Real-World Long-Term Experience on Endoxifen in Bipolar Disorder with Psychotic Symptoms

Abstract

Evidence suggests that inhibition of protein kinase C (PKC) signalling may have a contributing role in the treatment of bipolar affective disorder (BPAD). Endoxifen, an active metabolite of tamoxifen, is a potent direct PKC inhibitor. This report presents a severe case of a BPAD patient with a baseline Young Mania Rating Scale (YMRS) score of 49, associated family history and addiction to psychostimulants, with no improvement by the first and second-generation antipsychotics. Treatment with endoxifen 8 mg once a day showed improvement in manic symptoms with a YMRS score of 4 and a reduction in the use of psychostimulants as well as other antipsychotic concomitant medications. No adverse effects were noted up to 8-month follow-up. Long-term treatment with endoxifen is safe and effective in severe BPAD.

Efficacy and safety of endoxifen in bipolar disorder: A systematic review

“…The patients' ages ranged from 21 to 61 years, with all but one subject being male. Comorbid substance use or dependence was recorded in 4 reports (Dave & Shanmugasundaram, 2023; Dubey, 2022; Thanvi, 2022; Tharoor, 2023), while 2 patients had medical comorbidities (Kurariya et al., 2023; Tharoor, 2023). The dosage of endoxifen used varied from 8 to 16 mg per day, and the duration of use ranged from 6 weeks to 8 months.…”

“…Additionally, alongside endoxifen, all patients were administered mood stabilizers and second‐generation antipsychotics. Only one case documented the tapering of other medications, continuing treatment solely with endoxifen 8 mg and risperidone 2 mg (Thanvi, 2022). In one case (Kurariya et al., 2023), the immediate introduction of endoxifen within a week of commencing mood stabilizers and olanzapine could potentially have limited the ability to attribute observed antimanic effects solely to endoxifen.…”

“…Improvement in manic symptoms was rapid, noticeable as early as 2 days after administration (Kurariya et al, 2023). Additionally, a reduction in substance use was observed alongside an improvement in mood symptoms (Dave & Shanmugasundaram, 2023;Dubey, 2022;Thanvi, 2022;Tharoor, 2023). None of the cases had any adverse effects attributed to endoxifen.…”

“…Regarding the published case reports, two were presented at conferences (Garg et al, 2023;Kurariya et al, 2023), and one was published on a preprint server (Chakladar et al, 2022), hence lacking peer review. Apart from one report (Thanvi, 2022), all other reports were published in journals not indexed in Medline or Scopus, indicating a lower quality of publication.…”

“…Some researchers highlighted potential flaws in research design and outcome measurements in the studies supporting endoxifen's approval in India (Ghosh et al., 2021). Beyond these two clinical trials, evidence supporting endoxifen in BD remains limited, mainly confined to a few case reports (Dubey, 2022; Thanvi, 2022). Therefore, a comprehensive review of existing studies is imperative to consolidate available data and offer a more reliable assessment of endoxifen's efficacy in managing BD.…”