In the Journals

Treatment failure risk higher with later antipsychotic discontinuation in schizophrenia

Results from a nationwide, 20-year follow-up study in Finland revealed that the later antipsychotic medication is discontinued, the greater the relative risk for treatment failure in the first 8 years after first episode of schizophrenia. The study also reported that long-term antipsychotic treatment is linked to increased survival.

“Formulating a more precise estimate for the optimal duration of the initiated antipsychotic treatment would require large patient populations and follow-up periods of 10 years or more,” Jari Tiihonen, MD, PhD, department of clinical neuroscience, Karolinska Institute, Sweden, and colleagues wrote. “A recent randomized controlled trial in first-episode patients found that after 1 year of maintenance treatment, deterioration occurred in 53% of patients after discontinuation of antipsychotic medication. However, because of a lack of long-term studies including sufficient numbers of patients, it is not known whether the relapse risk remains elevated after 2 to 5 years of stability.”

No published evidence verifies that the risk for relapse decreases with time in stabilized patients with schizophrenia after first episode, according to the study. Therefore, the researchers used prospectively gathered nationwide register data to examine the risk for treatment failure (psychiatric rehospitalization or death) after discontinuation of antipsychotic treatment among patients with first-episode schizophrenia. They analyzed outcomes among 8,738 patients hospitalized for the first time with schizophrenia diagnosis in Finland from 1996 to 2014 using multivariate Cox regression.

The researchers found that treatment failure occurred in 1,449 of 4,217 (34.3%) adults who initiated antipsychotic use and 1,818 of 3,217 (56.5%) who did not initiate use, and the median duration of treatment prior to discontinuation was 7.9 years among patients who discontinued use after 5 or more years. Adults with first-episode schizophrenia who did not initiate antipsychotic use and those with early discontinuation had a 174% to 214% higher risk for death than adults who received antipsychotic treatment continuously for up to 16.4 years, according to Tiihonen and colleagues.

Analysis showed that the risk for treatment failure grew with duration of antipsychotic treatment before discontinuation (P < .05). According to the researchers, patients who received treatment with antipsychotic medications continuously experienced the lowest risk for rehospitalization or death (adjusted HR = 1) followed by patients who stopped antipsychotic use right after discharge from the first hospitalization (HR = 1.63; 95% CI, 1.52-1.75), within 1 year (HR = 1.88; 95% CI, 1.57-2.24), within 1 to 2 years (HR = 2.12; 95% CI, 1.43-3.14), within 2 to 5 years (HR = 3.26; 95% CI, 2.07-5.13), and after 5 years (HR = 7.28; 95% CI, 2.78-19.05).

“Whatever the mechanism is, the practical conclusion for clinicians is the same: if antipsychotic treatment has been used continuously for several years, it is risky to discontinue the treatment,” Tiihonen and colleagues wrote.

“Our results indicate that mortality was substantially lower among those patients diagnosed with schizophrenia who used antipsychotics continuously for up to 16.4 years compared with those who discontinued or never started antipsychotics after their first hospitalization,” they continued. “This suggests that, in general, there is no valid argument for stopping antipsychotic treatment in patients with a first episode of schizophrenia on the basis of concerns about their long-term physical well-being.” – by Savannah Demko

Disclosures: Tiihonen reports personal fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, the European Medicines Agency, Finnish Medicines Agency (Fimea), GlaxoSmithKline, Hoffman–La Roche, Janssen-Cilag, Lundbeck, Novartis, Organon, Otsuka and Pfizer. He also reports grants from Eli Lilly, Janssen-Cilag, the Sigrid Jusélius Foundation and the Stanley Foundation. Please see the study for all other authors’ relevant financial disclosures.

Results from a nationwide, 20-year follow-up study in Finland revealed that the later antipsychotic medication is discontinued, the greater the relative risk for treatment failure in the first 8 years after first episode of schizophrenia. The study also reported that long-term antipsychotic treatment is linked to increased survival.

“Formulating a more precise estimate for the optimal duration of the initiated antipsychotic treatment would require large patient populations and follow-up periods of 10 years or more,” Jari Tiihonen, MD, PhD, department of clinical neuroscience, Karolinska Institute, Sweden, and colleagues wrote. “A recent randomized controlled trial in first-episode patients found that after 1 year of maintenance treatment, deterioration occurred in 53% of patients after discontinuation of antipsychotic medication. However, because of a lack of long-term studies including sufficient numbers of patients, it is not known whether the relapse risk remains elevated after 2 to 5 years of stability.”

No published evidence verifies that the risk for relapse decreases with time in stabilized patients with schizophrenia after first episode, according to the study. Therefore, the researchers used prospectively gathered nationwide register data to examine the risk for treatment failure (psychiatric rehospitalization or death) after discontinuation of antipsychotic treatment among patients with first-episode schizophrenia. They analyzed outcomes among 8,738 patients hospitalized for the first time with schizophrenia diagnosis in Finland from 1996 to 2014 using multivariate Cox regression.

The researchers found that treatment failure occurred in 1,449 of 4,217 (34.3%) adults who initiated antipsychotic use and 1,818 of 3,217 (56.5%) who did not initiate use, and the median duration of treatment prior to discontinuation was 7.9 years among patients who discontinued use after 5 or more years. Adults with first-episode schizophrenia who did not initiate antipsychotic use and those with early discontinuation had a 174% to 214% higher risk for death than adults who received antipsychotic treatment continuously for up to 16.4 years, according to Tiihonen and colleagues.

Analysis showed that the risk for treatment failure grew with duration of antipsychotic treatment before discontinuation (P < .05). According to the researchers, patients who received treatment with antipsychotic medications continuously experienced the lowest risk for rehospitalization or death (adjusted HR = 1) followed by patients who stopped antipsychotic use right after discharge from the first hospitalization (HR = 1.63; 95% CI, 1.52-1.75), within 1 year (HR = 1.88; 95% CI, 1.57-2.24), within 1 to 2 years (HR = 2.12; 95% CI, 1.43-3.14), within 2 to 5 years (HR = 3.26; 95% CI, 2.07-5.13), and after 5 years (HR = 7.28; 95% CI, 2.78-19.05).

“Whatever the mechanism is, the practical conclusion for clinicians is the same: if antipsychotic treatment has been used continuously for several years, it is risky to discontinue the treatment,” Tiihonen and colleagues wrote.

“Our results indicate that mortality was substantially lower among those patients diagnosed with schizophrenia who used antipsychotics continuously for up to 16.4 years compared with those who discontinued or never started antipsychotics after their first hospitalization,” they continued. “This suggests that, in general, there is no valid argument for stopping antipsychotic treatment in patients with a first episode of schizophrenia on the basis of concerns about their long-term physical well-being.” – by Savannah Demko

Disclosures: Tiihonen reports personal fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, the European Medicines Agency, Finnish Medicines Agency (Fimea), GlaxoSmithKline, Hoffman–La Roche, Janssen-Cilag, Lundbeck, Novartis, Organon, Otsuka and Pfizer. He also reports grants from Eli Lilly, Janssen-Cilag, the Sigrid Jusélius Foundation and the Stanley Foundation. Please see the study for all other authors’ relevant financial disclosures.