Study design and setting
An institutional-based multicenter cross-sectional study was conducted from April to July 2021 at five comprehensive and specialized hospitals in Northwest Ethiopia. These hospitals include the University of Gondar Comprehensive and Specialized Hospital (UoGCSH), Felege-Hiwot Comprehensive and Specialized Hospital (FHCSH), Tibebe-Ghion Comprehensive and Specialized Hospital (TGCSH), Debre-Markos Comprehensive and Specialized Hospital (DMCSH), and Debre-Tabor Comprehensive and Specialized Hospital (DTCSH). These hospitals have provided healthcare services for over 26.5 million people in their total catchment areas.
Study participants and inclusion criteria
All adult patients with a psychiatric problem who were admitted to the psychiatric wards of selected hospitals in Northwest Ethiopia were included in the study population. Patients aged 18 years or older, diagnosed with any psychiatric disorder and received a combination of medications were included in the study. Pregnant and lactating mothers, critically ill patients who couldn’t respond to self-response interview questions, and patients with incomplete medical records during the study period did not participate in this study.
Sample size determination and sampling techniques
The single population proportion formula was used to calculate the required sample size by considering the following assumptions: the proportion of drug–drug interactions to be 81.8% (P = 0.82) , the reliability coefficient for 95% confidence level (Z = 1.96) and 5% margin of error (d = 0.05); n = z2pq/d2.
After adding a 10% contingency of non-response, the total sample size of participants to be selected was 325. Participants from the selected hospitals were included based on a proportional allocation formula: ni = n*Ni/N, where, ni = sample size from each hospital, n = total sample size to be selected, N = total population, Ni = total population from each selected hospital. Consequently, the total population from all selected study areas was 984 per year (264 from UoGCSH, 192 from FHCSH, 180 from TGCSH, 192 from DMCSH, and 156 from DTCSH) based on the previous admission. Considering this, 87, 63, 60, 63, and 52 study participants were included from the respective hospitals in the final study.
The participants were included in the final study using a consecutive sampling technique, and all eligible participants from respective sites were enrolled consecutively until the required sample size was obtained.
Definition of terms
Psychiatric disorders: according to the DSM-5 definition, “a syndrome characterized by clinically significant disturbance in an individual’s cognition, emotion regulation, or behavior reflecting a dysfunction in the psychological, biological, or developmental processes underlying mental function.”.
Drug-drug interactions: defined as the pharmacological or clinical response to the administration or co-exposure of a drug with another drug that modifies the patient’s response to the drug index .
Potential drug-drug interactions: According to Consensus recommendations for systematic evaluation of drug-drug interaction evidence for clinical decision support “a potential DDI is defined as the co-prescription of two drugs known to interact, and therefore a DDI could occur in the exposed patient” .
The severity of drug-drug interactions: it is the level of evidence of the severity of the outcome from interactive medications. It can either be contraindicated, the drug-pair is contraindicated in the patient for current use, serious; such an interaction may have a risk of death and/or may result in some serious negative outcome, and recommended to use an alternative, significant; it may have a harmful effect on the patient’s condition and can require close monitoring, or minor (no change required); it may have an increase in frequency or severity of side effects, but would not require therapeutic change and, they are self-limited effects on patients .
Comorbidity: is the presence of one or more additional conditions, often co-occurring with the primary condition.
Duration of treatment: refers to how long (in years) a patient was treated with a manual method for any given problem.
Data collection instruments, procedures and quality management
The data was collected using a structured English questionnaire developed after reviewing various literature [13,14,15,16,17,18,19,20,21]. It was collected by both patient interviews and retrospective medical recording methods for primary and secondary data, respectively. Patient socio-demographic characteristics include: age, gender, monthly income, alcohol drinking habit, substance use (Khat and cigarettes), educational level, occupations, residency, etc. Whereas medications and clinical characteristics like history of allergy, type of medication, number of medications, the duration of treatment, presence of comorbidities, type of psychiatric disorders, and number of hospitalizations were also extracted from the medical records of the participants. Data were collected by five trained clinical pharmacists and five trained psychiatric nurses, who were overseen by two clinical pharmacy lecturers. The chart numbers were entered into Microsoft Office Excel 2016 and checked for duplication.
To ensure the quality of the data, data collectors were trained for two days, and orientation was also provided by the principal investigator. The principal investigator (PI) closely supervised the data collection process, and the collected data was checked daily for completeness during the data collection period. The data collection tool was pretested on 5% of the calculated sample size of patients admitted to the psychiatric ward of Dessie comprehensive specialized hospital to check the acceptability and consistency of the data collection tool two weeks before the actual data collection. The data from the pretest was excluded in the analysis. The questionnaire was sent to senior clinical pharmacists and senior physicians, who were academicians and researchers, for face validity and approval.
Data entry and statistical analysis
The data was coded, cleared, and checked for completeness before being entered into EPI-data version 4.6 and exported to the statistical software package for social sciences (SPSS) version 26 for analysis. Then, it was reviewed and cleaned manually for its completeness and consistency. The results were summarized using descriptive statistics including frequency and percentage for categorical and mean and standard division for continuous variables. The Medscape drug-interaction checker was used to check for pDDIs. To make the assessment of the existing pDDIs consistent, the severity of identified drug-drug interactions was also characterized using evidence from Medscape. Finally, we analyzed only clinically significant drug-drug interactions with most of the pDDIs resulting in significant and serious levels of drug-drug interactions. Independent variables having a p-value < 0.25 in the univariate logistic regression analysis entered into the multivariable logistic regression analysis to control the confounding effect. The odds ratio (OR) with a 95% confidence interval was also computed. In the final model, a p-value < 0.05 was statistically significant.