Raising the standard of care for schizophrenia is an achievable goal

Catts and O’Toole’s (2016) review article presents a proposal for a ‘re-engineered’ algorithm for the treatment of first-episode schizophrenia. We agree with many of their recommendations including that a careful diagnostic assessment is the critical first step to formulating any treatment plan, while recognizing that psychiatric diagnoses may not be completely stable. If information accrues that means the diagnosis should change, then the treatment plan can be adjusted accordingly without having missed a critical opportunity for disease-modifying early intervention. We also agree that treatment with an antipsychotic drug should be promptly initiated to limit the duration of untreated psychosis to facilitate a faster response and better outcome (Perkins et al., 2005). Continuation of treatment clearly reduces relapse rates for 2 years or longer (Leucht et al., 2012).

Before starting treatment, we recommend a discussion based on the principles of shared decision making to help ensure that each patient understands the available options and is given opportunity to explore preferences before making a choice. We support the use of the lowest effective dosage of antipsychotics, no matter which drug is selected. Unfortunately, this must be determined empirically on an individual basis. Regarding drug selection, because of high antipsychotic response rates among individuals experiencing a first episode of psychosis, the selection of drug should minimize side effects that are bothersome to specific individuals. Clozapine is not a good first choice as someone’s first antipsychotic medication because of its association with weight gain and agranulocytosis; olanzapine is not a good first option because of weight gain (Buchanan et al., 2010).

Because people experiencing a first episode of psychosis are highly likely to stop taking medications, it is important to monitor treatment adherence from the outset. Unit-of-use packaging and pill counts may be helpful, along with information from family members and others, such as pharmacists, who can provide relevant information. A random blood level can determine if a patient is taking a medication and may be useful in other situations. However, because the benefit of obtaining routine blood levels of antipsychotic medications for adherence monitoring has not been firmly established, a controlled study examining this relatively costly and intrusive procedure is needed before this is widely recommended.

Catts and O’Toole make many fine recommendations for psychosocial treatments. An ‘integrated specialist multidisciplinary, multicomponent treatment program’ for first-episode psychosis, known in the United States as Collaborative Specialty Care (CSC), is now considered evidence-based and should be the standard of care. We also believe that family and patient psychoeducation are important components of treatment for schizophrenia, and that motivational interviewing can be useful in helping reluctant patients to recognize that antipsychotic medications might have an important role in helping them to achieve personal goals.

Medication recommendations when the initial treatment options do not help adequately are challenging because there is little guidance from rigorous research. However, as Catts and O’Toole suggest, there is an important potential role for clozapine and for long-acting injectable antipsychotics (LAIAs) in the early months of treatment if patients are unresponsive to treatment or non-adherent. In routine clinical situations, it is often unclear which of these special treatments is most appropriate. After careful diagnostic review and attempts to optimize antipsychotic choice and dose, LAIAs are a reasonable treatment recommendation for anyone who does not consistently take prescribed antipsychotic medication. Recent research has shown the potential benefit of long-acting injectable medication for first-episode patients. We agree with Catts and O’Toole’s recommendation to use clozapine when ‘impaired insight or residual disability are indicative of treatment resistance’ and generally support clozapine’s use sooner rather than later. While some recommend LAIAs before clozapine to rule out ‘pseudo-resistance’, this may unnecessarily delay clozapine initiation. Careful adherence monitoring as suggested by Catts and O’Toole and elsewhere may be the best way to identify non-adherence that warrants LAIA use as well as treatment resistance that requires a clozapine trial (Howes et al., 2016). For individuals who are partially adherent and sub-optimally functioning, we advocate considering clozapine because its superior efficacy may lead to better outcomes and better adherence for people who respond only incompletely to standard antipsychotics in any formulation. Empirical evidence is needed to guide the choice between clozapine and LAIAs in this common situation.

Catts and O’Toole suggest parenthetically that when clozapine is used in the situation of impaired insight and poor adherence that it should ideally be combined with a LAIA. While this recommendation is appealing and defensible, it is without supporting evidence. We agree with long-standing recommendations against using combinations of antipsychotics to avoid unnecessary medication interactions and potentially worsened adverse effects.

The combination of comprehensive, person-centered psychosocial treatments and optimal pharmacotherapy can indeed raise the standard of care for individuals with schizophrenia. This is true with currently available treatments but does not obviate the need for strenuous efforts to identify new treatments and new services. A high standard of clinical care is currently possible. Continued innovation and research holds the hope for ever higher standards and rates of recovery.