Medication exposure and predictors of first mood episode in offspring of parents with bipolar disorder: a prospective study

Abstract

Objectives: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. Methods: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). Results: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. Conclusions: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.

N‐acetylcysteine for depression and glutamate changes in the left prefrontal cortex in adolescents and young adults at risk for bipolar disorder: A pilot study

“…NAC was well‐tolerated. Given the lack of evidence‐based treatment to treat depression and anxiety in at‐risk youth, previous observations of poor tolerability to antidepressants (Strawn et al, 2014), and possible deterioration of mood in at‐risk youth exposed to antidepressants (Nery et al, 2020), NAC appears to be a promising efficacious and safe alternative to treat mild to moderate depressive symptoms in at‐risk youth.…”

“…Mild or subthreshold affective symptomatology, especially depressive symptoms, first manifest during adolescence or early adulthood in individuals at familial risk for bipolar disorder, and increases the risk of a later development of a full‐blown mood disorder (Duffy et al, 2014; Hafeman et al, 2016). Although depression in these at‐risk youth often require the use of medication, antidepressant exposure may accelerate the development of bipolar disorder among them (Chang et al, 2010; Goldstein et al, 2010; Nery et al, 2020), and is associated with poor tolerability leading to treatment discontinuation, particularly in younger at‐risk individuals (Strawn et al, 2014). Therefore, alternatives to antidepressants to treat depression in at‐risk youth are highly needed.…”

The Management of Prodromal Symptoms of Bipolar Disorder: Available Options and Future Perspectives

“…The rate of antidepressant-induced activation is nearly 50% in children and youth at high risk for BD [46], while a retrospective study found that up to 83% of patients that switched to mania were previously treated with SSRIs [47]. This increased risk of conversion was confirmed in a recent naturalistic RCT that included 93 bipolar offspring with anxiety or depressive symptoms treated with antidepressants [48]. In this work, 68% of at-risk patients who met full criteria for major depressive disorder, hypomania or mania, had been previously treated with antidepressants.…”

Index depressive episode and antidepressant exposure were associated with illness characteristics of pediatric bipolar disorder

“…21 Likewise, anxiety disorders, subsyndromal mood symptoms, and antidepressant exposure increased the likelihood of conversion to a first mood episode in BD offsprings. 22 Previous suicide attempts, the number of previous antidepressant exposures, and the family history of psychiatric disorders could be additional risk factors for treatment-emergent mania in youth. 15 Therefore, when used for bipolar depression, antidepressant monotherapy can be considered an imprudent treatment decision regarding the risk of the manic switch.…”