Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-27T22:29:48.246Z Has data issue: false hasContentIssue false
  • English
  • Français

Adjunctive Atypical Antipsychotics in Medication-Resistant Depression

Published online by Cambridge University Press:  07 November 2014

J. Craig Nelson
Get access Rights & Permissions [Opens in a new window]

Extract

Conventional antipsychotics have a substantial literature of >30 placebo-controlled studies supporting their use in depression. Reports describing the use of antipsychotic treatment in depression appeared as early as 1959. In the 1970s, combination products of perphenazine and amitrip-tyline were quite popular. Antipsychotic agents were effective for selected symptoms or in selected patients; yet, these agents were not viewed as “true” antidepressants, perhaps because of their lack of effects on loss of interest. The use of antipsychotics in patients with nonpsychotic depression declined rapidly in the 1980s when tardive dyskinesia (TD) surfaced as a potential adverse effect of this class of medications. Depressed patients were thought to be at increased risk. Interest in the potential utility of antipsychotics in depression resurfaced with the availability of the second-generation antipsychotics (SGAs), which possess a considerably lower risk for TD.

Most of the SGAs are inhibitors of the serotonin (5-HT)2A receptor and the dopamine (D)2 receptor. In fact, the ratio of these effects has been considered one attribute of an SGA. The SGAs have a variety of other receptor actions that might contribute to antidepressant effects but which vary substantially among the drugs. These include agonist effects at the 5-HT1A serotonin receptor, inhibition of the 5-HT2C receptor, and partial D2 agonism of aripiprazole (Slide 1). In addition, ziprasidone blocks 5-HT and norepinephrine (NE) reuptake and the metabolite of quetiapine has NE reuptake blocking effects.

Type
Research Article
Information
CNS Spectrums , Volume 15 , supplement S7: Current Evidence and Future Directions: Augmentation and Dosing Strategies for Major Depressive Disorder , June 2010 , pp. 10 - 13
Copyright
Copyright © Cambridge University Press 2010

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

REFERENCES

1.Nelson, JC. The use of antipsychotic drugs in the treatment of depression. In: Treating Resistant Depression Zohar, J, Belmaker, RH, eds. New York, NY: PMA Publishing Corp; 1987:131–146.Google Scholar
2.Cohen, S. TP-21, a new phenothiazine. Am J Psychiatry. 1958;115:358.CrossRefGoogle ScholarPubMed
3.Richelson, E, Souder, T. Binding of antipsychotic drugs to human brain receptors: Focus on newer generation compounds. Life Sciences 2000;68:29–39.CrossRefGoogle ScholarPubMed
4.Shapiro, DA, Renock, S, Arrington, E, et al. Aripiprazole: a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003;28:1400–1411.CrossRefGoogle ScholarPubMed
5.Tadori, Y. Forbes, RA, McQuade, RD, Kikuchi, T. Characterization of aripiprazole partial agonist activity at human dopamine D(3) receptors. Eur J Pharmacol. 2008;597:27–33.CrossRefGoogle Scholar
6.Tatsumi, M, Jansen, K, Blakely, RD, Richelson, E. Pharmacologic profile of neuroleptics at human monoamine transporters. Eur J Pharmacol. 1999;368:277–283.CrossRefGoogle ScholarPubMed
7.Jensen, NH, Rodriguiz, RM, Caron, MG, Wetsel, WC, Rothman, RB, Roth, BL. N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antide-pressant activity. Neuropsychopharmacology. 2008;33:2303–2312.CrossRefGoogle Scholar
8.Ostroff, R, Nelson, JC. Risperidone augmentation of selective serotonin reuptake inhibitors in major depression J Clin Psychiatry. 1999;60(4):256–259.CrossRefGoogle ScholarPubMed
9.Shelton, RC, Tollefson, GD, Tohen, M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry. 2001;158(1):131–134.CrossRefGoogle ScholarPubMed
10.Nelson, JC, Papakostas, G. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry. 2009;166:980–991.CrossRefGoogle ScholarPubMed
11.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;68(6):935–940.CrossRefGoogle ScholarPubMed
12.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;66:1289–1297.CrossRefGoogle ScholarPubMed
13.Corya, SA, Williamson, DJ, Sanger, TM, Briggs, SD, Case, M, Tollefson, GD. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression. Depress Anxiety. 2006;23:364–372.CrossRefGoogle ScholarPubMed
14.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;70(4):540–549.CrossRefGoogle Scholar
15.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 Feb 23:1–16. [Epub ahead of print]Google Scholar
16.Dunner, DL, Amsterdam, JD, Shelton, RC, Loebel, A, Romano, SJ. Efficacy and tolerability of adjunctive ziprasidone in treatment-resistant depression: a randomized, open-label, pilot study. J Clin Psychiatry. 2007;68:1071–1077.CrossRefGoogle ScholarPubMed
17.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;331:2505–2513.CrossRefGoogle Scholar
18.Nelson, JC, Thase, ME, Trivedi, MH, et al. Safety and tolerability of adjunctive aripiprazole in major depressive disorder: a pooled post hoc analysis (studies CN138-139 and CN138-163). Prim Care Companion J Clin Psychiatry. 2009;11(6):344–352.CrossRefGoogle ScholarPubMed
19. Product information available at: www.accessdata.fda.govGoogle Scholar
20.Lieberman, JALieberman, JA, Stroup, TS, McEvoy, JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Eng J Med. 2005;353(12): 1209–1223CrossRefGoogle ScholarPubMed
21.Meyers, BS, Flint, AJ, Rothschild, AJ, et al. A double-blind randomized controlled trial of olanzapine plus sertraline vs. olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD). Arch Gen Psychiatry. 2009;66(8):838–847.CrossRefGoogle Scholar
22.Beasley, CM, Dellva, MA, Tamura, RN, et al. Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol. Br J Psychiatry. 1999;174:23–30.CrossRefGoogle ScholarPubMed
23.Lemmens, P, Brecher, M, Van Baelen, B. A combined analysis of double-blind studies with risperidone vs placebo and other antipsychotic agents: factors associated with extrapyramidal symptoms. Acta Psychiatr Scand. 1999;99:160–170.CrossRefGoogle ScholarPubMed
24.Berman, RMet al. Presented at the 161st Annual Meeting of the American Psychiatric Assoc, Washington DC, May 3-6, 2008.Google Scholar
25.Corya, SA, Andersen, SW, Detke, HC, et al. Long-term antidepressant efficacy and safety of olanzapine/fluoxetine combination: a 76-week open-label study. J Clin Psychiatry. 2003;64:1349–1356.CrossRefGoogle ScholarPubMed