Coproporphyrin I (CPI) is an established endogenous biomarker for detecting drug-drug interactions (DDIs) involving the hepatic uptake transporter Organic Anion Transporting Polypeptide 1B1 (OATP1B1, gene SLCO1B1). While CPI has been extensively studied in healthy volunteers using controlled pre- and post-OATP1B1-inhibitor sampling, its applicability in samples obtained in clinical routine from multimorbid, polymedicated patients remains poorly characterized. In this study, we evaluated whether single timepoint CPI concentrations obtained in clinical routine can be used to assess in vivo OATP1B1 activity by integrating genetic and pharmacological information. Serum CP levels were measured in patients undergoing pharmacist-led medication reviews following therapy failure or adverse drug reactions. CPI concentrations were analyzed in relation to genotype-predicted OATP1B1 phenotypes and exposure to drugs with potential impact on OATP1B1, which were identified following a previously published work by Stäuble et al., and their interaction with OATP1B1 was further evaluated with the herein presented in vitro transporter assay. CPI levels showed an association with drug intake and genotype-predicted phenotypes. Moreover, patients with decreased- or normal function phenotypes taking putative OATP1B1 inhibitors exhibited CPI levels comparable to patients carrying the poor-function or decreased-function phenotype without intake of such drugs, respectively, consistent with phenoconversion. These findings provide initial evidence that CPI may serve as an endogenous biomarker for identifying drug-drug-gene interactions in clinical routine to support a safer and more effective drug therapy. Furthermore, our data emphasize the need for further investigations in larger and more diverse patient populations to validate the findings on CPI.

Objectives:Interindividual variability in analgesic responsiveness often results in therapy failure (TF) or adverse drug reactions (ADR) and poses a major challenge in chronic pain management, as it is influenced by multiple factors. This exploratory study investigated whether pharmacogenetic (PGx) testing could identify drug-gene interactions (DGIs) explaining variability in drug response. In addition, we explored whether genetic predispositions in CYP2D6 and COMT, indicating increased pain sensitivity, are linked to TF.Methods:We analyzed data from chronic pain patients who underwent pharmacogenotyping due to suspected TF or ADR. PGx panel testing was carried out by a commercial provider. Additional genotyping of COMT rs6269, rs4633, and rs4818 was performed using PCR, RFLP, and Sanger sequencing.Results:PGx panel testing confirmed at least one relevant genetic variant in 45% of the suspected DGIs. Notably, 41% involved the pharmacogenes CYP2D6, CYP2C19, and CYP2C9. Subgroup analyses revealed that patients carrying the COMT high pain sensitivity (HPS) allele, COMT high pain phenotype, or CYP2D6 intermediate metabolizer (IM) phenotype were significantly more likely to experience TF. Logistic regression confirmed both phenotypes as significant predictors of TF.Discussion:Our findings support the relevance of CYP2D6, CYP2C19, and CYP2C9 as key pharmacogenes for PGx testing in chronic pain management. The results suggest that a genetic predisposition in CYP2D6 and COMT, associated with increased pain sensitivity, may contribute to insufficient analgesia and subsequent TF. These insights indicate the potential value of incorporating CYP2D6 and COMT as pain-modulating genetic markers into the broader framework of PGx testing.

