Defining treatment-resistant schizophrenia and response to antipsychotics: A review and recommendation

Suzuki, Takefumi; Remington, Gary; Mulsant, Benoit H.; Uchida, Hiroyuki; Rajji, Tarek K.; Graff‐Guerrero, Ariel; Mimura, Masaru; Mamo, David C.

doi:10.1016/j.psychres.2012.02.013

Cited by 149 publications

(100 citation statements)

References 48 publications

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“…Finally, clinical evidence has demonstrated that a relatively large proportion of patients with schizophrenia do not respond adequately to existing antipsychotic medications (Conley and Kelly, 2001;Suzuki et al, 2012). Although the molecular mechanisms that are responsible for this lack of efficacy remain poorly understood, results of the present study raise the possibility that DFosB induction may contribute.…”

Section: Discussionmentioning

confidence: 75%

ΔFosB Induction in Prefrontal Cortex by Antipsychotic Drugs is Associated with Negative Behavioral Outcomes

Dietz

Kennedy

Sun

et al. 2013

Neuropsychopharmacol

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DFosB, a FosB gene product, is induced in the prefrontal cortex (PFC) by repeated exposure to several stimuli including antipsychotic drugs such as haloperidol. However, the functional consequences of increased DFosB expression following antipsychotic treatment have not been explored. Here, we assessed whether DFosB induction by haloperidol mediates the positive or negative consequences or clinical-related actions of antipsychotic treatment. We show that individuals with schizophrenia who were medicated with antipsychotic drugs at their time of death display increased DFosB levels in the PFC, an effect that is replicated in rats treated chronically with haloperidol. In contrast, individuals with schizophrenia who were medication-free did not exhibit this effect. Viral-mediated overexpression of DFosB in the PFC of rodents induced cognitive deficits as measured by inhibitory avoidance, increased startle responses in prepulse inhibition tasks, and increased MK-801-induced anxiety-like behaviors. Together, these results suggest that DFosB induction in the PFC by antipsychotic treatment contributes to the deleterious effects of these drugs and not to their therapeutic actions.

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Section: Discussionmentioning

confidence: 75%

ΔFosB Induction in Prefrontal Cortex by Antipsychotic Drugs is Associated with Negative Behavioral Outcomes

Dietz

Kennedy

Sun

et al. 2013

Neuropsychopharmacol

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“…One study reported that these symptoms were present in 23% of subjects, which increased to 70% at the end of 3 years of treatment. The presence of these negative symptoms in early psychosis [24] is also associated with treatment resistance, indicating treatment resistance may potentially set in fairly early in the development of schizophrenia [26]. A study by Makinen (2010) [27], in a ten-year follow-up of FEP reported that 41% of the subjects had negative symptoms at the first episode, 39% in the follow-up phase, and 24% of subjects have persistent symptoms after 10 years.…”

Section: Discussionmentioning

confidence: 99%

Study of negatives symptoms in first episode schizophrenia

Bambole¹,

Shah²,

Sonavane³

et al. 2013

OJPsych

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Background: Prevalence of negative symptoms in the early phase of schizophrenia remains uncertain. Negative symptoms are the primary cause of long term disability and poor functional outcome. The purpose of this study is to examine the presence of negative symptoms in patients with fist episode psychosis in schizophrenia who were hospitalized. Methods: Negative symptoms were measured in 72 patients presenting with FEP using the scale for assessment of negative symptoms (SANS) and ascertained diagnosis using DSM-IV. Prevalence of SANS items and subscales were examined for both schizophrenia and bipolar disorder. Results: This study shows that a significant number of patients with first episode schizophrenia had negative symptoms 66 (87.5%). All five subtypes of negative symptoms were present in 47% of patients suggesting primary negative symptoms, and about 40% have secondary negative symptoms. Independently, each subtype of negative symptoms was seen in 48% -76% of patients. The most prevalent negative symptom in first-episode schizophrenia was found to be blunting (72%). 46% of patients had significant level of depression, overall psychopathology was severe and level of functioning was poor. We found that 45.8% patients were prescribed anticholinergic medications which indicated that at least 45% subjects had extra-pyramidal symptoms (EPS). Conclusion: Primary negative symptoms are prevalent in about half of First episode Psychosis (FEP) schizophrenia patients. These findings have implications for identification, early treatment, and reduced treatment resistance for negative symptoms in order to increase social and clinical outcome of schizophrenia. Further research is required in this area.

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“…Response rates were defined according to three levels: a 20% reduction, which is generally considered the minimum level of response 23 and 30% reduction, which correspond to "minimally improved" CGI level 24 , and 40% reduction, which correspond to the "much improved" CGI level adequate level 24 and considered an adequate level for ECT trials 15 . Secondary outcomes were clinical improvement on other PANSS subscales as well as the CGI.…”

Section: Methodsmentioning

confidence: 99%

Efficacy of electroconvulsive therapy augmentation for partial response to clozapine: a pilot randomized ECT – sham controlled trial

Melzer-Ribeiro

Rigonatti

Kayo

et al. 2017

Arch. Clin. Psychiatry (São Paulo)

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Background: Thirty percent of schizophrenia patients are treatment-resistant. Objective: This is a single-blinded sham-controlled trial to assess the efficacy of electroconvulsive therapy (ECT) as augmentation strategy in patients with clozapine-resistant schizophrenia. Methods: Twenty three subjects were randomly assigned to 12 sessions of ECT (N = 13) or placebo (Sham ECT) (N = 10). The primary outcome was improvement on psychotic symptoms as measured by the mean reduction of the PANSS positive subscale. The assessments were performed by blind raters. Results: At baseline both groups were similar, except for negative and total symptoms of the PANSS, which were higher in the Sham group. At the endpoint both groups had a significant decrease from basal score. In the ECT group the PANSS total score decreased 8.78%, from 81.23 to 74.75 (p = 0.042), while the positive subscale had a mean reduction of 19% (19.31 to 16.17, p = 0.006). In the Sham group, the mean reduction of PANSS total score was 15. 27% (96.80 to 87.43; p = 0.036), and the PANSS positive subscale decreased 27.81% (22.90 to 19.14, p = 0.008). The CGI score in ECT group decreased 23.0% (5.23 to 4.17; p = 0.001) and decreased 24.31% in the Sham ECT group (5.80 to 4.86; p = 0.004).

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Defining treatment-resistant schizophrenia and response to antipsychotics: A review and recommendation

Cited by 149 publications

References 48 publications

ΔFosB Induction in Prefrontal Cortex by Antipsychotic Drugs is Associated with Negative Behavioral Outcomes

ΔFosB Induction in Prefrontal Cortex by Antipsychotic Drugs is Associated with Negative Behavioral Outcomes

Study of negatives symptoms in first episode schizophrenia

Efficacy of electroconvulsive therapy augmentation for partial response to clozapine: a pilot randomized ECT – sham controlled trial

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