Areas for Further Research in Individuals With Schizophrenia

Improve the generalizability of study populations

Enhance study recruitment approaches and use a priori specification of subgroup analyses to obtain data on treatment effects in inpatients, minority groups, women, older individuals, individuals with multiple psychiatric or physical health conditions, and individuals with severe and/or treatment-resistant illness

Assure that sample sizes are adequate to achieve statistical power

Assure that studies report data in a consistent fashion and prespecify outcomes of interest

Assure that studies identify the magnitude of change in scale scores that constitutes a clinically meaningful difference

Increase collection of data on patient-centered outcomes (e.g., quality of life, social functioning, physical health, recovery)

Improve systematic collection of information on harms, including in studies of psychosocial interventions

Identify approaches (e.g., pharmacogenomics, biomarkers, symptom clusters, and other predictive variables) for optimizing treatment selection

Determine efficient, valid, and reliable approaches to quantitative measurement of positive symptoms, negative symptoms, functioning, quality of life, and treatment-related side effects

Determine ways in which demographic or sociocultural factors influence treatment outcomes

Determine the durability of treatment effects and potential for long-term harms through long-term studies (e.g., at least 1 year of treatment with follow-up assessments at 3–5 years)

Determine the benefits, harms, and appropriate use of treatments in individuals with co-occurring disorders (e.g., stimulants in co-occurring ADHD; benzodiazepines with co-occurring anxiety; smoking cessation interventions, including medication and nonmedication approaches with co-occurring nicotine dependence)

Identify methods that will allow information from mobile technologies, wearable technology, and large-scale data analytics to inform assessment, treatment, and future research

Determine optimal monitoring frequencies and approaches to detect treatment-related benefits and side effects

Identify optimal approaches to improving physical health in individuals with schizophrenia

Identify optimal approaches to treatment of co-occurring substance use disorders in individuals with schizophrenia

Identify approaches to redesigning workflows and models of care delivery to improve the use of best practices in the treatment of schizophrenia

Identify approaches to determining the optimal setting of care (e.g., inpatient, partial hospital, intensive outpatient, psychosocial rehabilitation, Clubhouse models)

Identify optimal approaches to integrate recovery-based and peer-based programs into other models of care delivery

Identify optimal approaches to care coordination and case management, including intensive case management

Determine the comparative effectiveness of newer SGAs (including LAI formulations) versus comparable doses of other SGAs and some FGAs

Determine the comparative harms of antipsychotic medications, including long-term harms and rare but serious harms

Determine optimal antipsychotic treatment approaches for individuals with suicidal or aggressive behaviors, including additional studies of clozapine for aggressive behavior

Identify risks and benefits of using other medications (e.g., lithium, anticonvulsants, antidepressants, stimulants, benzodiazepines, other sedative-hypnotics) in combination with antipsychotic medications to address specific target symptoms or treatment nonresponse

Identify risks and benefits of concomitant use of more than one antipsychotic medication

Identify risks and benefits of strategies to minimize or treat side effects of antipsychotic medications, including use of concomitant medications, reductions in antipsychotic dose, or changing to a different antipsychotic medication

Determine optimal approaches to making medication changes (i.e., switching from one antipsychotic to another) to minimize risk of relapse and reduce potential for treatment-related side effects

Identify optimal clinical approaches for determining when a treatment trial is adequate and when treatment resistance is present

Determine relationships between blood levels of antipsychotic medications (including active metabolites) and therapeutic response that can be used to guide dose titration and determination of treatment adequacy

Identify whether there are subgroups of patients for whom medication discontinuation may be possible

Determine whether intermittent treatment or early relapse is associated with increased long-term harms (e.g., greater treatment resistance, neurobiological changes)

Determine optimal approaches to prevention and treatment of specific side effects of antipsychotic medications, including neurological side effects, weight gain, diabetes, metabolic syndrome, and cardiovascular disease

Determine the optimal duration of treatments for neurological side effects (e.g., VMAT2 inhibitors for tardive dyskinesia, anticholinergic agents for parkinsonism)

Determine the efficacy and comparative effectiveness of neurostimulation approaches (e.g., ECT, TMS) in conjunction with other treatments for schizophrenia

Assure that psychosocial interventions are clearly defined and described and that measurements of fidelity to the intervention model are incorporated into the study design

Conduct research on optimizing long-term outcomes with psychosocial interventions (e.g., use of booster treatment sessions or continued treatment at a lower frequency for maintenance of therapeutic benefits in those with a good initial response)

Develop approaches to reduce the heterogeneity in usual care groups, which makes it difficult to interpret and compare studies of psychosocial interventions that use usual care as a control comparison

Assure that studies of psychosocial interventions determine the intensity, frequency, and duration of treatment that is needed to optimize outcomes

Develop methods to study psychosocial interventions to identify key contributors to benefit (e.g., clinician experience, treatment fidelity, use of shared decision-making, clinician-patient alliance, family engagement, setting of care)

Investigate the benefits and harms of other psychosocial interventions (e.g., mindfulness, acceptance and commitment therapy, metacognitive reflection and insight therapy, Open Dialogue, exercise, music and dance therapies)

Determine benefits, harms, and optimal approaches for implementation of peer-based services, recovery-oriented programs, and self-management strategies

Determine the components of multicomponent interventions (e.g., CSC) that are crucial to positive outcomes

Determine the effectiveness and sustainability of CSC with longer-term program participation

Determine the elements of supported employment programs that are most likely to foster long-term competitive employment