Lithium Versus Anticonvulsants and the Risk of Physical Disorders

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Lithium Versus Anticonvulsants and the Risk of Physical Disorders - Results From a Comprehensive Long-term Nation-wide Population-based Study Emulating a Randomised Trial

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Lithium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of bipolar disorder and subsequent exposure to either lithium, lamotrigine or valproate Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lithium|Sustained long-term exposure|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lithium, Lamotrigerne, Valproate, Physical disorders