Lars Søndergård

Lithium Treatment and Risk of Dementia

CONTEXT It has been suggested that lithium may have neuroprotective abilities, but it is not clear whether lithium reduces the risk of dementia. OBJECTIVE To investigate whether continued treatment with lithium reduces the risk of dementia in a nationwide study. DESIGN An observational cohort study with linkage of registers of all patients prescribed lithium and diagnosed as having dementia in Denmark from January 1, 1995, through December 31, 2005. SETTING We identified all patients treated with lithium in Denmark within community psychiatry, private specialist, and general practices and a random sample of 30% of the general population. Subjects A total of 16,238 persons who purchased lithium at least once and 1,487,177 persons from the general population who did not purchase lithium. Main Outcome Measure Diagnosis of dementia or Alzheimer disease during inpatient or outpatient hospital care. RESULTS Persons who purchased lithium at least once had an increased rate of dementia compared with persons not exposed to lithium (relative risk, 1.47; 95% confidence interval, 1.22-1.76). For persons who continued to take lithium, the rate of dementia decreased to the same level as the rate for the general population. The rate of dementia decreased early after the consumption of lithium tablets corresponding to 1 prescription (typically 100 tablets) and stayed at a low level, although with a slight increase according to the number of subsequent prescriptions. The association between the number of prescriptions for lithium and dementia was unique and different from the association between the number of prescriptions for anticonvulsants and dementia. All findings were replicated in subanalyses with Alzheimer disease as the outcome. CONCLUSIONS Continued lithium treatment was associated with reduction of the rate of dementia to the same level as that for the general population. Methodological reasons for this finding cannot be excluded, owing to the nonrandomized nature of data.

Mood-stabilizing pharmacological treatment in bipolar disorders and risk of suicide.

OBJECTIVES This study investigated the association between continued mood-stabilizing treatment (lithium and anticonvulsants) in bipolar disorder (BD) and the risk of suicide. METHODS Using linkage of national registers, the association between continued mood-stabilizing treatment and suicide was investigated among all patients discharged nationwide from hospital psychiatry as an in- or outpatient in a period from 1995 to 2000 in Denmark with a diagnosis of BD. RESULTS A total of 5,926 patients were included in the study and among these 51 patients committed suicide eventually during the study period. Although the rate of suicide was higher during periods when patients purchased anticonvulsants (293 suicides per 100,000 person-years) than during periods with lithium (136 suicides per 100,000 person-years), the suicide rate decreased with the number of prescriptions in a rather similar way for patients first treated with lithium and patients first treated with anticonvulsants: patients who continued treatment with mood-stabilizing drugs had a decreased rate of suicide compared to patients who purchased mood stabilizers once only [rate ratio for anticonvulsants = 0.28, 95% confidence interval (CI) = 0.19-0.41; rate ratio for lithium = 0.20, 95% CI = 0.10-0.38]. Further, the rate of suicide decreased consistently with the number of additional prescriptions. Switch to or augmentation with lithium to patients initiated on anticonvulsants was associated with a significantly reduced rate of suicide (rate ratio = 0.28, 95% CI = 0.20-0.40), whereas a switch to or augmentation with anticonvulsants to patients first started on lithium showed no additional effect on the suicide rate. CONCLUSIONS Although continued treatment with anticonvulsants and continued treatment with lithium was associated with a rather similar reduction in the rate of suicide, the results suggest that treatment with lithium may have some superiority in relation to prevention of suicide.

Antidepressants and dementia.

BACKGROUND It has been suggested that antidepressants may have neuroprotective abilities but it has newer been investigated lately whether treatment with antidepressants reduces the risk of dementia. METHOD Linkage of registers of all prescribed antidepressants and diagnoses of dementia in Denmark during a period from 1995 to 2005. RESULTS Persons who purchased antidepressants once (N=687,552) had an increased rate of dementia compared to persons unexposed to antidepressants (N=779,831). Nevertheless, the rate of dementia changed over time; thus during the initial prescription periods the rate increased with the number of prescriptions but continued long-term antidepressants treatment was associated with a reduction in the rate of dementia, however, not to the same level as the rate for the general population. This pattern was found for all classes of antidepressants (SSRIs, newer non-SSRI antidepressants and older antidepressants). All findings were replicated in sub-analyses with Alzheimers disease as outcome. LIMITATIONS Methodological reasons for the findings cannot be excluded due to the non-randomized nature of data. CONCLUSIONS Continued long-term antidepressant treatment was associated with a reduced rate of dementia, however, not to the same level as the rate for the general population.

Do antidepressants precipitate youth suicide?: a nationwide pharmacoepidemiological study.

