Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia

Tiihonen, Jari; Mittendorfer‐Rutz, Ellenor; Alexanderson, Kristina; Majak, Maila; Mehtälä, Juha; Hoti, Fabian; Jedenius, Erik; Enkusson, Dana; Levál, Amy; Sermon, Jan; Tanskanen, Antti; Taipale, Heidi

doi:10.1016/s0924-977x(17)31662-0

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…The role of antipsychotics in reducing premature mortality in schizophrenia has been better characterized. Despite antipsychotic treatment elevating cardiovascular risk factors, long‐term treatment is consistently associated with lower mortality rates compared to no long‐term treatment, but still higher rates than in individuals without schizophrenia.…”

Section: Physical Morbidity and Mortalitymentioning

confidence: 99%

What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?

2018

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The long-term benefit-to-risk ratio of sustained antipsychotic treatment for schizophrenia has recently been questioned. In this paper, we critically examine the literature on the long-term efficacy and effectiveness of this treatment. We also review the evidence on the undesired effects, the impact on physical morbidity and mortality, as well as the neurobiological correlates of chronic exposure to antipsychotics. Finally, we summarize factors that affect the risk-benefit ratio. There is consistent evidence supporting the efficacy of antipsychotics in the short term and mid term following stabilization of acute psychotic symptoms. There is insufficient evidence supporting the notion that this effect changes in the long term. Most, but not all, of the long-term cohort studies find a decrease in efficacy during chronic treatment with antipsychotics. However, these results are inconclusive, given the extensive risk of bias, including increasing non-adherence. On the other hand, long-term studies based on national registries, which have lower risk of bias, find an advantage in terms of effectiveness during sustained antipsychotic treatment. Sustained antipsychotic treatment has been also consistently associated with lower mortality in people with schizophrenia compared to no antipsychotic treatment. Nevertheless, chronic antipsychotic use is associated with metabolic disturbance and tardive dyskinesia. The latter is the clearest undesired clinical consequence of brain functioning as a potential result of chronic antipsychotic exposure, likely from dopaminergic hypersensitivity, without otherwise clear evidence of other irreversible neurobiological changes. Adjunctive psychosocial interventions seem critical for achieving recovery. However, overall, the current literature does not support the safe reduction of antipsychotic dosages by 50% or more in stabilized individuals receiving adjunctive psychosocial interventions. In conclusion, the critical appraisal of the literature indicates that, although chronic antipsychotic use can be associated with undesirable neurologic and metabolic side effects, the evidence supporting its long-term efficacy and effectiveness, including impact on life expectancy, outweighs the evidence against this practice, overall indicating a favorable benefit-to-risk ratio. However, the finding that a minority of individuals diagnosed initially with schizophrenia appear to be relapse free for long periods, despite absence of sustained antipsychotic treatment, calls for further research on patient-level predictors of positive outcomes in people with an initial psychotic presentation.

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Section: Physical Morbidity and Mortalitymentioning

confidence: 99%

What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?

2018

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“…In addition to SGAs potentially being less effective in reducing relapse rates, it is possible that partial treatment non-adherence (not noted by patients or in their clinical records) played a role in participants' relapse. Consistent evidence demonstrated clinical superiority in relation to relapse rates of LAIs compared to oral administration, even when the same antipsychotic medication is prescribed in different forms (Schooler 2003;Tiihonen et al, 2017;Tiihonen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

The impact of fluphenazine withdrawal: a mirror-image study

Meehan,

Moran,

Rainford

et al. 2024

Ir. j. psychol. Med.

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Background: Fluphenazine decanoate licenced as a long-acting injectable (LAI) first-generation antipsychotic (FGA) was withdrawn from sale in 2018. This study evaluates if its withdrawal resulted in increased relapse rates of psychosis in an Irish patient cohort and examines which prescribed alternative antipsychotic medications were associated with more optimal outcomes. Methods: Fifteen participants diagnosed with a psychotic disorder were included. A mirror-image study over 24-months’ pre-and post-withdrawal of fluphenazine was conducted. Kaplan-Meier survival and proportional hazards analyses were conducted. The impact of alternate antipsychotic agents (LAI flupenthixol compared to other antipsychotic medications) was evaluated. Semi-structured interviews with participants examined subjective opinions regarding the change in their treatment. Results: Seven participants (46.7%) relapsed in the 24-month period subsequent to fluphenazine discontinuation compared to one individual (6.7%) in the previous identical time-period (p = 0.035). Flupenthixol treatment was associated with reduced relapse rates compared to other antipsychotics (χ2 = 5.402, p = 0.02). Thematic analysis revealed that participants believed that the discontinuation of fluphenazine deleteriously impacted the stability of their mental disorder. Conclusion: The withdrawal of fluphenazine was associated with increased relapse rate in individuals previously demonstrating stability of their psychotic disorder. While acknowledging the limitation of small sample size, preliminary evidence from this study suggests that treatment with the first-generation antipsychotic (FGA) flupenthixol was associated with a lower risk of relapse compared to SGAs. Reasons for this lower risk of relapse are not fully clear but could be related to dopamine hypersensitivity with this treatment change.

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“…These results suggest that LAIs may be superior in increasing patients' tenure in the community. Also, SGA LAIs (particularly once-monthly paliperidone LAI and risperidone LAI) have been linked with a 30% lower all-cause mortality rate compared with other FGA and SGA oral agents, suggesting that different medications and routes of administration may have a major impact on life expectancy in SZ (Tiihonen et al, 2017).…”

Section: Medication Management Issuesmentioning

confidence: 99%