Life events: a complex role in the timing of suicidal behavior among depressed patients. Mol Psychiatry. 2014 Aug;19(8):902–909.
   PubMed Web of Science ®Google Scholar
• Trivedi MH, Morris DW, Wisniewski SR, et al. Increase in work productivity of depressed individuals with improvement in depressive symptom severity. Am J Psychiatry. 2013 Jun;170(6):633–641.
   PubMedGoogle Scholar
• Jie Y, Shuang D, Xinjie Z. Effects of concurrent treatment with amitriptyline hydrochloride tablets and fluoxetine hydrochloride on therapeutic indicator levels in patients with depression. Trop J Pharm Res. 2019;18(2):403–408.
   Google Scholar
• Gulrez G, Badyal DK, Deswal RS, et al. Bupropion as an augmenting agent in patients of depression with partial response. Basic Clin Pharmacol Toxicol. 2012 Mar;110(3):227–230.
   PubMed Web of Science ®Google Scholar
• Fornaro M, Martino M, Mattei C, et al. Duloxetine-bupropion combination for treatment-resistant atypical depression: a double-blind, randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2014 Aug;24(8):1269–1278.
   PubMed Web of Science ®Google Scholar
• Leuchter AF, Cook IA, Gilmer WS, et al. Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder. Psychiatry Res. 2009 Sep 30;169(2):132–138.
   PubMedGoogle Scholar
• Stewart JW, McGrath PJ, Blondeau C, et al. Combination antidepressant therapy for major depressive disorder: speed and probability of remission. J Psychiatr Res. 2014 May;52:7–14.
   PubMed Web of Science ®Google Scholar
• Zuilhof Z, Norris S, Blondeau C, et al. Optimized regimens of combined medications for the treatment of major depressive disorder: a double-blind, randomized-controlled trial. Neuropsychiatr Dis Treat. 2018;14:3209–3218.
   PubMed Web of Science ®Google Scholar
• Mohamed S, Johnson GR, Chen P, 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 Jul 11;318(2):132–145.
   PubMed Web of Science ®Google Scholar
• Trivedi MH, Fava M, Wisniewski SR, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1243–1252.
   PubMed Web of Science ®Google Scholar
• Nelson JC, Mazure CM, Jatlow PI, et al. Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biol Psychiatry. 2004 Feb 1;55(3):296–300.
   PubMed Web of Science ®Google Scholar
• Vezmar S, Miljkovic B, Vucicevic K, et al. Pharmacokinetics and efficacy of fluvoxamine and amitriptyline in depression. J Pharmacol Sci. 2009 May;110(1):98–104.
   PubMed Web of Science ®Google Scholar
• Ferreri M, Lavergne F, Berlin I, et al. Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone. Acta Psychiatr Scand. 2001 Jan;103(1):66–72.
   PubMed Web of Science ®Google Scholar
• Licht RW, Qvitzau S. Treatment strategies in patients with major depression not responding to first-line sertraline treatment. A randomised study of extended duration of treatment, dose increase or mianserin augmentation. Psychopharmacology (Berl). 2002 May;161(2):143–151.
   PubMed Web of Science ®Google Scholar
• Medhus A, Heskestad S, Tjemsland L. Mianserin added to tricyclic antidepressants in depressed patients not responding to a tricyclic antidepressant alone: a randomized, placebo-controlled, double-blind study. Nord J Psychiatry. 1994 Jan 01;48(5):355–358.
   Web of Science ®Google Scholar
• Dam J, Ryde L, Svejso J, et al. Morning fluoxetine plus evening mianserin versus morning fluoxetine plus evening placebo in the acute treatment of major depression. Pharmacopsychiatry. 1998 Mar;31(2):48–54.
   PubMed Web of Science ®Google Scholar
• Lauritzen L, Clemmesen L, Klysner R, et al. Combined treatment with imipramine and mianserin. A controlled pilot study. Pharmacopsychiatry. 1992 Jul;25(4):182–186
   PubMed Web of Science ®Google Scholar
• Maes M, Libbrecht I, van Hunsel F, et al. Pindolol and mianserin augment the antidepressant activity of fluoxetine in hospitalized major depressed patients, including those with treatment resistance. J Clin Psychopharmacol. 1999 Apr;19(2):177–182
   PubMed Web of Science ®Google Scholar
• Blier P, Gobbi G, Turcotte JE, et al. Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation. Eur Neuropsychopharmacol. 2009 Jul;19(7):457–465.
