CNS Drugs

, Volume 25, Issue 2, pp 109–127 | Cite as

Aripiprazole as Adjunctive Therapy for Patients with Major Depressive Disorder

Overview and Implications of Clinical Trial Data
Review Article

Abstract

Aripiprazole was initially approved to treat schizophrenia and later approved for bipolar mania, as a monotherapy and an adjunctive therapy (manic or mixed episodes), and for irritability associated with autism. Aripiprazole is a partial agonist at dopamine D2 and D3 and serotonin 5-HT1A receptors, and is an antagonist at 5-HT2a receptors. This profile, and convincing preliminary data from small-scale studies, provided the rationale for the large-scale exploration of aripiprazole for unipolar depression. Recently, three 6-week, large-scale, randomized, double-blind, placebo-controlled clinical trials demonstrated clinically meaningful efficacy for aripiprazole as an adjunctive therapy to antidepressants for treating major depressive disorder (MDD). In November 2007, aripiprazole was approved by the US FDA as an adjunctive therapy to antidepressants for treating MDD, with support from two of the above-mentioned trials. In the trials, aripiprazole was demonstrated to be safe and well tolerated, and showed a minimal trend for weight gain over the course of a 6-week treatment. The incidence of akathisia was higher than that reported in studies of patients with schizophrenia; however, most cases were mild to moderate and infrequently lead to discontinuation (5/1090 from all three trials).

This comprehensive review provides an overview of the data from all three 6-week studies (including a pooled analysis) and from an unpublished 52-week, open-label extension study, to inform physicians and facilitate reasonable treatment decisions. In addition, specific issues associated with the use of aripiprazole as an adjunctive therapy in patients with MDD, including possible early treatment effect, appropriate timing of therapy initiation, appropriate dosing and duration of treatment, possible differential effect on depressive subgroups and long-term tolerability, are also discussed.

Notes

Acknowledgements

This work was supported by a grant from the Medical Research Center, Korea Science and Engineering Foundation, Republic of Korea (R13-2002-005-04001-0). The authors did not receive any independent funding or payment from Otsuka Pharmaceuticals. Drs Pae and Patkar were involved in the commencement of the manuscript, data collection and review, and writing the draft and revised version of the manuscript. Dr Forbes reviewed the data accuracy and wrote specific parts of the manuscript (pharmacokinetics and pharmacodynamics).

Dr Pae has received research grants from GlaxoSmithKline Korea, GlaxoSmithKline, AstraZeneca Korea, Jansssen Pharmaceutcals Korea, Eli Lilly and Company Korea, Korea Science and Engineering Foundation, Korean Research Foundation, Otsuka Korea, Wyeth Korea and Korean Institute of Science and Technology Evaluation and Planning; has received honoraria and/or is on the speaker’s bureaux of GlaxoSmithKline Korea, GlaxoSmithKline Taiwan, Otsuka Taiwan, Lundbeck Korea, AstraZeneca Korea, Johnson & Johnson-Health Care Products & Pharmaceuticals, Janssen Pharmaceuticals Korea, Wyeth Korea, Abott Korea, Pfizer Korea, Eli Lilly and Company Korea, Norvatis Korea, McNeil Consumer and Specialty Inc., Otsuka Pharmaceutical Development & Commercialization and Otsuka Korea.

Dr Forbes is an employee of Otsuka Pharmaceutical Development & Commercialization.

Dr Patkar is a consultant for Bristol-Myers Squibb, GlaxoSmithKline and Reckitt Benckiser; is on the speaker’s bureaux of Bristol-Myers Squibb, GlaxoSmithKline and Reckitt Benckiser; has received research support from National Institutes of Health, AstraZeneca, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen, McNeil Consumer and Specialty Inc., Organon, Jazz Pharmaceuticals and Pfizer.

