Reframing Approaches to Schizophrenia

Psychiatric TimesVol 41, Issue 7

The history of new treatments coming to schizophrenia should serve as a warning...



I began my career when the major treatments for schizophrenia were haloperidol and chlorpromazine. Since then, treatments for schizophrenia have improved slowly and incrementally, especially when looking back in the rearview mirror of what treatment used to be like. Although these improvements are appreciated by senior clinicians who have been around long enough to see these changes, most patients do not know (or care) about what happened way back when and are more concerned with limitations of currently available treatments. However,
the slow pace of improvement may soon change.

At the time of this writing, the US Food and Drug Administration (FDA) is reviewing a new treatment approach of a nondopaminergic muscarinic agonist that, if approved as soon as late 2024, could be the beginning of a period of disruptive changes in how schizophrenia is treated.1 However, the history of new treatments coming to schizophrenia should also serve as a warning. The underuse of clozapine followed by the underuse of newer long-acting injectables (LAIs) is a reminder that treatment advances can be undone by indifference, inadequate training and leadership, and lack of accountability that have plagued the treatment of individuals with serious mental illness. These kinds of service delivery problems make it much harder to unlock the potential benefits of better treatments. Therefore, this article will take a closer look at basic aspects of current treatment and make suggestions to get more out of our current and future medication options.

It is common knowledge that high-quality treatment and availability of full range of services have remained out of reach for many patients with schizophrenia.2 Therefore, advances in drug development face headwinds when they become available into a treatment system that lacks the institutional infrastructure to adapt new treatments. Lack of training in currently available state-of-the-art pharmacologic and psychosocial treatments, lack of training in how to engage patients with severe mental illness, and gaps in continuity of care are leading examples of factors that derail the ability to execute a personalized treatment plan. To get the most from any treatment—let alone new ones—it will require not only prior approval of a new medication but also the ability to provide the treatment infrastructure to support these treatments. Here, we review 3 examples where additional focus or training is needed to get the most out of current and future pharmacologic treatments.

1. Using a Hierarchical Approach to Treatment Planning

FIGURE. Conceptual Depiction of Hierarchical Treatment Plan

Figure. Conceptual Depiction of Hierarchical Treatment Plan

Hierarchical treatment planning should be considered the default approach to long-term treatment planning for individuals with schizophrenia. As shown in the Figure,3 the basic idea of hierarchical treatment planning is to address problems in sequential order rather than trying to do everything at once or becoming overwhelmed with the sheer number of problems, which could lead to decision paralysis or seat-of-the-pants treatment decisions.

A hierarchical approach makes sense for a complex illness like schizophrenia. Thinking 1 or 2 steps ahead of the current situation can be helpful when thinking about the treatment approach for patients experiencing acute symptoms. The base of the pyramid in the Figure visually depicts those patients who present to your service for the first time acutely ill or unstable. One of the advantages of making a hierarchical approach an automatic routine is that it requires thinking about what to do beyond the resolution of the acute episode. These postacute considerations also better lend themselves to patient-centered approaches than what is happening in the here and now of acute treatment. The middle rung of the Figure shows the transition after the patient is stabilized, and planning can begin ahead of time. If there is a transition of care, it often helps to involve the patient, family, or other clinicians in choosing the next set of priorities aimed at reducing the burden of illness or its treatment.

Once stabilized, choose 1 target at a time. The specific target goal chosen will depend on priorities established by the patient and clinician and might include tackling a persistent symptom, eliminating a problematic adverse effect (AE), or improving physical health such as smoking cessation.4 As before, the choice of intervention will consider the likelihood of success, the risk of any change, and the ordering of the burden of specific AEs that are most problematic. The basic idea is to categorize the problems and then review them individually while considering priorities. What is most important to the patient? The family? The treatment team? Next, consider the likelihood of success by looking at these goals from a perspective of likelihood of meaningful response to the considered treatment intervention with leaning toward goals where the intervention is more likely to succeed. Finally, consider the risks of the potential intervention(s)—not only the absolute medical risk but also the risk tolerance of the patient and other stakeholders.

Another reason to use hierarchical treatment planning is to formalize the idea of sequential learning. It is likely that some interventions will succeed and others will fail. Focusing on 1 goal at a time makes it easier to use this knowledge to improve the likelihood of success later on. Here, patience is usually a virtue. Most interventions take time to evaluate before success or failure is known. Therefore, it is important to finish a sequential intervention because prematurely stopping before knowing the outcome will invalidate any useful information that might have been gained. It is hard to appreciate the value of information when things are not going well, so coaching the value of perseverance can be helpful.

Why use a name like hierarchical treatment planning? The current American Psychiatric Association (APA) guideline is comprehensive but does not emphasize sequencing.5 Conveying a plan that includes working on patient-centered goals later shows a level of commitment, even if these goals cannot be part of the immediate plan. It can also help with continuity of treatment planning across different services or when there is a change in staffing within the same service. Focusing on one priority at a time can be useful in training and can empower the treatment team to look beyond the immediate challenges and work on future steps that align with available treatments and the patient’s priorities. In that way, hierarchical treatment planning fits well with another high priority: establishing and nurturing positive therapeutic relationships.