   PubMed Web of Science ®Google Scholar
• Carpenter LL, Yasmin S, Price LH. A double-blind, placebo-controlled study of antidepressant augementation with mirtazapine. Biol Psychiatry. 2002 Jan 15;51(2):183–188.
   PubMed Web of Science ®Google Scholar
• Kato T, Furukawa TA, Mantani A, et al. Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUND study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial. BMC Med. 2018 Jul 11;16(1):103.
   PubMedGoogle Scholar
• Navarro V, Boulahfa I, Obach A, et al. Switching to imipramine versus add-on mirtazapine in venlafaxine-resistant major depression: a 10-week randomized open study. J Clin Psychopharmacol. 2019 Jan;39(1):63–66.
   PubMed Web of Science ®Google Scholar
• Matreja PS, Badyal DK, Deswal RS, et al. Efficacy and safety of add on low-dose mirtazapine in depression. Indian J Pharmacol. 2012 Mar;44(2):173–177.
   PubMed Web of Science ®Google Scholar
• Kessler DS, MacNeill SJ, Tallon D, et al. Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR). BMJ. 2018 Oct;31(363):k4218.
   Google Scholar
• McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006 Sep;163(9):1531–1541. quiz 1666.
   PubMed Web of Science ®Google Scholar
• Xiao L, Zhu X, Gillespie A, et al. Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial. Psychol Med. 2021 May;51(7):1166–1174.
   PubMedGoogle Scholar
• Kato M, Takekita Y, Koshikawa Y, et al. Non response at week 4 as clinically useful indicator for antidepressant combination in major depressive disorder. A sequential RCT. J Psychiatr Res. 2017 Jun;89:97–104.
   PubMed Web of Science ®Google Scholar
• Blier P, Ward HE, Tremblay P, et al. Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Am J Psychiatry. 2010 Mar;167(3):281–288.
   PubMed Web of Science ®Google Scholar
• Raisi F, Habibi N, Nasehi AA, et al. Combination of citalopram and nortriptyline in the treatment of severe major depression: a double-blind, placebo-controlled trial. Therapy. 2007;4(2):187–192.
   Google Scholar
• Yazicioglu B, Akkaya C, Sarandol A, et al. A comparison of the efficacy and tolerability of reboxetine and sertraline versus venlafaxine in major depressive disorder: a randomized, open-labeled clinical trial. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Sep 30;30(7):1271–1276.
   PubMedGoogle Scholar
• Navarro V, Boulahfa I, Obach A, et al. Lithium augmentation versus citalopram combination in imipramine-resistant major depression: a 10-week randomized open-label study. J Clin Psychopharmacol. 2019 May;39(3):254–257.
   PubMedGoogle Scholar
• Fava M, Rosenbaum JF, McGrath PJ, et al. Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: a double-blind, controlled study. Am J Psychiatry. 1994 Sep;151(9):1372–1374.
   PubMed Web of Science ®Google Scholar
• Fava M, Alpert J, Nierenberg A, et al. Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine. J Clin Psychopharmacol. 2002 Aug;22(4):379–387.
   PubMed Web of Science ®Google Scholar
• White K, Pistole T, Boyd JL. Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study. Am J Psychiatry. 1980 Nov;137(11):1422–1425.
   PubMedGoogle Scholar
• O’Brien S, McKeon P, O’Regan M. The efficacy and tolerability of combined antidepressant treatment in different depressive subgroups. Br J Psychiatry. 1993 Mar;162(3):363–368.
   PubMedGoogle Scholar
• Marcus RN, McQuade RD, Carson WH, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2008 Apr;28(2):156–165.
   PubMed Web of Science ®Google Scholar
• Berman RM, Fava M, Thase ME, et al. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009 Apr;14(4):197–206.
   PubMed Web of Science ®Google Scholar
• Yoshimura R, Kishi T, Hori H, et al. Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Dec 3;39(2):355–357.
   PubMed Web of Science ®Google Scholar
• Han C, Wang SM, Kwak KP, et al. Aripiprazole augmentation versus antidepressant switching for patients with major depressive disorder: a 6-week, randomized, rater-blinded, prospective study. J Psychiatr Res. 2015 Jul-Aug;66-67:84–94.
   PubMed Web of Science ®Google Scholar
• Fava M, Mischoulon D, Iosifescu D, et al. A double-blind, placebo-controlled study of aripiprazole adjunctive to antidepressant therapy among depressed outpatients with inadequate response to prior antidepressant therapy (ADAPT-A Study). Psychother Psychosom. 2012;81(2):87–97.
