Long-Acting Injectable Antipsychotics in First-Episode Schizophrenia

Long-Acting Injectable Antipsychotics in First-Episode Schizophrenia
Long-Acting Injectable Antipsychotics in First-Episode Schizophrenia

Treatment nonadherence poses one of the most difficult challenges to clinicians treating patients with schizophrenia. Causes of nonadherence are multifaceted, and include denial of the disease, fear of stigma, medication side-effects, cognitive impairment, comorbidities (especially substance abuse), and a problematic therapeutic relationship with the clinician.1 Nonadherence and partial adherence are associated with increased risk of relapse, rehospitalization, and suicide attempts.2

Nonadherence rates are very high: It is estimated that patients, on average, take only 58% of their prescribed medications, and 41.2% do not follow instructions.3 A study of 200 patients with early psychosis found that during the first year, 39% were nonadherent, and 20% were inadequately adherent. Nonadherent patients demonstrated more positive symptoms, more relapses, more substance abuse, reduced insight, and poorer quality of life.4 Even brief periods of partial adherence can increase the risk of relapse.5

Long-acting injectable (LAI) antipsychotics may improve medication adherence and reduce relapse in patients with schizophrenia.6 However, these agents are underused in routine clinical practice.7–9 One reason is that many psychiatrists have a negative attitude toward depot antipsychotics, regarding them as "old-fashioned, stigmatized, and less acceptable to patients."10 Some clinicians also believe that, contrary to available evidence, the side effects of LAI antipsychotics are worse than those of oral preparations of the same drug.11 There is a particular reluctance to prescribe LAI antipsychotics to patients with first-episode schizophrenia.12

Two recently published articles challenge these prescribing practices. An article by Kim et al. presents a broad review of the evidence supporting the use of LAI antipsychotics in first-episode schizophrenia,10 and a study by Viala et al. investigates of the use of LAI antipsychotics in treating 25 patients with early schizophrenia over an 18-month period.1

Kim et al. summarized the pros and cons of using LAI antipsychotics for the treatment of first-episode schizophrenia.

Benefits and Disadvantages of LAI Antipsychotics for First-Episode Schizophrenia




Prevention of relapse caused by poor adherence


First-episode psychosis may not necessarily lead to a diagnosis of schizophrenia, and the stigma of prescribing LAI drugs has potential of impeding the therapeutic relationship, thereby interfering with chances of correct diagnosis later.

Preference of high-functioning patients


These agents may discourage the patient's motive to recover because of the general perception that injectable treatment means more severe illness.

Favorable side effect profile, due to low variation in the peak and trough levels


For those with first-episode schizophrenia showing a positive outcome, the goal of treatment is to gradually reduce the dose antipsychotics, which does not fit the traditional goals of LAI drugs.

Best time to prescribe LAI drugs may be just before discharge.


It is difficult to adjust the dosage of LAI drugs quickly in response to side effects, therefore LAI treatment may negatively affect subsequent adherence during this critical period.

The authors cited the Texas Medication Algorithm Project Antipsychotic Algorithm for Schizophrenia, which states, "If a patient is inadequately adherent at any stage, the clinician should assess and consider a long-acting antipsychotic preparation, such as risperidone microspheres, haloperidol decanoate, or fluphenazine decanoate."13,14 They regard this recommendation as support for the use of LAI antipsychotics in first-episode schizophrenia.

The authors concluded that "given that low compliance is a frequent cause of relapse in the early course of schizophrenia, more active consideration of LAI drugs should be encouraged, and patients should be informed about the different types of medications that are available during the early stages of the illness."

A recent study of the use of a LAI antipsychotics in first-episode schizophrenia supports this contention. Viala et al. studied 25 patients over an 18-month period, using the Clinical Global Impression (CGI) scale and the Global Assessment of Function (GAF) scale to assess outcomes.1 The patients were treated with long-acting risperidone, with the first injection administered prior to discharge from the hospital, and subsequent injections administered bimonthly. In addition, patients received psychosocial interventions, consisting of day hospital, part-time therapy center, sheltered housing, protected employment, dietetic education, physical exercise, and an ongoing relationship with two nurses and a social worker.

The researchers found that "clinical improvement was coupled with a good reintegration rate and very few relapses or rehospitalizations." They concluded that "treating with LAI antipsychotic drugs as early as possible, from the first episode if possible, can reduce relapse, number and duration of rehospitalization and cognitive symptoms and can improve the quality of life and prognosis." 1 They noted that interactive, interdisciplinary follow-up enables patients to "progress from compliance to adherence," and that working with family and caregivers, providing psychoeducation and other ongoing psychosocial interventions "may improve adherence and outcomes" and provide "motivational enhancement." 1


1. Viala A, Cornic F, Vacheron M-N. Treatment adherence with early prescription of long-acting injectable antipsychotics in recent-onset schizophrenia. Schizophr Res Treatment. 2012:Article ID 368687.

2.    Kane J. Improving treatment adherence in patients with schizophrenia. J Clin Psychiatry. 2011;72(9):e28.

3. Přikryl R, Kucerová H, Vrzalová A, Cešková E. Role of long-acting injectable second-generation antipsychotics in the treatment of first-episode schizophrenia: a clinical perspective. Schizophr Res Treatment. 2012;2012:764769.

4. Coldham EL, Addington J, Addington D. Medical adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand. 2002;106(4):203–210.

5. Subotnik KL, Nuechterlein KH, Ventura J, et al. Risperidone nonadherence and return of positive symptoms in the early course of schizophrenia. Am J Psychiatry. 2011;168(3):286–292.

6. Kane JM. Review of treatments that can ameliorate nonadherence in patients with schizophrenia. J Clin Psychiatry. 2006;67(suppl 5):9–14.

7. Heres S, Hamann W, Kissling W, Leucht S. Attitudes of psychiatrists toward antipsychotic depot medication. J Clin Psychiatry. 2006;67(12):1948–1958.

8. Patel MX, Haddad PM, Chaudhry IB, et al. Psychiatrists' use, knowledge and attitudes to first- and second-generation antipsychotic long-acting injections: comparisons over 5 years. J Psychopharmacol. 2010;24(10):1473–1482.

9. Agid O, Foussias G, Remington G. Long-acting injectable antipsychotics in the treatment of schizophrenia: their role in relapse prevention. Expert Opin Pharmacother. 2010;11(14):2301–17.

10. Kim B, Lee SH, Yang YK, et al. Long-acting injectable antipsychotics for first-episode schizophrenia: the pros and cons. Schizophr Res Treatment. 2012: Article ID 560836.

11. Patel MX, Taylor M, David AS. Antipsychotic long-acting injections: mind the gap. Br J Psychiatry Suppl. 2009;52:S1–4.

12. Jaeger M, Rossler W. Attitudes toward long-acting depot antipsychotics: a survey of patients, relative and psychiatrists.” Psych Res. 2010;175(1-2):58–62.

13. Moore TA, Buchanan RW, Buckley PF, et al. The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry. 2007;68(11):1751–1762.

14. Texas Department of State Health Services. Algorithm for the treatment of schizophrenia. (2007). Available at: http://bellsouthpwp2.net/d/r/drcook/Lane/TMAP/TMAP%20Schizophrenia%20Web.pdf. Accessed: December 4, 2012.

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