OBJECTIVES:Interindividual variability in analgesic responsiveness often results in therapy failure (TF) or adverse drug reactions (ADR) and poses a major challenge in chronic pain management, as it is influenced by multiple factors. This exploratory study investigated whether pharmacogenetic (PGx) testing could identify drug-gene interactions (DGIs) explaining variability in drug response. In addition, we explored whether genetic predispositions in CYP2D6 and COMT , indicating increased pain sensitivity, are linked to TF. METHODS:We analyzed data from chronic pain patients who underwent pharmacogenotyping due to suspected TF or ADR. PGx panel testing was carried out by a commercial provider. Additional genotyping of COMT rs6269, rs4633, and rs4818 was performed using PCR, RFLP, and Sanger sequencing. RESULTS:PGx panel testing confirmed at least one relevant genetic variant in 45% of the suspected DGIs. Notably, 41% involved the pharmacogenes CYP2D6 , CYP2C19 , and CYP2C9 . Subgroup analyses revealed that patients carrying the COMT high pain sensitivity (HPS) allele, COMT high pain phenotype, or CYP2D6 intermediate metabolizer (IM) phenotype were significantly more likely to experience TF. Logistic regression confirmed both phenotypes as significant predictors of TF. DISCUSSION:Our findings support the relevance of CYP2D6 , CYP2C19 , and CYP2C9 as key pharmacogenes for PGx testing in chronic pain management. The results suggest that a genetic predisposition in CYP2D6 and COMT , associated with increased pain sensitivity, may contribute to insufficient analgesia and subsequent TF. These insights indicate the potential value of incorporating CYP2D6 and COMT as pain-modulating genetic markers into the broader framework of PGx testing.

Background: Chronic pain is a complex condition affecting patients’ health-related quality of life (HRQoL). Pharmacogenetic (PGx) testing offers an approach to personalize pain management by optimizing medication regimens. However, the impact of this approach on measurable patient reported outcomes (PROs) remains unexplored. Objectives: This study evaluated the association of PGx testing on PROs in chronic pain patients and investigated differences between those who received PGx-guided therapy and those who did not, focusing on changes in HRQoL and pain intensity from pre-to-post PGx. Design: An exploratory pre-post analysis was conducted as part of an observational case series assessing the influence of PGx testing and subsequent PGx-guided therapy on PROs in chronic pain patients with drug-related problems under their analgesic regimen. Methods: PROs were assessed in 29 patients pre-PGx (baseline) and post-PGx (follow-up, 4-6 weeks later). HRQoL was measured using the EQ-5D-5L. The EQ index was calculated using the German value set. Pain intensity was determined with the Numeric Rating Scale (NRS). Minimal important difference (MID) threshold was applied for both outcomes. Statistical analyses included Wilcoxon signed-rank tests, chi-square tests, and effect size calculations. Results: The mean EQ index score improved from pre-to-post PGx (0.379 ± 0.420-0.697 ± 0.307, P < .001, d = −0.84). Stratification revealed that the PGx-guided therapy group showed significantly greater improvements in HRQoL and NRS compared to the non-PGx guided therapy group ( P < .01). Among 19 patients who met the MID for the EQ index, 18 had undergone PGx-guided therapy. For NRS, MID was reached in 3 pain intensity categories in the PGx-guided therapy group. Conclusions: HRQoL and pain intensity significantly improved after PGx testing, with potentially clinically relevant results in the PGx-guided therapy group. Due to the observational nature of the study, further controlled studies are required to assess the clinical impact and economic feasibility of PGx-guided therapy.

Pharmacogenetic (PGx) testing is a promising approach for optimizing drug therapies. However, there is limited knowledge regarding its real-world utilization and long-term impact in clinical practice. This study assessed how often PGx information informs treatment decisions and evaluated patients’ perspectives on its use and non-use, identifying enablers for PGx implementation. A mixed-methods study was conducted with 24 patients with a median of 1 year after PGx testing. Medication and health-related data were collected at enrollment and at the follow-up 1 year later using a semi-structured questionnaire. At the follow-up, 62 medication changes were identified in 18 patients. A median of four medication changes per patient were initiated mainly by medical specialists (58%). PGx information was considered for 15 patients in 39 medication changes (63%). Patient-reported factors contributing to the non-use of PGx information included a lack of knowledge and interest among healthcare professionals (HCPs), structural and administrative barriers, and an over-reliance on patient advocacy. Potential enablers should address targeted PGx education, interprofessional collaboration, awareness among policymakers, and concise recommendations focused on PGx-actionable drugs from testing providers. By implementing these interdependent enablers, PGx can evolve into a long-term, clinically integrated cornerstone of individualized pharmacotherapy.

