Depression in Bipolar Disorder2022-02-12

How weary, stale, flat, and unprofitable seem to me all the uses of this world!

-W. Shakespeare, Hamlet

Depression in bipolar disorder is disabling, hard to treat, and can lead to suicide.

The ups and downs of mood that occur in bipolar disorder make the contrast of low moods (depressions) to previous high moods ((hypo)-manias) particularly distressing. In fact, the unhappiness caused by the amplitude of these depths, along with the lack of hope and despair at lack of progress and treatment, and the loss of meaning to one’s life by the social isolation created by mood episodes, are drivers of suicidality.

Why has diagnosis been so spotty, and treatment so hit-and-miss? For proper diagnosis, longitudinal data is important. People may not have had yet or recall the high mood periods, particularly as memory is colored by present state. That is why tracking mood quantitatively with an app can reveal the disorder and trends that aid diagnosis and treatment.

The lack of long-term success of antidepressants in depression that is part of a bipolar disorder is particularly vexing to patients and clinicians. Patients get labeled as difficult or refractory. In fact, simple biology underlies this. Mood disorders are driven by circadian clock genes, and anti-depressants increase cycling and switching between states. The solution is to revisit the use of mood stabilizers, particularly lithium, which at low doses has few if any noticeable side-effects.

Antipsychotics act indirectly, on the psychotic consequences of mood disorders, and most carry cardio-metabolic liabilities. A repurposed drugs combination identified using our biomarkers research could be developed as an useful add-on to current treatments for bipolar depression. It may not only improve efficacy, but also lower side-effects of existing medications and usual co-morbidities (cardiac, metabolic syndrome). We hope to study this in clinical trials done in a real-world format, and with the use of apps and biomarkers to track response.

Live. Happier. Longer.