Vitamin D and N-Acetyl cysteine supplementation in treatment resistant depressive disorder patients: a general review

Major Depressive Disorder (MDD) is often a lifetime and disabling mental illness as individuals with MDD might not benefit from standard-therapy both pharmacological and psychosocial interventions. Novel therapies are therefore required. It was shown by recent preclinical and clinical studies that a dysfunction of glutamatergic neurotransmission might be involved in the pathophysiology of MDD. Furthermore, neuroimmune alterations could have a significant role in the pathogenesis of MDD. Vitamin D is a neurosteroid hormone essential for several metabolic processes, immune responses, and for regulating neurotrophic- neuroprotective processes, neurotransmission and synaptic plasticity. Recent studies have also shown a Vitamin D deficiency in patients with severe psychiatric disorders, including MDD. Lately clinical studies have shown the neuroprotective action of N-acetyl cysteine (NAC) through a modulation of inflammatory pathways and via the modulation of synaptic release of glutamate in corticosubcortical brain regions the cysteine-glutamate antiporter. This paper reviews the therapeutic use of Vitamin D and NAC and among individuals with refractory MDD to the first- line pharmacological interventions, reviewing the clinical studies published in the last decade. A detail a summary of the current evidence in this area aims to better inform the psychiatrists and general pratictioners on the potential benefits of Vitamin D and NAC supplementation for this disorder. Nutraceutical supplementation with Vitamin D and NAC in treatment resistance MDD may be important not only for improving depressive clinical manifestations, but also for their safety and tolerability profile. This is of great interest especially considering the need of treatment special populations affected by MDD, such as youngsters and elders. Finally, the nutraceutical approach represents a good choice considering its better compliance by the patients compared to traditional psychopharmacological treatment.