Which Residual Symptoms Predict Relapse in major Depression? A Scoping Review: Quels symptômes résiduels constituent des prédicteurs de rechute de dépression majeure? Un examen de la portée
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Which Residual Symptoms Predict Relapse in major Depression? A Scoping Review: Quels symptômes résiduels constituent des prédicteurs de rechute de dépression majeure? Un examen de la portée
Preventing relapse following a successful acute treatment of major depressive disorder (MDD) remains a clinical challenge. The presence of residual depressive symptoms seems to be a reliable predictor of relapse. However, few studies have systematically evaluated the relative contribution of specific residual symptoms to relapse risk.
Objective
This review synthesizes studies investigating the association between individual residual depressive symptoms and relapse risk following a successful acute treatment of MDD.
Methods
A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A systematic literature search was performed using terms related to depression, residual symptoms and relapse.
Results
Eleven studies were included. Residual sleep disturbance and anxiety showed a statistically significant association with increased relapse risk in most studies assessing these symptoms. Most studies assessing residual fatigue, appetite, weight change, depressed mood or diminished interest did not observe statistically significant associations with relapse risk. Findings regarding agitation or restlessness and decreased libido were mixed, with some studies reporting statistically significant associations while others did not. A variety of symptom rating scales was used to assess residual depressive symptoms, resulting in substantial heterogeneity.
Conclusion
Specific residual depressive symptoms, notably sleep disturbance and anxiety, may serve as predictors of increased relapse risk and should alert clinicians. However, substantial heterogeneity across studies limits the consistency and generalizability of these findings. Standardized and multidimensional assessment strategies, integrating both clinician-rated and self-report instruments, are needed to comprehensively capture the residual symptom burden and improve relapse risk prediction.
KesslerRCBrometEJ. The epidemiology of depression across cultures. Annu Rev Public Health.2013;34:119–138. doi: 10.1146/annurev-publhealth-031912-114409.
2.
BitterISzekeresGCaiQ, et al.Mortality in patients with major depressive disorder: a nationwide population-based cohort study with 11-year follow-up. Eur Psychiatry. 2024;67(1):e63. doi: 10.1192/j.eurpsy.2024.1771.
3.
GeddesJRCarneySMDaviesC, et al.Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. 2003;361(9358):653–661. doi: 10.1016/S0140-6736(03)12599-8.
4.
BuckmanJEJUnderwoodAClarkeK, et al.Risk factors for relapse and recurrence of depression in adults and how they operate: a four-phase systematic review and meta-synthesis. Clin Psychol Rev. 2018;64:13–38. doi: 10.1016/j.cpr.2018.07.005.
5.
MöllerHJDemyttenaereKSacchettiERushJAMontgomerySA. Improving the chance of recovery from the short- and long-term consequences of depression. Int Clin Psychopharmacol. 2003;18(4):219–225. doi: 10.1097/01.yic.0000074785.11653.ca.
6.
FriedEINesseRM. Depression sum-scores don’t add up: why analyzing specific depression symptoms is essential. BMC Med. 2015;13(72). doi: 10.1186/s12916-015-0325-4.
7.
FunakiKNakajimaSSuzukiTMimuraMUchidaH.Early improvements in individual symptoms to predict later remission in major depressive disorder treated with mirtazapine. J Clin Pharmacol. 2016;56(9):1111–1119. doi: 10.1002/jcph.710.
8.
WojnarowskiCFirthNFineganMDelgadilloJ. Predictors of depression relapse and recurrence after cognitive behavioural therapy: a systematic review and meta-analysis. Behav Cogn Psychother. 2019;47(5):514–529. doi: 10.1017/S1352465819000080.
9.
MiljevicABaileyNWHerringSEFitzgeraldPB. Potential predictors of depressive relapse following repetitive transcranial magnetic stimulation: a systematic review. J Affect Disord. 2019;256:317–323. doi: 10.1016/j.jad.2019.06.006.
10.
TriccoACLillieEZarinW, et al.Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467–473. doi: 10.7326/M18-0850.
11.
YangHChuziSSinicropi-YaoL, et al.Type of residual symptom and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine. Eur Arch Psychiatry Clin Neurosci. 2010;260(2):145–150. doi: 10.1007/s00406-009-0031-3.
