Augmentation of clozapine with a second antipsychotic – a meta‐analysis

Taylor, David; Smith, Lance A.; Gee, Siobhan; Nielsen, Jimmi

doi:10.1111/j.1600-0447.2011.01792.x

Cited by 114 publications

(80 citation statements)

References 33 publications

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“…Howes et al 22 and AlessiSeverini et al 23 carried out studies at Mental Health Centers in England and Canada, respectively, and found out that polypharmacy and three or more tries of antipsychotic treatment was a common feature before the initiation of clozapine. Regarding the patients with TRS, some meta-analyses support combining another antipsychotic with clozapine in patients who do not respond fully to this medication 16,24,25 but the evidence of efficacy of these augmentation strategies is also scarce 24 .…”

Section: Discussionmentioning

confidence: 99%

Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in São Paulo, Brazil

Silveira¹,

Rocha²,

Àttux³

et al. 2015

Arch. Clin. Psychiatry (São Paulo)

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Background: Despite of its global underuse, clozapine is still the golden standard antipsychotic for patients with treatment-resistant schizophrenia (TRS). Objective: To evaluate the patterns of clozapine and other antipsychotic drugs prescription in TRS in community mental health centers in São Paulo, Brazil. Methods: A multiple-choice questionnaire was applied to fifteen psychiatrists at five centers inquiring about patients' clinical condition, adherence to oral treatment and current antipsychotic treatment. History of previous and current antipsychotic treatment was collected through medical chart review. Results: Out of 442 schizophrenia patients, 103 (23.3%) fulfilled the criteria for TRS. Fifty-eight patients (56.3%) were receiving polypharmacy; 30 (29.1%) were on atypical antipsychotic monotherapy, 14 (13.6%) were on typical antipsychotic monotherapy, 25 (24.3%) were taking depot antipsychotic medication and only 22 (21.4%) were receiving clozapine. Discussion: As well as in other parts of the world, many TRS patients (78.6%) receive other drugs instead of clozapine in São Paulo, the best evidence-based medication for patients with TRS. The government should make every effort to provide medical training and the equipment and logistic support to adequately serve those who could benefit from clozapine treatment at the community health centers.

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Section: Discussionmentioning

confidence: 99%

Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in São Paulo, Brazil

Silveira¹,

Rocha²,

Àttux³

et al. 2015

Arch. Clin. Psychiatry (São Paulo)

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“…Most positive findings stems from augmentation of clozapine, where some studies have shown efficacy in reducing positive symptoms (Muscatello et al, 2011;Shiloh et al, 1997), whereas others showed improving the metabolic burden from clozapine (Fleischhacker et al, 2010;Henderson et al, 2006). A meta-analysis by Taylor et al found only modest effects of combining another antipsychotic drug with clozapine (Taylor et al, 2012). In addition, worsening of psychosis has also been reported during APP (Nielsen et al, 2012a;Reeves and Mack, 2004).…”

Section: Introductionmentioning

confidence: 93%

Frequency and correlates of antipsychotic polypharmacy among patients with schizophrenia in Denmark: A nation-wide pharmacoepidemiological study

Sneider

Pristed

Correll

et al. 2015

European Neuropsychopharmacology

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“…Probably, the inclusion of studies with small sample sizes, heterogeneity in study quality and the inclusion of studies where a second AP is added to a first one together with studies where two AP drugs are simultaneously prescribed from the beginning of treatment, are possible explanations for such heterogeneity and uncertainty (Barbui et al 2009;Correll et al 2009;Sommer et al 2012;Taylor et al 2012).…”

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confidence: 99%

Antipsychotic combinations in schizophrenia

Gastaldon

Papola

Ostuzzi

2017

Epidemiol Psychiatr Sci

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This Section of Epidemiology and Psychiatric Sciences appears in each issue of the Journal to stress the role of the epidemiological approach to promote advances in the field of clinical psychopharmacology, with a particular attention to controversial findings. The ultimate aims are to help develop a more critical attitude towards the results of research studies published in the international literature, to promote original research projects with higher methodological standards, and to implement the most relevant results of research in every-day clinical practice. These contributions are written in house by the journal's editorial team or commissioned by the Section Editor (no more than 1000 words, short unstructured abstract, 4 key-words, one Table or In the treatment of resistant schizophrenia, a number of meta-analyses attempted to quantify the efficacy and tolerability of antipsychotic (AP) polypharmacy v. monotherapy with contradictory results. Recently, a systematic review and metaanalysis of randomised controlled trials investigated the efficacy and tolerability of AP combination v. monotherapy in schizophrenia. It included 31 studies: 21 double-blind (considered high-quality studies) and 10 open-label (considered low-quality studies). The meta-analysis showed that, overall, the combination of two APs was more effective than monotherapy in terms of symptom reduction (standardised mean difference (SMD) = −0.53, 95% confidence interval (CI) −0.87 to −0.19); however, this result was confirmed only in the subgroup of low-quality studies. Negative symptoms improved when combining a D2 antagonist with a D2 partial agonist (SMD = −0.41, 95% CI −0.79 to −0.03) both in double-blind and open-label studies. In the present commentary, the results of this systematic review are critically discussed in terms of their clinical and research implications. Key words: Antipsychotics, evidence-based psychiatry, randomised controlled trials, schizophrenia, systematic reviews.Despite some advances, the pharmacological treatment of schizophrenia continues to be a challenge (Kane & Correll, 2010), especially in poor treatment responders, who represent a difficult to treat population with low rates of recovery that have not increased over time (Jaaskelainen et al. 2013).In patients with poor response to antipsychotics (AP), current evidence-based guidelines recommend a range of different strategies, such as waiting for a delayed response, checking adherence, dose adjustment, switching to another AP. If these strategies are ineffective and at least two trials of different APs, prescribed at adequate dose and length of treatment, have failed to provide substantial benefit, patients are considered treatment-resistant (Suzuki et al. 2011(Suzuki et al. , 2012. In treatment-resistant cases, guidelines recommend clozapine and, only if this attempt has failed, the combination of clozapine with a second AP (Lehman et al. 2004; NICE, 2009). Although guidelines suggest this combination strategy in selected circumstances only, in clinical pr...

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Augmentation of clozapine with a second antipsychotic – a meta‐analysis

Abstract: Augmentation with a second antipsychotic is modestly beneficial in patients not responding fully to clozapine. Tolerability seems not to be adversely affected, at least in the short term. Longer studies do not appear to increase the probability of showing positive effects for augmentation.

Cited by 114 publications

References 33 publications

Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in São Paulo, Brazil

Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in São Paulo, Brazil

Frequency and correlates of antipsychotic polypharmacy among patients with schizophrenia in Denmark: A nation-wide pharmacoepidemiological study

Antipsychotic combinations in schizophrenia

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