Diagnosis and Management Considerations in Acute and Maintenance Treatment of Schizophrenia

Prognosis and Treatment

September 29, 2006

Peter F. Buckley, MD

Dr. Buckley is Professor and Chair of Psychiatry, Medical College of Georgia

Antipsychotic medications are the mainstay of treatment for schizophrenia. A host of new, second-generation antipsychotics (SGAs, Table 1) have increasingly replaced first-generation medications, largely because of lower risk of inducing motor side effects. These newer drugs are not without their own side effects, however. Most notably they are associated with a heightened risk of weight gain and metabolic disturbances-including diabetes.

The CATIE Study and Beyond

In an effort to evaluate the relative merits of current medications, the National Institute of Mental Health commissioned the largest ever treatment study in schizophrenia, the CATIE study.^5-7 The study had three phases (Figure 1), with patients being able to receive care for up to 18 months in this carefully conducted study. The results provide some guidance as to how each different drug will fit within the therapeutic armamentarium. For a summary of the results of Phases I and II of the CATIE study, see the Appendix.

The CATIE study does not address directly the tremendous amount of polypharmacy in clinical practice. Important areas to be further studied include effective augmentation strategies, duration, and sequence of treatment choices at various stages of the illness.⁸ For instance, the presentation of the first episode of psychosis is perplexing and highly stressful for patients and families alike. Here, the clinician is faced with several options on how to initiate treatment in a first-episode patient. However, this same variety brings doubts on which medication to start in a first-episode patient. In addition, there is particular interest in trying to identify and treat patients in the prodromal phase, before florid psychosis emerges. This approach is still in its infancy and in the research arena, although preliminary studies are showing promise.⁹

Additionally, there are indications from pharmacogenetic studies that efficacy for the domains of symptoms and reduced re-hospitalization may be predicted through genetic analysis. Moreover, there is also evidence that the side-effect profiles of SGAs and their propensity to cause weight gain, glucose and lipid abnormalities may be predicted by pharmacogenetic analysis in this patient population.¹⁰ This is an encouraging approach, particularly if improved “patient-to-drug” matching results in better treatment compliance overall.¹¹

Goals of Acute and Maintenance Treatment

Patients may require hospitalization for injurious behavior, deterioration in symptoms, and/or bizzare behavior. Several SGAs are available in different formulations (oral tablet, dissolvable waifer, liquid, or intramuscular) which helps with choice of medication toward the clinical scenario. The goal of acute care is stabilization and treatment planing so that there will be a successful transition to maintenance treatment.

The goals of long-term treatment are to maintain stabilization, prevent relapse, improve functional performance, and promote recovery. While medications are the bedrock of maintenance treatment, people need a host of other supports and services. Continuous antipsychotic therapy is recommended, although in practice there is a lot of switching of medications (as exemplified by the results of the CATIE study) and this is also often interrupted by either partial or complete medication noncompliance.

Improving Patient Outcomes

Compliance is complex issue,¹² involving illness-related factors, person (attitudinal) related factors, and more general (health system) factors (Table 3). Achieving optimum mediation compliance is important in schizophrenia, where failure to take antipsychotics has been repeatedly shown to be associated with an overwhelmingly higher risk of hospitalization. In addressing this need, there are now several novel approaches (using web-based, hand-held, and related technologies) to improving medication compliance.¹³ Less technical approaches such as skills training or cognitive-behavioral therapy (so-called “compliance therapy”) have also shown to be effective interventions to enhance medication compliance in patients with schizophrenia.¹⁴

The combination of new medications and effective rehabilitative and cognitive remediation interventions has the potential to improve patient outcomes significantly beyond what was expected previously. Patients with persistent symptoms and impairments in social competence can show benefit from social skills training. Importantly, supported employment programs show potential toward increasing the ability of patients with schizophrenia to obtain competitive employment. The use of computer-based cognitive remediation strategies for schizophrenia is also gaining ground.

Family members are strong advocates to positively impact the outcomes of schizophrenia and in planning for healthcare services. With the goal of promoting integrated and more effective mental health care, family members have joined together with other organizations to find more inclusive policy and practice approaches toward reducing the stigma against schizophrenia.

Additionally, patients who are recovering from mental illness disease are playing an ever-increasing role in public health policy and patient care in schizophrenia. The recovery philosophy which recognizes the unique contributions of those who have experienced mental illness is now a guiding approach for systems transformation and—in particular with the emergence of Peer Support Specialists—a fundamental direction for mental health care delivery in many states.¹⁵ Recovery is an unprecedented, concerted effort to change public opinion and to achieve integration and superior services at all levels for persons with mental illness. Although still at a nascent stage that is awaiting more widespread acceptance by clinicians, the introduction of Peer Support Services represent an innovation in mental health care.

To take the free, online CME post-test, go to www.mssmtv.org/psychweekly.

References

1. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.

2. Harvey PD, Green MF, Keefe RSE, Velligan D. Cognitive function in schizophrenia: Its role in the definition and evaluation of effective treatments for the illness. J Clin Psychiatry. 2004;65:361-372.

3. Saykin AJ, Shtasel DL, Gur RE, et al. Neuropsychological deficits in neuroleptic naive patients with first- episode schizophrenia. Arch Gen Psychiatry. 1994;51:124-131.

4. Robinson DG, Woerner MG, McMenamin M, et al. Symptomatic and functional improvement from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 2004;161:473-479.

5. O’Tuathaig CMP, Babovic D, O’Meara G, et al. Susceptibility genes for schizophrenia: characterization of mutant mouse models at the level of phenotypic behavior. Neurosci Behav Rev. 2006. In press.

6. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005:353:1209-1223.

7. Stroup TS, Lieberman JA, McEvoy JP, et al for the CATIE investigators. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry. 2006;163:611-622.

8. McEvoy JP, Lieberman JA, Stroup TS, et al for the CATIE investigators. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 2006;163:600-610.

9. Buckley PF. So which drug do I choose next? Curr Psychiatry. 2006. In press.

10. Narasimhan M, Buckley PF. Early interventions when symptoms suggest a psychotic prodrome: implications from research to clinical practice. Curr Psychiatry. 2005;4:32-46.

11. Miller DD, Ellingrod VL, Holman TL, Buckley PF, Arndt SV. Weight gain associated with the -759 C/T polymorphism of the 5HT2C receptor and clozapine. Am J Med Genet. 2005;133B(1):97-100.

12. Hwang R, Shinkai T, Deluca V, et al, Dopamine D2 receptor gene variants and quantitative measures of positive and negative symptom response following clozapine treatment. Eur Neuropsychopharmacol. 2006;16:248-259.

13. Ascher-Svanum, Faries DE, Zhu B, et al. Medication adherence and long-term functional outcomes in schizophrenia in usual care. J Clin Psychiatry. 2006;67:453-460.

14. Velligan DI, Lam YW, Glahn DC, et al. Defining and assessing adherence to oral antipsychotics: a review of the literature. Schizophr Bull. 2006. In press.

15. Turkington D, Kingdon D, Weiden PJ. Cognitive behavior therapy for schizophrenia. Am J Psychiatry. 2006;163:365-373.

16. Liberman, R, Kopelowicz A. Recovery from schizophrenia: a concept in search of research. Psychiatr Serv. 2005;56:735-742.

To take the free, online CME post-test, go to www.mssmtv.org/psychweekly.

Back to Page 2, Diagnosis and Etiology