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

Samara, Myrto; Leucht, Claudia; Leeflang, Mariska; Anghelescu, Ion‐George; Chung, Young‐Chul; Crespo‐Facorro, Benedicto; Elkis, Hélio; Hatta, Kotaro; Giegling, Ina; Kane, John M.; Kayo, Monica; Lambert, Martin; Lin, Ching‐Hua; Möller, Hans‐Jürgen; Pelayo-Terán, José María; Riedel, Michael; Rujescu, Dan; Schimmelmann, Benno Karl Edgar; Serretti, Alessandro; Correll, Christoph U.; Leucht, Stefan

doi:10.1176/appi.ajp.2015.14101329

Cited by 159 publications

(90 citation statements)

References 81 publications

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“…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]. It may be that early lack of response predicts later non-response for specific antipsychotics but not non-response in general (as characterised by treatment-resistance); however, this seems unlikely and it is much more plausible that the reported lack of association in the present review is due to the small sample size of the identified study.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…In a recent meta-analysis, Samara et al reported that people with schizophrenia who did not even minimally improve at week 2 of treatment with sufficiently high doses are unlikely to respond later and therefore may benefit from a change or augmentation of treatment. Ninety percent of subjects who do not show a minimal response (20% reduction in the PANSS/BPRS score) at the 2-week assessment will not show clinical improvement at week 6 [127]. Although the application of these results seems to be more appropriate for people who are not in their first episode of schizophrenia, they emphasize the need for a rapid titration model in order to achieve an adequate dose during the first days of treatment.…”

Section: Other Keystone Aspects In the Treatment Of First-episode Indmentioning

confidence: 99%

Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review

Crespo‐Facorro

Pelayo-Terán²,

Son³

2016

Neurol Ther

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Implementing the most suitable treatment strategies and making appropriate clinical decisions about individuals with a first episode of psychosis (FEP) is a complex and crucial task, with relevant impact in illness outcome. Treatment approaches in the early stages should go beyond choosing the right antipsychotic drug and should also address tractable factors influencing the risk of relapse. Effectiveness and likely metabolic and endocrine disturbances differ among second-generation antipsychotics (SGAs) and should guide the choice of the first-line treatment. Clinicians should be aware of the high risk of cardiovascular morbidity and mortality in schizophrenia patients, and therefore monitoring weight and metabolic changes across time is mandatory. Behavioral and counseling interventions might be partly effective in reducing weight gain and metabolic disturbances. Ziprasidone and aripiprazole have been described to be least commonly associated with weight gain or metabolic changes. In addition, some of the SGAs (risperidone, amisulpride, and paliperidone) have been associated with a significant increase of plasma prolactin levels. Overall, in cases of FEP, there should be a clear recommendation of using lower doses of the antipsychotic medication. If no or minimal clinical improvement is found after 2 weeks of treatment, such patients may benefit from a change or augmentation of treatment. Clinicians should provide accurate information to patients and relatives about the high risk of relapse if antipsychotics are discontinued, even if patients have been symptom free and functionally recovered on antipsychotic treatment for a lengthy period of time.

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“…More recently, Samara et al . performed a meta‐analysis of 34 studies with 9975 participants and reported finding a less than 20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) reduction at the week‐2 predicted non‐response at the end‐point with a specificity of 86% and a positive predictive value of 90% . In addition, when no remission was used as the definition of the non‐response, they also found similar results.…”

Section: How Does Practical Pharmacotherapy For Acute Schizophrenia Pmentioning

confidence: 82%

Practical pharmacotherapy for acute schizophrenia patients

Hatta

2015

Psychiatry Clin Neurosci

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Well-organized clinical guidelines of pharmacotherapy for schizophrenia are not necessarily applicable to emergency and acute-phase situations. Thus, practical pharmacotherapy for acute schizophrenia patients should be based on data from real clinical practice and be independent of pharmaceutical companies. This study investigated the current guidelines being used to determine the initially preferred antipsychotics, durations required before an antipsychotic is viewed as being ineffective, and the strategies utilized for early non-responders that include switching, high dose, and augmentation. In patients who develop side-effects to the preferred antipsychotic drug, continued use may depend on the specific characteristics of the side-effects. For acute-phase patients, antipsychotics with high efficacy and effectiveness may be chosen based on meta-analysis findings for not only double-blinded but also raterblinded randomized controlled trials. Many previous studies have reported being able to make an early prediction at 2 weeks regarding the later response. These predictions were supported by the findings of a recent meta-analysis of 34 studies that examined 9975 participants. In early non-responders to the initial antipsychotic, the effectiveness of the switching strategy appears to depend on the initial antipsychotic administered and the antipsychotic the patient is subsequently switched to. Furthermore, the effectiveness of the strategy between switching and augmentation might also depend on the initial antipsychotic administered. The current findings might serve as the basis for the use of dosing above the licensed range versus continuing the use of conventional dosing in non-responders, provided there is close monitoring of the side-effects. Further research is required before any modifications of routine practices are undertaken regarding the direction of new potential treatments.

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

Abstract: Patients not even minimally improved by week 2 of antipsychotic treatment are unlikely to respond later and may benefit from a treatment change.

Cited by 159 publications

References 81 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

Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review

Practical pharmacotherapy for acute schizophrenia patients

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