Sustaining remission of psychotic depression: rationale, design and methodology of STOP-PD ΙΙ

BMC Psychiatry

Patricia Marino⁴  Matthew V Rudorfer¹  Benoit H Mulsant³  Ellen M Whyte⁵  Anthony J Rothschild²  Barnett S Meyers⁴  Alastair J Flint⁶ 

[1] National Institute of Mental Health, Bethesda, USA;University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, USA;Centre for Addiction and Mental Health, Toronto, Canada;Department of Psychiatry Weill Medical College of Cornell University and New York Presbyterian Hospital–Westchester Division, New York, USA;Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA;Toronto General Hospital, 200 Elizabeth St., 8 Eaton North–Room 238, Toronto, Ontario, M5G 2C4, Canada

关键词: Multi-center study;    Aged;    Metabolic effects;    Relapse;    Antipsychotic discontinuation;    Randomized controlled trial;    Psychotic depression;    Major depressive disorder with psychotic features;   

Others  :  1124155
DOI  :  10.1186/1471-244X-13-38

 received in 2012-11-27, accepted in 2013-01-04,  发布年份 2013

【 摘 要 】

Background

Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Electroconvulsive therapy and pharmacotherapy are each efficacious in the treatment of PD. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the acute pharmacologic treatment of PD. However, little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical importance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder.

Methods/design

The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome.

Discussion

This trial will provide clinicians with much-needed evidence to guide the continuation and maintenance treatment of one of the most disabling and lethal of psychiatric disorders.

