Navigating to a Broader Population of First-Episode Patients

Psychiatric TimesVol 39, Issue 6

What are the benefits of early and comprehensive intervention for patients in their first episode of a serious mental illness?




One of the core and troubling lessons that I learned during my psychiatric residency in the late 1980s continues to haunt me. For patients with serious mental illnesses (SMI), the greater the duration of time before a patient is diagnosed and enters treatment, the longer a symptomatic episode lasts, the more episodes the patient has, the less adherent the patient is with treatment, the more psychosocial stressors the patient is challenged by, the greater the presence of comorbid substance abuse, and the more disconnected the patient becomes from mainstream society, the worse the patient’s long-term prognosis will be. Intuitively, this is simply common sense.


The human brain’s complex neurocircuitry develops beginning at conception and continues until well into the third decade of life. After this, with the basic neuronal circuits established, neuroplasticity is active until we breathe our final breath. A detailed exploration of neuroplasticity is a complex topic for another time. However, 2 foundational concepts of neuroplasticity are conveyed by 2 commonly used phrases: “Neurons that fire together wire together” and “Use it or lose it.”

Simply put, the more time that is spent reinforcing healthy behaviors and providing a plethora of positive psychosocial supports, the greater the likelihood is that the individual will maximize their recovery, functioning, and quality of life during times of acute stress/distress.

Therefore, it is not at all surprising that a staggering number of factors determine an individual’s risk for developing an SMI, and these will determine the likely life trajectory once an individual’s first episode begins. Similarly, providing a comprehensive treatment intervention early in the first episode of an individual’s SMI could profoundly impact that trajectory in a positive manner.

The RAISE Study

Identifying and treating individuals suffering from a first episode of psychosis (FEP) in the United States remains a daunting task on many fronts. In 2007, acknowledging the huge unmet need—and drawing upon the collective established experience from the United Kingdom, Canada, Australia, and Scandinavia, which had well-established, team-based, multimodal treatment programs for FEP—the National Institute of Mental Health initiated the Recovery After an Initial Schizophrenia Episode (RAISE) study. Not coincidentally, the established programs in these other countries all provide socialized medicine that allows ready access to a broad range of treatments, many of which are not reimbursed by our US current health care system.1

The RAISE study recruited patients with nonaffective FEP between the ages of 15 and 40 years who had been treated throughout their lives with a total of less than 6 months of antipsychotic medications. All treatment was provided over a 2-year period at US community mental health centers; the primary outcome was the Heinrichs-Carpenter Quality of Life Scale total score. A total of 34 clinics nationwide participated: 17 provided only the NAVIGATE treatment (Table 1) and 17 provided each clinic’s “treatment as usual.”

Table 1. NAVIGATE Interventions

Table 1. NAVIGATE Interventions

The study enrolled 223 patients into the highly structured NAVIGATE arm and 181 patients into treatment as usual. Patients in the NAVIGATE arm whose duration of untreated psychosis (DUP) was less than 74 weeks improved more than those whose DUP was 74 weeks or longer and those who were in the “treatment as usual” group.2,3

RAISE was a pilot study to assess the benefits of a comprehensive, albeit rigid and highly structured/manualized, program for patients with FEP as compared with treatment as usual in 34 community mental health centers in the United States. Enrollment occurred between July 2009 and July 2011; the treatment protocols for the NAVIGATE intervention were established prior to 2009.

A spinoff of the RAISE/NAVIGATE study is a consulting group that is considered the gold standard resource for clinics around the country to work with while establishing their own FEP programs. This group’s model and accompanying treatment manuals are based on the original pilot intervention for the RAISE study.

Unfortunately, this model promotes antipsychotic medications that were available as of 2009, which excludes the 6 newer atypical antipsychotics approved by the US Food and Drug Administration (FDA) since then. Although the ultimate medication choice is at the prescriber’s discretion, the model excludes these 6 newer medications and creates a bias against them. This is unfortunate, as all atypical antipsychotics have their unique risks and benefits and different propensities for adverse events. Because treatment nonadherence is so common in early pharmacological management, it would be beneficial to have updated medication options listed in the consulting group’s “The Quick Guide to NAVIGATE Psychopharmacological Treatment.”4 However, to their credit, the group has added some long-acting injectable formulations of the original medications to their list.

For the RAISE study, a prospective patient required a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder not otherwise specified. The NAVIGATE intervention is geared toward patients with a primary psychotic disorder, which greatly limits its applicability to a large percentage of patients with SMI presenting for psychiatric treatment in their first episode. Similarly, the modules taught by the consulting group in each of the different treatment team member manuals are designed to target patients with a schizophrenia spectrum disorder.

