Bipolar Disorder with Comorbid Substance Use Disorder in a Young Male not Responding to Combination Therapy: Endoxifen Use for 2 Years
Abstract
Impulsivity is common to both bipolar disorder (BD) and substance use disorder (SUD). Bipolar disorder is in fact a risk factor for SUD, wherein substances may be used to achieve symptom relief. Impulsivity is associated with excessive protein kinase C (PKC) activity, and is implicated in the development of BD. This case report describes the use of endoxifen, a direct PKC inhibitor, for the management of a young male with BD and SUD who was not responsive to combination therapy with pharmacotherapies including lithium, haloperidol, and risperidone. The inclusion of endoxifen in the treatment regimen while discontinuing haloperidol and tapering of the dose of lithium led to reduced substance use and improvement of the symptoms of bipolar I mania within 3 weeks. The patient tolerated the treatment well, including long-term use for 2 years. Therefore, the utility of endoxifen in the management of SUD could be explored in larger studies.
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Introduction
Impulsivity is a phenomenon that is common to bipolar disorder (BD) as well as substance use disorder (SUD). Excessive protein kinase C (PKC) activity is associated with prefrontal cortex deficits, and dysregulation in this brain region is associated with impulsivity.1,2 Inhibition of PKC may help alleviate impulsivity in both BD and SUD patients. BD is a risk factor for addictions to alcohol, tobacco, opiates, cannabis, etc.3 Comorbid addictions in BD could be mediated by shared neurobiology or involvement of neurotransmitter mechanisms. Furthermore, individuals with BD may “self-medicate” with substances to alleviate symptoms.4
This case report describes the management of a young male with BD and SUD (alcohol, tobacco, and cannabis), who was not responsive to combination therapy despite adherence to therapy. The inclusion of endoxifen in the treatment regimen led to a favorable response for mania, SUD and overall impulsivity. A full recovery was noted within 3 weeks of initiating endoxifen usage. Long-term treatment with endoxifen for 2 years did not lead to adverse effects and the patient did not consume substances during the treatment. Being a direct PKC inhibitor, endoxifen treatment leads to a faster response in reducing impulsivity in both SUD and BD.
Conclusion
Endoxifen is effective for the management of mania and comorbid SUD because it directly inhibits PKC and hence reduces impulsivity in both mania and SUD. This case study additionally demonstrates the safety of the 2 years of long-term use of endoxifen. It would be beneficial to explore the utility of endoxifen in the management of SUD based on its known tolerability profile and efficacy in reducing impulsivity.