Pharmaceutical combination for mood disorders

An in vitro method to determine the optimal and personalized concentration of melatonin and ketamine that a patient requires for the treatment of a neuropsychiatric disease, the in vitro method comprising:

• i) obtain a non-invasive sample of neuronal cells by exfoliation of a subject's nasal cavity;
• ii) culture the sample of neuronal cells of the step i) using a series of solutions for obtaining a clone and/or primary cultures;
• iii) incubate the clone and/or the primary cultures of the step ii) in only one concentration of ketamine and in increasing concentrations of melatonin, wherein the ketamine concentration is 10−7 M and the increasing concentrations of melatonin are in the range of 10−11 M to 10−11 M;
• iv) stain the incubating cells of the clone and/or the primary cultures of step iii) with specific biomarkers, wherein the specific biomarkers are selected from labeled antibodies for the detection of spinophylline;
• labeled antibodies or phalloidin-rhodamine for detection of filamentous actin;
• anti-doublecortin antibodies for detection of cell clusters;
• antibodies against nestin;
• and antibodies against Ki67;
• v) observe the induced cellular response of the stained cells through the formation of spines and/or cell clusters;
• and
• vi) determine the optimal and personalized concentration of ketamine and melatonin for the patient from the observed induced cellular response, wherein the optimal and personalized concentration of ketamine and melatonin is determined from the values of ketamine and melatonin concentrations that caused the appearance of spikes and/or cell clusters in the incubated cells that were observed in step v), the values of the concentrations of ketamine and melatonin used in said incubated cells being the optimal concentrations of ketamine and melatonin that must be achieved at the plasma level after administration of the such optimal and personalized concentration of ketamine and melatonin to the patient for the treatment of the neuropsychiatric disease, and wherein said optimal and personalized concentrations of ketamine and melatonin prevent or reduce psychotomimetic and dissociative adverse effects to the patient.