Antipsychotic treatment strategies for acute phase and treatment resistance in schizophrenia: A systematic review of the guidelines and algorithms

Shimomura, Yutaro; Kikuchi, Yuhei; Suzuki, Takefumi; Uchida, Hiroyuki; Mimura, Masaru; Takeuchi, Hiroyoshi

doi:10.1016/j.schres.2021.07.040

Cited by 22 publications

(13 citation statements)

References 42 publications

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“…A systematic review of evidence-based guidelines for antipsychotic treatment of patients with schizophrenia found that all 17 of the guidelines reviewed recommend initiating treatment with the antipsychotic drug clozapine when patients are diagnosed with TRS [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

et al. 2022

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Section: Introductionmentioning

confidence: 99%

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

et al. 2022

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“…However, this study, which had various limitations such as a retrospective design, lack of symptom assessments, and small sample size, was considered insufficient to answer to our clinical question of whether or not clozapine should be discontinued if patients did not respond to clozapine. Therefore, there is an urgent need to further examine clinical outcomes after clozapine discontinuation in patients with CRS, because current evidence recommends augmentation strategies with other antipsychotics or ECT for this population [7][8][9][10]. In addition, given that it is likely that patients responded to clozapine and then discontinued it due to poor tolerability, clinical outcomes should be examined not only by the response to clozapine but also by reason for clozapine discontinuation.…”

Section: Discussionmentioning

confidence: 99%

“…For TRS, clozapine is the gold standard of treatment [4,5]; however, approximately 60 % of patients with TRS do not respond to clozapine [6], a condi-tion referred to as clozapine-resistant schizophrenia (CRS). For CRS, augmentation strategies with other antipsychotics or electroconvulsive therapy (ECT) are currently recommended [7][8][9][10], which implies a continuation of clozapine treatment even for patients who fail to respond to clozapine. In the real world, however, a substantial number of patients discontinue clozapine treatment for various reasons, such as inefficacy, intolerance, physical complications, nonadher-Introduction Clozapine is the gold standard of treatment for patients with treatment-resistant schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Clinical Outcomes after Clozapine Discontinuation in Patients with Schizophrenia: A Systematic Review

Miura

Tanaka

Kemuriyama³

et al. 2022

Pharmacopsychiatry

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Introduction Clozapine is the gold standard of treatment for patients with treatment-resistant schizophrenia. However, approximately 60% of those patients do not respond to clozapine; moreover, clinical outcomes after clozapine discontinuation are unclear so far. Therefore, we conducted a systematic review to clarify the outcomes after clozapine discontinuation. Methods A systematic literature search was conducted, using MEDLINE and Embase with the following keywords: (clozapine AND (cessation* OR cease* OR withdraw* OR discontinu* OR halt* OR stop* OR switch*) AND (schizophreni* OR schizoaffective)). Results A total of 28 clinical studies from 27 articles were identified and included in this systematic review. Three randomized controlled trials reported worsening of psychiatric symptoms. In 10 single-arm studies, the results of worsening and improving psychiatric symptoms were inconsistent. In one large retrospective cohort study, clozapine rechallenge, olanzapine, and antipsychotic polypharmacy had lower rehospitalization rates compared to no medication after clozapine discontinuation. In the other 14 retrospective studies, the vast majority showed worsening of clinical status after clozapine discontinuation. Among five studies on clinical outcomes after clozapine rechallenge, four reported improvements in clinical status in more than half of patients who rechallenged clozapine. The remaining study reported that the clozapine discontinuation-rechallenge group had a worse remission assessment score than the clozapine discontinuation-no rechallenge group. Discussion Clinical outcomes generally worsen after clozapine discontinuation. Clozapine rechallenge and olanzapine may be considered following clozapine discontinuation. The outcomes after clozapine discontinuation in clozapine non-responders remain inconclusive; therefore, well-designed studies are warranted.

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“…The former has been recommended in instances where pseudo-resistance due to non-adherence to antipsychotics is suspected ( 5 ). The latter is less grounded in evidence; multiple guidelines have cautioned against the use of supratherapeutic doses of antipsychotics given the higher risk of side effects and little evidence of benefits ( 27 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…In existing literature, the recommendations on augmentation strategies for clozapine non-response have varied across different guidelines ( 27 ). This is perhaps a reflection of the lack of robust evidence to support one strategy over the other.…”

Section: Discussionmentioning

confidence: 99%

Managing treatment resistance in schizophrenia: A joint study in Hong Kong and Singapore

Zheng

Lee

2022

Front. Psychiatry

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ObjectiveThis study surveyed clinicians in psychiatry in Hong Kong and Singapore to understand their familiarity and prescribing practices in treatment-resistant schizophrenia (TRS) and clozapine-resistant schizophrenia (CRS).Materials and methodsAll clinicians in psychiatry in both regions were invited through email to participate in an anonymous online survey. The survey collected information on the participants’ characteristics, their familiarity and experience with clozapine use, and their treatment practices in TRS and CRS. Data collection took place between September 2019 and February 2020 in Hong Kong and December 2018 and March 2019 in Singapore.Results261 clinicians responded to the survey, with response rates of 19% (105 out of 556 participants) in Hong Kong and 50% (156 out of 309 participants) in Singapore. The majority of respondents (99.0% in Hong Kong; 87.9% in Singapore) were familiar with treatment guidelines for TRS. However, approximately half (54.2% in Hong Kong; 41.7% in Singapore) delayed the prescription of clozapine when indicated. In terms of alternatives to clozapine, approximately half or more of the clinicians in both regions would use high dose antipsychotics, long-acting injectable antipsychotics, antipsychotic polypharmacy, while the adjuvant use of mood stabilizers and electroconvulsive therapy differed between the two regions. In those with CRS, between 10 and 20% of the respondents added adjuvant mood stabilizers or antipsychotics, and 3-10% would use an antidepressant.ConclusionClozapine delays occur in spite of clinicians’ familiarity with treatment guidelines. More research is needed to guide the use of augmentation strategies and the search for effective treatments beyond clozapine.

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Antipsychotic treatment strategies for acute phase and treatment resistance in schizophrenia: A systematic review of the guidelines and algorithms

Cited by 22 publications

References 42 publications

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

Clinical Outcomes after Clozapine Discontinuation in Patients with Schizophrenia: A Systematic Review

Managing treatment resistance in schizophrenia: A joint study in Hong Kong and Singapore

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