Medications for treatment-resistant schizophrenia

What is treatment resistance? 

Antipsychotic medications provide symptom respite and improvement in quality of life for many people with schizophrenia. However, for a subset of people with schizophrenia, antipsychotic medications do not provide adequate relief from symptoms. Treatment-resistant schizophrenia has many definitions that vary depending on the individual study, but a broad definition includes those patients whose symptoms have not responded to antipsychotic medications, or only partially responded.

What is the evidence for treatment resistance?

Moderate to high quality evidence finds a general pattern of superiority of clozapine, olanzapine or risperidone over other antipsychotics for improving symptoms in people with treatment-resistant schizophrenia.

For people with inadequate response to clozapine, moderate to high quality evidence finds augmenting clozapine with other second-generation antipsychotics may improve negative and depressive symptoms, but not necessarily positive symptoms. Adjunctive sulpiride and adjunctive ziprasidone were particularly effective for negative symptoms, and adjunctive aripiprazole and adjunctive ziprasidone were particularly effective for depressive symptoms. Moderate to low quality evidence finds improved total symptoms with clozapine augmentation of antidepressants fluoxetine, paroxetine and duloxetine. Adding mood stabilisers topiramate, sodium valproate or lithium to clozapine may also improve total symptoms, while adding memantine, a glutamatergic agent, may improve negative symptoms. Adding electroconvulsive therapy may also improve treatment response.

High quality evidence finds better clozapine response in younger people and in people diagnosed with paranoid schizophrenia. Moderate to low quality evidence suggests patients with lower Positive And Negative Syndrome Scale negative subscale scores at baseline also have a better response to clozapine. There were no relationships between response to clozapine and gender, smoking, weight, years of education, marital status, age at onset, age at first hospitalisation, number of hospitalisations, duration of illness, length of stay during hospitalisations, baseline total scores on the Brief Psychiatric Rating Scale, the Clinical Global Impression scale, and the Positive And Negative Syndrome Scale, or on the Positive And Negative Syndrome Scale baseline positive subscale scores.

October 2020

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Last updated at: 2:20 am, 31st August 2021
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