2. Making the Therapeutic Relationship Your Top Priority

The default approach to treatment of schizophrenia is psychopharmacology. As discussed later, being skilled in psychopharmacology is essential, but the unintended consequence of emphasizing psychopharmacology has been a deprioritization of basic skills in how to communicate and collaborate with individuals who have psychotic symptoms. In clinical conferences, presentations emphasize pharmacologic treatments without having sessions on the advances in language and communication that are quite relevant to the relationship. There are many challenges working with schizophrenia that make the connection harder to achieve, including the lack of emotional connectedness that are part of negative symptoms, the off-putting nature of someone with a perseverative delusion, or deescalating a patient whose agitation is worsened by overstimulation in an emergency department (ED).

TABLE 1. Techniques to Help Build and Maintain the Therapeutic Alliance

Table 1. Techniques to Help Build and Maintain the Therapeutic Alliance6-10

The deemphasis on learning and practicing basic skills in therapeutic relationships is shortsighted. In fact, exclusively focusing on psychopharmacology while ignoring these skills will defeat the goal of psychopharmacology, assuming that goal is better outcomes. Studies show that patient engagement is one of the biggest predictors of outcome, including outcomes in medication studies (Table 16-10). However, it seems that the emphasis on how to make such an alliance or keep it going over time is something of a lost art. But this skill should not be optional; it should be embedded in the professional identity of those treating schizophrenia.

Table 16-10 covers 10 aspects of interviewing, such as techniques and alliance building that help form or maintain an alliance with the patient. Although this list is not definitive, it is a start. Focusing your efforts on the therapeutic relationship will help you remain on task. These efforts are often rewarded with better quality information coming from a less-defensive patient.

3. Embracing Expertise in Pharmacologic Management

The previous section discussed the problems of single-minded pursuit of psychopharmacology at the expense of other skills crucial to the therapeutic relationship, but there is another side to this problem: how often there are suboptimal outcomes to pharmacologic therapies.

Despite significant advances in our understanding of the neuropharmacology of antipsychotics in the treatment of schizophrenia over the past 30 years, a large gap exists between what we now know and actual clinical practices. Table 2 provides 10 management issues that deviate from important evidence-based information that is the standard of care today.11-18 The list is categorized by issues that are remnants from the past use of neuroleptics (first-generation antipsychotics), the present lack of awareness and/or implementation of the current evidence-based standards, and it looks to the future.

TABLE 2. Pharmacological Management Issues in Schizophrenia

Table 2. Pharmacological Management Issues in Schizophrenia11-18

Unfortunately, there has been a tendency to underuse the few therapeutic modalities that are known to make a difference, namely LAI antipsychotics and clozapine. These interventions do require training and take time to implement. The point here is that we have good evidence that clinicians have been slow to adapt to more effective treatments, and this is likely the tip of the iceberg. The acceptability to many clinicians of certain AEs is an example of complacency and continued status quo mentality.

A more serious example of ignoring changes in treatments is the continued widespread use of short-acting intramuscular (IM) haloperidol in EDs without knowing the patient’s history. Thirty years ago, the risks of IM haloperidol may have been acceptable because alternatives were not available. With today’s antipsychotic armamentarium, the risk is now much greater because other formulations do not have the same life-threatening risks of neuroleptic malignant syndrome, malignant hyperthermia, or laryngeal dystonia. The routine use of IM haloperidol for all patients with acute psychosis reflects a lost opportunity for better patient-centered outcomes.

Another example is the complacency in treating tardive dyskinesia (TD), passively accepting the status quo of underuse of clozapine or LAIs because of the extra time and effort needed to learn and implement these treatment options. Although this is a topic in its own right, that is not the main point here. The main point is asking questions like: “Why is our profession so accepting of clinicians who do not learn or adapt to better treatments?”

The aim of this section is to suggest that the sum is greater than the individual problems. There are too many lost opportunities in offering best practices to think of them as one-off problems. In my opinion, a better explanation is that the passivity and acceptance of outdated pharmacologic principles reflects problems in training, along with complacency and reluctance to try for better outcomes. To me, this goes beyond the individual clinician and can be traced to social factors such as relative neglect of the needs of schizophrenia and related disorders, and inadequate funding across the board for quality care, training, and reimbursement. Continuing this status quo of psychopharmacology that is “good enough to get by” will threaten the new opportunities for better outcomes as other treatments become available.

Concluding Thoughts

The past 70 years have focused on dopamine D2 receptor blockade as the center of pharmacologic treatments. Although useful, it has had the unintended effect of holding back progress for other treatment approaches. The dopamine monopoly has made it more difficult for the field to truly let go of believing that dopamine has just about everything and anything having to do with schizophrenia. The medication pipeline for the treatment of schizophrenia has more promise now than ever. At the time of this article, it seems that we are likely to have the first true nondopaminergic antipsychotic with the upcoming FDA review of the M1/M4 muscarinic agonist, xanomeline-trospium (KarXT). This muscarinic agonist will likely be the first of a series of medications and open a new era of treatments for schizophrenia. As new options become available, there will be a collective understanding of the role of new class(es) of medications and whether they will replace current medications as first-line treatments for schizophrenia. However, if the current status quo of complacency and low expectations stays unchanged, these advances may share the fate of clozapine and LAIs as representing important and life-changing medications that have remained underused and lost opportunities for better outcomes.

Dr Weiden is a clinical professor of psychiatry at the Renaissance School of Medicine at Stony Brook University in New York.


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