   PubMedGoogle Scholar
• Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2007 Jun;68(6):843–853.
   PubMed Web of Science ®Google Scholar
• Thase ME, Youakim JM, Skuban A, et al. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants. J Clin Psychiatry. 2015 Sep;76(9):1224–1231.
   PubMed Web of Science ®Google Scholar
• Thase ME, Youakim JM, Skuban A, et al. Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study. J Clin Psychiatry. 2015 Sep;76(9):1232–1240.
   PubMed Web of Science ®Google Scholar
• Hobart M, Skuban A, Zhang P, et al. Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study. Curr Med Res Opin. 2018 Apr;34(4):633–642.
   PubMed Web of Science ®Google Scholar
• Landen M, Bjorling G, Agren H, et 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 Dec;59(12):664–668.
   PubMed Web of Science ®Google Scholar
• Appelberg BG, Syvalahti EK, Koskinen TE, et 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):448–452.
   PubMed Web of Science ®Google Scholar
• 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 Apr;64(4):403–407.
   PubMed Web of Science ®Google Scholar
• Barbee JG, Thompson TR, Jamhour NJ, et al. A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression. J Clin Psychiatry. 2011 Oct;72(10):1405–1412.
   PubMed Web of Science ®Google Scholar
• Santos MA, Rocha FL, Hara C. 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.
   PubMedGoogle Scholar
• Normann C, Hummel B, Scharer LO, et al. Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. J Clin Psychiatry. 2002 Apr;63(4):337–344.
   PubMed Web of Science ®Google Scholar
• 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):179–182.
   PubMed Web of Science ®Google Scholar
• Cappiello A, McDougle CJ, Delgado PL, et al. Lithium and desipramine versus desipramine alone in the treatment of severe major depression: a preliminary study. Int Clin Psychopharmacol. 1998 Sep;13(5):191–198.
   PubMedGoogle Scholar
• Nierenberg AA, Papakostas GI, Petersen T, et al. Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants. J Clin Psychopharmacol. 2003 Feb;23(1):92–95.
   PubMed Web of Science ®Google Scholar
• Zusky PM, Biederman J, Rosenbaum JF, et al. Adjunct low dose lithium carbonate in treatment-resistant depression: a placebo-controlled study. J Clin Psychopharmacol. 1988 Apr;8(2):120–124.
   PubMedGoogle Scholar
• Katona CL, Abou-Saleh MT, Harrison DA, et al. Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine. Br J Psychiatry. 1995 Jan;166(1):80–86.
   PubMedGoogle Scholar
• Girlanda F, Cipriani A, Agrimi E, et al. Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial. BMC Res Notes. 2014 Oct 17;7(1):731.
   PubMedGoogle Scholar
• 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 Psychopharm. 1996 Aug;16(4):307–314.
   PubMed Web of Science ®Google Scholar
• Joffe RT, Sokolov ST, Levitt AJ. Lithium and triiodothyronine augmentation of antidepressants. Can J Psychiatry. 2006 Oct;51(12):791–793.
   PubMedGoogle Scholar
• Joffe RT, Singer W, Levitt AJ, et al. A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Arch Gen Psychiatry. 1993 May;50(5):387–393.
   PubMed Web of Science ®Google Scholar
• Shelton RC, Tollefson GD, Tohen M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry. 2001 Jan;158(1):131–134.
   PubMed Web of Science ®Google Scholar
• Thase ME, Corya SA, Osuntokun O, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry. 2007 Feb;68(2):224–236.
   PubMed Web of Science ®Google Scholar
• Shelton RC, Williamson DJ, Corya SA, et al. Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance. J Clin Psychiatry. 2005 Oct;66(10):1289–1297.
   PubMed Web of Science ®Google Scholar
• Maes M, Vandoolaeghe E, Desnyder R. Efficacy of treatment with trazodone in combination with pindolol or fluoxetine in major depression. J Affect Disord. 1996 Dec 16;41(3):201–210.
   PubMed Web of Science ®Google Scholar
• Moreno FA, Gelenberg AJ, Bachar K, et al. Pindolol augmentation of treatment-resistant depressed patients. J Clin Psychiatry. 1997 Oct;58(10):437–439.
   PubMedGoogle Scholar
• Perez V, Soler J, Puigdemont D, et al. A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Grup de Recerca en Trastorns Afectius. Arch Gen Psychiatry. 1999 Apr;56(4):375–379.
