Prescribing Trends in Bipolar I Disorder and Usage of Endoxifen: An Indian Perspectivez
Abstract
Objective: Bipolar I disorder (BD-I) is a psychiatric illness characterized by erratic moods and impulsive behaviors. This survey assesses the prescription preferences among Indian psychiatrists for BD-I, current unmet needs, and benefits of endoxifen (a direct protein kinase C inhibitor) as a mood stabilizing agent in BD-I patients.
Methods: A literature review was carried out based on data from the PubMed Database to identify relevant articles (published between January 1980 and May 2022) using specific keywords. Twenty clinically relevant questions belonging to six major domains were drafted: (i) key attributes in the selection of psychotropic medications as front-line therapy; (ii) preference for mania and mixed episodes in front-line therapy; (iii) key attributes for the selection of maintenance therapy; (iv) preference for maintenance therapy; (v) role and positioning of endoxifen in front-line and maintenance settings; and (vi) determination of patient subgroups who can experience benefits from endoxifen. A total of 77 psychiatrists with significant experience in managing patients with bipolar disorder were identified across different cities in India. An electronic survey link to the questionnaire was sent to all the participants to record their views.
Results: For BD-I mania, a combination of mood stabilizers and an atypical antipsychotic was preferred. Typical side effects noted in Indian BD-I patients on lithium, valproate, or carbamazepine therapy include drug-induced tremors, hepatic failure, and metabolic disturbances. Experts suggested endoxifen in patients with acute and severe BD-I mania due to its good efficacy and tolerability profile. For the management of mixed episodes of BD-I, experts preferred endoxifen in combination with an antipsychotic therapy or selective serotonin reuptake inhibitor. Maintenance therapy was suggested in patients with more relapse tendencies and after a severe manic episode that warrants hospitalization.
Conclusion: The good tolerability profile of endoxifen encourages its use in patients whose current treatment options for BDI bring challenging side effects.
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Introduction
Bipolar disorder (BD) is a chronic recurrent psychiatric illness associated with significant disability and high suicide risk [1]. It is characterized by mood instability (mania, depression, or both) and impulsive behaviors [2-4]. Bipolar disorder encompasses the following subtypes [5,6]:
• Bipolar I disorder (BD-I) is defined by manic episodes that last at least 1 week (most of the day, nearly every day) or by severe manic symptoms that require immediate hospitalization. Manic episodes may be preceded by and may be followed by hypomanic or major depressive episodes (Figure 1).
• Bipolar II disorder (BD-II) is defined by a pattern of hypomanic episodes lasting at least 4 consecutive days (most of the day, nearly every day) and major depressive episodes typically lasting at least 2 weeks.
• Cyclothymic disorder is defined by recurrent hypomanic and depressive episodes for 2 years or longer.
Conclusion
BD-I is a psychiatric illness characterized by unstable moods, impulsive behaviors, and reduced quality of life. The selection of psychotropic medications against BD-I is strongly dependent on drug efficacy (faster onset of action and reduced relapse rate) and safety profile (minimal metabolic disturbances, no weight gain, and no change in blood glucose or thyroid hormone levels). Treatment with endoxifen is efficacious in controlling mania and mixed episodes of BD-I, with no adverse effects. The major usage of endoxifen was in combination, except in mild-to–moderate mania. Key attributes of endoxifen that stand out to experts were faster remission of symptoms, reduced pill burden, and no incidences of drug-induced tremors, weight gain, and metabolic disturbances, unlike lithium and valproate therapy. The good tolerability profile of endoxifen encourages its use in a wide spectrum of BD-I patients. As per CANMAT guidelines, medications that have been found to be effective in the acute phase should be continued during the maintenance phase. Thus, endoxifen has the potential to be an effective therapeutic for BD-I for long-term use. With such an encouraging experience, experts unanimously agreed to try endoxifen in the maintenance settings of BD-I.