The Trimetazidine in Bipolar Depression (TIDE) trial looks at whether trimetazidine can help to reduce depressive symptoms in people with bipolar disorder. It is a double-blinded, randomised, placebo-controlled, phase 2/3 clinical trial which, if successful, may see trimetazidine used as the novel anti-depressant medication for bipolar depression around the world.
Mood stabilisers, like lithium and valproate, are less effective in treating depression compared to mania. Some atypical antipsychotics demonstrate efficacy in bipolar depression, but not all patients are responsive to such treatment. In addition, all abovementioned treatments may have substantial tolerability issues. Bipolar depression treatment is clearly an unmet need.
Interestingly, there is evidence that the activity of mitochondria, which exist in every cell and are responsible for producing the energy required by the cells, is reduced during the depressive phase and increased during the manic phase in people with bipolar disorder – which is consistent with the symptomatic profile. This suggests that mitochondria activity is related to the pathophysiology of bipolar disorder.
Trimetazidine directly promotes efficient energy generation in the mitochondria. It is an off-patent medication approved to treat angina (i.e. heart-related chest pain) around the world, including Europe, America, East Asia and India. It is highly safe and well-tolerated. Rigorous preclinical research showed its potential in anti-depressive effects. The Stanley Medical Foundation has funded the TIDE trial to clinically evaluate the adjunctive use of trimetazidine in treating bipolar depression.
The eight-week trial, which commenced recently, seeks to recruit 260 participants aged 18-65 experiencing moderate to severe bipolar depression. It involves four visits, featuring a series of clinical scales to evaluate the participant’s functioning, quality of life, health economics and mood symptoms.
The team is in the process of setting up international clinical trial sites in Ranchi, Bangalore, Seoul and Barcelona.
They are hopeful that trimetazidine will help treatment-resistant people with bipolar depression by directly targeting a different biological mechanism of depression compared to existing medications.
If the trial yields positive and statistically significant results, trimetazidine will move onto the next phase of clinical trial and its use in treating bipolar depression will be tested in a larger cohort of participants. Ultimately, these trials will provide a novel anti-depressant that is affordable, accessible and safe.
The TIDE trial is being led by Prof Michael Berk and Prof Jee Hyun Kim.
