Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Data Source
2.3. Potential Drug—Drug Interactions Dataset
2.4. Statistical Analysis
3. Results
3.1. General Characteristics of the Patients
3.2. Prevalence of Potential Drug-Drug Interactions
3.3. Risk Factors for Type X Potential Drug—Drug Interactions
3.4. Risk Factors for the Development of Clinically Observed Symptoms and Signs
3.5. Replicate Analysis of Potential Drug-Drug Interactions in 2021
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Total No. (%) | Group 1 a | Group 2 b | |
---|---|---|---|
Patients, n | 311 (100) | 41 (13) | 35 (11) |
Men, n | 179 (58) | 17 (42) | 23 (66) |
Women, n | 132 (43) | 24 (59) | 12 (34) |
Age [years], median (Q1–Q3) | 42 (31–52) | 44 (32–52) | 43 (27–51) |
Smokers, n | 213 (68) | 30 (73) | 28 (80) |
Time of hospitalization [days], median (Q1–Q3) | 34 (18–69) | 79 (50–142) | 31.0 (16–61) * |
Number of hospitalizations, median (Q1–Q3) | 1 (1–2) | 1 (1–2) | 1 (1–1) * |
Number of prescribed drugs, median (Q1–Q3) | 7 (5–10) | 12 (8–15) | 4 (2–6) * |
Polypharmacotherapy, n (%) c | 242 (77.8) | 41 (100) | 13 (37.1) * |
Number of antipsychotics, median (Q1–Q3) | 2 (2–3) | 4 (3–5) | 2 (1–2) * |
Antipsychotic PDD/DDD, median (Q1–Q3) | / | 1.7 (1.3–2.1) | 0.93 (0.73–1.50) * |
Type X Potential Drug—Drug Interaction | No. of Patients (%) | Summary | Patient Management | Interaction Severity | Reliability Rating | |
---|---|---|---|---|---|---|
Diazepam | Olanzapine | 59 (19.0) | Olanzapine may enhance the adverse/toxic effect of benzodiazepines. | Additive adverse effects: cardiorespiratory depression, excessive sedation. | major | good |
Lorazepam | Olanzapine | 26 (8.4) | ||||
Alprazolam | Olanzapine | 23 (7.4) | ||||
Midazolam | Olanzapine | 12 (3.9) | ||||
Haloperidol | Quetiapine | 24 (7.7) | QT-prolonging antipsychotics. | Monitor for QTc interval prolongation and ventricular arrhythmias. | major | good |
Haloperidol | Flupenthixol | 9 (2.9) | ||||
Clozapine | Flupenthixol | 12 (3.9) | Anticholinergic agents may enhance the adverse/toxic effect of other anticholinergic agents. | Additive anticholinergic effects: dry mouth, dry eyes, blurred vision, urinary retention, and constipation. | major | good |
Clozapine | Quetiapine | 10 (3.2) | major | good | ||
Quetiapine | Zuclopenthixol | 9 (2.9) | major | good | ||
Amisulpride | Clozapine | 9 (2.9) | Amisulpride may enhance the adverse/toxic effect of antipsychotics. | Symptoms and signs of neuroleptic malignant syndrome. | major | fair |
Variables | Univariate Model | Multivariate Model | ||
---|---|---|---|---|
OR (95% CI) | p-Value | OR (95% CI) | P-Value | |
Age | 1.02 (0.98–1.06) | 0.293 | 0.97 (0.89–1.04) | 0.376 |
Sex | 0.37 (0.14–0.93) | 0.037 | 0.48 (0.07–2.81) | 0.425 |
Number of drugs | 2.67 (1.79–5.02) | <0.001 | 2.85 (1.84–5.73) | <0.001 |
Number of antipsychotics | 6.62 (3.19–18.04) | <0.001 | / # | / # |