Background Direct oral anticoagulants (DOAC) effectively prevent recurrent ischaemic events in atrial fibrillation (AF) patients with recent stroke. However, excellent adherence to DOAC is mandatory to guarantee sufficient anticoagulation as the effect quickly subsides. Aim To investigate the effect of intake reminders on adherence to DOAC. Methods MAAESTRO was a randomised, cross-over study in DOAC-treated AF patients hospitalised for ischaemic stroke. Adherence was measured by electronic monitoring for 12 months. After an observational phase, patients were randomised to obtain an intake reminder either in the first or the second half of the subsequent 6-month interventional phase. The primary outcome was 100%-timing adherence . Secondary outcomes were 100%-taking adherence , and overall timing and taking adherence. We analysed adherence outcomes using McNemar’s test or mixed-effects logistic models. Results Between January 2018 and March 2022, 130 stroke patients were included, of whom 42 dropped out before randomisation. Analysis was performed with 84 patients (mean age: 76.5 years, 39.3% women). A 100%-timing adherence was observed in 10 patients who were using the reminder, and in zero patients without reminder ( p = 0.002). The reminder significantly improved adherence to DOAC, with study participants having 2.7-fold increased odds to achieve an alternative threshold of 90%-timing adherence (OR 2.65; 95% CI 1.05–6.69; p = 0.039). A similar effect was observed for 90%-taking adherence (OR 3.06; 95% CI 1.20–7.80; p = 0.019). Overall timing and taking adherence increased significantly when using the reminder (OR 1.70; 95% CI 1.55–1.86, p < 0.01; and OR 1.67; 95% CI 1.52–1.84; p < 0.01). Conclusion Intake reminders increased adherence to DOAC in patients with stroke attributable to atrial fibrillation. Trial registration ClinicalTrials.gov: NCT03344146.

BackgroundIn clinical practice, family medication history is not routinely assessed as part of a patient's family health history (FHH). The information is self-reported and can depend on the individual's subjective perception. To illustrate how pharmacogenetic (PGx) testing results could be used to validate self-reported family medication history on drug-related problems (DRP), as well as to inform medication-related decisions, we herein present a case involving ten members of the same family.Case PresentationPrior to a planned surgery, a preemptive PGx panel test was performed for a nine-year-old girl due to self-reported family medication history. The PGx panel test was also performed for her three siblings, parents, and grandparents. The focus was directed to the paternal grandmother, as she reported DRP from the hypnotic agent propofol, and to the maternal grandmother, as she described DRP after the administration of codeine and tramadol. A commercial PGx panel test of 100 variations in 30 different genes was conducted and analyzed focusing on genetic variants in cytochrome P450 enzyme 2B6 (CYP2B6), and CYP2D6 as they are involved in the biotransformation of propofol and the bioactivation of codeine and tramadol, respectively. The girl was identified as (1) CYP2B6 intermediate metabolizer (IM) with reduced enzyme activity and (2) CYP2D6 poor metabolizer (PM) with no enzyme activity. Regarding the planned surgery, it was recommended (1) to carefully titrate propofol dosage with increased monitoring of potential DRP and (2) to avoid opioids whose activation is mediated by CYP2D6 (e.g. codeine and tramadol). Further PGx testing revealed (1) the paternal grandmother as CYP2B6 normal metabolizer (NM) and (2) the maternal grandmother as CYP2D6 NM.ConclusionThe original trigger for PGx testing was the self-reported, conspicuous family medication history of DRP reported by the grandmothers. However, the girl's genotype predicted phenotypes of CYP2B6 IM and CYP2D6 PM, differed from the grandmothers'. With this exemplary case, we propose that hereditary concerns based on self-reported information on DRP should be verified by a PGx panel test, when the respective drug exhibits a PGx association. Also, the girl's PGx testing results provided important medication recommendations, which were considered perioperatively by the anesthetist suggesting to use PGx testing results preemptively to inform medication-related decisions.

