Transitioning From Acute to Long-Term Treatment in Schizophrenia

John M. Kane, MD

Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, and the Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY

Treatment of schizophrenia can be divided into acute, maintenance, and recovery phases. The goal of the acute phase is treatment response, or, in best-case scenarios, symptom resolution. The longer-term maintenance phase is focused on preventing relapse and promoting symptomatic and syndromal remission through the stabilization of gains made during acute treatment. In recovery, patients should be regaining premorbid levels of functionality, such that they can return to work or school, have a meaningful social life, and be reasonably able to take care of themselves.

The Importance of Measurement-Based Treatment

Clinical decisions made in the acute phase of treatment are intended to help patients reach a state of relative remission. Full remission may not always be achievable, so clinicians should focus on inducing as meaningful a clinical response as possible before transitioning the patient into long-term treatment. Clinicians must decide how much improvement is adequate; if, when, and under what circumstances treatment should be changed; how to manage adverse effects (eg, changing treatment or lowering the dose); and, if in a hospital setting, when to discharge a patient to a lower level of care. In making these decisions, questions about defining and measuring response are raised.


To measure response, many physicians use clinical intuition instead of rating scales, which makes tracking response throughout treatment difficult. An evidence-based approach using a CGI assessment or some method of measuring percentage of improvement in symptomatology better informs physicians during the clinical decision-making process. Using a rating scale during the initial evaluation not only helps to confirm the diagnosis, which is, to some extent, based on characteristic symptoms presenting above a certain severity threshold, but also establishes a baseline against which future assessments can be compared. Comparing the results of a current assessment against the baseline score helps to determine pharmacotherapeutic efficacy and highlights treatment targets by providing insight into how well different illness domains have responded to treatment. Rating scales that track tolerability also provide greater insight than a clinician might get from an informal interview. Overall, implementing a measurement-based treatment approach to schizophrenia can improve the quality of care as well as assist in medical record documentation.

As with response, remission should be defined by measurable criteria so that clinicians have established treatment targets. In 2005, Andreasen and colleagues1 defined remission as a PANSS score of mild or less on 8 specific symptom items for at least 6 months (AV 1AV 1).

Acute Pharmacotherapy Considerations

When choosing a pharmacotherapeutic agent for schizophrenia, clinicians should consider 3 different domains: the illness profile, the patient profile, and the medication profile. The illness profile includes the age at onset and course, the presenting signs and symptoms, and past treatment response. Developing a patient’s profile requires knowledge of the patient’s comorbid medical and psychiatric conditions; the patient’s vulnerability to, and tolerance of, specific types of adverse effects; and the patient’s insight and attitude toward the illness and personal preferences regarding treatment. Understanding the patient’s social support network is also beneficial. The medication profile includes the risk-benefit ratio, short- and long-term tolerability, and available formulations and delivery methods. Other medication considerations are the possible need for blood monitoring, the availability and cost of each agent, and potential drug-drug interactions.

When to switch medications. In the field, disagreement about how long to wait before switching antipsychotics during acute treatment is common.2 Often, a patient’s length of stay in a treatment facility may be shorter than the time required to determine a medication’s efficacy. As such, clinicians might feel pressured to change medications sooner than necessary if patients do not achieve a sufficient response quickly.

Assuming that an adequate treatment duration has been possible and the patient has not had a clinically meaningful response, several steps should be taken before treatment is switched. First, the diagnosis should be re-evaluated to confirm that factors that might affect treatment outcome were not missed. If the initial diagnosis is correct, clinicians should determine whether or not the patient has been taking the medicine as prescribed. Dose optimization comes next; many clinicians will increase the dose when response is inadequate or decrease the dose if side effects appear to be hampering treatment response. Additionally, checking patients’ blood levels to determine whether they are idiosyncratic metabolizers may be useful. If the dose is determined to be optimal, then adding an adjunctive antipsychotic or mood stabilizer, which is a controversial but common approach, may benefit some patients. If the patient is still experiencing inadequate symptom improvement, switching to another medication, perhaps with some different characteristic that might improve treatment response, is a reasonable option. Nonpharmacologic options, such as intensifying a psychosocial approach, should always be considered.


Nonadherence and Relapse in the Maintenance Phase


Once a patient has achieved an adequate response to acute treatment, the maintenance phase of treatment begins. Many patients, particularly those who are doing relatively well, may feel that they no longer need medication. However, a 5-year follow-up study3 of patients who responded to acute treatment for first-episode schizophrenia or schizoaffective disorder found that those who discontinued their medication relapsed at a rate almost 5 times greater than those who remained adherent. One study4 comparing antipsychotic maintenance treatment with guided medication discontinuation in patients who remitted after first-episode psychosis found that relapse occurred twice as often in the discontinuation group as in the maintenance group (AV 2AV 2). Even among patients in long-term remission (ie, remitted for 1–5 years), relapse rates after drug discontinuation are high.5–7 As such, nonadherence to antipsychotic medication is one of the greatest challenges to successful maintenance treatment.

Relapse prevention is critical for many reasons.8 With every relapse, subsequent recovery is less complete and takes longer to reach, the illness becomes more resistant to treatment, and regaining previous levels of functioning becomes more difficult. Vocational and social disruption is also increased, lessening patients’ self-esteem. Further, hospital admissions and general usage of health care resources increase,9 as does the burden on patients’ families and caregivers. So, clinicians should work hard to promote and maintain remission by educating patients about the importance of medication adherence.

For Clinical Use


  • Use rating scales to establish a baseline measurement of patients’ symptomatology during initial diagnosis, and compare results of follow-up assessments to the baseline score
  • Ensure that a medication has had an adequate trial at an optimized dose before augmenting or switching agents to address poor response
  • Educate patients about the importance of treatment adherence to prevent relapse



CGI = Clinical Global Impressions
DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
PANSS = Positive and Negative Syndrome Scale

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  1. Andreasen NC, Carpenter WT Jr, Kane JM, et al. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162(3):441–449.
  2. Kane JM, Leucht S, Carpenter D, et al. The Expert Consensus Guideline Series: optimizing pharmacologic treatment of psychotic disorders. J Clin Psychiatry. 2003;64(suppl 12):1–100.
  3. Robinson D, Woerner MG, Alvir JM, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999;56(3):241–247.
  4. Wunderink L, Nienhuis FJ, Systema S, et al. Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry. 2007;68(5):654–661.
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  7. Wistedt B. A depot neuroleptic withdrawal study: a controlled study of the clinical effects of the withdrawal of depot fluphenazine decanoate and depot flupenthixol decanoate in chronic schizophrenic patients. Acta Psychiatr Scand. 1981;64(1):65–84.
  8. Kane JM. Treatment adherence and long-term outcomes. CNS Spectr. 2007;12(10 suppl 17):21–26.
  9. Sun SX, Liu GG, Christensen DB, et al. Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States. Curr Med Res Opin. 2007;23(10):2305–2312.