12.
YangHSinicropi-YaoLChuziS, et al.Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine. Ann Gen Psychiatry. 2010;9(10). doi: 10.1186/1744-859X-9-10.
13.
DombrovskiAYMulsantBHHouckPR, et al.Residual symptoms and recurrence during maintenance treatment of late-life depression. J Affect Disord. 2007;103(1–3):77–82. doi: 10.1016/j.jad.2007.01.020.
14.
DombrovskiAYCyranowskiJMMulsantBH, et al.Which symptoms predict recurrence of depression in women treated with maintenance interpersonal psychotherapy? Depress. Anxiety. 2008;25(12):1060–1066.
15.
TaylorDJWaltersHMVittenglJRKrebaumSJarrettRB.Which depressive symptoms remain after response to cognitive therapy of depression and predict relapse and recurrence?J Affect Disord. 2010;123(1–3):181–187. doi: 10.1016/j.jad.2009.08.007.
16.
LovienoNvan NieuwenhuizenAClainABaerLNierenbergAA. Residual symptoms after remission of major depressive disorder with fluoxetine and risk of relapse. Depress Anxiety. 2011;28(2):137–144.
17.
SakuraiHSuzukiTYoshimuraKMimuraMUchidaH. Predicting relapse with individual residual symptoms in major depressive disorder: a reanalysis of the STAR*D data. Psychopharmacology (Berl). 2017;234(16):2453–2461.
18.
LambrichtsSVansteelandtKVHebbrechtK, et al.Which residual symptoms predict relapse after successful electroconvulsive therapy for late-life depression?J Psychiatr Res. 2022;154:111–116. doi: 10.1016/j.jpsychires.2022.07.056.
19.
VittenglJRClarkLAThaseMEJarrettRB. Levels of depressed mood and low interest for two years after response to cognitive therapy for recurrent depression. Behav Res Ther. 2022;148:103996.
20.
FlintAJRifatSL.Two-year outcome of elderly patients with anxious depression. Psychiatry Res. 1997;66(1):23–31. doi: 10.1016/S0165-1781(96)02964-2.
21.
NierenbergAAHusainMMTrivediMH, et al.Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report. Psychol Med.2010;40(1):41–50. doi: 10.1017/S0033291709006011.
22.
CombsKSmithPJSherwoodA, et al.Impact of sleep complaints on depression outcomes among participants in the Standard Medical Intervention and Long-term Exercise study of exercise and pharmacotherapy for depression. J Nerv Ment Dis. 2014;202(2):167–171.
23.
FranzenPLBuysseDJ. Sleep disturbances and depression: risk relationships for subsequent depression and therapeutic implications. Dialogues Clin Neurosci. 2008;10(4):473–481. doi: 10.31887/DCNS.2008.10.4/plfranzen.
24.
BuysseDJAncoli-IsraelSEdingerJDLichsteinKLMorinCM. Recommendations for a standard research assessment of insomnia. Sleep. 2006;29(9):1155–1173. doi: 10.1093/sleep/29.9.1155.
25.
ButtonKSIoannidisJPMokryszC, et al.Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci.2013;14(5):365–376. doi: 10.1038/nrn3475.
26.
FavaMMcCallWVKrystalA, et al.Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry. 2006;59(11):1052–1060. doi: 10.1016/j.biopsych.2006.01.016.
27.
KrystalAD. Sleep and psychiatric disorders: future directions. Psychiatr Clin North Am. 2006;29(4):1115–1130. doi: 10.1016/j.psc.2006.09.001.
28.
LenzeEJMulsantBHShearMKAlexopoulosGSFrankEReynoldsCF. Comorbidity of depression and anxiety disorders in later life. Depress Anxiety. 2001;14(2):86–93. doi: 10.1002/da.1050.
29.
AndreescuCLenzeEJMulsantBH, et al.High worry severity is associated with poorer acute and maintenance efficacy of antidepressants in late-life depression. Depress Anxiety. 2009;26(3):266–272. doi: 10.1002/da.20544.
30.
MontgomerySAAsbergM. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–389. doi: 10.1192/bjp.134.4.382.