   PubMedGoogle Scholar
• Sokolski KN, Conney JC, Brown BJ, et al. Once-daily high-dose pindolol for SSRI-refractory depression. Psychiatry Res. 2004 Feb 15;125(2):81–86.
   PubMedGoogle Scholar
• El-Khalili N, Joyce M, Atkinson S, et al. Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol. 2010 Aug;13(7):917–932.
   PubMed Web of Science ®Google Scholar
• McIntyre A, Gendron A, McIntyre A. Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms: a randomized, placebo-controlled pilot study. Depress Anxiety. 2007;24(7):487–494.
   PubMed Web of Science ®Google Scholar
• Bauer M, Pretorius HW, Constant EL, et al. Extended-release quetiapine as adjunct to an antidepressant in patients with major depressive disorder: results of a randomized, placebo-controlled, double-blind study. J Clin Psychiatry. 2009 Apr;70(4):540–549.
   PubMed Web of Science ®Google Scholar
• Keitner GI, Garlow SJ, Ryan CE, et al. A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression. J Psychiatr Res. 2009 Jan;43(3):205–214.
   PubMed Web of Science ®Google Scholar
• Reeves H, Batra S, May RS, et al. Efficacy of risperidone augmentation to antidepressants in the management of suicidality in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychiatry. 2008 Aug;69(8):1228–1236.
   PubMed Web of Science ®Google Scholar
• Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):593–602.
   PubMed Web of Science ®Google Scholar
• Rapaport MH, Gharabawi GM, Canuso CM, et al. Effects of risperidone augmentation in patients with treatment-resistant depression: results of open-label treatment followed by double-blind continuation. Neuropsychopharmacology. 2006 Nov;31(11):2505–2513.
   PubMed Web of Science ®Google Scholar
• Appelhof BC, Brouwer JP, van Dyck R, et al. Triiodothyronine addition to paroxetine in the treatment of major depressive disorder. J Clin Endocrinol Metab. 2004 Dec;89(12):6271–6276.
   PubMedGoogle Scholar
• Gitlin MJ, Weiner H, Fairbanks L, et al. Failure of T3 to potentiate tricyclic antidepressant response. J Affect Disord. 1987 Nov-Dec;13(3):267–272.
   PubMedGoogle Scholar
• Papakostas GI, Fava M, Baer L, et al. Ziprasidone augmentation of escitalopram for major depressive disorder: efficacy results from a randomized, double-blind, placebo-controlled study. Am J Psychiatry. 2015 Dec;172(12):1251–1258.
   PubMed Web of Science ®Google Scholar
• Cuijpers P, Sijbrandij M, Koole SL, et al. The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta-analysis of direct comparisons. World Psychiatry. 2013 Jun;12(2):137–148.
   PubMed Web of Science ®Google Scholar
• Gaynes BN, Warden D, Trivedi MH, et al. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009 Nov;60(11):1439–1445.
   PubMed Web of Science ®Google Scholar
• Henssler J, Bschor T, Baethge C. Combining antidepressants in acute treatment of depression: a meta-analysis of 38 studies including 4511 patients. Can J Psychiatry. 2016 Jan;61(1):29–43.
   PubMed Web of Science ®Google Scholar
• Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015 Apr;76(4):e487–98.
   PubMed Web of Science ®Google Scholar
• Strawbridge R, Carter B, Marwood L, et al. Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis. Br J Psychiatry. 2019 Jan;214(1):42–51.
   PubMed Web of Science ®Google Scholar
• Marcantoni WS, Akoumba BS, Wassef M, et al. A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: january 2009 - January 2019. J Affect Disord. 2020 Dec 1;277:831–841.
   PubMed Web of Science ®Google Scholar
• McInnes GT. Antihypertensive drugs in combination: additive or greater than additive? J Hum Hypertens. 2007 Dec;21(12):914–916.
   PubMedGoogle Scholar
• Law MR, Wald NJ, Morris JK, et al. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003 Jun 28;326(7404):1427.
   PubMed Web of Science ®Google Scholar
• Henssler J, Alexander D, Schwarzer G, et al. Combining antidepressants vs antidepressant monotherapy for treatment of patients with acute depression: a systematic review and meta-analysis. JAMA Psychiatry. 2022 Feb 16;79(4):300.
   PubMedGoogle Scholar
• Stahl SM. Stahl’s essential psychopharmacology: neuroscientific basis and practical applications. Cambridge university press; 2021.
   Google Scholar
• Anttila SA, Leinonen EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001 Jun;7(3):249–264.
