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.