Dataset Information

Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review.

ABSTRACT:

Background

When schizophrenia patients have insufficient response to clozapine, pharmacological augmentation is often applied. This meta-analysis summarizes available evidence on efficacy of pharmacological augmentation of clozapine treatment in schizophrenia spectrum disorder.

Methods

Only double-blind randomized controlled studies were included. Primary outcome measure was total symptom severity, and secondary outcome measures were subscores for positive and negative symptoms. Effect sizes were calculated from individual studies and combined to standardized mean differences (Hedges's g).

Results

Twenty-nine studies reporting on 15 different augmentations were included. Significant better efficacy than placebo on total symptom severity was observed for lamotrigine, citalopram, sulpiride, and CX516 (a glutamatergic agonist). The positive effect of lamotrigine disappeared after outlier removal. The other positive findings were based on single studies. Significantly better efficacy on positive symptom severity was observed for topiramate and sulpiride. The effect of topiramate disappeared after outlier removal. Results for sulpiride were based on a single randomized controlled trial. Citalopram, sulpiride, and CX516 showed better efficacy for negative symptoms than placebo, all based on single studies.

Conclusions

Evidence for efficacy of clozapine augmentation is currently scarce. Efficacy of lamotrigine and topiramate were both dependent on single studies with deviating findings. The effect of citalopram, sulpiride, and CX516 were based on single studies. Thus, despite their popularity, pharmacological augmentations of clozapine are not (yet) demonstrated to be superior to placebo.

SUBMITTER: Sommer IE

PROVIDER: S-EPMC3446238 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review.

Sommer Iris E IE Sommer Iris E IE Begemann Marieke J H MJ Temmerman Anke A Leucht Stefan S

Schizophrenia bulletin 20110321 5

<h4>Background</h4>When schizophrenia patients have insufficient response to clozapine, pharmacological augmentation is often applied. This meta-analysis summarizes available evidence on efficacy of pharmacological augmentation of clozapine treatment in schizophrenia spectrum disorder.<h4>Methods</h4>Only double-blind randomized controlled studies were included. Primary outcome measure was total symptom severity, and secondary outcome measures were subscores for positive and negative symptoms. E ...[more]

PMID: 21422107

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Project description:BackgroundEvidence for the management of inadequate clinical response to clozapine in treatment-resistant schizophrenia is sparse. Accordingly, an international initiative was undertaken with the aim of developing consensus recommendations for treatment strategies for clozapine-refractory patients with schizophrenia.MethodsWe conducted an online survey among members of the Treatment Response and Resistance in Psychosis (TRRIP) working group. An agreement threshold of ≥75% (responses "agree" + "strongly agree") was set to define a first-round consensus. Questions achieving agreement or disagreement proportions of >50% in the first round, were re-presented to develop second-round final consensus recommendations.ResultsForty-four (first round) and 49 (second round) of 63 TRRIP members participated. Expert recommendations at ≥75% agreement included raising clozapine plasma levels to ≥350 ng/ml for refractory positive, negative, and mixed symptoms. Where plasma level-guided dose escalation was ineffective for persistent positive symptoms, waiting for a delayed response was recommended. For clozapine-refractory positive symptoms, combination with a second antipsychotic (amisulpride and oral aripiprazole) and augmentation with ECT achieved consensus. For negative symptoms, waiting for a delayed response was recommended, and as an intervention for clozapine-refractory negative symptoms, clozapine augmentation with an antidepressant reached consensus. For clozapine-refractory suicidality, augmentation with antidepressants or mood-stabilizers, and ECT met consensus criteria. For clozapine-refractory aggression, augmentation with a mood-stabilizer or antipsychotic medication achieved consensus. Generally, cognitive-behavioral therapy and psychosocial interventions reached consensus.ConclusionsGiven the limited evidence from randomized trials of treatment strategies for clozapine-resistant schizophrenia (CRS), this consensus-based series of recommendations provides a framework for decision making to manage this challenging clinical situation.

Project description:BACKGROUND:Advanced dementia is characterized by severe cognitive and functional impairments that lead to almost total dependency in self-care. Neuropsychiatric symptoms (NPS) are common in advanced dementia, diminishing quality of life and increasing the care burden. The challenge for health care providers is to find safe and effective treatments. Non-pharmacological interventions offer the potential for safer alternatives to pharmacotherapy, but little is known about their efficacy. This review evaluates the published literature on non-pharmacological interventions for treating NPS in advanced dementia. METHODS:A literature search was undertaken to find non-pharmacological intervention studies published between 1998 and 2008 that measured NPS outcomes in individuals diagnosed with advanced dementia. Strict inclusion criteria initially required that all study participants have severe or very severe dementia, but this range was later broadened to include moderately severe to very severe stages. RESULTS:Out of 215 intervention studies, 21 (9.8%) specifically focused on treatments for individuals with moderately severe to very severe dementia. The studies provide limited moderate to high quality evidence for the use of sensory-focused strategies, including aroma, preferred or live music, and multi-sensory stimulation. Emotion-oriented approaches, such as simulated presence may be more effective for individuals with preserved verbal interactive capacity. CONCLUSIONS:Most studies of interventions for dementia-related NPS have focused on individuals with mild to moderate cognitive impairment. Individuals with severe cognitive impairment do not necessarily respond to NPS treatments in the same manner. Future studies should be specifically designed to further explore the stage-specific efficacy of non-pharmacological therapies for patients with advanced dementia. Areas of particular need for further research include movement-based therapies, hands-on (touch) therapies, and interventions that can be provided during personal care routines. Interventions appear to work best when they are tailored to balance individual arousal patterns.

Dataset Information

Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review.

Background

Methods

Results

Conclusions

Publications

Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review.

Similar Datasets

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