   PubMedGoogle Scholar
• Rush AJ, Trivedi MH, Stewart JW, et al. Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study. Am J Psychiatry. 2011 Jul;168(7):689–701.
   PubMed Web of Science ®Google Scholar
• Dodd S, Horgan D, Malhi GS, et al. To combine or not to combine? A literature review of antidepressant combination therapy. J Affect Disord. 2005 Dec;89(1–3):1–11.
   PubMed Web of Science ®Google Scholar
• Lopes Rocha F, Fuzikawa C, Riera R, et al. Antidepressant combination for major depression in incomplete responders–a systematic review. J Affect Disord. 2013 Jan 10;144(1–2):1–6.
   PubMed Web of Science ®Google Scholar
• Rocha FL, Fuzikawa C, Riera R, et al. Combination of antidepressants in the treatment of major depressive disorder: a systematic review and meta-analysis. J Clin Psychopharmacol. 2012 Apr;32(2):278–281.
   PubMed Web of Science ®Google Scholar
• Goldstein BJ, Goodnick PJ. Selective serotonin reuptake inhibitors in the treatment of affective disorders–III. Tolerability, safety and pharmacoeconomics. J Psychopharmacol. 1998;12(3Suppl B):S55–87.
   PubMedGoogle Scholar
• Gitlin MJ, Suri R, Altshuler L, et al. Bupropion-sustained release as a treatment for SSRI-induced sexual side effects. J Sex Marital Ther. 2002 Mar-Apr;28(2):131–138.
   PubMed Web of Science ®Google Scholar
• Safarinejad MR. Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study. J Psychopharmacol. 2011 Mar;25(3):370–378.
   PubMed Web of Science ®Google Scholar
• Clayton AH, Warnock JK, Kornstein SG, et al. A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction. J Clin Psychiatry. 2004 Jan;65(1):62–67.
   PubMed Web of Science ®Google Scholar
• Kennedy SH, McCann SM, Masellis M, et al. Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. J Clin Psychiatry. 2002 Mar;63(3):181–186.
   PubMedGoogle Scholar
• DeBattista C, Solvason B, Poirier J, et al. A placebo-controlled, randomized, double-blind study of adjunctive bupropion sustained release in the treatment of SSRI-induced sexual dysfunction. J Clin Psychiatry. 2005 Jul;66(7):844–848.
   PubMed Web of Science ®Google Scholar
• Masand PS, Ashton AK, Gupta S, et al. Sustained-release bupropion for selective serotonin reuptake inhibitor-induced sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel-group study. Am J Psychiatry. 2001 May;158(5):805–807.
   PubMed Web of Science ®Google Scholar
• Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014 Feb;19(348):g1626.
   Google Scholar
• Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013 Dec;13(4):533–540.
   PubMedGoogle Scholar
• Fox MA, Jensen CL, Gallagher PS, et al. Receptor mediation of exaggerated responses to serotonin-enhancing drugs in serotonin transporter (SERT)-deficient mice. Neuropharmacology. 2007 Oct;53(5):643–656.
   PubMedGoogle Scholar
• Papadimitropoulou K, Vossen C, Karabis A, et al. Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis. Curr Med Res Opin. 2017 Apr;33(4):701–711.
   PubMed Web of Science ®Google Scholar
• Ruberto VL, Jha MK, Murrough JW. Pharmacological treatments for patients with treatment-resistant depression. Pharmaceuticals (Basel). 2020 Jun 4;13(6):116.
   PubMedGoogle Scholar
• Corya SA, Williamson D, Sanger TM, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression. Depress Anxiety. 2006;23(6):364–372.
   PubMed Web of Science ®Google Scholar
• Nelson JC, Papakostas GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry. 2009 Sep;166(9):980–991.
   PubMed Web of Science ®Google Scholar
• Gerhard T, Stroup TS, Correll CU, et al. Mortality risk of antipsychotic augmentation for adult depression. PLoS One. 2020;15(9):e0239206.
   PubMedGoogle Scholar
• Heninger GR, Charney DS, Sternberg DE. Lithium carbonate augmentation of antidepressant treatment. An effective prescription for treatment-refractory depression. Arch Gen Psychiatry. 1983 Dec;40(12):1335–1342.
   PubMedGoogle Scholar
• Taylor RW, Marwood L, Oprea E, et al. Pharmacological augmentation in unipolar depression: a guide to the guidelines. Int J Neuropsychopharmacol. 2020 Dec3;23(9):587–625. DOI:10.1093/ijnp/pyaa033
   PubMed Web of Science ®Google Scholar
• Rush AJ, Trivedi MH, Wisniewski SR, et al. 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):1905–1917.
