Treatment-Resistant to Antipsychotics: A Resistance to Everything? Psychotherapy in Treatment-Resistant Schizophrenia and Nonaffective Psychosis: A 25-Year Systematic Review and Exploratory Meta-Analysis

Abstract

Background: Roughly 30% of schizophrenia patients fail to respond to at least two antipsychotic trials. Psychosis has been traditionally considered to be poorly sensitive to psychotherapy. Nevertheless, there is increasing evidence that psychological interventions could be considered in treatment-resistant psychosis (TRP). Despite the relevance of the issue and the emerging neurobiological underpinnings, no systematic reviews have been published. Here, we show a systematic review of psychotherapy interventions in TRP patients of the last 25 years. Methods: The MEDLINE/PubMed, ISI WEB of Knowledge, and Scopus databases were inquired from January 1, 1993, to August 1, 2018, for reports documenting augmentation or substitution with psychotherapy for treatment-resistant schizophrenia (TRS) and TRP patients. Quantitative data fetched by Randomized Controlled Trials (RCTs) were pooled for explorative meta-analysis. Results: Forty-two articles have been found. Cognitive behavioral therapy (CBT) was the most frequently recommended psychotherapy intervention for TRS (studies, n = 32, 76.2%), showing efficacy for general psychopathology and positive symptoms as documented by most of the studies, but with uncertain efficacy on negative symptoms. Other interventions showed similar results. The usefulness of group therapy was supported by the obtained evidence. Few studies focused on negative symptoms. Promising results were also reported for resistant early psychosis. Limitations: Measurement and publication bias due to the intrinsic limitations of the appraised original studies. Conclusions: CBT, psychosocial intervention, supportive counseling, psychodynamic psychotherapy, and other psychological interventions can be recommended for clinical practice. More studies are needed, especially for non-CBT interventions and for all psychotherapies on negative symptoms.

Clozapine resistant schizophrenia: Newer avenues of management

“…Two systematic reviews of psychosocial interventions have concluded that CBT can be effective among patients with poor response to clozapine[ 33 , 68 ]. As shown in Table 5 , the evidence-base for CBT until recently had consisted of a few trials with small numbers and inadequate study designs[ 69 - 71 ] or RCTs that included some patients with CRS[ 72 - 74 ].…”

“…A re-evaluation of psychosocial augmentation strategies: Although the evidence reviewed in Table 5 suggests that augmentation with CBT does not yield consistent benefits in CRS, there are several reasons to re-examine the usefulness of psychosocial augmentation strategies. To begin with, CBT augmentation appears to be effective for persistent positive symptoms in TRS[ 20 , 68 , 75 , 76 ]. Moreover, the largest and most meticulously conducted CBT trial has shown a small but significant benefit for patients with CRS following the active intervention phase[ 66 , 75 , 76 ].…”

“…Moreover, symptomatic remission appears to be faster with CBT augmentation, and the benefits obtained may persist longer[ 71 , 72 , 74 ]. CBT augmentation early in the course of clozapine treatment may further enhance its benefits[ 68 - 70 , 74 ].…”

Effectiveness of mindfulness‐based intervention on psychotic symptoms for patients with schizophrenia: A meta‐analysis of randomized controlled trials

“…Other recent studies found that non‐pharmacological interventions including psychological and psychosocial interventions could improve positive symptoms (Bighelli et al., 2018) and negative symptoms (Lutgens et al., 2017). The findings of a recent meta‐analysis study demonstrate that psychotherapy contributes to the positive effects on improving positive symptoms for schizophrenic patients with medication treatment resistance (Polese et al., 2019). However, it remains not clear about the impacts of psychotherapy on negative symptoms for this study subjects.…”

<p>Clozapine Use in Patients with Early-Stage Schizophrenia in a Chinese Psychiatric Hospital</p>

“…A 25-year systematic review and exploratory meta-analysis of 42 articles suggested that psychotherapy, especially cognitive behavioral therapy (CBT), could be beneficial for improving general psychopathology and positive symptoms among patients with TRS. 40 ECT also plays an important role in treating schizophrenia. ECT has been proven to be effective and safe in patients with first-episode schizophrenia and chronic schizophrenia, especially in TRS.…”