31.
RushAJTrivediMHIbrahimHM, et al.The 16-item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 2003;54(5):573–583. doi: 10.1016/S0006-3223(02)01866-8.
32.
BeckATWardCHMendelsonMMockJErbaughJ. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561–571. doi: 10.1001/archpsyc.1961.01710120031004
33.
BuysseDJReynoldsCF3rdMonkTHBermanSRKupferDJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213. doi: 10.1016/0165-1781(89)90047-4.
34.
van LooHMde JongePRomeijnJWKesslerRCSchoeversRA. Data-driven subtypes of major depressive disorder: a systematic review. BMC Med. 2012;10(156). doi: 10.1186/1741-7015-10-156.
35.
FriedEI. The 52 symptoms of major depression: lack of content overlap among seven common depression scales. J Affect Disord. 2017;208:191–197. doi: 10.1016/j.jad.2016.10.019.
36.
PastuszakMCubałaWJKwaśnyAMechlińskaA. The search for consistency in residual symptoms in major depressive disorder: a narrative review. J Pers Med. 2024;14(8):828. doi: 10.3390/jpm14080828.
37.
BorsboomD. A network theory of mental disorders. World Psychiatry. 2017;16(1):5–13. doi: 10.1002/wps.20375.
38.
CuijpersPLiJHofmannSGAnderssonG. Self-reported versus clinician-rated symptoms of depression as outcome measures in psychotherapy research on depression: a meta-analysis. Clin Psychol Rev.2010;30(6):768–778. doi: 10.1016/j.cpr.2010.06.001.
39.
TrivediMHRushAJIbrahimHM, et al.The inventory of depressive symptomatology, clinician rating (IDS-C) and self-report (IDS-SR), and the quick inventory of depressive symptomatology, clinician rating (QIDS-C) and self-report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation. Psychol Med. 2004;34(1):73–82.
40.
FavaGAFabbriSSoninoN. Residual symptoms in depression: an emerging therapeutic target. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(6):1019–1027.
41.
PaykelES. Partial remission, residual symptoms, and relapse in depression. Dialogues Clin Neurosci.2008;10(4):431–437.
42.
ConradiHJOrmelJde JongeP. Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study. Psychol Med. 2011;41(6):1165–1174.
43.
EdingerJDMeansMK. Cognitive–behavioral therapy for primary insomnia. Clin Psychol Rev. 2005;25(5):539–558.
44.
ManberREdingerJDGressJLPedro-SalcedoMGKuoTFKalistaT. Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia. Sleep. 2008;31(4):489–495.
45.
HofmannSGAsnaaniAVonkIJSawyerATFangA. The efficacy of cognitive behavioral therapy: a review of meta-analyses. Cogn Ther Res. 2012;36(5):427–440.
46.
SegalZVDimidjianSBeckA, et al.Outcomes of online mindfulness-based cognitive therapy for patients with residual depressive symptoms: a randomized clinical trial. JAMA Psychiatry. 2020;77(6):563–573.
47.
ZisookSLesserIStewartJW, et al.Effect of age at onset on the course of major depressive disorder. Am J Psychiatry. 2007;164(10):1539–1546.
48.
SegalZVWilliamsJMGTeasdaleJD. Mindfulness-based cognitive therapy for depression: a new approach to preventing relapse. New York, USA: Guilford Press; 2002.
49.
KendlerKSGatzMGardnerCOPedersenNL. Personality and major depression: a Swedish longitudinal, population-based twin study. Arch Gen Psychiatry. 2006;63(10):1113–1120.
50.
HarveyAG. Sleep and circadian rhythms in bipolar disorder: seeking synchrony, harmony, and regulation. Am J Psychiatry. 2008;168(12):1241–1243.
51.
FriedEIEpskampSNesseRMTuerlinckxFBorsboomD. What are ‘good’ depression symptoms? Comparing the centrality of DSM and non-DSM symptoms of depression in a network analysis. J Affect Disord. 2016;189:314–320.
52.
McKnightPEKashdanTB. The importance of functional impairment to mental health outcomes: a case for reassessing our goals in depression treatment research. Clin Psychol Rev.2009;29(3):243–259.
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