References

  1. 1.
    Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003 Jun 18; 289(23): 3095–105PubMedGoogle Scholar
  2. 2.
    Fava M, Rush AJ, Trivedi MH, et al. Background and rationale for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Psychiatr Clin North Am 2003 Jun; 26(2): 457–94, xPubMedGoogle Scholar
  3. 3.
    Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006 Jan; 163(1): 28–40PubMedGoogle Scholar
  4. 4.
    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): 1905–17PubMedGoogle Scholar
  5. 5.
    Papakostas GI, Petersen T, Denninger JW, et al. Psychosocial functioning during the treatment of major depressive disorder with fluoxetine. J Clin Psychopharmacol 2004 Oct; 24(5): 507–11PubMedGoogle Scholar
  6. 6.
    Trivedi MH, Corey-Lisle PK, Guo Z, et al. Remission, response without remission, and nonresponse in major depressive disorder: impact on functioning. Int Clin Psychopharmacol 2009 May; 24(3): 133–8PubMedGoogle Scholar
  7. 7.
    Moller HJ. Outcomes in major depressive disorder: the evolving concept of remission and its implications for treatment. World J Biol Psychiatry 2008; 9(2): 102–14PubMedGoogle Scholar
  8. 8.
    Nierenberg AA, Husain MM, Trivedi MH, et al. Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report. Psychol Med 2009 May; 22: 1–10Google Scholar
  9. 9.
    American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000 Apr; 157(4 Suppl. ): 1–45Google Scholar
  10. 10.
    Bauer M, Whybrow PC, Angst J, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders: part 1._Acute and continuation treatment of major depressive disorder. World J Biol Psychiatry 2002 Jan; 3(1): 5–43PubMedGoogle Scholar
  11. 11.
    Anderson IM, Ferrier IN, Baldwin RC, et 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): 343–96PubMedGoogle Scholar
  12. 12.
    Kennedy SH, Lam RW, Cohen NL, et al. Clinical guidelines for the treatment of depressive disorders: IV. Medications and other biological treatments. Can J Psychiatry 2001 Jun; 46 Suppl. 1: 38S–58SGoogle Scholar
  13. 13.
    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): 448–52PubMedGoogle Scholar
  14. 14.
    Blier P, Ward NM. Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry 2003; 53(3): 193–203PubMedGoogle Scholar
  15. 15.
    Corrigan MH, Denahan AQ, Wright CE, et al. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety 2000; 11(2): 58–65PubMedGoogle Scholar
  16. 16.
    Cassano P, Lattanzi L, Fava M, et al. Ropinirole in treatment-resistant depression: a 16-week pilot study. Can J Psychiatry 2005 May; 50(6): 357–60PubMedGoogle Scholar
  17. 17.
    Rasmussen NA, Schroder P, Olsen LR, et al. Modafinil augmentation in depressed patients with partial response to antidepressants: a pilot study on self-reported symptoms covered by the Major Depression Inventory (MDI) and the Symptom Checklist (SCL-92). Nord J Psychiatry 2005; 59(3): 173–8PubMedGoogle Scholar
  18. 18.
    DeBattista C, Doghramji K, Menza MA, et al. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry 2003 Sep; 64(9): 1057–64PubMedGoogle Scholar
  19. 19.
    Konuk N, Atasoy N, Atik L, et al. Open-label study of adjunct modafinil for the treatment of patients with fatigue, sleepiness, and major depression treated with selective serotonin reuptake inhibitors. Adv Ther 2006 Jul–Aug; 23(4): 646–54PubMedGoogle Scholar
  20. 20.
    Thase ME, Fava M, DeBattista C, et al. Modafinil augmentation of SSRI therapy in patients with major depressive disorder and excessive sleepiness and fatigue: a 12-week, open-label, extension study. CNS Spectr 2006 Feb; 11(2): 93–102PubMedGoogle Scholar
  21. 21.
    Dunlop BW, Crits-Christoph P, Evans DL, et al. Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study. J Clin Psychopharmacol 2007 Dec; 27(6): 614–9PubMedGoogle Scholar
  22. 22.
    Fava M, Thase ME, DeBattista C. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry 2005 Jan; 66(1): 85–93PubMedGoogle Scholar
  23. 23.
