The effects of polypharmacy on plasma concentrations of therapeutic drug monitoring in patients with dependence and bipolar disease: A retrospective study for Turkish population

The aim of the study is to examine the prevalence of polypharmacy and its effects on the changes of therapeutic drug levels and also to examine patient and practice characteristics associated with polypharmacy. Data for all 12.734 registrations pertaining to 1.530 inpatients were from NP Hospitals. Aim of the study is to analyze the changes related to the number of drugs and to detect the risk of potentially serious therapeutic drug levels and biochemical parameters over time. As part of clinical routine; serum levels of antidepressants, antipsychotics, fasting blood sugar, AST, ALT, creatinine, urea were recorded from patients' charts of in-patient and evaluated retrospectively. The mean age for all patients was 35.23 ± 0.12 (Mean ± SEM) years. The average of total prescribed drugs for these hospitalized patients is 6.51 ± 0.26 (range, 1-23) drugs. For male, it is 6.69 ± 0.03 (range, 1-21) and for female it is 6.14 ± 0.04 (range, 1-23) drugs. Firstly, the probable effects of polypharmacy on diagnostic types, age and blood chemistry values were examined. Significant increases were observed about the number of drugs in patients with alcohol dependence (7.86±0.08), substance dependence (6.51±0.03); and also number of drugs were highest in their late years. Greater than 70 years old it was (9.3±0.15) and in 20-29 age group it was (5.97 ± 0.03). The number of drugs did not change the levels of fasting blood glucose. The levels of fasting blood glucose (FBG) were increased significantly in diagnosis of substance dependence groups compared to other diagnosis groups. The effects of number of drugs, age, diagnosis and gender on ALT levels were also analyzed but not observed significant effects on ALT. AST levels were not changed by the number of drugs and age, but the gender and diagnosis of the patients significantly changed AST levels. Creatinine levels were not changed by the number of drugs, but the gender, age and diagnosis changed the levels of creatinine. Pearson correlation coefficients between the number of drugs and creatinine levels were r =-0.27, r =-0.209 of male and female, respectively. The number of drugs, gender, age, and diagnosis indicated significant changes on the levels of urea. In male patients group and patients with bipolar disorder, the number of drugs increased the levels of urea. In female patients group, 13 and upper amount of drugs increased the levels of urea more than the other number of drug groups. Secondly, the effects of number of drug on plasma concentrations of drug were analyzed. The number of drug significantly; increased the plasma concentrations of Aripiprazole in 4-6 and 7-9 drug used groups; decreased the plasma concentrations of Bupropion in 7-9 and 13 and upper amount of drugs used groups; decreased the plasma concentrations of Clomipramine in 4-6, 7-9, 10-12 and 13 and upper amount of drug used groups; increased the plasma concentrations of pregabaline in 7-9, 10-12 and 13 and upper amount of drugs used groups; increased sulpiride plasma concentrations in all drug groups; decreased the plasma concentrations of valproic acid in 7-9 and 10-12 drugs group, except 13 and upper drugs group ; increased the plasma concentrations of Zuclopenthixol in 4-6, 7-9, 10-12 and 13 and upper amount of drugs groups. When examined the plasma concentrations of drug abuse, the number of drugs significantly; increased the plasma concentrations of benzodiazepine in 7-9, 10-12 and 13 and upper amount of drugs used groups; not changed the plasma concentrations of phencyclidine; increased plasma concentrations of ecstasy in all drug groups, except 1-3 drugs used group; not changed the plasma concentrations of opioids in all drug groups. As a conclusion, the study showed that there were significant correlations between the number of drugs and alcohol dependence, and also between the number of drugs and age. The number of drugs did not change FBG and ALT and AST levels, but increased creatinine levels in female patients, and urea levels in both male and females. The number of drugs significantly increased the plasma levels of aripiprazole, bupropion, pregabaline, sulpiride, zuclopenthixol, benzodiazepine, ecstasy and opiate but, decreased clomipramine, valproic acid.