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The Importance of Early Treatment of Schizophrenia (PDF)

April 01, 2007

Joseph P. McEvoy, MD
With the onset of schizophrenia, patients need reliable, consistent control of their symptoms to begin to rebuild their lives. The early and effective treatment of schizophrenia can make a significant difference in the long-term recovery of most patients. 1

The improved understanding of schizophrenia as a neurobiologic disorder and the recognition that intervention is needed as early as possible following the onset of illness offer the potential to optimize long-term treatment outcomes.1 Persons experiencing symptoms of schizophrenia may have limited insight into the nature of the illness, thus limiting their ability to seek and adhere to treatment. Therefore, it is important for those who play key roles in the development of young adults, such as teachers, counselors, and physicians, to recognize the symptoms of schizophrenia and help patients seek treatment.2

Family members and friends may believe that the individual is going through a growing phase or trying out a new philosophy of life rather than experiencing the early stages of a mental illness. For family members, the diagnosis of schizophrenia is further complicated because the onset of illness is usually in the late teens or early 20s, when young people may harbor ideas that may be perceived as unconventional. When these seemingly odd ideas are accompanied by a reversal in normal sleep cycles, withdrawal from social activities to spend more time alone, neglect of normal hygiene and self-care, or loss of jobs with ill-defined attribution of persecution or maltreatment, family members and other adults should consider seeking medical attention for the individual.

Unfortunately, there are often delays between the appearance of initial psychotic episodes and the correct diagnosis and treatment, which can result in decreased responsiveness to treatment and diminished social and occupational functioning. By identifying and treating psychotic episodes soon after onset, it may be possible to limit the damage, reduce recovery time, and help patients resume daily activities and social functioning.3

Early Negative Outcomes

A longer duration of untreated psychosis prior to starting therapy with antipsychotic medications is correlated with more significant, persistent psychopathology and poorer functional outcomes, according to recent studies.4 Therefore, to prevent deterioration in the quality of patients' lives, it is extremely important to identify individuals experiencing the onset of schizophrenia as early as possible in workplaces, schools, or physician offices.

Brain imaging studies suggest that many individuals experience a loss of brain volume following their initial psychotic episode. Even if persons with schizophrenia receive treatment immediately after onset, they still may lose brain volume, according to the latest studies.5

Figure 1is from a longitudinal follow-up study of patients experiencing a first psychotic episode and matched control subjects, conducted by Lieberman et al.5 The x-axis reflects the time in days between the baseline and follow-up brain scans. The y-axis reflects change in ventricular volume from baseline to follow-up. The greater the number, the greater the increase in ventricular volume and, consequently, the greater the loss of brain tissue volume. Control subjects, depicted by the diamonds, show no change in ventricular volume irrespective of the time between scans. The patients who had good therapeutic outcomes, depicted by the squares, similarly show no changes in ventricular volume. However, those patients who had poor therapeutic outcomes (triangles) show consistent increases in ventricular volume, and the longer the duration of follow-up, the greater the loss of brain tissue volume.

Reprinted from Biological Psychiatry; Volume 49; Lieberman J, Chakos M, Wu H, et al; Longitudinal study of brain morphology in first episode schizophrenia; pages 487-99.

Finally, recent studies show that patients who do lose brain volume clearly have a worse prognosis for recovery than those who do not. The longer antipsychotic medication is delayed, the more persistent and treatment-resistant the psychopathology may become, meaning that patients are more likely to suffer long-term functional impairments such as inability to sustain employment.4

Unfortunately, even after the early stages of the illness are treated, there is a high risk for psychotic exacerbations, especially if patients do not believe they need treatment or the treatment is incompletely effective. These individuals often do not want to view themselves as ill or needing treatment.6

In addition to a lack of insight, an ineffective response to an initially selected antipsychotic can lead to distress or apathy and ultimately, discontinuation of treatment.7 Moreover, without effective treatment, most patients will experience a diminution in the quality of their lives as they become increasingly impaired. These patients may engage in progressively unusual behavior that makes it difficult for them to maintain normal relationships at home, at school, at work, and in the community. Some patients may even attempt suicide.5

Early and Effective Treatment

Patients who experience negative outcomes from their early treatment are less likely to adhere to their antipsychotic medication regimen; those whose symptoms are rapidly and effectively controlled are more likely to adhere to their prescribed medications.7 Therefore, it is important for practitioners to carefully monitor the patient's response to medication once treatment of psychotic episodes has been initiated.

Polypharmacy often complicates treatment adherence and increases the likelihood of adverse events. In treating schizophrenia, it may thus be preferable to switch rather than add antipsychotics to augment response. Expert consensus guidelines published in 2003 recommend that practitioners wait three to five weeks prior to switching to another therapy.8 However, recent evidence suggests that the effects of most antipsychotic agents can be recognized within two weeks of treatment and, therefore, a practitioner may consider the decision to switch earlier than the recommended three to five weeks.9,10

In a 2005 study by Leucht et al, acutely psychotic patients treated with an effective antipsychotic showed a 40 to 50% reduction over time in their mean Brief Psychiatric Rating Scale (BPRS) total scores (figure 2).9 This improvement was “front-loaded.” There was an 18 to 19% improvement during the first week of treatment, and an additional 12 to 13% improvement during the second week (for a total of 30 to 32% improvement during the first two weeks). The next two weeks of treatment (weeks three and four) brought only an additional 11 to 12% improvement. Although further gradual improvement accrued during the ensuing months, the rate of improvement was much less than during the initial two weeks.