    Fava M, Thase ME, DeBattista C, et al. Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann Clin Psychiatry 2007 Jul–Sep; 19(3): 153–9PubMedGoogle Scholar
  24. 24.
    Lavretsky H, Park S, Siddarth P, et al. Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial. Am J Geriatr Psychiatry 2006 Feb; 14(2): 181–5PubMedGoogle Scholar
  25. 25.
    Papakostas GI, Shelton RC, Smith J, et al. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry 2007 Jun; 68(6): 826–31PubMedGoogle Scholar
  26. 26.
    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): 540–9PubMedGoogle Scholar
  27. 27.
    Cutler AJ, Montgomery SA, Feifel D, et al. Extended release quetiapine fumarate monotherapy in major depressive disorder: a placebo- and duloxetine-controlled study. J Clin Psychiatry 2009 Apr; 70(4): 526–39PubMedGoogle Scholar
  28. 28.
    Chaput Y, Magnan A, Gendron A. The co-administration of quetiapine or placebo to cognitive-behavior therapy in treatment refractory depression: a preliminary trial. BMC Psychiatry 2008; 8: 73PubMedGoogle Scholar
  29. 29.
    Anderson IM, Sarsfield A, Haddad PM. Efficacy, safety and tolerability of quetiapine augmentation in treatment resistant depression: an open-label, pilot study. J Affect Disord 2009 Sep; 117(1–2): 116–9PubMedGoogle Scholar
  30. 30.
    Garakani A, Martinez JM, Marcus S, et al. A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder. Int Clin Psychopharmacol 2008 Sep; 23(5): 269–75PubMedGoogle Scholar
  31. 31.
    Pae CU, Sohi MS, Seo HJ, et al. Quetiapine XR: current status for the treatment of major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2010 Oct 1; 34(7): 1165–73PubMedGoogle Scholar
  32. 32.
    Croxtall JD, Scott LJ. Olanzapine/fluoxetine: a review of its use in patients with treatment-resistant major depressive disorder. CNS Drugs Mar 1; 24 (3): 245-62Google Scholar
  33. 33.
    Swainston Harrison T, Perry CM. Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. Drugs 2004; 64(15): 1715–36PubMedGoogle Scholar
  34. 34.
    Molden E, Lunde H, Lunder N, et al. Pharmacokinetic variability of aripiprazole and the active metabolite dehydroaripiprazole in psychiatric patients. Ther Drug Monit 2006 Dec; 28(6): 744–9PubMedGoogle Scholar
  35. 35.
    Kim JR, Seo HB, Cho JY, et al. Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients. Br J Clin Pharmacol 2008 Dec; 66(6): 802–10PubMedGoogle Scholar
  36. 36.
    Kubo M, Koue T, Maune H, et al. Pharmacokinetics of aripiprazole, a new antipsychotic, following oral dosing in healthy adult Japanese volunteers: influence of CYP2D6 polymorphism. Drug Metab Pharmacokinet 2007 Oct; 22(5): 358–66PubMedGoogle Scholar
  37. 37.
    Zocchi A, Fabbri D, Heidbreder CA. Aripiprazole increases dopamine but not noradrenaline and serotonin levels in the mouse prefrontal cortex. Neurosci Lett 2005 Oct 28; 387(3): 157–61PubMedGoogle Scholar
  38. 38.
    DeLeon A, Patel NC, Crismon ML. Aripiprazole: a comprehensive review of its pharmacology, clinical efficacy, and tolerability. Clin Ther 2004 May; 26(5): 649–66PubMedGoogle Scholar
  39. 39.
    Pae CU, Serretti A, Patkar AA, et al. Aripiprazole in the treatment of depressive and anxiety disorders: a review of current evidence. CNS Drugs 2008; 22(5): 367–88PubMedGoogle Scholar
  40. 40.
    Burris KD, Molski TF, Xu C, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 2002 Jul; 302(1): 381–9PubMedGoogle Scholar
  41. 41.
    Dhir A, Kulkarni SK. Involvement of dopamine (DA)/ serotonin (5-HT)/sigma (sigma) receptor modulation in mediating the antidepressant action of ropinirole hydrochloride, a D2/D3 dopamine receptor agonist. Brain Res Bull 2007 Sep 14; 74(1–3): 58–65PubMedGoogle Scholar
  42. 42.
    Renard CE, Fiocco AJ, Clenet F, et al. Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test? Psychopharmacology 2001 Dec; 159(1): 42–50PubMedGoogle Scholar
  43. 43.
    Abilifys R (aripiprazole): US prescribing information. Rockville (MD): Otsuka Pharmaceuticals Co. Inc., 2009Google Scholar