The biggest unanswerable question about the RAISE study is: Which component of the treatment interventions contributed most to the positive outcome as compared with treatment as usual? From an evidence-based perspective, each of the components (Table 1) is known to improve outcomes. Keeping this unanswerable question in mind, do novel FEP treatment programs really need to be modeled exactly after the RAISE pilot study protocol? And to take it a step further, why not establish a first episode program that is flexible to address the different needs across a range of SMIs?

Validation of Early and Aggressive Intervention

A significant literature has evolved to demonstrate that minimizing a patient’s time spent with active symptoms will improve their long-term disease progression, quality of life, and overall lifetime functioning. In the RAISE study, the DUP of patients who received the NAVIGATE treatment intervention clearly demonstrated that earlier intervention in a FEP results in significantly better outcomes than those of patients whose FEP symptoms were more chronic. Table 2 documents the dramatic differences in improvement in participants whose DUP was greater than versus less than 74 weeks.

Table 2. Outcomes in Patients Treated With NAVIGATE Over 24 Months Based on DUP

Table 2. Outcomes in Patients Treated With NAVIGATE Over 24 Months Based on DUP

Although limited by patients with diagnoses in the schizophrenia spectrum, it is reasonable to extrapolate this phenomenon to individuals with all SMIs.

This finding further supports the benefits of early diagnosis, a comprehensive treatment plan that addresses all aspects of the individual’s life, development of a collaborative treatment alliance, and retention in treatment. Ideally, in a first episode of any SMI, treatment would begin within 4 weeks following symptom onset. The finding in the RAISE study that the median DUP in the United States was 74 weeks is quite concerning, identifying a major potentially modifiable failure of our current medical system. As previously stated, the longer the brain dwells in dysfunctional circuitry associated with SMIs, the harder that SMI is to treat and the poorer the long-term prognosis is for improved function and degree of recovery.

Concluding Thoughts

The results of the RAISE/NAVIGATE study reinforced the benefits of early access for patients in FEP to a comprehensive and coordinated specialty team, as has been demonstrated in other countries. A dramatic and significant finding was the demonstration of a greater benefit and improved long-term outcome with enrollment in the program earlier in the FEP. This study, although limited to patients with schizophrenia-spectrum disorders, most likely extrapolates to benefits of early and comprehensive intervention for any patient in a first episode of an SMI.

In urban areas, where there is likely to be a large population of patients in FEP with a schizophrenia- spectrum diagnosis, the current NAVIGATE model will likely have access to many patients whose needs will be well met by it. The NAVIGATE consulting group should seriously consider updating the training manuals as our treatments expand and become more refined.

In more rural areas, in my opinion, a modified treatment intervention that draws upon the basic tenets of NAVIGATE but broadens the treatment interventions to target the specific needs of any individual in their first episode of an SMI would be welcome and likely significantly more cost effective. Expanding the pharmacological options to target patients presenting with their first episode of psychosis or mania or depression, and possibly of complex posttraumatic stress disorder (PTSD) or a crippling anxiety disorder, would not be difficult for any competent psychiatric prescriber. The various treatment team-specific manuals could contain a menu of modules depending on the patient’s primary diagnosis. The 6 core components of NAVIGATE listed in Table 1 would remain the same.

With our current limited financial and clinician resources, a broader model that expands enrollment for a range of individuals presenting with a first episode of an SMI—the earlier, the better—would provide comprehensive treatment to a vulnerable population. This short-term investment in resources would likely pay for itself many times over in improved functional outcome, quality of life, and contributions to society.

Dr Miller is medical director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric TimesTM; staff psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; consulting psychiatrist, Insight Meditation Society, Barre, Massachusetts.


1. Heinssen RK, Goldstein AB, Azrin ST. Evidence-based treatments for first episode psychosis: components of coordinated specialty care. National Institute of Mental Health. April 14, 2014. Accessed May 11, 2022.

2. Kane JM, Schooler NR, Marcy P, et al. The RAISE Early Treatment Program for first-episode psychosis: background, rationale, and study designJ Clin Psychiatry. 2015;76(3):240-246.

3. Kane JM, Robinson DG, Schooler NR, et al. Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE Early Treatment ProgramAm J Psychiatry. 2016;173(4):362-372.

4. Robinson D. Quick guide to NAVIGATE psychopharmacological treatment. NAVIGATE Consultants. April 2020. Accessed May 11, 2022.

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