TY - JOUR

T1 - Association of benzodiazepines and antidepressants with 180-day mortality among patients with dementia receiving antipsychotic pharmacotherapy

T2 - A nationwide registry-based study

AU - Nørgaard, Ane

AU - Jensen-Dahm, Christina

AU - Gasse, Christiane

AU - Wimberley, Theresa

AU - Hansen, Elsebet Steno

AU - Waldemar, Gunhild

PY - 2020

Y1 - 2020

N2 - Objective: Antipsychotic drugs are known to increase mortality among patients with dementia. Many patients receive concomitant treatment with other psychotropic agents. The aim of this retrospective cohort study was to investigate the impact of benzodiazepines and antidepressants on the risk of death in patients with dementia initiating antipsychotic drug treatment. Methods: Nationwide registry data on all incident dementia cases among individuals aged 65 years and older in Denmark between 2009 and 2013 for which antipsychotic treatment was initiated were used. The 180-day mortality was evaluated by crude and adjusted hazard ratios (HRs, including adjustment for somatic and psychiatric comorbidity, other prescription drugs, nursing home residency, and time since diagnosis), comparing periods of antipsychotic treatment with periods of concomitant treatment with benzodiazepines or antidepressants. Results: Among 41,494 incident dementia cases, antipsychotic treatment was initiated for 10,291 (24.8%). After 3,140 people were excluded due to recent antipsychotic drug use or hospitalization, 7,151 people were included in the analysis. The total follow-up time during current antipsychotic treatment was 1,146 person-years, and 831 died during antipsychotic treatment. Compared with antipsychotic treatment alone, the risk of death increased during antipsychotic treatment in combination with benzodiazepines (adjusted HR = 2.19; 95% CI, 1.83-2.63), while there was a decreased risk of death during antipsychotic treatment in combination with antidepressants (adjusted HR = 0.61; 95% CI, 0.50-0.74). Conclusions: The diverse impact of concomitant use of benzodiazepines and antidepressants on mortality may be due to a direct drug-related effect. Alternatively, the findings could reflect differential mortality associated with different indications for therapy. Although the results cannot prove causality, and there may be residual confounding, clinicians should be cautious when considering the combination of antipsychotics and benzodiazepines in patients with dementia.

AB - Objective: Antipsychotic drugs are known to increase mortality among patients with dementia. Many patients receive concomitant treatment with other psychotropic agents. The aim of this retrospective cohort study was to investigate the impact of benzodiazepines and antidepressants on the risk of death in patients with dementia initiating antipsychotic drug treatment. Methods: Nationwide registry data on all incident dementia cases among individuals aged 65 years and older in Denmark between 2009 and 2013 for which antipsychotic treatment was initiated were used. The 180-day mortality was evaluated by crude and adjusted hazard ratios (HRs, including adjustment for somatic and psychiatric comorbidity, other prescription drugs, nursing home residency, and time since diagnosis), comparing periods of antipsychotic treatment with periods of concomitant treatment with benzodiazepines or antidepressants. Results: Among 41,494 incident dementia cases, antipsychotic treatment was initiated for 10,291 (24.8%). After 3,140 people were excluded due to recent antipsychotic drug use or hospitalization, 7,151 people were included in the analysis. The total follow-up time during current antipsychotic treatment was 1,146 person-years, and 831 died during antipsychotic treatment. Compared with antipsychotic treatment alone, the risk of death increased during antipsychotic treatment in combination with benzodiazepines (adjusted HR = 2.19; 95% CI, 1.83-2.63), while there was a decreased risk of death during antipsychotic treatment in combination with antidepressants (adjusted HR = 0.61; 95% CI, 0.50-0.74). Conclusions: The diverse impact of concomitant use of benzodiazepines and antidepressants on mortality may be due to a direct drug-related effect. Alternatively, the findings could reflect differential mortality associated with different indications for therapy. Although the results cannot prove causality, and there may be residual confounding, clinicians should be cautious when considering the combination of antipsychotics and benzodiazepines in patients with dementia.

U2 - 10.4088/JCP.19m12828

DO - 10.4088/JCP.19m12828

M3 - Journal article

C2 - 32526104

AN - SCOPUS:85086354706

VL - 81

JO - Journal of Clinical Psychiatry

JF - Journal of Clinical Psychiatry

SN - 0160-6689

IS - 4

M1 - 19m12828

ER -