Belief Update: The Effects of Depression and Antidepressants in Older People

Overview

People in good health do not perceive the future in the same way as those suffering from depression. This difference in perception affects behaviour and emotions and warrants further investigation, both before and after treatment with antidepressants. Research shows that past negative experiences with medication can reduce the effectiveness of treatment, whilst positive expectations can increase it. It is important to gain a better understanding of how antidepressants influence the way in which elderly people with major depressive disorder (MDD) change their beliefs, and to determine whether an improvement in their depressive symptoms is linked to these changes in their beliefs. This study aims to understand whether antidepressants can alter the way people view the future and whether this contributes to their effectiveness. It also seeks to determine whether patients' expectations regarding treatment influence clinical outcomes, and whether changes in their mood may in turn affect these expectations. The study will involve 31 patients aged 65 and over who are suffering from a depressive disorder and require a change of antidepressant, and 31 healthy subjects, also aged 65 and over. The participants' involvement will last for 12 weeks. During a medical consultation, once the doctor has checked that the participant meet all the study's eligibility criteria, they will ask for the participant consent to take part in the study. The participant will then be asked to answer one question about what you hope to gain from the new antidepressant treatment that the doctor will prescribe for the participant. Finally, the participant will carry out a belief-updating exercise, which involves : presenting the participant with a series of events and ask them to indicate how likely they think each of them is to occur, and then. Once they have received further information about these events, ask them to reassess the likelihood of them occurring. This task will be carried out again 12 weeks after the participant start taking their antidepressant, during a consultation required as part of their individual care plan. From the first week of antidepressant treatment until week 12, the participant will be contacted by telephone once a week to answer two short questions about their expectations regarding the treatment and any changes in your mood.

Interventions

• Behavioral Response to questionnaire
  The patients are assessed using the MADRS score upopn inclusion (after the wash-out, before the new treatment) and 12 weeks later, after the treatment. The patient are also assessed by looking at the overall changes in atitude, the first time upon inclusion and after every week until the end of the treatment 12 weeks later.

Primary outcome measures

• Difference in MADRS (Montgomery-Asberg Depression Rating Scale) score before versus after treatment. [Time frame: From enrollment to the end of the data collecting process : 3 months.]

Secondary outcome measures (2)

• Difference in treatment expectations [Time frame: From enrollment to the end of the data collecting process : 3 months]
• Difference in treatment expectations [Time frame: From enrollment to the end of the data collecting process : 3 months]

Eligibility criteria

Inclusion Criteria for patients with major depressive disorder :

• Patient over 65 years old in outpatient care
• Patients with major depressive disorder or patients with bipolar major depressive disorder as evaluated by the Mini International Neuropsychiatric Interview (MINI) semi-structured interview for the group suffering from depression
• Absence of cognitive impairment as evidenced by an MMSE (Mini Mental State Examination) ≥ 24
• MADRS ≥ 20
• MMSE ≥ 24
• Change of antidepressants
• Person affiliated with a social security scheme
• Patients who have received informed information about the study and have signed a consent form to participate in the study

Exclusion Criteria with major depressive disorder :

• mental disorders other than mood disorders : attention deficit dissorder, borderline personality disorder, schizophrenia, autism spectrum disorder, anorexia-bulimia disorder, obsessive-compulsive disorder, anxiety disorders and substance use disorder (except tobacco).
• Inability to understand task instructions and perform the behavioral task
• Neurological or neurosurgical comorbidities
• Major visual impairment
• Adults under state medical aid
• Adults under legal protection (legal guardianship, curatorship, trusteeship), persons deprived of their liberty

Inclusion Criteria for patients with major depressive disorder :

• Absence of psychiatric disorders attested by administration of the MINI
• Absence of cognitive impairment as evidenced by an MMSE ≥ 24

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

France · 2 centers

• Centre Hospitalier Guillaume Regnier — Rennes
• Centre Hospitalier Guillaume Régnier — Rennes

Publications

• Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr. 2016 Jun;39(3):76-83. doi: 10.18773/austprescr.2016.039. Epub 2016 Jun 1. PMID 27346915
• Kozyra E, Lau T. Medication Strategies: Switching, Tapering, Cross-Over, Overmedication, Drug-Drug Interactions, and Discontinuation Syndromes. In: Fenn HH, Hategan A, Bourgeois JA, éditeurs. Inpatient Geriatric Psychiatry : Optimum Care, Emerging Limitations, and Realistic Goals [Internet]. Cham: Springer International Publishing; 2019 [cité 3 févr 2025]. p. 325-38
• Pecina M, Chen J, Karp JF, Dombrovski AY. Dynamic Feedback Between Antidepressant Placebo Expectancies and Mood. JAMA Psychiatry. 2023 Apr 1;80(4):389-398. doi: 10.1001/jamapsychiatry.2023.0010. PMID 36857039
• Krell HV, Leuchter AF, Morgan M, Cook IA, Abrams M. Subject expectations of treatment effectiveness and outcome of treatment with an experimental antidepressant. J Clin Psychiatry. 2004 Sep;65(9):1174-9. doi: 10.4088/jcp.v65n0904. PMID 15367043
• Colloca L, Barsky AJ. Placebo and Nocebo Effects. N Engl J Med. 2020 Feb 6;382(6):554-561. doi: 10.1056/NEJMra1907805. No abstract available. PMID 32023375
• Mondloch MV, Cole DC, Frank JW. Does how you do depend on how you think you'll do? A systematic review of the evidence for a relation between patients' recovery expectations and health outcomes. CMAJ. 2001 Jul 24;165(2):174-9. PMID 11501456
• Perlman K, Benrimoh D, Israel S, Rollins C, Brown E, Tunteng JF, You R, You E, Tanguay-Sela M, Snook E, Miresco M, Berlim MT. A systematic meta-review of predictors of antidepressant treatment outcome in major depressive disorder. J Affect Disord. 2019 Jan 15;243:503-515. doi: 10.1016/j.jad.2018.09.067. Epub 2018 Sep 18. PMID 30286415
• Bottemanne H, Morlaas O, Claret A, Sharot T, Fossati P, Schmidt L. Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression. JAMA Psychiatry. 2022 Nov 1;79(11):1124-1132. doi: 10.1001/jamapsychiatry.2022.2996. PMID 36169969

Identifiers

NCT: NCT07681492 · RNI24_01_GR · 2024-A02279-38

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