Citalopram in first episode schizophrenia: The DECIFER trial

Goff, Donald C.; Freudenreich, Oliver; Cather, Corrine; Holt, Daphne J.; Bello, Iruma; Diminich, Erica D.; Tang, Yingying; Ardekani, Babak A.; Worthington, Michelle; Zeng, Botao; Wu, Renrong; Fan, Xiaoduo; Li, Chenxiang; Troxel, Andrea B.; Wang, Jijun; Zhao, Jingping

doi:10.1016/j.schres.2019.01.028

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…Antidepressant (AD) or mood stabilizer (MS) use as adjuvants to antipsychotics has been investigated in treatment for symptoms such as depressive and negative symptoms [4] and aggression [5], but they are rarely recommended in clinical guidelines due to lack of high quality evidence of their efficacy [3,6,7]. Evidence on benefits in clinical trials is mixed which was represented by a recent study reporting that add-on citalopram was associated with reduced levels of negative symptoms but had no impact on depressive symptoms [8]. In a recent observational study, antidepressant use was associated with lowered risk of psychiatric hospitalization and emergency department visits, whereas mood stabilizers had no impact on these outcomes [9].…”

Section: Introductionmentioning

confidence: 99%

Use of antidepressants and mood stabilizers in persons with first-episode schizophrenia

Puranen

Koponen

Tanskanen

et al. 2020

Eur J Clin Pharmacol

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Purpose Antipsychotics are first-line treatment of schizophrenia. They are often accompanied by adjunctive treatments, such as antidepressant (AD) or mood stabilizer (MS), although there is only limited information of their use in first-episode schizophrenia. This study aimed to investigate AD and MS initiation and factors associated with initiation in persons with first-episode schizophrenia. Methods Register-based data was utilized to identify persons who received inpatient care due to schizophrenia during 1996-2014 in Finland and who did not use AD or MS at the time of first inpatient care diagnosis of schizophrenia (N = 7667, mean age 40.2, SD 18.2). Drug purchase data (1995-2017) was obtained from the National Prescription register and modelled with PRE2DUP method. Initiations of AD and MS use were followed up 3 years from first schizophrenia diagnoses. Cox proportional hazard models were used to investigate factors associated with AD or MS initiation. Results Among persons with first-episode schizophrenia, 35.4% initiated AD and 14.1% initiated MS use within three years from diagnoses. Female gender, younger age, and benzodiazepine use were associated with higher risk of AD and MS initiation. The number of previous psychoses was associated with decreased risk of AD and increased risk of MS initiation. Conclusion Clinical guidelines rarely recommend the use of AD or MS as adjunctive treatment in persons with schizophrenia. However, this population is often treated with AD or MS. More studies are needed to evaluate benefits and risks of these medications as adjunctive treatment of schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Use of antidepressants and mood stabilizers in persons with first-episode schizophrenia

Puranen

Koponen

Tanskanen

et al. 2020

Eur J Clin Pharmacol

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“… 31 However, in the DECIFER study, in which citalopram improved negative symptoms, depressive symptoms were not improved by citalopram and neither change in hippocampal volume nor disengagement status differed between citalopram and placebo groups. 18 , 20 This possible differential effect of antidepressants on hippocampal volume in individuals with depression versus individuals without depression was also found in a study of nonhuman primates. 32 In this study, a selective serotonin reuptake inhibitor increased anterior hippocampal volume in animals exhibiting depressive behaviors following stress but was associated with hippocampal volume loss in animals that were not previously stressed.…”

Section: Discussionmentioning

confidence: 53%

“…The DECIFER study has been previously described 18 and was registered at clinicaltrials.gov NCT01041274. The study was a 12 month, four-site, randomized, parallel-group, placebo-controlled trial of add-on citalopram in the maintenance treatment of first episode schizophrenia patients who were first stabilized with clinician-determined second generation antipsychotic medication.…”

Section: Methodsmentioning

confidence: 99%

“…We recently completed a series of studies examining potential molecular mechanisms underlying hippocampal volume loss in early psychosis and identifying clinical correlates. 18–21 To explore hippocampal volume as a potential biomarker for risk of disengagement from treatment in early psychosis, we now examine data from the DECIFER Study, a 12-month placebo-controlled trial of add-on citalopram in first episode schizophrenia patients after initial stabilization on second generation antipsychotics. 18 Because this study examined participants who disengaged from treatment under conditions of a randomized clinical trial rather than under usual clinical conditions, and since, to the best of our knowledge, there is no prior evidence linking hippocampal volume to treatment disengagement, the results of this study must be considered exploratory.…”

Section: Introductionmentioning

confidence: 99%

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Hippocampal Subfield Volumes Predict Disengagement from Maintenance Treatment in First Episode Schizophrenia

