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Open Access 01-12-2013 | Study protocol

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

Authors: Alastair J Flint, Barnett S Meyers, Anthony J Rothschild, Ellen M Whyte, Benoit H Mulsant, Matthew V Rudorfer, Patricia Marino

Published in: BMC Psychiatry | Issue 1/2013

Abstract

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

Available only for authorised users

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.CrossRefPubMed

Rothschild AJ: Challenges in the treatment of depression with psychotic features. Biol Psychiatry. 2003, 53: 680-690. 10.1016/S0006-3223(02)01747-X.CrossRefPubMed

Post F: The significance of affective symptoms in old age; a follow-up study of one hundred patients. 1962, New York: Oxford University Press

Meyers BS, Greenberg R: Late-life delusional depression. J Affect Disord. 1986, 11: 133-137. 10.1016/0165-0327(86)90019-4.CrossRefPubMed

Kroessler D: Relative efficacy rates for therapies of delusional depression. Convulsive Ther. 1985, 1: 173-182.

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.

American Psychiatric Association: Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry. 2000, 157 (Suppl 4): 1-45.

National Institute for Clinical Excellence: Depression: management of depression in primary and secondary care - NICE guidance. Vol Clinical Guideline 23. 2004, London: NICE

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. 10.4088/JCP.11r07324.CrossRefPubMedPubMedCentral

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. 10.1503/cmaj.071068.CrossRefPubMedPubMedCentral

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. 10.1016/0010-440X(88)90032-6.CrossRefPubMed

12.

Rothschild AJ, Duval SE: How long should patients with psychotic depression stay on the antipsychotic medication?. J Clin Psychiatry. 2003, 64: 390-396. 10.4088/JCP.v64n0405.CrossRefPubMed

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.CrossRefPubMed

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. 10.1097/JGP.0b013e318170a6fa.CrossRefPubMed

15.

Clower CG: Recurrent psychotic unipolar depression. J Clin Psychiatry. 1983, 44: 216-218.PubMed

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. 10.1097/00004850-199707000-00002.CrossRefPubMed

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. 10.1001/archgenpsychiatry.2009.79.CrossRefPubMedPubMedCentral

18.

First MB, Spitzer RL, Gibbon M, Williams JBW: Structured clinical interview for DSM-IV-TR axis I disorders - patient edition (SCID-I/P). 2001, New York: Biometrics Research Department

19.

Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960, 23: 56-62. 10.1136/jnnp.23.1.56.CrossRefPubMedPubMedCentral

20.

Guy W: Clinical Global Impressions. ECDEU Assessment Manual for Psychopharmacology. 1976, Washington, DC, US: Dept. of Health, Education, and Welfare, 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. 10.1016/0022-3956(75)90026-6.CrossRefPubMed

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, 1-86. October; Special No Pharmacotherapy

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. 10.1017/S0033291797005436.CrossRefPubMed

24.

Pollock BG: The pharmacokinetic imperative in late-life depression. J Clin Psychopharmacol. 2005, 25 (4 Suppl 1): S19-S23.CrossRefPubMed

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. 10.1016/S0006-3223(98)00110-3.CrossRefPubMed

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. 10.1080/00048679109077732.CrossRefPubMed

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. 10.1016/j.biopsych.2006.05.033.CrossRefPubMed

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. 10.1002/(SICI)1099-1166(199704)12:4<462::AID-GPS510>3.0.CO;2-Q.CrossRefPubMed

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. 10.1034/j.1600-0579.2003.00215.x.CrossRefPubMed

32.

Applebaum PS, Grisso T: MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). 2001, Sarasota, Fl: Professional Resource Press

33.

Spitzer RL, Endicott J: Schedule for Affective Disorders and Schizophrenia (third edition). 1979, New York: New York State Psychiatric Institute, Biometrics Research

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-CrossRefPubMed

36.

Jorm AF: The informant questionnaire on cognitive decline in the elderly (IQCODE): a review. Int Psychogeriatrics. 2004, 16: 275-293. 10.1017/S1041610204000390.CrossRef

37.

Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983, 67 (6): 361-370. 10.1111/j.1600-0447.1983.tb09716.x.CrossRefPubMed

38.

Miller MD, Paradis CF, Houck PR, Mazumdar S, Stack JA, Rifai AH, Mulsant B, Reynolds CF: Rating chronic medical illness burden in geropsychiatric practice and research: application of the cumulative illness rating scale. Psychiatry Res. 1992, 41: 237-248. 10.1016/0165-1781(92)90005-N.CrossRefPubMed

39.