  44. 44.
    Bowles TM, Levin GM. Aripiprazole: a new atypical antipsychotic drug. Ann Pharmacother 2003 May; 37(5): 687–94PubMedGoogle Scholar
  45. 45.
    Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977 Oct; 229(2): 327–36PubMedGoogle Scholar
  46. 46.
    Steru L, Chermat R, Thierry B, et al. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 1985; 85(3): 367–70PubMedGoogle Scholar
  47. 47.
    Regenthal R, Koch H, Kohler C, et al. Depression-like deficits in rats improved by subchronic modafinil. Psychopharmacology 2009 Jul; 204(4): 627–39PubMedGoogle Scholar
  48. 48.
    Carlezon Jr WA, Mague SD, Andersen SL. Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry 2003 Dec 15; 54(12): 1330–7PubMedGoogle Scholar
  49. 49.
    Shimazu S, Minami A, Kusumoto H, et al. Antidepressant-like effects of selegiline in the forced swim test. Eur Neuropsychopharmacol 2005 Oct; 15(5): 563–71PubMedGoogle Scholar
  50. 50.
    Bourin M, Chenu F, Prica C, et al. Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology 2009 Sep; 206(1): 97–107PubMedGoogle Scholar
  51. 51.
    Kamei J, Miyata S, Sunohara T, et al. Potentiation of the antidepressant-like effect of fluoxetine by aripiprazole in the mouse tail suspension test. J Pharmacol Sci 2008 Nov; 108(3): 381–4PubMedGoogle Scholar
  52. 52.
    Bortolozzi A, Diaz-Mataix L, Toth M, et al. In vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain. Psychopharmacology 2007 Apr; 191(3): 745–58PubMedGoogle Scholar
  53. 53.
    Papp M, Klimek V, Willner P. Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine. Psychopharmacology 1994 Aug; 115(4): 441–6PubMedGoogle Scholar
  54. 54.
    Moresco RM, Colombo C, Fazio F, et al. Effects of fluvoxamine treatment on the in vivo binding of [F-18]FESP in drug naive depressed patients: a PET study. Neuroimage 2000 Oct; 12(4): 452–65PubMedGoogle Scholar
  55. 55.
    Bowden C, Theodorou AE, Cheetham SC, et al. Dopamine D1 and D2 receptor binding sites in brain samples from depressed suicides and controls. Brain Res 1997 Mar 28; 752(1–2): 227–33PubMedGoogle Scholar
  56. 56.
    Willner P, Hale AS, Argyropoulos S. Dopaminergic mechanism of antidepressant action in depressed patients. J Affect Disord 2005; 86(1): 37–45PubMedGoogle Scholar
  57. 57.
    Tadori Y, Kitagawa H, Forbes RA, et al. Differences in agonist/antagonist properties at human dopamine D(2) receptors between aripiprazole, bifeprunox and SDZ 208-912. Eur J Pharmacol 2007 Nov 28; 574(2–3): 103–11PubMedGoogle Scholar
  58. 58.
    Adson DE, Kushner MG, Fahnhorst TA. Treatment of residual anxiety symptoms with adjunctive aripiprazole in depressed patients taking selective serotonin reuptake inhibitors. J Affect Disord 2005 May; 86(1): 99–104PubMedGoogle Scholar
  59. 59.
    Papakostas GI, Petersen TJ, Kinrys G, et al. Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder. J Clin Psychiatry 2005 Oct; 66(10): 1326–30PubMedGoogle Scholar
  60. 60.
    Pae CU, Patkar AA, Jun TY, et al. Aripiprazole augmentation for treatment of patients with inadequate antidepressants response. Depress Anxiety 2007; 24(7): 522–6PubMedGoogle Scholar
  61. 61.
    Simon JS, Nemeroff CB. Aripiprazole augmentation of antidepressants for the treatment of partially responding and nonresponding patients with major depressive disorder. J Clin Psychiatry 2005 Oct; 66(10): 1216–20PubMedGoogle Scholar
  62. 62.
    Patkar AA, Peindl K, Mago R, et al. An open-label, rater-blinded, augmentation study of aripiprazole in treatment-resistant depression. Prim Care Companion J Clin Psychiatry 2006; 8(2): 82–7PubMedGoogle Scholar
  63. 63.
    Rutherford B, Sneed J, Miyazaki M, et al. An open trial of aripiprazole augmentation for SSRI non-remitters with late-life depression. Int J Geriatr Psychiatry 2007 Oct; 22(10): 986–91PubMedGoogle Scholar
  64. 64.
    Barbee JG, Conrad EJ, Jamhour NJ. Aripiprazole augmentation in treatment-resistant depression. Ann Clin Psychiatry 2004 Oct–Dec; 16(4): 189–94PubMedGoogle Scholar
