Antidepressant Treatment and Manic Switch in Bipolar I Disorder: A Clinical and Molecular Genetic Study

Summary & key facts

Researchers studied 1004 people with bipolar I disorder who had at least one depressive episode. They found that people who received antidepressant treatment were more likely to have a manic episode within eight weeks after their depression got better. A genetic marker (rs10262219) showed a strong signal in the first analysis but was not confirmed in a separate group, so the genetic finding is uncertain.

Key facts:

• The study included 1004 patients with bipolar I disorder who had at least one depressive episode and complete treatment/outcome data.
• Mean age at first depressive episode was 30.7 years (SD 12.5); 56% of patients were female.
• Overall rate of manic switch (manic episode within 8 weeks of remission from depression) was 39.7% (399 of 1004).
• Among patients treated with antidepressants, 46.2% had a manic switch, compared with 33.1% of those not treated with antidepressants.
• In the study’s main analysis, antidepressant treatment was associated with higher odds of manic switch (odds ratio 1.7; 95% CI 1.3–2.2; p < 0.001).
• In a logistic regression that included a genetic variant, the CC genotype at rs10262219 had an odds ratio of 3.0 (95% CI 1.7–5.2) for manic switch, and antidepressant treatment had an odds ratio of 2.3 (95% CI 1.4–3.7); together they showed
• The top SNP from the genome-wide scan (rs10262219 on chromosome 7) had a strong signal in the discovery GWAS (p = 2.21 × 10^-7) but this result was not significantly replicated in an independent group, making the genetic finding uncertain.
• Median duration of antidepressant treatment was 9.0 weeks (range 1–168 weeks).
• Median time from remission of depression to manic switch was 3.0 weeks (range 0–8 weeks); 39.1% of those who switched did so within one week.

Abstract

Affective switch is an important clinical issue when treating bipolar disorder. Though commonly seen in clinical practice, the benefits of prescribing antidepressants for bipolar depression are still controversial. To date, there have been few genetic studies and no genome-wide association study (GWAS), focusing on manic switch following bipolar depression. This study aims to investigate the effects of individual genomics and antidepressant medication on the risk of manic switch in bipolar I disorder (BPI). A total of 1004 patients with BPI who had at least one depressive episode with complete data on antidepressant treatment and outcome were included. Clinical assessment of mania and depression was performed by trained psychiatric nurses and psychiatrists using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), and the diagnosis of BPI was made according to DSM-IV criteria. Manic switch was defined as a manic episode occurring within eight weeks of remission from an acute depressive episode. The age at first depressive episode of the study patients was 30.7 years (SD 12.5) and 56% of all patients were female. GWAS was carried out in a discovery group of 746 patients, followed by replication in an independent group of 255 patients. The top SNP rs10262219 on chromosome 7 showed the strongest allelic association with manic switch (p = 2.21 × 10−7) in GWAS, which was however not significantly replicated. Antidepressant treatment significantly (odds ratio 1.7; 95% CI 1.3−2.2; p < 0.001) increased the risk of manic switch. In logistic regression analysis, the CC genotype of rs10262219 (odds ratio 3.0; 95% CI 1.7−5.2) and antidepressant treatment (odds ratio 2.3; 95% CI 1.4−3.7) significantly increased the risk of manic switch with a joint effect (odds ratio 5.9; 95% CI 3.7−9.4). In conclusion, antidepressant medication and rs10262219 variants jointly increased the risk of manic switch after bipolar depression.

Topics

Adolescent and Pediatric Healthcare Bipolar Disorder and Treatment Genetics and Neurodevelopmental Disorders

Categories

Health Sciences Medicine Psychiatry and Mental health

Tags

Antidepressant Anxiety Biology Bipolar disorder Bipolar I disorder Bipolar II disorder Depression (economics) Economics Gene Genetics Genome-wide association study Genotype Internal medicine Macroeconomics Major depressive disorder Major depressive episode Mania Medicine Mood Odds ratio Psychiatry Psychology Single-nucleotide polymorphism

Conditions & symptoms

Depression Sadness or low mood