Sub-threshold manic symptoms in recurrent major depressive disorder are a marker for poor outcome

A small but significant proportion of patients with major depressive disorder (MDD) report mild manic symptoms which are below the diagnostic threshold for a hypomanic episode.

We tested for an association between sub-threshold manic symptoms and clinical outcome in almost 600 patients with recurrent MDD who also had no known family history of bipolar disorder.

9.6% of this large sample had a life-time history of sub-threshold manic symptoms. These patients were significantly more likely to have a history of poor response to antidepressants (OR 2.84; 95% CI 1.23-6.56; P < 0.02) and more likely to have experienced psychosis (OR 2.07; 95% CI 1.05-4.09; P < 0.04). They had also experienced more depressive episodes on average (P = 0.006) and were more likely to have been admitted to hospital (P < 0.03).

Sub-threshold manic symptoms in patients with recurrent MDD may be a useful clinical marker for poor response to antidepressants and a more morbid long-term clinical course.