Death, Sudden, Cardiac, Arrythmia, Antipsychotics and Neuroleptics Toxicity
Conditions
Brief summary
Antipsychotics may be associated to life-threatening arrhythmias and sudden cardiac death. This is the fist study to estimated the arrhythmic burden using long-term monitoring by implantable loop recorder in patients treated with antipsychotics.
Detailed description
Aims and objectives To estimate frequency of potential malign arrhythmias and cardiovascular outcome in a population with patients treated with antipsychotic drugs compared to healthy controls. Background Life expectancy is about 20 years shorter for patients with mental illness compared to the general population. Increasing evidence suggest that antipsychotic drugs can cause cardiac arrhythmias and hence sudden death. However, the evidence as well as the incidence of rhythm disturbances in patients treated with antipsychotic drugs is insufficient reported. Prolonged monitoring with external portable monitors is difficult for practical and technical reasons. In addition, long-term consistent and structured timing of clinical visits is often a challenge in this vulnerable patient group. In recent years, patients who have been suspected of rarely occurring arrhythmias, have been offered long-term monitoring using an 'implantable loop recorder' (ILR). However, no study has evaluated the arrhythmic burden in patients treated with antipsychotic drugs using ILR. Methods and materials The study is a national joint project between departments of psychiatry and cardiology across Denmark. After written informed consent and a baseline evaluation including echocardiography, ecg and biochemistry, an ILR will be implanted. During follow-up, arrhythmias will be monitored at regular clinical visits. Cardiovascular endpoints will be monitored using Danish national registries. Expected outcome and perspectives The present study is the first to reveal arrhythmias among patients treated with antipsychotics using consistent long-term monitoring. The results will give valuable insights into possible mechanism of the observed early death and risk of sudden death in patients treated with antipsychotics.
Interventions
DRUGAntipsychotic
Antipsychotic treatment \>0.5 DDD
Sponsors
Rigshospitalet, Denmark
Bispebjerg Hospital
Nordsjaellands Hospital
University Hospital, Gentofte, Copenhagen
Zealand University Hospital
Odense University Hospital
Aarhus University Hospital
Aalborg University Hospital
Herlev and Gentofte Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients with SMI defined according to ICD-10 as: * F20.0-F20.9 schizophrenia * F22.0-F22.9 paranoid psychosis * F25.0-F25.9 schizo-affective psychosis * F28 other non-organic psychosis * F29 non-organic psychosis unspecified * F31.0-F31.9 bipolar affective disorder. * Patients treated with or initiating antipsychotics with ≥ 0.5 daily defined dosage * \>18 years old and \<50 years.
Exclusion criteria
* Patients not capable to understand the aim of the study as judged by investigator. * Current in treatment with methadone. * Left ventricular hypertrophy (echocardiographic septal thickness ≥1.3 cm for women and ≥1.4 cm for men, or LVM/BSA ≥109 g/m2 for women or ≥132 g/m2 for men). * Heart failure (echocardiographic LVEF \<35%). * Ischemic heart disease (patient reported coronary bypass grafting or percutaneous coronary intervention. * Congenital cardiovascular disease (patient reported).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventricular arrhythmias | 2 years from insertion og loop recorder | Number of patients with ventricular arrhythmias detected on insertable loop recorder |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Supraventricular arrhythmias | 2 years from insertion og loop recorder | Number of patients with supraventricular arrhythmias including atrial fibrillation or flutter detected on insertable loop recorder. |
| Bradycardia | 2 years from insertion og loop recorder | Number of patients with bradycardia (defined as resting rate lower than 40/min) detected on insertable loop recorder. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular mortality | 2 years from insertion og loop recorder | Number of patients who experiences cardiovascular mortality using national death and diagnosis register. |
| All-cause mortality | 2 years from insertion og loop recorder | Number of patients who experiences all-cause mortality using national death and diagnosis register. |
| Suicide or death caused by non-cardiac factors | 2 years from insertion og loop recorder | Number of patients who experiences suicide or death caused by non-cardiac factors using national death and diagnosis register. |
| Frequency of primary endpoint in controls | 2 years from insertion og loop recorder | Frequency of primary endpoint in controls detected on insertable loop recorder. |
| Long QT interval | 2 years from insertion og loop recorder | Number of patients with long QT interval on routine ECG or detected on insertable loop recorder defined as QTc \> 500 ms. |
| Frequency of primary endpoint related to the presence of long QTc interval | 2 years from insertion og loop recorder | Frequency of primary endpoint related to the presence of long QTc interval detected on insertable loop recorder |
| Frequency of primary endpoint in poor metabolizers compared to normal metabolizers | 2 years from insertion og loop recorder | Frequency of primary endpoint in poor metabolizers compared to normal metabolizers detected on insertable loop recorder |
| Frequency of primary endpoint by genetic analysis | 2 years from insertion og loop recorder | Frequency of primary endpoint by genetic analysis detected on insertable loop recorder. |
| Frequency of primary endpoint related to specific psychiatric drugs / dose | 2 years from insertion og loop recorder | Frequency of primary endpoint related to specific psychiatric drugs / dose detected on insertable loop recorder |
| Pacemaker/ICD implantation. | 2 years from insertion og loop recorder | Number of patients who receives pacemaker/ICD implantation using questionnaire and national pace- and ICD register. |
| Sudden cardiac death. | 2 years from insertion og loop recorder | Number of patients who experiences sudden cardiac death using national death and diagnosis register. |
Countries
Denmark
Contacts
Primary ContactCasper N Bang, MD, PhD
Backup ContactGunnar H Gislason, MD, PhD
Outcome results
None listed