Trial registration and URL

NCT:NCT01427608

【 授权许可】

   
2013 Flint et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Schatzberg AF, Rothschild AJ: Psychotic (delusional) major depression: should it be included as a distinct syndrome in DSM-IV? Am J Psychiatry 1992, 149:733-745.
• [2]Rothschild AJ: Challenges in the treatment of depression with psychotic features. Biol Psychiatry 2003, 53:680-690.
• [3]Post F: The significance of affective symptoms in old age; a follow-up study of one hundred patients. New York: Oxford University Press; 1962.
• [4]Meyers BS, Greenberg R: Late-life delusional depression. J Affect Disord 1986, 11:133-137.
• [5]Kroessler D: Relative efficacy rates for therapies of delusional depression. Convulsive Ther 1985, 1:173-182.
• [6]Andreescu C, Mulsant B, Rothschild A, Flint A, Meyers B, Whyte E: Pharmacotherapy of major depression with psychotic features: what is the evidence? Psychiatr Ann 2006, 36(1):31-38.
• [7]American Psychiatric Association: Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000, 157(Suppl 4):1-45.
• [8]National Institute for Clinical Excellence: Depression: management of depression in primary and secondary care - NICE guidance. Vol Clinical Guideline 23. London: NICE; 2004.
• [9]Farahani A, Correll CU: Are antipsychotics or antidepressants needed for psychotic depression? A systematic review and meta-analysis of trials comparing antidepressant or antipsychotic monotherapy with combination treatment. J Clin Psychiatry 2012, 73(4):486-496.
• [10]Deshauer D, Moher D, Fergusson D, Moher E, Sampson M, Grimshaw J: Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials. CMAJ 2008, 178(10):1293-1301.
• [11]Aronson TA, Shukla S, Gujavarty K, Hoff A, DiBuono M, Khan E: Relapse in delusional depression: a retrospective study of the course of treatment. Compr Psychiatry 1988, 29(1):12-21.
• [12]Rothschild AJ, Duval SE: How long should patients with psychotic depression stay on the antipsychotic medication? J Clin Psychiatry 2003, 64:390-396.
• [13]Reynolds CF, Frank E, Kupfer DJ, Thase ME, Perel JM, Mazumdar S, Houck PR: Treatment outcome in recurrent major depression: a post hoc comparison of elderly (“young old”) and midlife patients. Am J Psychiatry 1996, 153:1288-1292.
• [14]Navarro V, Gasto C, Torres X, Masana G, Penades R, Guarch J, Vasquez M, Serra M, Pujol N, Pintor L, Catalan R: Continuation/maintenance treatment with nortriptyline versus combined nortriptyline and ECT in late-life psychotic depression: A two-year randomized study. Am J Geriatr Psychiatry 2008, 16:498-505.
• [15]Clower CG: Recurrent psychotic unipolar depression. J Clin Psychiatry 1983, 44:216-218.
• [16]Zanardi R, Franchini L, Gasperini M, Smeraldi E, Perez J: Long-term treatment of psychotic (delusional) depression with fluvoxamine: an open pilot study. Int Clin Psychopharmacol 1997, 12:195-197.
• [17]Meyers BS, Flint AJ, Rothschild AJ, Mulsant BH, Whyte E, Peasley-Miklus C, Heo M, Papademetriou E, Leon A, for the STOP-PD Study Group: A double-blind randomized controlled trial of olanzapine plus sertraline versus olanzapine plus placebo for psychotic depression - the STOP-PD study. Arch Gen Psychiatry 2009, 66:838-847.
• [18]First MB, Spitzer RL, Gibbon M, Williams JBW: Structured clinical interview for DSM-IV-TR axis I disorders - patient edition (SCID-I/P). New York: Biometrics Research Department; 2001.
• [19]Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960, 23:56-62.
• [20]Guy W: Clinical Global Impressions. ECDEU Assessment Manual for Psychopharmacology. Washington, DC, US: Dept. of Health, Education, and Welfare; 1976:pp 217-pp 222.
• [21]Folstein M, Folstein S, McHugh P: “Mini mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975, 12:189-198.
• [22]Alexopoulos GS, Katz IR, Reynolds CF, Carpenter DL, Docherty JP: The expert consensus guideline series: pharmacotherapy of depressive disorders in older patients. Postgrad Med Special Report 2001, (October; Special No Pharmacotherapy):1-86.
• [23]Brodaty H, Luscombe G, Parker G, Wilhelm K, Hickie I, Austin M-P, Mitchell P: Increased rate of psychosis and psychomotor change in depression with age. Psychol Med 1997, 27:1205-1213.
• [24]Pollock BG: The pharmacokinetic imperative in late-life depression. J Clin Psychopharmacol 2005, 25(4 Suppl 1):S19-S23.
• [25]Keller MB, Boland RJ: Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression. Biol Psychiatry 1998, 44:348-360.
• [26]Parker G, Hadzi-Pavlovic D, Hickie I, Mitchell P, Wilhelm K, Brodaty H, Boyce P, Eyers K, Pedic F: Psychotic depression: a review and clinical experience. Aust N Z J Psychiatry 1991, 25:169-180.
• [27]Meyers BS, English J, Gabriele M, Peasley-Miklus C, Moonseong H, Flint AJ, Mulsant BH, Rothschild AJ, for the STOP-PD Study Group: A delusion assessment scale for psychotic major depression: reliability, validity, and utility. Biol Psychiatry 2006, 60:1336-1342.
• [28]Flint AJ: Delusions, hallucinations and depression in Alzheimer’s disease: a biological perspective. Am J Alzheimer’s Care Relat Disord Res 1991, 21-28.
• [29]Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003, 26(Suppl 1):S5-S20.
• [30]De Jonghe JFM: Differentiating between demented and psychiatric patients with the Dutch version of the IQCODE. Int J Geriatr Psychiatry 1997, 12:462-465.
• [31]Pisani MA, Inouye SK, McNicoll L, Redlich CA: Screening for preexisting cognitive impairment in older intensive care unit patients: use of a proxy assessment. J Am Geriatr Soc 2003, 51:689-693.
• [32]Applebaum PS, Grisso T: MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Sarasota, Fl: Professional Resource Press; 2001.
