The role of ethnicity in treatment refractory schizophrenia
Introduction
Schizophrenia is prevalent in about 1% of the general population. This means that more than one million people in North America are diagnosed with schizophrenia.
Within these numbers, there is an estimation of about 20 to 40% of individuals who are resistant to treatment. Even with the introduction of several second-generation antipsychotic medications, the numbers still remain stable [1], [2], [3], [4]. It is generally accepted that within the population at risk, 10 to 60% of patients responds poorly or only partially to treatment [1], [3], [5], [6]. Even with compliance to medications, 20 to 30% of patients will still suffer a relapse in the first or second year of maintenance treatment with antipsychotics [3], [7]. Since these patients remain symptomatic, there is a cumulative increase in the number of patients who are resistant to antipsychotic treatment [8], [9], [10], [11]. This depicts a significant public health problem. Individuals with treatment resistant schizophrenia typically have longer hospitalizations, are low functioning when out in the community and 80 to 90% of them develops some kind of social or occupational dysfunction [12], [13].
There have been multiple debates over the criteria of treatment-resistance. There are operational definitions, the most widely used are those by Kane et al. [7] which are three-dimensional (historical, current, or psychopathological and prospective). The historical definition stating that “at least 3 treatments with antipsychotics of at least 2 different chemical classes with doses equivalent to 1,000 mg/day of chlorpromazine for a period of 6 weeks, without significant improvement and no period of good functioning within the preceding 5 years”. The current/psychopathological criterion is “a score of ≥45 in the BPRS, with scores of ≥4 in 2 of the following items: conceptual disorganization, suspiciousness, hallucinatory behaviour or unusual thought content and CGI ≥4 (moderately ill). Finally, the prospective criteria indicates “no improvement after 6 weeks of treatment with haloperidol (≤60 mg/day), defining improvement as a reduction of at least 20% in the BPRS total score.
Both genetic and environmental factors influence resistance to antipsychotic medications, however the specific interaction between them is unknown. Clinical and social factors related to the efficacy of treatment include compliance, family support, milder psychotic symptoms, better attention at baseline, few obstetric complications, later age of onset, and duration of illness less than nine years [14], [15], [16]. In addition, the lack of early treatment in ethnic minorities, is also a contributing factor to eventual resistance to antipsychotics.
However, a study conducted by Archie et al. on the ethnic diversity and pathways to care in Ontario shows that there was no ethnic differences for duration of untreated psychosis [20]. The fact that Ontario has a public healthcare system seems to explain the lack of biasness towards any group of individuals who seeks help for mental health treatment.
Cantor-Graae and Selten [21] conducted a meta-analysis of incidence rate of schizophrenia, combining 18 studies from different countries. Their findings showed a three times increased risk for schizophrenia in first- and second-generation migrants as compared to non-migrants. The same study showed higher risk in second-generation migrants and in migrants from developing countries and from countries where the majority of the population is black.
Despite the fact that there are publications on the schizophrenia risk in ethnic minorities little is known about resistance to antipsychotics in different ethnicities. The aim of this work is to explore ethnic effect in treatment refractory schizophrenia. The secondary aim is to test whether treatment resistance is associated with clinical variables in our sample.
Section snippets
Methods
In this study, subjects were either referred by staff clinicians or responded to advertisements. Patients over the age of 18 years who satisfied the DSM-IV diagnostic criteria for schizophrenia or schizoaffective disorder (depressive subtype only) were included, while patients with history of major neurological disorders, head injury with significant loss of consciousness, or major substance abuse were excluded from the study.
The sample comprised 497 patients assessed using a structure
Treatment resistance and clinical variables
According to the SCID in our sample (n = 497) there were 19 patients with schizoaffective disorder and 478 with schizophrenia (297 with paranoid subtype).
According to our review 156 were classified as resistant and 337 were classified as non-resistant. Four patients were excluded from the analysis after the consensus conference because the resistant status was unclear.
Duration of illness was significantly longer in the resistant group (21.0 vs 15.1 years; p < 0.001) and when we applied the
Discussion
The primary aim of this study was to explore the role of ethnicity in influencing the treatment resistance in schizophrenia and the main finding was that white European ethnicity is a risk factor for treatment resistant schizophrenia. The cause of this association could be mainly cultural in fact most studies involving access to care have shown significant ethnic differences in relation to social factors which include employment, living situation, family support, or general practitioner
References (34)
- et al.
Psychobiologic correlates of treatment response in schizophrenia
Neuropsychopharmacology
(1996) - et al.
Measuring pathways to care in first-episode psychosis: a systematic review
Schizophr Res
(2006) - et al.
Sex, ethnicity, and antipsychotic medication use in patients with psychosis
Schizophr Res
(2004) - et al.
