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Psychiatric Times. Vol. 25 No. 2
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Prevention and Early Interventions

By Matcheri S. Keshavan, MD | February 1, 2006
Dr. Keshavan is professor and associate chair in the department of psychiatry and behavioral neurosciences at Wayne State University. Dr. Keshavan is a consultant to Eli Lilly and Company, Pfizer Inc., Bristol-Meyers Squibb and AstraZeneca.

Preventing Relapse

Tertiary prevention seeks to prevent disability and relapse in patients who have already developed psychosis. First-episode patients show higher response rates to treatment (46% to 96%) compared to multi-episode patients but also show high rates of relapse due to noncompliance (Robinson et al., 2005). There is increasing evidence that relapse rates are reduced by early introduction of family intervention to reduce levels of expressed emotion, CBT to address cognitive distortions and individual psychotherapy aimed at restoring a sense of self and achieving mastery over the illness (for a review, see Haddock and Lewis, 2005).

Comprehensive early psychosis treatment packages involving pharmacologic and psychosocial treatments as outlined above are more cost-effective than treatment as usual in improving long term recovery, as shown by recent controlled trials. Petersen et al. (2005) randomized 547 patients to either integrated treatment over two years, consisting of assertive community treatment with family involvement and social skills training or standard treatment offering contact with a community mental health center. Patients in the integrated treatment limb had significantly better recovery of positive and negative symptoms, less comorbid substance misuse, better adherence to treatment, and more satisfaction with treatment. Investing in early and comprehensive intervention can therefore improve our patients' lives in the longer term as well as reduce overall costs of treatment.

First-episode patients with schizophrenia also have high rates of comorbid substance abuse, depression, noncompliance, and impairments in cognition and social skills. Dual diagnosis patients with psychosis and substance abuse are more likely to relapse. A recent controlled trial has shown that, compared to standard care, such patients are likely to benefit from combined psychosocial treatment packages including motivational enhancement (Barrowclough et al., 2001).

Patients with the first episode of psychosis are also likely to experience a high likelihood of depression and suicidal behavior during the early course of their illness. Controlled trials are underway showing initial promising results (Power et al., 2003). Noncompliance rates are high in the first episode of psychosis, perhaps related to high rates of poor insight. Motivational enhancement therapies may help improve compliance as shown in controlled trials in patients with psychotic disorders (Kemp et al., 1998). An uncontrolled study showed a lack of efficacy of this treatment in patients with schizophrenia or schizoaffective disorder (Byerly et al., 2005). Results from controlled studies in early schizophrenia are awaited. Finally, cognitive remediation studies have also begun to provide encouraging results in regard to improvements in functional outcome when introduced early in the course of schizophrenia (Hogarty et al., 2004).

Conclusion

In summary, the evidence base of early interventions in schizophrenia is rapidly gaining acceptance in the field. However, as the field matures, it will be necessary to more extensively replicate the findings of the handful of early prevention studies, more conclusively validate the criteria currently defining the prodrome, further extend the range of potential interventions to include treatments other than antipsychotics, and to target specific prodromal and possibly premorbid phases of illness. Evidence-based demonstrations of cost-effectiveness of such interventions are critically needed if this field of research is to sustain and solidify this paradigm shift.

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References
1. Barrowclough C, Haddock G, Tarrier N et al. (2001), Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders. Am J Psychiatry 158(10):1706-1713.
2. Bechdolf A, Ruhrmann S, Wagner M et al. (2005), Interventions in the initial prodromal states of psychosis in Germany: concept and recruitment. Br J Psychiatry 48(suppl):45-48.
3. Byerly MJ, Fisher R, Carmody T, Rush AJ (2005), A trial of compliance therapy in outpatients with schizophrenia or schizoaffective disorder. J Clin Psychiatry 66(8):997-1001.
4. Cornblatt B, Lencz T, Correll C et al. (2002), Treating the prodrome: naturalistic findings from the RAP Program. Acta Psychiatr Scand 106(suppl 1):44.
5. Haddock G, Lewis S (2005), Psychological interventions in early psychosis. Schizophr Bull 31(3):697-704.
6. Hogarty GE, Flesher S, Ulrich R et al. (2004), Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. Arch Gen Psychiatry 61(9):866-876.
7. Johnstone EC, Lawrie SM, Cosway R (2002), What does the Edinburgh high-risk study tell us about schizophrenia? Am J Med Genet 114(8):906-912.
8. Kemp R, Kirov G, Everitt B et al. (1998), Randomised controlled trial of compliance therapy. 18-month follow-up. Br J Psychiatry 172:413-419 [see comment].
9. Keshavan MS, Berger G, Zipursky RB et al. (2005a), Neurobiology of early psychosis. Br J Psychiatry 48(suppl):8-18.
10. Keshavan MS, Diwadkar VA, Montrose DM et al. (2005b), Premorbid indicators and risk for schizophrenia: a selective review and update. Schizophr Res 79(1):45-57.
11. McGorry PD, Yung AR, Phillips LJ et al. (2002), Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry 59(10):921-928.
12. Morrison AP, Bentall RP, French P et al. (2002), Randomised controlled trial of early detection and cognitive therapy for preventing transition to psychosis in high-risk individuals. Study design and interim analysis of transition rate and psychological risk factors. Br J Psychiatry 43(suppl):78-84.
13. Petersen L, Jeppesen P, Thorup A et al. (2005), A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness.[Published erratum BMJ 331(7524):1065.] BMJ 331(7517):602 [see comment].
14. Power PJ, Bell RJ, Mills R et al. (2003), Suicide prevention in first episode psychosis: the development of a randomised controlled trial of cognitive therapy for acutely suicidal patients with early psychosis. Aust N Z J Psychiatry 37(4):414-420.
15. Robinson DG, Woerner MG, Delman HM, Kane JM (2005), Pharmacological treatments for first-episode schizophrenia. Schizophr Bull 31(3):705-722.
16. Ruhrmann S, Schultze-Lutter F, Maier W, Klosterkotter J (2005), Pharmacological intervention in the initial prodromal phase of psychosis. Eur Psychiatry 20(1):1-6.
17. Woods SW, Breier A, Zipursky RB et al. (2003), Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome.[Published erratum Biol Psychiatry 54(4):497.] Biol Psychiatry 54(4):453-464.
18. Woods SW, D'Souza DC, Wexler BE et al. (2002), Novel early interventions for prodromal states. Acta Psychiatr Scand 106(S413):12.


 
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