Neglected but not negligible aspects of antidepressants and their availability in bipolar depression

OBJECTIVES: Although many antidepressants are available, they are not always used appropriately. For appropriate use of antidepressants, the old concept of a linear dose–response relationship, in which the dose is linearly increased to achieve a sufficient antidepressant effect, should be reconsidered. Furthermore, there is ongoing debate on the safe and appropriate use of antidepressants in patients with bipolar depression. Antidepressants may be used under certain conditions in patients with bipolar depression. These neglected—but not negligible—aspects of antidepressants have been discussed herein. METHODS: A narrative qualitative review RESULTS: Dose–response relationships of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are not linear. They may be bell‐shaped, with efficacy initially increasing with an increase in dose but decreasing when the dose is increased beyond a certain point. Despite using international diagnostic criteria, uncertainty remains on whether operationally diagnosed depression is latent bipolar I depression, latent bipolar II depression, or true depression. Furthermore, operationally diagnosed bipolar II depression may be latent bipolar I depression, true bipolar II depression, or depression with false hypomanic episodes. Manic/hypomanic switches are most likely to occur in patients receiving tricyclic antidepressants, followed by those receiving serotonin and noradrenaline reuptake inhibitors and SSRIs, in that order. Also, these switches are most likely to occur in patients with bipolar I depression, followed by those with bipolar II depression and true depression, in that order. CONCLUSIONS: Considering the diagnostic subtype of bipolar depression and antidepressant properties may help to determine the optimal treatment strategy.