Wilhelm K: Rating the CORE: A user’s guide. Melancholia: A Disorder of Movement and Mood. Edited by: Parker G, Hadzi-Pavlovic D. 1996, Cambridge: Cambridge University Press, pp 211-pp 219.CrossRef

40.

Delis D, Kaplan E, Kramer J: Delis-Kaplan Executive Function Scale. 2001, San Antonio, TX: The Psychological Corporation

41.

Randolph C: The repeatable battery for the assessment of neuropsychological status. 1998, San Antonio, TX: The Psychological Corporation

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. 10.4088/JCP.v64n0714.CrossRefPubMed

43.

Ware JE, 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. 10.1097/00005650-199206000-00002.CrossRefPubMed

44.

Flint AJ, Rifat SL: Two-year outcome of elderly patients with anxious depression. Psychiatry Res. 1997, 66: 23-31. 10.1016/S0165-1781(96)02964-2.CrossRefPubMed

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. 10.1192/bjp.170.3.268.CrossRefPubMed

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. 10.1001/archpsyc.57.3.285.CrossRefPubMed

47.

Parker G, Hickie I, Mason C: Validity of the CORE measure: III. Outcome and treatment prediction. Melancholia: A Disorder of Movement and Mood. Edited by: Parker G, Hadzi-Pavlovic D. 1996, Cambridge: Cambridge University Press, 160-171.CrossRef

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. 10.1002/da.1028.CrossRefPubMed

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. 10.1176/appi.ajp.161.6.996.CrossRefPubMed

50.

Butters MA, Whyte EM, Nebes RD, Begley AE, Dew MA, Mulsant BH, Zmuda MD, Bhalla R, Meltzer CC, Pollock BG, Reynolds CF, Becker JT: The nature and determinants of neuropsychological functioning in late-life depression. Arch Gen Psychiatry. 2004, 61: 587-595. 10.1001/archpsyc.61.6.587.CrossRefPubMed

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.CrossRef

52.

Simpson GM, Angus JW: A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl. 1970, 212: 11-19.CrossRefPubMed

53.

Barnes TR: A rating scale for drug-induced akathisia. Br J Psychiatry. 1989, 154: 672-676. 10.1192/bjp.154.5.672.CrossRefPubMed

54.

Guy W: Abnormal Involuntary Movement Scale (AIMS). ECDEU Assessment Manual for Psychopharmacology. 1976, Washington, DC: US Dept. of Health, Education, and Welfare, 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.CrossRef

56.

Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet. 2005, 365: 1415-1428. 10.1016/S0140-6736(05)66378-7.CrossRefPubMed

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. 10.2337/dc07-1067.CrossRefPubMed

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.CrossRef

59.

Bigos KL, Bies RB, Pollock BG: Population pharmacokinetics in geriatric psychiatry. Am J Geriatr Psychiatry. 2006, 14: 993-1003. 10.1097/01.JGP.0000224330.73063.6c.CrossRefPubMed

60.

Beal SL, Sheiner LB: Estimating population kinetics. Crit Rev Biomed Eng. 1982, 8 (3): 195-222.PubMed

61.

Feng Y, Pollock BG, Ferrell RE, Kimak MA, Reynolds CF, Bies RR: Paroxetine: population pharmacokinetic analysis in late-life depression using sparse concentration sampling. Br J Clin Pharmacol. 2006, 61 (5): 558-569. 10.1111/j.1365-2125.2006.02629.x.CrossRefPubMedPubMedCentral

62.

Muller DJ, Kennedy JL: Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics. 2006, 7 (6): 863-887. 10.2217/14622416.7.6.863.CrossRefPubMed

63.

Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK: The DISC locus in psychiatric illness. Mol Psychiatry. 2008, 13: 36-64. 10.1038/sj.mp.4002106.CrossRefPubMed

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. 10.1038/mp.2009.49.CrossRefPubMed

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.CrossRefPubMed

66.

Flint AJ, Rifat SL: Two-year outcome of psychotic depression in late life. Am J Psychiatry. 1998, 155: 178-183.PubMed

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. 10.1001/archgenpsychiatry.2010.199.CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/13/38/prepub

Title: Sustaining remission of psychotic depression: rationale, design and methodology of STOP-PD ΙΙ
Authors: Alastair J Flint
Barnett S Meyers
Anthony J Rothschild
Ellen M Whyte
Benoit H Mulsant
Matthew V Rudorfer
Patricia Marino
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Psychiatry / Issue 1/2013
Electronic ISSN: 1471-244X
DOI: https://doi.org/10.1186/1471-244X-13-38

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Methods/design

Discussion

Trial registration and URL

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods/design

Discussion

Trial registration and URL

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