Journal of Evaluation in Clinical PracticeEarly View COMMENTARY The 8-item Morisky Medication Adherence Scale translated in German and validated against objective and subjective polypharmacy adherence measures in cardiovascular patients Arnet Isabelle PhD, Corresponding Author Arnet Isabelle PhD [email protected] orcid.org/0000-0001-7591-4104 Pharmaceutical Care, Pharmaceutical Sciences, University of Basel, Basel, Switzerland Correspondence Arnet Isabelle, PhD, Pharmaceutical Care Research Group, University of Basel, Klingelbergstrasse 50, 4056 Basel. Email: [email protected]Search for more papers by this authorMetaxas Corina PhD, Metaxas Corina PhD Erlenhof Zentrum, department pharmacy, Reinach, SwitzerlandSearch for more papers by this authorHersberger Kurt, Hersberger Kurt orcid.org/0000-0001-8678-697X Pharmaceutical Care, Pharmaceutical Sciences, University of Basel, Basel, SwitzerlandSearch for more papers by this authorOrtiz Michael PhD, Ortiz Michael PhD St Vincent's Clinical School, University of New South Wales, Sydney, AustraliaSearch for more papers by this authorAllemann Samuel, Allemann Samuel orcid.org/0000-0003-4067-9401 Pharmaceutical Care, Pharmaceutical Sciences, University of Basel, Basel, SwitzerlandSearch for more papers by this author Arnet Isabelle PhD, Corresponding Author Arnet Isabelle PhD [email protected] orcid.org/0000-0001-7591-4104 Pharmaceutical Care, Pharmaceutical Sciences, University of Basel, Basel, Switzerland Correspondence Arnet Isabelle, PhD, Pharmaceutical Care Research Group, University of Basel, Klingelbergstrasse 50, 4056 Basel. Email: [email protected]Search for more papers by this authorMetaxas Corina PhD, Metaxas Corina PhD Erlenhof Zentrum, department pharmacy, Reinach, SwitzerlandSearch for more papers by this authorHersberger Kurt, Hersberger Kurt orcid.org/0000-0001-8678-697X Pharmaceutical Care, Pharmaceutical Sciences, University of Basel, Basel, SwitzerlandSearch for more papers by this authorOrtiz Michael PhD, Ortiz Michael PhD St Vincent's Clinical School, University of New South Wales, Sydney, AustraliaSearch for more papers by this authorAllemann Samuel, Allemann Samuel orcid.org/0000-0003-4067-9401 Pharmaceutical Care, Pharmaceutical Sciences, University of Basel, Basel, SwitzerlandSearch for more papers by this author First published: 21 March 2024 https://doi.org/10.1111/jep.13975Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Arnet I, Metaxas C, Walter PN, Morisky DE, Hersberger KE. The 8-item morisky medication adherence scale translated in German and validated against objective and subjective polypharmacy adherence measures in cardiovascular patients. J Eval Clin Pract. 2015; 21(2): 271-277. 10.1111/jep.12303 PubMedWeb of Science®Google Scholar 2Desteghe L, Kluts K, Vijgen J, et al. Corrigendum and editorial warning regarding use of the MMAS-8 scale (The health buddies app as a novel tool to improve adherence and knowledge in atrial fibrillation patients: A pilot study). JMIR Mhealth Uhealth. 2018; 6(11):e12202. 10.2196/12202 PubMedGoogle Scholar 3Casebeer AW, Antol DD, Hopson S, et al. 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Background Non-adherence to antihypertensive agents is common, mainly because of the low perceived burden of high blood pressure. General practitioners (GPs) are unable to predict whether patients are adhering to a recommended treatment. Knowledge about adherence might be of clinical interest in patients non-responding to antihypertensive treatment.Aim To assess the usefulness of an Adherence Monitoring Package (AMoPac) to identify non-adherence in patients non-responding to antihypertensive treatment.Methods AMoPac consists of (1) 4 weeks of electronic adherence monitoring, (2) pharmacist’s feedback on patient’s intake behaviour and (3) adherence metrics including clinical-pharmaceutical recommendations to the GP. AMoPac-HYP (‘Adherence Monitoring Package to identify non-adherence in ambulatory HYPertensive patients’) is an observational study among GPs and ambulatory patients with hypertension in a real-world setting. The primary outcome was GPs’ perceived usefulness of AMoPac. Secondary outcomes were (1) frequency of medication problems and prescribing errors; (2) types of pharmacist’s’ recommendations; (3) acceptance of the recommendations by GPs; (4) medication adherence and (5) patients’ satisfaction. Outcomes are reported descriptively. Data were collected with questionnaires and electronic monitoring of medicine intake.Results Fifteen GPs and 15 patients with hypertension participated in the AMoPac-HYP Study. Patients were on average 62 years old, and mean blood pressure was 137/83 mmHg. All GPs rated AMoPac as useful. The most frequently mentioned use was excluding non-adherence in patients with hypertension (93%). Medication problems and prescribing errors were observed in 80% of the patients. The study pharmacist recommended adherence support (N=9 patients) and treatment optimisation (N=8 patients). The recommendations were accepted and implemented in 10 of 17 cases by the GP. Patients’ mean taking and timing adherence were 90% and 86%, respectively. Satisfaction with the study procedures among patients was high.Conclusion AMoPac was rated as useful for identifying and excluding non-adherence in patients with hypertension and was highly accepted among patients. Including adherence data in clinical decision-making could contribute to optimising patient care.