   PubMed Web of Science ®Google Scholar
• Schopf J, Baumann P, Lemarchand T, et al. Treatment of endogenous depressions resistant to tricyclic antidepressants or related drugs by lithium addition. Results of a placebo-controlled double-blind study. Pharmacopsychiatry. 1989 Sep;22(5):183–187.
   PubMedGoogle Scholar
• Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357–1366.
   PubMed Web of Science ®Google Scholar
• Keith N. Some different types of essential hypertension: their course and prognosis. Am J Med Sci. 1974;268(6):336–345.
   PubMed Web of Science ®Google Scholar
• Bostwick JM, Pabbati C, Geske JR, et al. Suicide attempt as a risk factor for completed suicide: even more lethal than we knew. Am J Psychiatry. 2016 Nov 1;173(11):1094–1100.
   PubMed Web of Science ®Google Scholar
• Jordan JT, McNiel DE. Characteristics of persons who die on their first suicide attempt: results from the national violent death reporting system. Psychol Med. 2020 Jun;50(8):1390–1397.
   PubMed Web of Science ®Google Scholar
• Reinstatler L, Youssef NA. Ketamine as a potential treatment for suicidal ideation: a systematic review of the literature. Drugs R D. 2015 Mar;15(1):37–43.
   PubMed Web of Science ®Google Scholar
• Grunebaum MF, Ellis SP, Keilp JG, et al. Ketamine versus midazolam in bipolar depression with suicidal thoughts: a pilot midazolam-controlled randomized clinical trial. Bipolar Disord. 2017 May;19(3):176–183.
   PubMed Web of Science ®Google Scholar
• Grunebaum MF, Galfalvy HC, Choo TH, et al. Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial. Am J Psychiatry. 2018 Apr 1;175(4):327–335.
   PubMed Web of Science ®Google Scholar
• Murrough JW, Soleimani L, DeWilde KE, et al. Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. Psychol Med. 2015 Dec;45(16):3571–3580.
   PubMed Web of Science ®Google Scholar
• McGirr A, Berlim MT, Bond DJ, et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med. 2015 Mar;45(4):693–704.
   PubMed Web of Science ®Google Scholar
• Hu YD, Xiang YT, Fang JX, et al. Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study. Psychol Med. 2016 Feb;46(3):623–635.
   PubMed Web of Science ®Google Scholar
• Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 2018 Jul 1;175(7):620–630.
   PubMed Web of Science ®Google Scholar
• Ionescu DF, Fu DJ, Qiu X, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: results of a phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021 Jan;24(1):22–31.
   PubMed Web of Science ®Google Scholar
• Fu DJ, Ionescu DF, Li X, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: double-blind, randomized study (ASPIRE I). J Clin Psychiatry. 2020 May 12;81(3):3.
   Google Scholar
• Faden J, Citrome L. Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used? Ther Adv Psychopharmacol. 2020;10:2045125320968658.
   Google Scholar
• Zheng W, Cai DB, Zheng W, et al. Brexanolone for postpartum depression: a meta-analysis of randomized controlled studies. Psychiatry Res. 2019 Sep;279:83–89.
   PubMed Web of Science ®Google Scholar
• Gunduz-Bruce H, Silber C, Kaul I, et al. Trial of SAGE-217 in patients with major depressive disorder. N Engl J Med. 2019 Sep 5;381(10):903–911.
   PubMed Web of Science ®Google Scholar
• Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, et al. Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial. JAMA Psychiatry. 2021 Sep 1;78(9):951–959.
   PubMedGoogle Scholar
• Khajavi D, Farokhnia M, Modabbernia A, et al. Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2012 Nov;73(11):1428–1433.
   PubMed Web of Science ®Google Scholar
• Jaffe RJ, Novakovic V, Peselow ED. Scopolamine as an antidepressant: a systematic review. Clin Neuropharmacol. 2013 Jan-Feb;36(1):24–26.
   PubMed Web of Science ®Google Scholar
• Furey ML, Drevets WC. Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry. 2006 Oct;63(10):1121–1129.
   PubMed Web of Science ®Google Scholar
• Park L, Furey M, Nugent AC, et al. Neurophysiological changes associated with antidepressant response to ketamine not observed in a negative trial of scopolamine in major depressive disorder. Int J Neuropsychopharmacol. 2019 Jan 1;22(1):10–18.