Changes in weight and body mass index during treatment with melperone, clozapine and typical neuroleptics
Psychiatry Res
(2010) - et al.
Neuropsychological correlates of cognitive insight in schizophrenia
Psychiatry Res
(2010) - et al.
Evaluation of treatment-resistant schizophrenia
Schizophr Bull
(1997) - et al.
Important issues in the drug treatment of schizophrenia
Schizophr Bull
(1980) - et al.
Time course and biologic correlates of treatment response in first-episode schizophrenia
Arch Gen Psychiatry
(1993) - et al.
Mazure CM: Olanzapine for treatment-refractory psychosis in patients responsive to, but intolerant of, clozapine
J Clin Psychopharmacol
(1999) - et al.
Rehospitalization rates of patients with schizophrenia discharged on haloperidol, risperidone or clozapine
Rev Bras Psiquiatr
(2007)
Prediction of outcome in first-episode schizophrenia
J Clin Psychiatry
Clozapine in treatment-resistant schizophrenics
Psychopharmacol Bull
Defining ‘response’ in antipsychotic drug trials: recommendations for the use of scale-derived cutoffs
Neuropsychopharmacology
Early detection and intervention with schizophrenia: rationale
Schizophr Bull
Neuroleptics and the natural course of schizophrenia
Schizophr Bull
Treatment Resistant Schizophrenia
Reduction of suicidality during clozapine treatment of neuroleptic-resistant schizophrenia: impact on risk-benefit assessment
Am J Psychiatry
Cited by (20)
Systematic review of racial disparities in clozapine prescribing
2020, Schizophrenia ResearchCitation Excerpt :There are several other potential factors that were not accounted for in the reviewed studies. These include: higher prevalence of treatment-resistant schizophrenia in European whites (Teo et al., 2013), higher risk of weight gain in Caucasians (Sickert et al., 2009), potential for ethnic variability in pharmacokinetic processes (Johnson, 2000), and higher overall rates of psychiatric service expenditures in white patients (Le Cook et al., 2013). Furthermore, reviewed studies could not differentiate the factors that drive CLZ non-initiation vs. early discontinuation, as most of the studies measured cross-sectional prescription frequencies.
Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives
2019, Neurobiology of DiseaseCitation Excerpt :Systematic reviews have identified only a limited number of papers comparing the clinical characteristics of TRS to non-TRS patients (Gillespie et al., 2017; Seppälä et al., 2016), yet these papers yield important insights. Multiple studies have shown that TRS patients are more often of European descent (Meltzer et al., 1997; Teo et al., 2013) and of the paranoid subtype (Teo et al., 2013; Wimberley et al., 2016). Two studies indicated an earlier age of onset (Meltzer et al., 1997; Wimberley et al., 2016), but a third found that duration of illness may be a confounder (Teo et al., 2013).
The effect of ethnicity and immigration on treatment resistance in schizophrenia
2019, Comprehensive PsychiatryCitation Excerpt :These factors may contribute to differences in the incidence of treatment-resistant schizophrenia among ethnicities. For example, a study on risk for treatment-resistant schizophrenia conducted by Teo et al. [12] found that White European ethnicity confers risk for treatment resistance schizophrenia. Teo et al. [12] suggested that this risk is not genetic because family history was not associated with treatment resistance.
Increased prevalence of Toxoplasma gondii seropositivity in patients with treatment-resistant schizophrenia
2018, Schizophrenia ResearchAssessing patient-rated vs. clinician-rated adherence to the therapy in treatment resistant schizophrenia, schizophrenia responders, and non-schizophrenia patients
2017, Psychiatry ResearchCitation Excerpt :Patients already under clozapine, or that were switched to clozapine in our unit, were automatically included in the TRS diagnosis. Several non-pharmacological factors may affect response to antipsychotics (Hassan and De Luca, 2015; Teo et al., 2013). Indeed, possible causes of pseudo-resistance were investigated (Iasevoli et al., 2016) and removed, were possible.
Geographic variation in efficacy of atypical antipsychotics for the acute treatment of schizophrenia - An individual patient data meta-analysis
2014, European NeuropsychopharmacologyCitation Excerpt :However, only limited evidence is available on the potentially modifying effect of geographic factors on the efficacy of pharmacological compounds in schizophrenia. For example, studies investigating the influence of race–ethnicity on the effect of antipsychotics in the treatment of patients with schizophrenia suggest that such differences may exist due to differences in metabolism (Bersani et al., 2011; Bigos et al., 2011), differences in side effects (Stauffer et al., 2010), differences in compliance/drop-out, or other race–ethnicity related factors, ultimately resulting in differences in overall treatment response (Teo et al., 2013). However, other studies found no effect of race–ethnicity on treatment response to antipsychotics in patients with schizophrenia (Ciliberto et al., 2005; Stauffer et al., 2010).