Evaluations recognize healthy living champions (HLCs) as key contributors to the Health Living Pharmacy (HLP) project's success; the project has served to reduce pressure on family doctor services and clients who would have otherwise not sought professional advice have accessed HLP services.To investigate the impact of innovative networking opportunities in supporting HLCs to function within their role and to explore the network's potential in promoting sustained HLP participation.Twenty of Portsmouth's (England) HLCs (n = 33) agreed to participate in focus groups. Transcripts were subjected to interpretative phenomenological analysis guided by grounded theory. The transcripts were read repeatedly; recurrent themes were identified and coded manually and consensus was reached by discussion within the research team.Network meetings provide HLCs with professional development, networking opportunities and continued encouragement. Recommendations to develop and sustain the network included the formation of a group committee and establishing of a communication facility accessible between meetings.The successful Portsmouth HLP project informed the design of UK HLP projects. The current focus is to build a successful strategy to sustain the positive outcomes, building on the recognized enablers. This study contributes further lessons learned to guide health commissioners and service implementers to best support staff development, involvement and motivation through innovative practice.

Introduction: Opioid agonist treatment (OAT) is the first-line treatment for opioid use disorder (OUD). Simultaneously, opioids are essential medicines in acute pain management. The literature is scarce on acute pain management in individuals with OUD, and guidelines are controversial for patients on OAT. We aimed at analyzing rescue analgesia in opioid-dependent individuals on OAT during hospitalization in the University Hospital Basel, Switzerland. Methods: Patient hospital records were extracted from the database over 6 months (Jan-Jun) in 2015 and 2018. Of the 3,216 extracted patient records, we identified 255 cases on OAT with full datasets. Rescue analgesia was defined according to established principles of acute pain management, e.g., i) the analgesic agent is identical to the OAT medication, and ii) the opioid agent is dosed above 1/6th morphine equivalent dose of the OAT medication. Results: The patients were on average 51.3 ± 10.5 years old (range: 22–79 years), of which 64% were men. The most frequent OAT agents were methadone and morphine (34.9% and 34.5%). Rescue analgesia was not documented in 14 cases. Guideline-concordant rescue analgesia was observed in 186 cases (72.9%) and consisted mostly of NSAIDs, including paracetamol (80 cases), and identical agents such as the OAT opioid (70 cases). Guideline-divergent rescue analgesia was observed in 69 (27.1%) cases, predominantly due to an underdosed opioid agent (32 cases), another agent other than the OAT (18 cases), or contraindicated agents (10 cases). Discussion: Our analysis suggests that rescue analgesia in hospitalized OAT patients was predominantly concordant with guidelines, while divergent prescriptions seemed to follow common principles of pain medicine. Clear guidelines are needed to appropriately treat acute pain in hospitalized OAT patients.

