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Nationwide population-based register linkage study covering the entire 5.9 million inhabitants in Denmark systematically investigating the associations between sustained long-term use of lithium versus lamotrigine and valproate, and the risk of a range of physical disorders emulating a randomized trial.
The study includes two cohorts. Cohort 1: all 12.607 patients with a diagnosis of bipolar disorder (ICD-10 code: DF30-31.9) who subsequently were exposed to either lithium, lamotrigine or valproate between 1997 and 2021. Cohort 2: as Cohort 1, but regardless of prior diagnosis of bipolar disorder (N= 156.678).
Main analyses considered a patient exposed to a drug 92 days after a prescription and a 10-year follow-up and 4 sensitivity analyses considered a patient exposed to a drug for 60 and 180 days after a prescription, respectively, and with 5- and 15-years follow-up, respectively.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lithium | Drug | Sustained long-term exposure |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incident stroke (separately for intracerebral hemorrhage and cerebral infarction) | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| Arteriosclerosis | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| Angina pectoris | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| Myocardial infarction | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| Diabetes mellitus (separately for type 1 diabetes and type 2 diabetes) | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| Myxoedema | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| Osteoporosis | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| Dementia (separately for Alzheimer's disease and other dementia) | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
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Inclusion Criteria:
Exclusion Criteria:
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Nationwide population-based register linkage study covering the entire 5.9 million inhabitants in Denmark and two cohorts. Cohort 1: all 12.607 patients with a diagnosis of bipolar disorder (ICD-10 code: DF30-31.9) who subsequently were exposed to either lithium, lamotrigine or valproate between 1997 and 2021. Cohort 2: as Cohort 1, but regardless of prior diagnosis of bipolar disorder (N= 156.678).
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| Name | Affiliation | Role |
|---|---|---|
| Lars V Kessing, Professor | Psychiatric Center Copenhagen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Psychiatric Center Copenhagen | Copenhagen | 2000 | Denmark |
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D008094 | Lithium |
| D014635 | Valproic Acid |
| ID | Term |
|---|---|
| D008672 | Metals, Alkali |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D019565 | Metals, Light |
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| Parkinson's disease | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| Chronic kidney disease (definite chronic kidney disease and possible Chronic kidney disease) | Diagnosis in the Danish National Hospital Register | 1997 to 2021 |
| D008670 |
| Metals |
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |