Real-world effectiveness of antipsychotic monotherapy and polytherapy in 1543 patients with acute-phase schizophrenia

Hatta, Kotaro; Hasegawa, Hana; Sudo, Yasuhiko; Morikawa, Fumiyoshi; Katayama, S; Watanabe, Hiroyoshi; Ishizuka, Takuya; Nakamura, Mitsuru; Misawa, Fuminari; Fujita, Kiyoshi; Ozaki, Shigeru; Umeda, Kentaro; Nakamura, Hiroyuki; Sawa, Yoshiki; Sugiyama, Naoya

doi:10.1016/j.ajp.2019.02.005

Cited by 20 publications

(14 citation statements)

References 35 publications

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“…Likewise a recent, large naturalistic study including acute-phase schizophrenia in Japan (n=1,543) 21 also showed the clinical benefit of APP when the primary and secondary APM strategies failed in clinical practice where approximately 59% of the patients overall were responders to an initial or a second APM. As a next step treatment, APP (first or third AP combination to the second AP) was administered to the non-responders (n=581, 37.7%) where 522 (89.8%) showed a CGI-I score ≤3, while only 10.2% of the remaining patients showed a CGI-I score of ≥4.…”

Section: What Benefits Do We Expect From App?mentioning

confidence: 83%

“…Such high prevalences of APP has been also consistently found in numerous independent studies in different geographic regions such as Korea, China, Brazil, Canada, America, and Japan. [18][19][20][21][22][23] There has been no clear determination of how many number of APs are commonly used in APP, which is found to create a variable range of AP numbers. According to the extensive meta-analysis, 17 17.8% were taking two APs and 0.2% were taking ≥3 antipsychotics.…”

Section: Prevalence Of Appmentioning

confidence: 99%

Section: Prevalence Of Appmentioning

confidence: 99%

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Antipsychotic Polypharmacy in Treatment of Schizophrenia; Should or Should Not?

Pae

2020

Chonnam Med J

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Antipsychotics have been utilized as the standard treatment for schizophrenia regardless of illness phase where antipsychotic monotherapy (APM) is routinely recommended as the gold standard rather than antipsychotic polypharmacy (APP). However, approximately 20 to 40% of patients with schizophrenia do not respond to APM based on randomized controlled clinical trials and large practical clinical trials indicating that the subgroup of patients with schizophrenia would need differential treatment approaches beyond traditional treatment strategies such as APM. Numerous studies have supported the use of APP in particular for patients with certain clinical situations including: failure to show efficacy or tolerability from treatment with APM, need for different treatment for targeting specific symptom domains, severe illness, failure to treatment with clozapine, skepticism about following treatment guidelines, or cross titration periods. Furthermore, recent large cohort studies and practical clinical trials have proposed more benefits of APP rather than APM in terms of rehospitalization, mortality, and specific symptoms. APP has recently become more widely utilized and recognized as one of the next treatment strategies to clinicians for patients with schizophrenia. Some experts have already proposed the revision of treatment guidelines incorporating APP as evidence-based treatment option for certain patients with schizophrenia. Taken together, APP now deserves an evidence-based and acceptable treatment strategy, not an empirical or preferential treatment approach for treatment of schizophrenia in contemporary clinical practice.

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Section: What Benefits Do We Expect From App?mentioning

confidence: 83%

Section: Prevalence Of Appmentioning

confidence: 99%

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Antipsychotic Polypharmacy in Treatment of Schizophrenia; Should or Should Not?

Pae

2020

Chonnam Med J

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“…For acute phase schizophrenia, a recent naturalistic study demonstrated that adding another antipsychotic in patients who had not responded to two previous antipsychotics was associated with significant global symptom improvement. However, this study did not control for total dose, and thus, the improvement with antipsychotic polypharmacy in non‐responders to monotherapy may also be partly explained by increased total antipsychotic dosage.…”

Section: Antipsychotic Polypharmacymentioning

confidence: 99%

“…38 As a minimal requirement, treatment guidelines recommend systematically monitoring for side effects and careful documentation of these as well as of any therapeutic effect to be sure to maintain a favourable risk-benefit ratio. 38 For acute phase schizophrenia, a recent naturalistic study 39 demonstrated that adding another antipsychotic in patients who had not responded to two previous antipsychotics was associated with significant global symptom improvement. However, this study did not control for total dose, and thus, the improvement with antipsychotic polypharmacy in non-responders to monotherapy may also be partly explained by increased total antipsychotic dosage.…”