Marx

Zingman

et al. 2022

Schizophrenia Bulletin

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Objectives Disengagement from treatment is common in first episode schizophrenia (FES) and is associated with poor outcomes. Our aim was to determine whether hippocampal subfield volumes predict disengagement during maintenance treatment of FES. Methods FES patients were recruited from sites in Boston, New York, Shanghai, and Changsha. After stabilization on antipsychotic medication, participants were randomized to add-on citalopram or placebo and followed for 12 months. Demographic, clinical and cognitive factors at baseline were compared between completers and disengagers in addition to volumes of hippocampal subfields. Results Baseline data were available for 95 randomized participants. Disengagers (n = 38, 40%) differed from completers (n = 57, 60%) by race (more likely Black; less likely Asian) and in more alcohol use, parkinsonism, negative symptoms and more impairment in visual learning and working memory. Bilateral dentate gyrus (DG), CA1, CA2/3 and whole hippocampal volumes were significantly smaller in disengagers compared to completers. When all the eight volumes were entered into the model simultaneously, only left DG volume significantly predicted disengagement status and remained significant after adjusting for age, sex, race, intracranial volume, antipsychotic dose, duration of untreated psychosis, citalopram status, alcohol status, and smoking status (P < .01). Left DG volume predicted disengagement with 57% sensitivity and 83% specificity. Conclusions Smaller left DG was significantly associated with disengagement status over 12 months of maintenance treatment in patients with FES participating in a randomized clinical trial. If replicated, these findings may provide a biomarker to identify patients at risk for disengagement and a potential target for interventions.

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“…A total of 3245 studies were identified, of which 62 studies, published between 1997-2020, satisfied the inclusion criteria and were included in the studyBitter et al, 2019;Bugarski-Kirola, 2014;Cantillon et al, 2017;Canuso, Schooler, et al, 2010;Casey et al, 2008;Chouinard et al, 1993;Cooper et al, 2000;Coppola et al, 2011;Correll et al, 2015;Cutler et al, 2008Cutler et al, , 2010Daniel et al, 1999;Danion et al, 1999;Davidson et al, 2007;Downing et al, 2014;Durgam et al, 2014Durgam et al, , 2015Egan et al, 2013;Fabre, Jr. et al, 1995;Garcia et al, 2009;Goff et al, 2019;Gopal et al, 2010;Kane et al, 2003Kane et al, , 2007Kane et al, , 2014 Kane, Skuben, et al, 2015;Kane, Zukin, et al, 2015;Kantrowitz et al, 2020;Keck, Jr. et al, 1998;Kinon et al, 2011;Kinoshita et al, 2016;Klieser & Lehmann, 1989;Kramer et al, 2010;Landbloom et al, 2017;Lieberman et al, 2016;Litman et al, 2014Litman et al, , 2016Macek et al, 2019;Marder et al, 2007;Marder & Meibach, 1994;McGuire et al, 2018;…”

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confidence: 99%

Response efficacy and heterogeneity of antipsychotic drugs in schizophrenia: Systemic review and meta‐analysis

Zhang

Tang

Zhang

et al. 2021

Human Psychopharmacology

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BackgroundsThis meta‐analysis aimed to assess antipsychotic and placebo effects in patients with schizophrenia at the level of symptom factors.MethodsA systematic literature search up to June 2020 was undertaken and 62 studies were included, with 23,478 patients with schizophrenia at the study baseline point. We calculated mean differences with 95% confidence intervals. The comparison was made according to the study content using a continuous method with a random‐effects model.ResultsPatients with schizophrenia treated by antipsychotic drugs had a significantly lower psychiatric rating scale total score; lower clinical global impression of severity; lower positive and negative syndrome scale; and lower assessment of negative symptoms total score, when compared to placebo treated patients.ConclusionsPatients with schizophrenia treated with an antipsychotic drug show a much greater improvement and lower inconsistency in the level of symptom factors when compared to the effects of placebo. Our findings evidence for a comparatively homogeneous outcome of the antipsychotic‐treatment in improving schizophrenia symptoms. This opposes the notion of the presence of patient sub‐groups with treatment non‐responsive schizophrenia.

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Citalopram in first episode schizophrenia: The DECIFER trial

Cited by 14 publications

References 28 publications

Use of antidepressants and mood stabilizers in persons with first-episode schizophrenia

Use of antidepressants and mood stabilizers in persons with first-episode schizophrenia

Hippocampal Subfield Volumes Predict Disengagement from Maintenance Treatment in First Episode Schizophrenia

Response efficacy and heterogeneity of antipsychotic drugs in schizophrenia: Systemic review and meta‐analysis

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