Bipolar disorder is a mental disorder characterized by periods of mania and depression. While there are a high number of treatments that can effectively manage the acute mania, there is a striking lack of treatments for bipolar depression, with this unmet need set to be only partially met over the next decade, says GlobalData, a leading data and analytics company.

Philippa Salter, Neurology Analyst at GlobalData, comments: “The lack of bipolar disorder treatments was consistently highlighted by key opinion leaders (KOLs) interviewed by GlobalData — and for good reason. Bipolar patients experience more depression than mania, so this is a huge unmet need.

“However, where there is a need, there is an opportunity. The ideal outcomes for a future product to meet would be a treatment that can be effective in the long-term prevention of acute depressive episodes in both bipolar I and bipolar II patients, that does so without the risk of triggering mania or affecting mood-cycling rates, and has fewer (or milder) side effects than currently approved treatments. Something like that could see significant uptake in the bipolar market.”

The currently approved treatments for bipolar depression in the US are Latuda (lurasidone), Seroquel/Seroquel XR (quetiapine/quetiapine ER), Vraylar (cariprazine), and Symbyax (fluoxetine + olanzapine). However, the long-term use of these products is often avoided due to their association with notable side effects — also known as adverse events (AEs) — including weight gain, a movement disorder called akathisia, and other motor control symptoms.

There are currently no antidepressant monotherapies approved for the treatment of bipolar depression. In fact, their use is a point of debate among psychiatrists, as they are believed to trigger manic episodes.

Salter continues: “Antidepressant monotherapies are thought to increase the frequency of mood swings, and evidence of their effectiveness is mixed. As such, antidepressants are typically prescribed alongside antimanic drugs, and their long-term use is avoided — particularly in bipolar I patients.”

Patients that experience frequent depressive relapses are commonly prescribed generic lamotrigine as a long-term ‘maintenance treatment’. KOLs interviewed by GlobalData indicated that this drug is weak, in terms of efficacy, and is rarely suitable on its own as a monotherapy. However pairing it with other drugs simply increases the pill burden for patients, and raises the risk of treatment-related AEs.

As for upcoming treatments, the late-stage pipeline features three products for bipolar depression: Intra-Cellular Therapies’ Caplyta (lumateperone), Sunovion Pharmaceuticals’ SEP-4199 (amisulpride), and Celon Pharma’s Falkieri (esketamine hydrochloride).

Caplyta looks to be the most promising, having demonstrated efficacy in both bipolar I and bipolar II disorder patients in Phase III clinical trials. As it is currently in pre-registration in the US, GlobalData expects Caplyta to launch in Q1, 2022. However, it has only been evaluated as a therapy for acute depressive episodes to date, so its potential to fulfill the need for maintenance therapies for bipolar depression remains unknown. Both SEP-4199 and Falkieri have yet to demonstrate their efficacy in Phase III trials, and more data is required to fully evaluate their potential. However, it is likely that they will also be developed for acute episodes of depression before being evaluated as maintenance therapies.

Salter adds: “Overall, while acute episodes of depression will likely be met by the drugs in the bipolar disorder pipeline, the need for a maintenance therapy that can prevent depressive episodes will remain.”

ENDS