Approaches to Schizophrenia Through Phases of the Illness

S. Charles Schulz, MD, Kristin Cadenhead, MD, John M. Kane, MD, Peter Weiden, MD,

As the chairperson for this presentation, Dr. Schulz explained the overall goals: “1) Be aware of the different approaches fordifferent phases of schizophrenia; and 2) be able to adjusttheir interventions to meet the patient’s individual needs.”

Although schizophrenia “is known to be a common (1% prevalence)and significantly debilitating illness as measured byfunctional disability and mortality,” began Schulz, “many articles andbooks are published about the illness that focus onthe disease as monolithic entity rather than describingapproaches to different phases of the illness. As researchhas progressed on schizophrenia, unique characteristics ofthe prodrome, first-episode, mid-life illness, and issues ofthe older, poorly responsive patient have been uncovered.”

Thus, Drs. Schulz, Cadenhead, Kane, and Weiden felt it necessary to focus attention on the various stages of schizophrenia so that attendees can understand how to refine their approaches. Cadenhead took the floor first with “Early Identification of the Psychosis Prodrome and Clinical Practice.”

“Early identification of individuals at clinical high risk and potentially in the prodromal phase of a psychotic illness can lead to earlier treatment and perhaps prevention of many of the devastating effects of a first psychotic episode,” began Cadenhead. “International research efforts have demonstrated the success of community outreach and education regarding the schizophrenia prodrome, and it is now possible to use empirically defined criteria to identify individuals at a substantially increased risk for a psychotic illness.”

The speaker moved on to discuss the Structured Interview for Prodromal Syndromes (SIPS), not that the “clinical high-risk sample meets criteria for 1 of 3

prodromal syndromes defined by SIPS based on subsyndromal psychotic symptoms and/or a family history of psychosis and deterioration in functioning.” Although those who meet SIPS criteria are clinically heterogeneous, they typically seek help and receive a range of treatments before entering into prodromal research programs, she explained. And although less that 40% of people who meet SIPS criteria will likely become psychotic, those with “a family history of psychosis, more severe ratings on delusional-like symptoms, social functioning deficits, or substance abuse are even more likely to develop schizophrenia or an affective disorder.”

Cadenhead next explained that given “the many potential clinical presentations, treatments, and ethical issues connected with the clinical high-risk syndrome, it is not surprising that clinicians administer a broad range of interventions.” And although preliminary “treatment studies have demonstrated initial success in reducing the severity of symptoms and improving functional outcome in clinical high-risk samples…, these studies are underpowered,” and large scale trials of psychological and pharmacologic interventions are thus needed for informing better treatment decisions. Further, translational “studies are needed to better understand the neuropathological changes in the early stages of psychosis and to assess neuroprotective strategies that might be beneficial in the prodormal period.”

The presenter concluded that the best recommendations for clinicians now “is to treat

the clinical high-risk state using a needs based approach, recognizing that the prodromal syndrome may be transient or evolve into a more serious condition with a range of diagnostic and functional outcomes.

Next on the mike was Kane, who presented “Management of First Episode Schizophrenia.” He began, noting that many challenges are posed in the early phase of the disease, with both patients and families needing “enormous support and psychoeducation,” engagement and retention in treatment critical, and appropriate medication management an important element in successful treatment. Further, first-episode “patients are particularly vulnerable to adverse effects, and in the presence of considerable ambivalence toward medication-taking, success in preventing or managing such side effects is critical,” Kane noted. Thus, to ensure patient acceptance, shared decision making is important. Additionally, the “careful and consistent integration of psychopharmacologic and psychosocial treatment modalities is essential in facilitating optimum outcome and, ideally, recovery.”

Following Kane was the presentation of “Approaches to Schizophrenia” by Weiden, who began by noting that if “there were an easy answer to the problem of medication adherence in schizophrenia, we would have found it by now.” The problem is that before adherence problems can be addressed, they must be understood, and no one definition of adherence or non-adherence is satisfactory, according to Kane. Also, “there is no one single intervention approach or model that will work all the time for all patients,” partly because non-adherence is just one of many reasons behind poor outcomes.

Thus, clinicians “need to be careful not to automatically attribute unsatisfactory outcome to poor adherence without other confirmatory evidence,” explained the presenter. “The tendency for clinicians to misattribute the inadequate efficacy problems to adherence problems can mean a lost opportunity to find a more effective pharmacological treatment regimen.”

Compounding the issue is that medication adherence can be viewed as a behavior or an attitude; although they are sometimes related, they must be evaluated differently, says Kane. “When it comes to whether or not patients take their medication, there is behavior (is the medication taken?), and there is attitude (what does the patient think of the

medication?),” explained the speaker. “While attitude and behavior can be aligned (patient wants to take medication and is actually taking medication), there can be a misalignment as well (patient does not want to take medication but is taking it despite unfavorable attitude) and the reverse (patient wants to take medication but does not).”

Kane next dove into the topic of the role of long-acting antipsychotic medications for improving long-term outcomes in patients with schizophrenia. “The simple notion that

long-acting antipsychotics are only useful in patients who are currently non-adherent is outdated, and needs to be replaced with a more sophisticated understanding of how to match route of medication with the patient’s specific adherence and medication response profile,” he explained.

The use of alternate psychoeducation approaches and development of a working therapeutic alliance are critical aspects of successful long-term schizophrenia treatment, Kane concluded.

Schulz returned to the podium to close out the session with a presentation of “Evaluation and Intervention for the Persistently Ill Schizophrenic Person.” He noted that treatment “at various stages of schizophrenia can lead to significant reduction in symptoms, and new social skills treatment and cognitive approaches are enhancing outcomes.”

The problem lies in the emerging understanding that it appears some patients become less responsive to treatment as they age. He explained that an initial step in approaching people who are persistently ill with schizophrenia is to evaluate lack of response by looking at such things as family and/or living situations, medical causes, pharmacokinetics, and everything in between. When doing so, standardized rating scales can be helpful in evaluating illness severity and providing a baseline for measuring progress against.

Schulz also noted that while many “studies have examined augmentation strategies to antipsychotic medication utilizing agents such as lithium, anticonvulsants,

or benzodiazepines,” showing that they are generally safe, more recent data is less encouraging than when first reported.”

The presenters directed attendees to “Treatment-resistant Schizophrenia,” in the 2003 publication Schizophrenia for additional information.