   PubMedGoogle Scholar
• Lee JD, Nunes EV Jr., Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018 Jan 27;391(10118):309–318.
   PubMed Web of Science ®Google Scholar
• Fava M, Memisoglu A, Thase ME, et al. Opioid modulation with buprenorphine/samidorphan as adjunctive treatment for inadequate response to antidepressants: a randomized double-blind placebo-controlled trial. Am J Psychiatry. 2016 May 1;173(5):499–508.
   PubMed Web of Science ®Google Scholar
• Serafini G, Adavastro G, Canepa G, et al. The efficacy of buprenorphine in major depression, treatment-resistant depression and suicidal behavior: a systematic review. Int J Mol Sci. 2018 Aug 15;19(8):2410.
   PubMed Web of Science ®Google Scholar
• Latif ZE, Saltyte Benth J, Solli KK, et al. Anxiety, depression, and insomnia among adults with opioid dependence treated with extended-release naltrexone vs buprenorphine-naloxone: a randomized clinical trial and follow-up study. JAMA Psychiatry. 2019 Feb 1;76(2):127–134.
   PubMed Web of Science ®Google Scholar
• Ahmadi J, Jahromi MS, Ehsaei Z. The effectiveness of different singly administered high doses of buprenorphine in reducing suicidal ideation in acutely depressed people with co-morbid opiate dependence: a randomized, double-blind, clinical trial [journal article]. Trials. 2018 Aug 29;19(1):462.
   PubMedGoogle Scholar
• Striebel JM, Kalapatapu RK. The anti-suicidal potential of buprenorphine: a case report. Int J Psychiatry Med. 2014;47(2):169–174.
   PubMedGoogle Scholar
• Yovell Y, Bar G, Mashiah M, et al. Ultra-low-dose buprenorphine as a time-limited treatment for severe suicidal ideation: a randomized controlled trial. Am J Psychiatry. 2016 May 1;173(5):491–498.
   PubMed Web of Science ®Google Scholar
• Carhart-Harris R, Giribaldi B, Watts R, et al. Trial of psilocybin versus escitalopram for depression. N Engl J Med. 2021 Apr 15;384(15):1402–1411.
   PubMed Web of Science ®Google Scholar
• Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2021 May 1;78(5):481–489.
   PubMed Web of Science ®Google Scholar
• Jelen LA, Young AH. New antidepressants: new day or false Dawn? Eur Neuropsychopharmacol. 2022 Oct;63:1–3.
   PubMedGoogle Scholar
• Papakostas GI, Perlis RH, Scalia MJ, et al. A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder. J Clin Psychopharmacol. 2006 Feb;26(1):56–60.
   PubMed Web of Science ®Google Scholar
• Taylor MJ, Freemantle N, Geddes JR, et al. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Arch Gen Psychiatry. 2006 Nov;63(11):1217–1223.
   PubMed Web of Science ®Google Scholar
• Hieronymus F, Nilsson S, Eriksson E. A mega-analysis of fixed-dose trials reveals dose-dependency and a rapid onset of action for the antidepressant effect of three selective serotonin reuptake inhibitors. Transl Psychiatry. 2016 Jun 7;6(6):e834.
   PubMedGoogle Scholar
• Quitkin FM, Petkova E, McGrath PJ, et al. When should a trial of fluoxetine for major depression be declared failed? Am J Psychiatry. 2003 Apr;160(4):734–740.
   PubMed Web of Science ®Google Scholar
• Szegedi A, Muller MJ, Anghelescu I, et al. Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression. J Clin Psychiatry. 2003 Apr;64(4):413–420.
   PubMed Web of Science ®Google Scholar
• Stassen HH, Angst J, Delini-Stula A. Fluoxetine versus moclobemide: cross-comparison between the time courses of improvement. Pharmacopsychiatry. 1999 Mar;32(2):56–60.
   PubMedGoogle Scholar
• Stassen HH, Angst J, Delini-Stula A. Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses. Pharmacopsychiatry. 1996 May;29(3):87–96.
   PubMedGoogle Scholar
• Stassen HH, Delini-Stula A, Angst J. Time course of improvement under antidepressant treatment: a survival-analytical approach. Eur Neuropsychopharmacol. 1993 Jun;3(2):127–135.
   PubMedGoogle Scholar
• Nierenberg AA, Farabaugh AH, Alpert JE, et al. Timing of onset of antidepressant response with fluoxetine treatment. Am J Psychiatry. 2000 Sep;157(9):1423–1428.