Figure 2. Reprinted from Biological Psychiatry; Volume 57; Leucht S, Busch R, Hamann J, et al; Early-onset hypothesis of antipsychotic drug action: A hypothesis tested, confirmed and extended; pages 1543-9.

Treatment Adherence and Avoiding Relapse

Additional studies are needed to determine the most effective treatments for initial episodes of schizophrenia. However, it seems clear that those individuals who experience better therapeutic responses or perceive early improvements in their condition after their first psychotic episode are much more likely to adhere to their medication regimen and, not surprisingly, fare better in long-term recovery.11

Two key influencers that predict whether patients will give up on their medication are lack of insight into the need for treatment and lack of perceived therapeutic response. In a recent large 18-month study,11 the second most common reason patients discontinued their medication was that they didn't perceive it was improving their condition. Perhaps counter to common expectations, the influence of negative side effects was a less important trigger of discontinuation in this study. These findings support the view that a switch in antipsychotic medication should be considered sooner rather than later if satisfactory improvement is not seen.

If patients with schizophrenia don't perceive themselves as having a mental illness and they receive medication that they don't perceive as beneficial, the chances of treatment adherence and successful outcomes diminish tremendously.12 To optimize adherence and, ultimately, better outcomes, practitioners should encourage patients to incorporate their medicines into their daily routines. Setting up practical behavioral routines will have more useful effects on adherence than abstract discussions about the importance of adherence in relapse prevention.13 Examples of behavioral routines include having a daily pillbox in a prominent location where it will be seen every day, and linking medication ingestion to an event that happens around the same time every day, such as waking up in the morning, having dinner, or going to bed at night.

Connecting With Patients

In addition, when working with individuals with schizophrenia, it is important to maintain consistent, sympathetic contact with patients and family members.14 Patients with schizophrenia may have limited social lives with few personal connections, and they often respond well to physicians they perceive as truly interested in their lives.

To treat individuals with schizophrenia successfully, it is also important to understand that these patients may have impaired verbal learning.15 For this reason, adherence is best encouraged by providing practical evidence that medication is improving patients' lives—for example, patients’ subjective experience that they are sleeping better, or that they are experiencing less misery, anxiety, or discomfort, is more compelling than a lecture about the importance of medication in preventing relapse.

It is better to avoid traditional adherence strategies that review the medical nature of schizophrenia and discuss the importance of treatment and the necessity of adherence. Such approaches are based on explicit memory, which allows us to remember lecture points or the rules of a game, and patients with schizophrenia have severely impaired explicit memory.16 However, these patients have intact implicit memory, which is the faculty that helps us get the hang of a game by playing it. It's far more useful to develop the habit of taking prescribed medications regularly than to listen to fluent verbal explanations of why it is important to take them.

Since patients with schizophrenia have much better implicit than explicit memories, employment programs that immediately place them in jobs with the support of on-site coaches have been much more successful than programs that rely on verbal training. Traditional vocational rehabilitation programs, therefore, which stress classroom learning about proper behavior in the workplace, are usually not a good fit for persons with schizophrenia. For example, handing out employee manuals to individuals with schizophrenia and expecting them to understand the rules of the workplace may not yield desired goals. It is much better to have an on-site coach who encourages these individuals, shows them how to do the necessary tasks well by working with them, and provides pragmatic support.17


It is extremely important to treat schizophrenia as soon as possible after the onset.14 With delay in effective treatment, patients may be at increased risk for brain volume loss with adverse implications for long-term treatment outcomes.

Providers should not try to “instruct” patients with schizophrenia, who often have impaired verbal learning abilities, about the necessity of adhering to their medication regimen, but instead should try to demonstrate that the treatment can effectively improve their lives. To this end, it is crucial to find a medication at a dose that relieves psychotic and affective psychopathology as quickly as possible. To optimize treatment adherence, it seems more practical for providers to help patients with schizophrenia feel subjectively better and recognize improvement than to impress them with the logic of the argument for taking medications.18

In treating schizophrenia, physicians also should be involved and accessible to patients and caregivers. Providers should treat their patients with respect, express their viewpoint succinctly and consistently, and make clear that the betterment of the patient is their goal.

Schizophrenia is a devastating illness, taking a tremendous toll on patients, families, employers, and communities. Early and effective intervention is vital. In this article, Joseph P. McEvoy, MD, shares his thoughts on the importance of responding to the early signs of psychosis and suggests ways to help patients with adherence to antipsychotic medication treatment. Dr. McEvoy is an associate professor of psychiatry at Duke University Medical Center and deputy clinical director at John Umstead Hospital in Butner, North Carolina.


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  11. Lieberman JA, Stroup TS, McEvoy JP, et al; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209-23.
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  15. Saykin AJ, Shtasel DL, Gur RE, et al. Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia. Arch Gen Psychiatry 1994; 51:124-31.
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  • Early and effective treatment of schizophrenia can make a significant difference in many patients' recovery.

  • Prescribers should consider switching earlier from an ineffective antipsychotic and trying another agent that may offer more therapeutic benefit.

  • Physicians preferably should switch rather than add antipsychotics, because polypharmacy can complicate adherence and increase tolerability issues.

  • Caregivers should encourage patients to incorporate medication administration into their daily routines.

  • Instead of trying to improve adherence with traditional methods that review the medical nature of schizophrenia and discuss the importance of treatment, clinicians may be more effective by demonstrating to patients that the medication is improving their lives and easing discomfort.

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