Bipolar disorder (BPD) is one of the most severe psychiatric disorders and ranks in the top 10 causes of medical disability worldwide. The lifetime prevalence is approximately 4% in the United States,¹ with depressive symptomatology dominating the longitudinal course of the illness.² Currently approved treatments for bipolar depression include lithium, quetiapine, and the combination olanzapine and fluoxetine. Other treatments used during the depressive phase of the illness include lamotrigine, antidepressants, and atypical antipsychotics. However, many patients with bipolar depression do not respond adequately to these medications despite adequate trials.^2-4 Another limitation of existing therapeutics is that they are associated with a considerable lag of onset; only a fraction of patients meet response criteria by the end of the first week of treatment.^5-7 This delayed onset of antidepressant effects can result in considerable morbidity, including increased suicide risk.^8,9 Therefore, rapid-onset pharmacological strategies with pronounced and sustained effects would have an enormous impact on public health; this is particularly true because BPD is perhaps the psychiatric disorder with the highest mortality rate.¹⁰

Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy. 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease. These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration. Clinicaltrials.gov NCT00954525