Does lack of improvement in the first two weeks predict treatment resistance in recent-onset psychosis?

Kayo, Monica; Tassell, Ivson; Hiroce, Vivian; Menezes, A.K.P.M.; Elkis, Hélio

doi:10.6061/clinics/2012(12)20

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…There was one prospective study [40] of Positive and Negative Syndrome Scale (PANSS) scores2 in which patients with no previous regular antipsychotic use and an illness onset within the last five years were randomised to receive either first or second generation non-clozapine antipsychotics in an open trial. Those that did not respond after one trial were then switched to another antipsychotic, and those that failed two trials were deemed treatment-resistant (4 patients in total).…”

Section: Resultsmentioning

confidence: 99%

“…The one identified prospective study on PANSS scores reported that a lower score at baseline predicted treatment-resistance at 12 weeks, and found no association between improvement in the first 2 weeks of antipsychotic treatment and later treatment-response [40]. These are surprising findings, especially the latter as a 2014 review of treatment response (looking only at single-antipsychotic trials, and thus not included in the review) found that early lack of response was one of the most robust predictors of later lack of response [75], and a 2015 meta-analysis (again looking at only single-antipsychotic trials) found that lack of response at two weeks had high specificity and positive predictive validity for predicting later non-response [76].…”

Section: Discussionmentioning

confidence: 99%

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Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

et al. 2017

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BackgroundSchizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes.MethodA systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics).ResultsNineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons.ConclusionsTentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-1177-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

et al. 2017

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“…In these studies, the criteria for TR are relatively consistent but also vary depending on the goal of the study. The core criteria for TR patients includes unsuccessful use of two or more non-clozapine antipsychotics and/or the use of clozapine in their past history [ 2 – 4 , 9 , 10 ]. Thus far, these studies that compare between TR patients and non-TR patients have mainly focused on clinical and demographic markers, and reported that TR patients tend to have a longer duration of untreated psychosis (DUP), more severe negative symptoms, younger age of onset, and poor pre-morbid functioning [ 4 , 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Olfactory functions were also evaluated in this study, since olfactory deficits frequently accompany FEP and may have a predictive value for disease severity and poor prognosis [ 28 , 32 , 33 ]. The goal of this study is to identify markers that can differentiate TR from non-TR patients, in which TR is defined based on medication history [ 2 – 4 , 9 , 11 – 15 ], rather than treatment response [ 16 – 24 ]. By taking advantage of multimodal datasets, rather than single layer data, we aimed to obtain a comprehensive landscape associated with TR in psychosis.…”

Section: Introductionmentioning

confidence: 99%

A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

et al. 2021

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Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy, from a first episode psychosis cohort that includes 136 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC GSH, HP and SFG volumes, and age at onset could potentially be biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

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“…This "early onset of antipsychotic drug action hypothesis" was corroborated by a subsequent analysis using longer-term, individual patient data (8). As a consequence, numerous studies have since examined whether the degree of early improvement could predict later response (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Most studies showed such associations, but the lack of consensus about the definitions of early improvement and later response made uniform guideline recommendations impossible.…”

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confidence: 97%

Early Improvement As a Predictor of Later Response to Antipsychotics in Schizophrenia: A Diagnostic Test Review

Samara

Leucht²,

Leeflang

et al. 2015

AJP

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151

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Does lack of improvement in the first two weeks predict treatment resistance in recent-onset psychosis?

Cited by 10 publications

References 14 publications

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

Early Improvement As a Predictor of Later Response to Antipsychotics in Schizophrenia: A Diagnostic Test Review

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