Role of pharmacological treatment in bipolar disorder

Abstract

Bipolar disorder (BPD) is a severe mental illness characterized by fluctuations in mood episodes and energy. It affects approximately 1% of the population worldwide and is one of the leading causes of disabilities, which leads to high rates of morbidities and mortalities. Particularly, the rate of premature mortality in patients with BPD is 7 times higher than general population. Therefore, pharmacological treatment is crucial for patients with BPD. Lithium, antipsychotics and mood stabilizing antiepileptics (valproate, carbamazepine, and lamotrigine) are recommended mood stabilizing treatment options for patients with BPD in the clinical guidelines and patients usually require lifelong treatment. Lithium has been recommended mutually as first-line treatment for BPD in various clinical guidelines from different regulatory bodies. The utilization of mood stabilizing treatment has not been systematically compared between ethnicities. Despite the effectiveness of mood stabilizing treatment in relieving mood symptoms and preventing relapse were recognized, it remains uncertain whether mood stabilizing treatment could prevent traumatic injuries, suicide attempts and all-cause fractures. To address these knowledge gaps, this thesis has two overarching aims, namely 1) to compare the prevalence of BPD and the prescribing trend of its treatment in Hong Kong and the United Kingdom (UK) and 2) to assess the effectiveness of mood stabilizing treatment for BPD, using population-based electronic healthcare databases from Hong Kong and the UK with observational study designs. To reduce the potential bias arising from the baseline characteristics differences between individuals, a range of approaches, including self-controlled case series, and propensity score method, were adopted. The main findings of this thesis revealed that: 1) Lithium prescribing declined substantially while antipsychotics and mood stabilizing antiepileptics prescribing simultaneously increased in Hong Kong and the UK, reflecting not all new patients were offered lithium as first-line; 2) Increased risks of traumatic injuries and suicide attempts were observed before initiation of mood stabilizing treatment. The risks were attenuated with decreasing magnitude during the treatment period. A lower risk of traumatic injuries was observed after the initiation of lithium but not for antipsychotics and antiepileptics. For suicide attempts, there was a decreased risk during the treatment of lithium and antiepileptics but not for antipsychotics. The risks of traumatic injuries and suicide attempts were elevated when the treatment was with-held, suggesting close monitoring of relapse of symptoms and signs of suicidal ideation when treatment cessation is warranted; 3) Lithium was associated with a lower risk of all-cause fractures compared with antipsychotics and mood stabilizing antiepileptics. The research undertaken in this thesis suggests that lithium is associated with lower risks of traumatic injuries, suicide attempts and all-cause fractures. These new findings can hopefully aid clinical decisions to balance the potential risks and benefits of lithium and provide guidance to inform better treatment choices for patients with BPD.