We summarized and compared meta-analyses of pharmacological and non-pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 meta-analyses were included, representing 128 meta-analyzed trials and 47,231 study participants. While meta-analyses were generally of adequate or high quality, meta-analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=–0.98) and exercise interventions (SMD=–0.96), followed by psychoeducation (SMD=–0.77), aripiprazole augmentation (SMD=–0.73), topiramate (SMD=–0.72), d-fenfluramine (SMD=–0.54) and metformin (SMD=–0.53). Regarding waist circumference reduction, aripiprazole augmentation (SMD=–1.10) and topiramate (SMD=–0.69) demonstrated the best evidence, followed by dietary interventions (SMD=–0.39). Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=–0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=–0.71) and metformin (SMD=–0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon-like peptide-1 receptor agonists (SMD=–0.39), dietary interventions (SMD=–0.37) and aripiprazole augmentation (SMD=–0.34), whereas insulin resistance improved the most with metformin (SMD=–0.75) and rosiglitazone (SMD=–0.44). Topiramate had the greatest efficacy for triglycerides (SMD=–0.68) and low-density lipoprotein (LDL)-cholesterol (SMD=–0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=–0.51) and high-density lipoprotein (HDL)-cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL-cholesterol (SMD=–0.35 to –0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non-pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND:: Treatment options for clozapine resistance are diverse whereas, in contrast, the evidence for augmentation or combination strategies is sparse.
AIMS:: We aimed to extract levels of evidence from available data and extrapolate recommendations for clinical practice.
METHODS:: We conducted a systematic literature search in the PubMed/MEDLINE database and in the Cochrane database. Included meta-analyses were assessed using Scottish Intercollegiate Guidelines Network criteria, with symptom improvement as the endpoint, in order to develop a recommendation grade for each clinical strategy identified.
RESULTS:: Our search identified 21 meta-analyses of clozapine combination or augmentation strategies. No strategies met Grade A criteria. Strategies meeting Grade B included combinations with first- or second-generation antipsychotics, augmentation with electroconvulsive therapy for persistent positive symptoms, and combination with certain antidepressants (fluoxetine, duloxetine, citalopram) for persistent negative symptoms. Augmentation strategies with mood-stabilisers, anticonvulsants, glutamatergics, repetitive transcranial magnetic stimulation, transcranial direct current stimulation or cognitive behavioural therapy met Grades C-D criteria only.
CONCLUSION:: More high-quality clinical trials are needed to evaluate the efficacy of add-on treatments for symptom improvement in patients with clozapine resistance. Applying definitions of clozapine resistance would improve the reporting of future clinical trials. Augmentation with second-generation antipsychotics and first-generation antipsychotics can be beneficial, but the supporting evidence is from low-quality studies. Electroconvulsive therapy may be effective for clozapine-resistant positive symptoms.
We summarized and compared meta-analyses of pharmacological and non-pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 meta-analyses were included, representing 128 meta-analyzed trials and 47,231 study participants. While meta-analyses were generally of adequate or high quality, meta-analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=–0.98) and exercise interventions (SMD=–0.96), followed by psychoeducation (SMD=–0.77), aripiprazole augmentation (SMD=–0.73), topiramate (SMD=–0.72), d-fenfluramine (SMD=–0.54) and metformin (SMD=–0.53). Regarding waist circumference reduction, aripiprazole augmentation (SMD=–1.10) and topiramate (SMD=–0.69) demonstrated the best evidence, followed by dietary interventions (SMD=–0.39). Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=–0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=–0.71) and metformin (SMD=–0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon-like peptide-1 receptor agonists (SMD=–0.39), dietary interventions (SMD=–0.37) and aripiprazole augmentation (SMD=–0.34), whereas insulin resistance improved the most with metformin (SMD=–0.75) and rosiglitazone (SMD=–0.44). Topiramate had the greatest efficacy for triglycerides (SMD=–0.68) and low-density lipoprotein (LDL)-cholesterol (SMD=–0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=–0.51) and high-density lipoprotein (HDL)-cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL-cholesterol (SMD=–0.35 to –0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non-pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.
