Clinicians treating patients with first-episode (FE) schizophrenia can draw upon the vast literature on the treatment of patients with multiple-episode schizophrenia. Studies with multi-episode patients, however, may not fully generalize to the treatment of FE patients. Studies with multi-episode patients typically recruit from hospitals or other acute care units, settings where patients usually have been either non-responsive or non-adherent to previous treatment, or mixtures of both. Studies of multi-episode patients therefore tend to include patients who are not fully responsive to treatment. Without the filter of prior treatment history, FE compared with multi-episode patients may show a broader range of treatment patterns, ranging from extremely good to very poor. Further, studies of FE patients may be very instructive about side effects, as the confounding effect of prior medication use is particularly important with side effects. Finally, data suggest that much of the deterioration (eg, more severe negative symptoms) associated with schizophrenia may occur during the 5 years following illness onset. Providing patients with better treatment at illness onset offers the hope of improving their long-term outcome.

FE studies do have limitations. Relatively few new cases of schizophrenia occur each year. The typically chronic course of schizophrenia results in a large number of patients with multi-episode schizophrenia for every FE patient at any one time. Recruitment for studies of FE schizophrenia compared with those of multi-episode schizophrenia is often more difficult given the smaller number of available patients. We systematically know less about the treatment of FE patients than we do about the treatment of multi-episode patients.

Pharmacologic knowledge can inform clinical decision-making, particularly the dosing and switching decisions made with antipsychotics. Of relevance are the pharmacokinetic (what does the body do to the drug) and the pharmacodynamic (what does the drug do to the body) properties of antipsychotics.

The goal of antipsychotic dosing is to achieve sufficient dopa-mine blockade in areas where dopamine excess can lead to psychosis, mania, or aggression. Using positron emission topography, one investigation showed that response rates were considerably higher in patients who achieved >65% striatal dopamine blockade. Conversely, striatal dopamine blockade >80% predicted the emergence of extrapyramidal symptoms (EPS) or akathisia.

There is, however, considerable intra-individual variability in achieving the desired 60% to 80% striatal dopamine blockade. Such variability is likely due to inter-individual differences in the absorption, distribution, metabolism and elimination of medications. At the same time, antipsychotics themselves differ in their general pharmacokinetic profiles. For example, ziprasidone absorption is ~50% less when ingested on an empty stomach than when taken with a meal; the degree of absorption depends on the caloric content, while the fat content is not relevant.

A key consideration in the discussion of maintenance treatment in schizophrenia is how to first help bring patients to the point where acute psychopathology is sufficiently controlled, so that we can focus on consolidating the gains achieved and prevent a recurrence of illness.

The different phases of treatment and response in schizophrenia include the acute phase, wherein we look for response and resolution; remission, where we control symptoms to levels of mild or less and work toward preventing relapse or any exacerbation of psychopathology; and recovery, meaning the ability to function in the community in the workplace, school, family roles, etc.

In preparing patients with schizophrenia for maintenance treatment, clinicians must ensure that they have done everything possible to alleviate the acute signs and symptoms of illness to the extent possible.

There are several questions to consider at this stage: How much improvement is enough? When do we change treatments, and why? What about adverse effects and the locus of care? In the context of this process of deciding how to bring about the best possible treatment response, we must consider that, if a patient is not responding, the diagnosis may need to be reevaluated. Adherence must be assessed and blood levels should be done (if feasible) to ensure that patients have an adequate amount of medication in their system. If blood levels are unavailable and adherence is an issue, the use of long-acting injectable medication should be considered. The clinician might decide to alterthe medication dose—to increase it, or perhaps decrease it if significant side effects are impeding therapeutic response. Adjunct medications or a switching strategy may be employed. Non-pharmacologic therapy, such as cognitive behavioral therapy, which can be effective at reducing symptoms of schizophrenia, should also be considered.