The Year in Psychiatry: Studies Not to Miss From 2011

Christoph U. Correll, MD; Maren Carbon, MD


November 23, 2011

In This Article

Long-acting Injectable Antipsychotics vs Orals: A Look at Hospitalization

Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168:603-609.

The real-world effectiveness of LAIs might be best studied in a complete sample of patients treated in general clinical practice. A database cohort study enables the comparison of effects of LAIs and oral antipsychotics including those patients at greatest need for an LAI, ie, those with low illness insight, high nonadherence, and very high risk for nonadherence and relapse or rehospitalization. This study examined the risk for rehospitalization and all-cause drug discontinuation in a nationwide cohort of consecutive patients hospitalized for the first time with a diagnosis of schizophrenia between 2000 and 2007 in Finland. The authors linked national databases of hospitalization, mortality, and antipsychotic prescriptions and computed hazard ratios, adjusting for the effects of sociodemographic and clinical variables, the temporal sequence of the antipsychotics used, and the choice of the initial antipsychotic for each patient. Of 2588 patients, 41.8% failed to collect a prescription for an antipsychotic within 30 days after hospital discharge, and 54.3% stopped their initial treatment for 30 days or longer, confirming low medication persistence rates. Of the patients discontinuing their antipsychotic throughout the study period, 50.6% of switched to a different antipsychotic, 34.3% stopped the antipsychotic entirely, and 14.8% were hospitalized.

Notably, in a pairwise comparison between LAIs and their equivalent oral formulations, the risk for rehospitalization for patients receiving LAIs was significantly reduced, being about one third of that for patients receiving oral medications (adjusted hazard ratio [AHR] = 0.36, 95% CI, 0.17-0.75, P = .007). Moreover, compared with oral risperidone, clozapine (AHR = 0.48, 95% CI, 0.31-0.76, P =.001) and olanzapine (AHR = 0.54, 95% CI, 0.40-0.73, P < .0001) were each associated with a significantly lower rehospitalization risk, while use of any antipsychotic was associated with lower mortality rates compared with use of no antipsychotic (AHR = 0.45, 95% CI, 0.31-0.67). In addition to rehospitalization rates, all-cause drug discontinuation was also significantly reduced with LAIs compared with their oral counterpart (AHR = 0.41, 95% CI, 0.27-0.61, < .0001). While the LAI formulation was superior to the respective oral formulation regarding all-cause discontinuation for 3 of the 4 investigated individual antipsychotics (ie, haloperidol, perphenazine and risperidone, but not zuclopenthixol), only trend-level superiority existed for rehospitalization rates for these same three LAIs (P = .06-.16), likely due to insufficient power.

The results of this nationwide register study showed that the use of LAI antipsychotics was associated with a significantly lower risk for all-cause treatment discontinuation well as of rehospitalization than the use of oral formulations of the same compounds. Thus, removing the "randomization bias," ie, the inclusion of patients willing and able to consent and comply with the complex requirements of randomized controlled trials, uncovered the superior effectiveness of LAIs vs oral antipsychotics in first-hospitalized patients with schizophrenia. This suggests that randomized trials might not necessarily be the best study design to answer all clinical questions.


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