  65. 65.
    Worthington 3rd JJ, Kinrys G, Wygant LE, et al. Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients. Int Clin Psychopharmacol 2005 Jan; 20(1): 9–11PubMedGoogle Scholar
  66. 66.
    Schule C, Baghai TC, Eser D, et al. Mirtazapine monotherapy versus combination therapy with mirtazapine and aripiprazole in depressed patients without psychotic features: a 4-week open-label parallel-group study. World J Biol Psychiatry 2007; 8(2): 112–22PubMedGoogle Scholar
  67. 67.
    Hellerstein DJ, Batchelder S, Hyler S, et al. Aripiprazole as an adjunctive treatment for refractory unipolar depression. Prog Neuropsychopharmacol Biol Psychiatry 2008 Apr 1; 32(3): 744–50PubMedGoogle Scholar
  68. 68.
    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): 843–53PubMedGoogle Scholar
  69. 69.
    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): 156–65PubMedGoogle Scholar
  70. 70.
    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): 197–206PubMedGoogle Scholar
  71. 71.
    Thase ME, Trivedi MH, Nelson JC, et al. Examining the efficacy of adjunctive aripiprazole in major depressive disorder: a pooled analysis of 2 studies. Prim Care Companion J Clin Psychiatry 2008; 10(6): 440–7PubMedGoogle Scholar
  72. 72.
    Vis PM, van Baardewijk M, Einarson TR. Duloxetine and venlafaxine-XR in the treatment of major depressive disorder: a meta-analysis of randomized clinical trials. Ann Pharmacother 2005 Nov; 39(11): 1798–807PubMedGoogle Scholar
  73. 73.
    Rudolph RL, Feiger AD. A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. J Affect Disord 1999 Dec; 56(2–3): 171–81PubMedGoogle Scholar
  74. 74.
    Thase ME, Kornstein SG, Germain JM, et al. An integrated analysis of the efficacy of desvenlafaxine compared with placebo in patients with major depressive disorder. CNS Spectr 2009 Mar; 14(3): 144–54PubMedGoogle Scholar
  75. 75.
    Hansen R, Gaynes B, Thieda P, et al. Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants. Psychiatr Serv 2008 Oct; 59(10): 1121–30PubMedGoogle Scholar
  76. 76.
    Data on file, Otsuka Pharmaceuticals, Inc., 2009Google Scholar
  77. 77.
    Berman RM, Hazel J, Swanink R, et al. Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder (study CN138-164). American Psychiatric Association 161st Annual Meeting; 2008 May 3–8; Washington, DCGoogle Scholar
  78. 78.
    Pae CU. A review of the safety and tolerability of aripiprazole. Expert Opin Drug Saf 2009 May; 8(3): 373–86PubMedGoogle Scholar
  79. 79.
    Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002 Sep; 63(9): 763–71PubMedGoogle Scholar
  80. 80.
    Marder SR, McQuade RD, Stock E, et al. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res 2003 Jun 1; 61(2–3): 123–36PubMedGoogle Scholar
  81. 81.
    Potkin SG, Saha AR, Kujawa MJ, et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 2003 Jul; 60(7): 681–90PubMedGoogle Scholar
  82. 82.
    Gao K, Kemp DE, Ganocy SJ, et al. Antipsychotic-induced extrapyramidal side effects in bipolar disorder and schizophrenia: a systematic review. J Clin Psychopharmacol 2008 Apr; 28(2): 203–9PubMedGoogle Scholar
  83. 83.
    Lane RM. SSRI-induced extrapyramidal side-effects and akathisia: implications for treatment. J Psychopharmacol 1998; 12(2): 192–214PubMedGoogle Scholar
  84. 84.
    Pigott TA, Carson WH, Saha AR, et al. Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo-controlled 26-week study. J Clin Psychiatry 2003 Sep; 64(9): 1048–56PubMedGoogle Scholar
  85. 85.
    Spina E, de Leon J. Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol 2007 Jan; 100(1): 4–22PubMedGoogle Scholar
  86. 86.
    Urichuk L, Prior TI, Dursun S, et al. Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab 2008 Jun; 9(5): 410–8PubMedGoogle Scholar
  87. 87.
    Conley RR, Kelly DL. Drug-drug interactions associated with second-generation antipsychotics: considerations for clinicians and patients. Psychopharmacol Bull 2007; 40(1): 77–97PubMedGoogle Scholar
  88. 88.
