Abstract
Introduction: Sleep-promoting antidepressants are of interest because they are used not only as
antidepressants, but also to promote sleep.
Methods: We reviewed case reports describing the switch to mania during treatment with trazodone,
mirtazapine, or agomelatine.
Results: Trazodone, mirtazapine, and agomelatine may induce manic symptoms. However, the risk
of switching is related, first of all, to doses recommended for antidepressant treatment,
administered without mood-stabilizer co-therapy. Low doses of these antidepressants,
used for their hypnotic or sedative effects, were observed to cause mania only in
patients with other risk factors for switching. There is no evidence for trazodone
or mirtazapine and only sparse evidence for agomelatine, claiming that treatment with
these antidepressants is related to an increased risk of switching to mania when administered
in combination with a mood stabilizer.
Discussion: These findings suggest that low doses of trazodone and mirtazapine are safe in bipolar
disorder, and should still be considered important alternatives to hypnotics when
long-term pharmacological treatment of insomnia is necessary. It seems that these
antidepressants and agomelatine can also be used safely in antidepressant doses when
combined with a mood stabilizer.
Key words
bipolar disorder - switch to mania - antidepressants - trazodone - mirtazapine - agomelatine