   PubMed Web of Science ®Google Scholar
• Katz MM, Tekell JL, Bowden CL, et al. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology. 2004 Mar;29(3):566–579.
   PubMed Web of Science ®Google Scholar
• Heiligenstein JH, Hoog SL, Wagner KD, et al. Fluoxetine 40-60 mg versus fluoxetine 20 mg in the treatment of children and adolescents with a less-than-complete response to nine-week treatment with fluoxetine 10-20 mg: a pilot study. J Child Adolesc Psychopharmacol. 2006 Feb-Apr;16(1–2):207–217.
   PubMedGoogle Scholar
• Posternak MA, Baer L, Nierenberg AA, et al. Response rates to fluoxetine in subjects who initially show no improvement. J Clin Psychiatry. 2011 Jul;72(7):949–954.
   PubMedGoogle Scholar
• Dold M, Bartova L, Rupprecht R, et al. Dose escalation of antidepressants in unipolar depression: a meta-analysis of double-blind, randomized controlled trials. Psychother Psychosom. 2017;86(5):283–291.
   PubMedGoogle Scholar
• Jakubovski E, Varigonda AL, Freemantle N, et al. Systematic review and meta-analysis: dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. Am J Psychiatry. 2016 Feb 1;173(2):174–183.
   PubMed Web of Science ®Google Scholar
• Bollini P, Pampallona S, Tibaldi G, et al. Effectiveness of antidepressants. Meta-analysis of dose-effect relationships in randomised clinical trials. Br J Psychiatry. 1999 Apr;174(4):297–303.
   PubMedGoogle Scholar
• Furukawa TA, Cipriani A, Cowen PJ, et al. Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis. Lancet Psychiatry. 2019 Jul;6(7):601–609.
   PubMed Web of Science ®Google Scholar
• Rink L, Adams A, Braun C, et al. Dose-response relationship in selective serotonin and norepinephrine reuptake inhibitors in the treatment of major depressive disorder: a meta-analysis and network meta-analysis of randomized controlled trials. Psychother Psychosom. 2022;91(2):84–93.
   PubMedGoogle Scholar
• Meyer JH, Wilson AA, Sagrati S, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry. 2004 May;161(5):826–835.
   PubMed Web of Science ®Google Scholar
• Sorensen A, Ruhe HG, Munkholm K. The relationship between dose and serotonin transporter occupancy of antidepressants-a systematic review. Mol Psychiatry. 2022 Jan;27(1):192–201.
   PubMedGoogle Scholar
• Thase ME. Antidepressant combinations: widely used, but far from empirically validated. Can J Psychiatry. 2011 Jun;56(6):317–323.
   PubMedGoogle Scholar
• Falit BP, Singh SC, Brennan TA. Biosimilar competition in the United States: statutory incentives, payers, and pharmacy benefit managers. Health Affairs. 2015;34(2):294–301.
   Google Scholar
• Desai RJ, Sarpatwari A, Dejene S, et al. Comparative effectiveness of generic and brand-name medication use: a database study of US health insurance claims. PLoS Med. 2019 Mar;16(3):e1002763.
   PubMed Web of Science ®Google Scholar
• Tabuteau H, Jones A, Anderson A, et al. Effect of AXS-05 (Dextromethorphan-Bupropion) in major depressive disorder: a randomized double-blind controlled trial. Am J Psychiatry. 2022 Jul;179(7):490–499.
   PubMed Web of Science ®Google Scholar
• Cosci F, Guidi J, Mansueto G, et al. Psychotherapy in recurrent depression: efficacy, pitfalls, and recommendations. Expert Rev Neurother. 2020 Nov;20(11):1169–1175.
   PubMed Web of Science ®Google Scholar
• Guidi J, Fava GA. Sequential Combination of pharmacotherapy and psychotherapy in major depressive disorder: a systematic review and meta-analysis. JAMA Psychiatry. 2021 Mar 1;78(3):261–269.
   PubMedGoogle Scholar
• Carvalho AF, Sharma MS, Brunoni AR, et al. The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother Psychosom. 2016;85(5):270–288.
   PubMed Web of Science ®Google Scholar
• Dubovsky SL, Marshall D. Benzodiazepines remain important therapeutic options in psychiatric practice. Psychother Psychosom. 2022;91(5):307–334.
   PubMedGoogle Scholar
• Boldrini M, Butt TH, Santiago AN, et al. Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders. Int J Neuropsychopharmacol. 2014 Dec;17(12):1923–1933.
   PubMedGoogle Scholar