PDD/DDD | 4.85 (1.75–14.73) | 0.003 | / # | / # |
Symptoms and Signs | Multivariate Model | Variables | ||||
---|---|---|---|---|---|---|
Age | Sex | Number of Drugs | PDD/DDD | Type X pDDIs | ||
Nervous system and psychiatric disorders | IRR (95% CI) | 1.00 (0.99–1.01) | 1.09 (0.86–1.39) | 1.06 (1.04–1.09) | 1.33 (1.12–1.58) | 1.46 (0.99–2.17) |
p-value | 0.913 | 0.499 | <0.001 | 0.012 | 0.099 | |
Gastrointestinal, hepatobiliary, metabolic, endocrine, renal and urinary disorders | IRR (95% CI) | 1.00 (0.99–1.01) | 0.66 (0.45–0.97) | 1.14 (1.09–1.19) | 1.10 (0.84–1.43) | 0.81 (0.48–1.38) |
p-value | 0.799 | 0.031 | <0.001 | 0.540 | 0.562 | |
Cardiac and vascular disorders | IRR (95% CI) | 1.03 (0.99–1.08) | 0.50 (0.18–1.36) | 1.22 (1.02–1.45) | 0.73 (0.40–1.35) | 0.55 (0.09–3.48) |
p-value | 0.116 | 0.212 | 0.012 | 0.429 | 0.523 | |
Respiratory disorders | IRR (95% CI) | 1.06 (1.01–1.09) | 0.67 (0.16–2.75) | 1.19 (1.04–1.37) | 1.26 (0.55–2.89) | / |
p-value | 0.095 | 0.530 | <0.043 | 0.647 | / | |
Others | IRR (95% CI) p-value | 1.00 (0.98–1.03) 0.705 | 0.78 (0.47–1.31) 0.335 | 1.22 (1.15–1.30) <0.001 | 1.42 (1.02–1.97) 0.102 | 0.28 (0.12–0.61) 0.006 |
Analysis 2014 | Analysis 2021 | |
---|---|---|
pDDIs in all patients | ||
Patients with type X pDDIs | 170 ** | 121 |
Patients with type D pDDIs | 240 ** | 207 |
Total number of type X pDDIs | 308 | 217 |
Total number of type D pDDIs | 942 | 1043 |
Number of different type X pDDIs | 78 | 54 |
Number of different type D pDDIs | 166 | 158 |
Max number of type X pDDIs per patient (type D) | 10 (21) | 9 (24) |
pDDIs in specific group | ||
Group 1 a | 41 | 17 |
Group 2 b | 35 | 63 |
Changes of pDDI in all patients | ||
X → X | / | 38 |
X → D | / | 5 |
X → C, B, A, N | / | 35 |
New X | / | 16 |
D → D | / | 75 |
D → X | / | 0 |
D → C, B, A, N | / | 91 |
New D | / | 83 |
Most frequent pDDIs | ||
1. type X pDDIs (n) | Diazepam—Olanzapine (59) | Diazepam—Olanzapine (59) |
2. type X pDDIs (n) | Lorazepam—Olanzapine (26) | Lorazepam—Olanzapine (26) |
3. type X pDDIs (n) | Alprazolam—Olanzapine (23) | Alprazolam—Olanzapine (23) |
4. type X pDDIs (n) | Haloperidol—Quetiapine (24) | Midazolam—Olanzapine (12) |
5. type X pDDIs (n) | Midazolam—Olanzapine (12) | Amisulpride—Clozapine (9) |
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Bačar Bole, C.; Nagode, K.; Pišlar, M.; Mrhar, A.; Grabnar, I.; Vovk, T. Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021. Medicina 2023, 59, 284. https://doi.org/10.3390/medicina59020284
Bačar Bole C, Nagode K, Pišlar M, Mrhar A, Grabnar I, Vovk T. Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021. Medicina. 2023; 59(2):284. https://doi.org/10.3390/medicina59020284
Chicago/Turabian StyleBačar Bole, Cvetka, Katja Nagode, Mitja Pišlar, Aleš Mrhar, Iztok Grabnar, and Tomaž Vovk. 2023. "Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021" Medicina 59, no. 2: 284. https://doi.org/10.3390/medicina59020284