    Boulton D, Balch A, Royzman K, et al. The pharmacokinetics of standard antidepressants with aripiprazole as adjunctive therapy: studies in healthy subjects and in patients with major depressive disorder. J Psychopharmacol 2010 Apr; 24(4): 537–46PubMedGoogle Scholar
  89. 89.
    Bauman JN, Frederick KS, Sawant A, et al. Comparison of the bioactivation potential of the antidepressant and hepatotoxin nefazodone with aripiprazole, a structural analog and marketed drug. Drug Metab Dispos 2008 Jun; 36(6): 1016–29PubMedGoogle Scholar
  90. 90.
    Raggi MA, Mandrioli R, Sabbioni C, et al. Atypical antipsychotics: pharmacokinetics, therapeutic drug monitoring and pharmacological interactions. Curr Med Chem 2004 Feb; 11(3): 279–96PubMedGoogle Scholar
  91. 91.
    Schieber FC, Boulton DW, Balch AH, et al. A non-randomized study to investigate the effects of the atypical antipsychotic aripiprazole on the steady-state pharmacokinetics of lamotrigine in patients with bipolar I disorder. Hum Psychopharmacol 2009 Mar; 24(2): 145–52PubMedGoogle Scholar
  92. 92.
    Nierenberg AA, McLean NE, Alpert JE, et al. Early non-response to fluoxetine as a predictor of poor 8-week outcome. Am J Psychiatry 1995 Oct; 152(10): 1500–3PubMedGoogle Scholar
  93. 93.
    Nierenberg AA, Farabaugh AH, Alpert JE, et al. Timing of onset of antidepressant response with fluoxetine treatment. Am J Psychiatry 2000 Sep; 157(9): 1423–8PubMedGoogle Scholar
  94. 94.
    Papakostas GI, Petersen T, Sklarsky KG, et al. Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. Psychiatry Res 2007 Jan 15; 149(1–3): 195–200PubMedGoogle Scholar
  95. 95.
    Henkel V, Seemuller F, Obermeier M, et al. Does early improvement triggered by antidepressants predict response/remission? Analysis of data from a naturalistic study on a large sample of inpatients with major depression. J Affect Disord 2009 Jun; 115(3): 439–49PubMedGoogle Scholar
  96. 96.
    Huynh NN, McIntyre RS. What are the implications of the STAR*D trial for primary care? A review and synthesis. Prim Care Companion J Clin Psychiatry 2008; 10(2): 91–6PubMedGoogle Scholar
  97. 97.
    Papakostas GI, Montgomery SA, Thase ME, et al. Comparing the rapidity of response during treatment of major depressive disorder with bupropion and the SSRIs: a pooled survival analysis of 7 double-blind, randomized clinical trials. J Clin Psychiatry 2007 Dec; 68(12): 1907–12PubMedGoogle Scholar
  98. 98.
    Stewart JW. Treating depression with atypical features. J Clin Psychiatry 2007; 68 Suppl. 3: 25–9PubMedGoogle Scholar
  99. 99.
    Liebowitz MR, Quitkin FM, Stewart JW, et al. Antidepressant specificity in atypical depression. Arch Gen Psychiatry 1988 Feb; 45(2): 129–37PubMedGoogle Scholar
  100. 100.
    Stewart JW, McGrath PJ, Fava M, et al. Do atypical features affect outcome in depressed outpatients treated with citalopram? Int J Neuropsychopharmacol 2010 Feb; 13(1): 15–30PubMedGoogle Scholar
  101. 101.
    Fava M, Rush AJ, Alpert JE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 2008 Mar; 165(3): 342–51PubMedGoogle Scholar
  102. 102.
    Trivedi MH, Thase ME, Fava M, et al. Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features. J Clin Psychiatry 2008 Dec; 69(12): 1928–36PubMedGoogle Scholar
  103. 103.
    Fredman SJ, Fava M, Kienke AS, et al. Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current “next-step” practices. J Clin Psychiatry 2000 Jun; 61(6): 403–8PubMedGoogle Scholar
  104. 104.
    Marks DM, Pae CU, Patkar AA. Triple reuptake inhibitors: a premise and promise. Psychiatry Investig 2008 Sep; 5(3): 142–7PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Department of Psychiatry, Bucheon St. Mary’s HospitalThe Catholic University of Korea College of MedicineKyounggi-DoRepublic of Korea
  2. 2.Department of Psychiatry and Behavioral SciencesDuke University Medical CenterDurhamUSA
  3. 3.Otsuka Pharmaceutical Development & CommercializationPrincetonUSA

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