Section: Antipsychotic Polypharmacymentioning

confidence: 99%

Polypharmacy in schizophrenia

Baandrup

2020

Basic Clin Pharma Tox

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Schizophrenia is a severe mental disorder characterized by a heterogeneous symptom profile which comprises a clinical platform for widespread use of polypharmacy even though antipsychotic monotherapy is the recommended treatment regimen. This narrative review provides a summary of the current gap between evidence and practice for use of antipsychotic combination therapy in patients with schizophrenia. Antipsychotic polypharmacy is frequently prescribed instead of following international consensus of clozapine monotherapy in treatment‐resistant patients. Antipsychotic‐benzodiazepine combination therapy clearly has a role in the treatment of acute agitation whereas there is no evidence to support an effect on core schizophrenia symptoms when chronically prescribed. Antidepressants are typically added to antipsychotic treatment in case of persistent negative symptoms. Available evidence suggests that antidepressants may improve negative symptom control in schizophrenia. Combining an antipsychotic with an antiepileptic is not supported by any firm evidence, but individual mood stabilizers have come out positively in single trials. Generally, the evidence base for polypharmacy in schizophrenia maintenance treatment is sparse but may be warranted in certain clinical situations. Therapeutic benefits and side effects should be carefully monitored and considered to ensure a beneficial risk‐benefit ratio if prescribing polypharmacy for specific clinical indications.

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Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations

Lähteenvuo

Tiihonen

2021

Drugs

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Schizophrenia is a debilitating illness with a lifetime prevalence estimate of 0.6% and consists of symptoms from the positive, negative, and cognitive domains. Social support, therapy, psychoeducation, and overall case management are very important aspects of the treatment of schizophrenia. However, as abnormalities in neurotransmission are one of the key findings of schizophrenia pathology, pharmacotherapies are cornerstones of the management of schizophrenia. Antipsychotics have been used as the primary pharmacological treatment of schizophrenia. These agents often have a good effect on reducing positive symptoms, but may not markedly improve negative symptoms or cognitive defects. However, at least 20% of individuals with schizophrenia do not experience a substantial response from monotherapy with antipsychotics. Further, despite evolving treatment protocols and advances in early recognition of the disorder, 70% of patients with schizophrenia require long-term, even lifetime, medication to control their symptoms and do not achieve complete recovery. To address these shortcomings, clinicians and research scientists have explored different combinations of treatments, polypharmacy, to improve the treatment of patients. Antipsychotic polypharmacy has been shown to cause more side effects than monotherapy, which is the main reason why most treatment guidelines caution against it. Antipsychotic monotherapy should be strived for and clozapine should be tried at the latest if two monotherapy trials with other antipsychotics have failed and no absolute contraindications exist. If residual symptoms exist despite trials of adequate dose and duration, other reasons that may reduce treatment effect should be ruled out. Long-acting injectables or blood concentration measurements should be considered to affirm compliance and proper serum levels. Antipsychotic polypharmacy should be considered and discussed with patients from whom the aforementioned procedures do not produce a satisfactory treatment result. In some cases, antipsychotic polypharmacy may produce better results than other forms of treatment augmentation, such as benzodiazepines. In particular, combining aripiprazole with clozapine may be effective in reducing treatment side effects or residual symptoms, and this is likely to hold true for combining other partial dopamine D 2 agonists with clozapine as well, although currently scant data exist. More research is needed, both in controlled but also real-world settings, to define optimal antipsychotic polypharmacy and/or other psychotropic treatment augmentation strategies for specific patient groups and situations.

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Real-world effectiveness of antipsychotic monotherapy and polytherapy in 1543 patients with acute-phase schizophrenia

Cited by 20 publications

References 35 publications

Antipsychotic Polypharmacy in Treatment of Schizophrenia; Should or Should Not?

Antipsychotic Polypharmacy in Treatment of Schizophrenia; Should or Should Not?

Polypharmacy in schizophrenia

Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations

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