The association between treatment with Selective serotonin reuptake inhibitors (SSRIs) and suicide in children and adolescents on the individual and ecological level were examined in a nationwide Danish pharmacoepidemiological register-linkage study including all persons aged 10–17 years treated with antidepressants during the period 1995–1999 (n=2,569) and a randomly selected control population (n=50,000). A tripartite approach was used. In Part 1, changes in youth suicide and use of antidepressants were examined. In Part 2, we made an assessment of youth suicide characteristics. In Part 3, we analysed the relative risk (RR) of suicide according to antidepressant treatment corrected for psychiatric hospital contact to minimize the problem of confounding by indication. The use of SSRIs among children and adolescents increased substantially during the study period, but the suicide rate remained stable (Part 1). Among 42 suicides nationally aged 10–17 years at death, none was treated with SSRIs within 2 weeks prior to suicide (Part 2). There was an increased rate of suicide associated with SSRIs (RR=4.47), however, not quite significant (95% CI: 0.95–20.96), when adjusted for severity of illness (Part 3). Conclusively, we were not able to identify an association between treatment with SSRIs and completed suicide among children and adolescents.

Continued Antidepressant Treatment and Suicide in Patients with Depressive Disorder

Antidepressant use in Denmark, as in many developed countries, has substantially increased during recent years, coinciding with a decreasing suicide rate. In a nationwide observational cohort study with linkage of registers of all prescribed antidepressants and recorded suicides in Denmark from 1995 to 2000, we investigated the relation between continued treatment with antidepressants and suicide in a population of all patients discharged from hospital psychiatry with a diagnosis of depressive disorder. Patients discharged from hospital psychiatry with a diagnosis of depressive disorder had a highly increased rate of suicide. Those who continued treatment with antidepressants had a decreased rate of suicide compared with those who purchased antidepressants once (rate ratio: 0.31, 95% confidence interval: 0.26–0.36). Further, the rate of suicide decreased consistently with the number of prescriptions. On individualized data from a cohort of patients with a known history of depressive disorder, continued antidepressant treatment was associated with reduced risk of suicide.

Temporal changes in suicide rates for persons treated and not treated with antidepressants in Denmark during 1995-1999

Objective:  To compare the temporal changes in suicide rate among patients treated with antidepressants with the change in suicide rate among persons who have not been treated with antidepressants during 1995–1999.

Do antidepressants prevent suicide

As in many developed countries, the use of antidepressants in Denmark has been substantially increasing during recent years, coinciding with a decreasing suicide rate. We aimed to investigate the relationship between treatment with antidepressants and suicide on individualized data from a nationwide study comprising an observational cohort study with linkage of registers of all prescribed antidepressants and recorded suicides in Denmark during the period 1995–99. A total of 438 625 patients who purchased at least one prescription of antidepressants and 1073 862 individuals from the general population were included in the study. Patients who continued treatment with selective serotonin reuptake inhibitors (SSRIs) (i.e. who purchased SSRIs twice or more) had a decreased rate of suicide compared with patients who purchased SSRIs once only [rate ratio (RR)=0.63; 95% confidence interval (CI)=0.56–0.71]. Furthermore, the rate of suicide decreased consistently with the number of prescriptions. Similarly, among patients treated with newer antidepressants other than SSRIs, the rate of suicide was decreased compared with the rate for patients who purchased other newer antidepressants once only (RR=0.70; 95% CI=0.52–0.94). Continued antidepressant treatment with SSRIs or other newer antidepressants is found to be associated with a reduced risk of suicide.

Association between consistent purchase of anticonvulsants or lithium and suicide risk: a longitudinal cohort study from Denmark, 1995-2001

BACKGROUND Prior studies suggest anticonvulsants purchasers may be at greater risk of suicide than lithium purchasers. METHODS Longitudinal, retrospective cohort study of all individuals in Denmark purchasing anticonvulsants (valproic acid, carbamazepine, oxcarbazepine or lamotrigine) (n=9952) or lithium (n=6693) from 1995-2001 who also purchased antipsychotics at least once (to select out nonpsychiatric anticonvulsant use). Poisson regression of suicides by medication purchased (anticonvulsants or lithium) was conducted, controlling for age, sex, and calendar year. Confounding by indication was addressed by restricting the comparison to individuals prescribed the same medication: individuals with minimal medication exposure (e.g., who purchased only a single prescription of anticonvulsants) were compared to those individuals with more consistent medication exposure (i.e., purchasing > or = 6 prescriptions of anticonvulsants). RESULTS Demographics and frequency of anticonvulsant, lithium, or antipsychotic use were similar between lithium and anticonvulsant purchasers. Among patients who also purchased antipsychotic at least once during the study period, purchasing anticonvulsants more consistently (> or = 6 prescriptions) was associated with a substantial reduction in the risk of suicide (RR=0.22, 95% CI=0.11-0.42, p<0.0001), similar to patients consistently purchasing lithium (RR=0.27, 95% CI=0.12-0.62, p=0.006). Absolute suicide risks of consistent anticonvulsant and consistent lithium purchasers were similar. LIMITATIONS Lack of information about diagnoses and potential confounders, as well as other covariates that may differ between minimal and consistent medication purchasers, are limitations to this study. CONCLUSIONS In this longitudinal study of anticonvulsant purchasers likely to have psychiatric disorders, consistent anticonvulsant treatment was associated with decreased risk of completed suicide.