A Phase 2A Study of Soy Isoflavones in the Treatment of Major Depression

Recurrent mood disorders can have devastating long-term effects, and the cost of these illnesses in terms of human suffering, productivity and health care is enormous. It is now recognized that, for many patients, the long-term outcome is often much less favorable than previously thought, with incomplete inter-episode recovery, and a progressive decline in overall functioning observed. Indeed, according to the Global Burden of Disease Study, mood disorders are among the leading causes of disability worldwide, and are likely to represent an increasingly greater health, societal, and economic problem in the coming years. Dietary and nutritionally derived botanical compounds offer promise both for experimental therapeutics of complex diseases and for chemoprevention of illnesses such as depression.

Genistein is a polyphenolic molecule and the active form of the soy isoflavone, genistin. It has both phytoestrogen and protein tyrosine kinase inhibiting properties. Since tyrosine phosphorylation is involved in central nervous system regulation of neurotransmission inhibition by genistein may be a novel strategy to directly modulate synaptic activity and treat neuropsychiatric illnesses. Genistein's specific hormonal properties may also have salutary effects on brain function in depressed patients. Genistein increases dopamine and other monoamine activity, affects neurotrophic factor transcription, and has neuroprotective properties.

This is an 8-week double blind parallel study that will examine the efficacy and safety of Novasoy® (Registered Trademark) (CAS 446-72-0), a marketed botanical dietary supplement, in acutely depressed male and female patients (n&eq;60 in each group). The study has two Periods. Study Period I is a washout phase (1 week) and evaluation period. Study Period II is a monotherapy 8-week parallel, placebo controlled, acute treatment phase in which the efficacy and tolerability of isoflavones is compared to baseline. After completing the 8-week study period, subjects will be followed at the mood disorders clinic at NIMH for any necessary treatment adjustment and referred back to their clinician for further treatment.

Patients, ages 18 and over, with a diagnosis of major depression (without psychotic features), will be titrated onto an isoflavone mixture, Novasoy® (Registered Trademark), to a specific target dose (genistin &eq; 270mg/day in divided doses). At the end of week 5 nonresponders (less or equal to 50% improvement) will have one further titration to a higher dose (genistin&eq;360 mg/day in divided doses). Primary efficacy will be determined by demonstrating a greater response rate using a well-validated rating scale. Subjects will be randomized 1:1 with stratification for sex. Improvement in depressive symptoms is hypothesized to be significantly greater in the active soy isoflavone group.