Individualizing antipsychotic treatment selection in schizophrenia: characteristics of empirically derived patient subgroups

Abstract

Treatment of schizophrenia with antipsychotic drugs is frequently sub-optimal. One reason for this may be heterogeneity between patients with schizophrenia. The objectives of this study were to identify patient, disease and treatment attributes that are important for physicians in choosing an antipsychotic drug, and to identify empirically subgroups of patients who may respond differentially to antipsychotic drugs. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients with schizophrenia. Information on 39 variables was collected. Multiple component analysis was used to identify dimensions that explained the variance between patients. Three axes, accounting for 99% of the variance, were associated with disease severity (64%), socioeconomic status (27%) and patient autonomy (8%). These dimensions discriminated between six discrete patient subgroups, identified using ascending hierarchical classification analysis. The six subgroups differed regarding educational level, illness severity, autonomy, symptom presentation, addictive behaviors, comorbidities and cardiometabolic risk factors. Subgroup 1 patients had moderately severe physician-rated disease and addictive behaviours (23.2%); Subgroup 2 patients were well-integrated and autonomous with mild to moderate disease (6.7%); Subgroup 3 patients were less well-integrated with mild to moderate disease, living alone (11.2%); Subgroup 4 patients were women with low education levels (5.4%), Subgroup 5 patients were young men with severe disease (36.8%); and Subgroup 6 patients were poorly-integrated with moderately severe disease, needing caregiver support (16.7%). The presence of these subgroups, which require confirmation and extension regarding potentially identifiable biological markers, may help individualizing treatment in patients with schizophrenia.

Long-acting antipsychotic drugs for the treatment of schizophrenia: use in daily practice from naturalistic observations

“…About 57% of outpatients treated with oral SGAs adhere to the therapy after 6 months [16]. The efficacy and safety of LAIs have been well established through several randomized controlled trials and therapy choice criteria for these patients have been published recently [17], categorized by disease severity, patients’ socioeconomic level, and patients’ autonomy.…”

How to Interpret Findings Concerning Newly Approved Antipsychotic Agents

“…The development of new antipsychotics with proven efficacy and improved safety profiles represents progress, but further developments are needed to achieve enhanced outcomes for patients with schizophrenia� For example, a "safer clozapine" is needed that will be effective when first-and second-line dopamine blockers are ineffective� 7 Response predictors and biomarkers also need to be developed in order to provide more individualized treatment by predicting which patients might benefit most from which medications, helping to refine treatment selection� 43…”

“…Although it is hoped that research in areas such as genomics, metabolomics, imaging, and genetics will provide clinicians with more accurate tools for medication selection, 7,43 clinicians currently need to base treatment decisions on available data� Dr Correll noted that, in selecting the most appropriate medication for a specific patient, clinicians draw on 4 main sources of information ( Table 2)� 44 While one goal of personalized medicine is the development of biomarkers to predict response or AEs, as of 2012 these do not reliably exist for antipsychotics� As clinicians strive to integrate newer agents into their practice, the items listed in Table 2 are the critical elements in determining the most appropriate antipsychotic for a particular patient at a particular moment in the course of treatment� The weighting of the different items in the decisionmaking process will depend greatly on the stage of illness, prior medication experience and response, psychosocial factors, and patient preference� 45 Younger patients early in their course of treatment will be more sensitive to EPS and weight gain, 46,47 while more chronic patients may be more concerned about symptomatic relief and be willing to tolerate a certain level of side effect burden� The panel recommended using lower risk agents first, to achieve response with safer agents in as many patients as possible, before moving on to higher risk agents� This paradigm is important because the goal is not simply to achieve acute treatment response, but to maintain that response on a long-term basis with agents that patients can tolerate and that do not significantly increase cardiovascular risk� 28,48 Many of these will be individualized decisions, but one important concept that applies to most patients has been gleaned from trials in patients with chronic schizophrenia: early nonresponse after 2 weeks of treatment predicts high likelihood of inadequate response by week 6� 31,[49][50][51] The implication is that minimal response after 2 weeks necessitates a rethinking of strategy� The issue may be one of nonadherence, substance use, inadequate dosing, stressors, or the medication itself, but the clinician needs to decide at this stage the next step, and not assume that time alone will solve the problem� Note that this finding does not apply to patients with a first episode of illness, among whom time to initial response varies widely� 52,53 Thus, for first-episode patients, a trial of at least 6-8 weeks with gradually increasing dose is generally recommended; target doses for first-episode patients generally turn out to be lower than for patients with more chronic illness� 54 The availability of new atypical antipsychotics such as lurasidone presents options for clinicians who want agents with limited potential for metabo...…”

Early Nonresponse Determined by the Clinical Global Impressions Scale Predicts Poorer Outcomes in Youth with Schizophrenia Spectrum Disorders Naturalistically Treated with Second-Generation Antipsychotics

“…T he time course of response to antipsychotic (AP) medications in schizophrenia spectrum disorders has attracted considerable interest (Agid et al 2003;Correll et al 2003;Leucht et al 2007;Kinon et al 2008;Leucht et al 2008;Kinon et al 2010). This is in part because no reliable response predictors/biomarkers exist that can guide clinicians as to when to give up on a medication trial and initiate another one (Kane et al 2003;Kane and Correll 2010;Correll et al 2011a). In this context, a clinical marker of AP response/nonresponse has gained significant traction.…”