• [33]Spitzer RL, Endicott J: Schedule for Affective Disorders and Schizophrenia (third edition). New York: New York State Psychiatric Institute, Biometrics Research; 1979.
• [34]Williams JBW, Kobak KA, Bech P, Engelhardt N, Evans K, Lipsitz J, Olin J, Pearson J, Kalali A: The GRID-HAMD: standardization of the Hamilton depression rating scale. Int Clin Psychopharmacology 2008, 23:12.
• [35]Beck AT, Kovacs M, Weissman M: Scale for suicide ideation. J Consult Clin Psychol 1979, 47:343.
• [36]Jorm AF: The informant questionnaire on cognitive decline in the elderly (IQCODE): a review. Int Psychogeriatrics 2004, 16:275-293.
• [37]Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 1983, 67(6):361-370.
• [38]Miller MD, Paradis CF, Houck PR, Mazumdar S, Stack JA, Rifai AH, Mulsant B, Reynolds CF 3rd: Rating chronic medical illness burden in geropsychiatric practice and research: application of the cumulative illness rating scale. Psychiatry Res 1992, 41:237-248.
• [39]Wilhelm K: Rating the CORE: A user’s guide. In Melancholia: A Disorder of Movement and Mood. Edited by Parker G, Hadzi-Pavlovic D. Cambridge: Cambridge University Press; 1996:pp 211-pp 219.
• [40]Delis D, Kaplan E, Kramer J: Delis-Kaplan Executive Function Scale. San Antonio, TX: The Psychological Corporation; 2001.
• [41]Randolph C: The repeatable battery for the assessment of neuropsychological status. San Antonio, TX: The Psychological Corporation; 1998.
• [42]Oquendo MA, Baca-Garcia E, Kartachov A, Khait V, Campbell CE, Richards M: A computer algorithm for calculating the adequacy of antidepressant treatment in unipolar and bipolar depression. J Clin Psychiatry 2003, 64:825-833.
• [43]Ware JE Jr, Sherbourne CD: The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992, 30(6):473-483.
• [44]Flint AJ, Rifat SL: Two-year outcome of elderly patients with anxious depression. Psychiatry Res 1997, 66:23-31.
• [45]Flint AJ, Rifat SL: The effect of treatment on the two-year course of late-life depression. Br J Psychiatry 1997, 170:268-272.
• [46]Alexopoulos GS, Meyers BS, Young RC, Kalayam B, Kakuma T, Gabrelle M, Sirey JA, Hull J: Executive dysfunction and long-term outcomes of geriatric depression. Arch Gen Psychiatry 2000, 57:285-290.
• [47]Parker G, Hickie I, Mason C: Validity of the CORE measure: III. Outcome and treatment prediction. In Melancholia: A Disorder of Movement and Mood. Edited by Parker G, Hadzi-Pavlovic D. Cambridge: Cambridge University Press; 1996:160-171.
• [48]Flint AJ, Rifat SL: Nonresponse to first-line pharmacotherapy may predict relapse and recurrence of remitted geriatric depression. Depress Anxiety 2001, 13:125-131.
• [49]Hill SK, Keshavan MS, Thase ME, Sweeney JA: Neuropsychological dysfunction in antipsychotic-naïve first-episode unipolar psychotic depression. Am J Psychiatry 2004, 161:996-1003.
• [50]Butters MA, Whyte EM, Nebes RD, Begley AE, Dew MA, Mulsant BH, Zmuda MD, Bhalla R, Meltzer CC, Pollock BG, Reynolds CF 3rd, Becker JT: The nature and determinants of neuropsychological functioning in late-life depression. Arch Gen Psychiatry 2004, 61:587-595.
• [51]Lingjaerde O, Ahlfors UG, Bech P, Dencher SJ, Elgen K: The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand 1987, 334(Suppl):1-100.
• [52]Simpson GM, Angus JW: A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970, 212:11-19.
• [53]Barnes TR: A rating scale for drug-induced akathisia. Br J Psychiatry 1989, 154:672-676.
• [54]Guy W: Abnormal Involuntary Movement Scale (AIMS). ECDEU Assessment Manual for Psychopharmacology. Washington, DC: US Dept. of Health, Education, and Welfare; 1976:pp 534-pp 537.
• [55]American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity: Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004, 27:596-601.
• [56]Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 2005, 365:1415-1428.
• [57]McAuley KA, Mann JI, Chase JG, Lotz TF, Shaw GM: HOMA: The best bet for the simple determination of insulin sensitivity, until something better comes along. Diabetes Care 2007, 30(9):2411-2413.
• [58]Bigos KL, Pollock BG, Coley KC, Miller DD, Marder SR, Aravagiri M, Kirshner MA, Schneider LS, Bies RR: Sex, race, and smoking impact olanzapine exposure. J Clin Pharmacol 2008, 489:157-165.
• [59]Bigos KL, Bies RB, Pollock BG: Population pharmacokinetics in geriatric psychiatry. Am J Geriatr Psychiatry 2006, 14:993-1003.
• [60]Beal SL, Sheiner LB: Estimating population kinetics. Crit Rev Biomed Eng 1982, 8(3):195-222.
• [61]Feng Y, Pollock BG, Ferrell RE, Kimak MA, Reynolds CF 3rd, Bies RR: Paroxetine: population pharmacokinetic analysis in late-life depression using sparse concentration sampling. Br J Clin Pharmacol 2006, 61(5):558-569.
• [62]Muller DJ, Kennedy JL: Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics 2006, 7(6):863-887.
• [63]Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK: The DISC locus in psychiatric illness. Mol Psychiatry 2008, 13:36-64.
• [64]Green EK, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, Gordon-Smith K, Fraser C, Forty L, Russell E, Hamshere ML, Moskvina V, Nikolov I, Farmer A, McGuffin P, Holmans PA, Owen MJ, O’Donovan MC, Craddock N, Wellcome Trust Case Control Consortium: The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry 2010, 15(10):1016-1022.
• [65]Meyers BS, Klimstra SA, Gabriele M, Hamilton M, Kakuma T, Tirumalasetti F, Alexopoulos GS: Continuation treatment of delusional depression in older adults. Am J Geriatr Psychiatry 2001, 9:415-422.
• [66]Flint AJ, Rifat SL: Two-year outcome of psychotic depression in late life. Am J Psychiatry 1998, 155:178-183.
• [67]Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V: Long-term antipsychotic treatment and brain volumes. A longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry 2011, 68(2):128-137.