A woman with ocular hypertension suffered from severe bradycardia, hypotension and syncope attacks in temporal relation with ophthalmic timolol application. Topically applied timolol is nasally absorbed and has been shown to reach potentially relevant systemic concentrations. Timolol is mainly metabolized by CYP2D6, which exhibits interindividual metabolic capacity due to genetic variations. A reactive pharmacogenetic panel test identified the patient as a CYP2D6 homozygous *4 allele carrier, which has been associated with a poor metabolizer phenotype and lacking enzyme activity. Thus, the adverse drug reactions possibly resulted from increased systemic timolol exposure. This case report highlights that pharmacogenetic panel testing can contribute to safe and effective pharmacotherapy, even for topically applied drugs.

BACKGROUND:Hepatitis C virus (HCV) infections are a public health burden worldwide and often go undetected until sequelae develop. Offering HCV screening for the different vulnerable populations in community pharmacies could help prevent further undetected HCV infections. This pilot aimed to assess the feasibility and pharmacist acceptance of HCV rapid antibody saliva testing in community pharmacies.METHODS:A structured pharmaceutical care intervention was developed that included addressing, informing, and screening clients, as well as referral and reporting to subsequent health care providers. Participating pharmacies from French-, German- and Italian-speaking parts of Switzerland were trained to provide this service to local vulnerable populations. Information on client recruitment, feasibility, and acceptability of HCV screening was collected.RESULTS:Of 36 pharmacies initially recruited, 25 started the pilot and approached 435 clients, 145 of whom (33%) were interested in screening. Eight of these rapid antibody tests returned positive (prevalence rate: 5.5%). Facilitators were being able to offer a free rapid test (73%), followed by having training prior to the project (67%) and having a new service to offer (67%). The possibility of clients reacting dismissively (53%) and of unsettling clients (47%) were reported to be the main barriers.CONCLUSIONS:This pilot demonstrated the general feasibility of an HCV screening service with rapid antibody saliva testing in Swiss community pharmacies, which achieved a higher prevalence rate than national estimates. With appropriate communication training and remuneration, Swiss community pharmacies could be an important partner in implementing HCV elimination strategies.

Purpose:Pharmacogenetics (PGx) is an emerging aspect of personalized medicine with the potential to increase efficacy and safety of pharmacotherapy. However, PGx testing is still not routinely integrated into clinical practice. We conducted an observational case series study where PGx information from a commercially available panel test covering 30 genes was integrated into medication reviews. The aim of the study was to identify the drugs that are most frequently object of drug-gene-interactions (DGI) in the study population.Patients and Methods:In out-patient and in-patient settings, we recruited 142 patients experiencing adverse drug reaction (ADR) and/or therapy failure (TF). Collected anonymized data from the individual patient was harmonized and transferred to a structured database.Results:The majority of the patients had a main diagnosis of a mental or behavioral disorder (ICD-10: F, 61%), of musculoskeletal system and connective tissue diseases (ICD-10: M, 21%), and of the circulatory system (ICD-10: I, 11%). The number of prescribed medicines reached a median of 7 per person, resulting in a majority of patients with polypharmacy (≥5 prescribed medicines, 65%). In total, 559 suspected DGI were identified in 142 patients. After genetic testing, an association with at least one genetic variation was confirmed for 324 suspected DGI (58%) caused by 64 different drugs and 21 different genes in 141 patients. After 6 months, PGx-based medication adjustments were recorded for 62% of the study population, whereby differences were identified in subgroups.Conclusion:The data analysis from this study provides valuable insights for the main focus of further research in the context of PGx. The results indicate that most of the selected patients in our sample represent suitable target groups for PGx panel testing in clinical practice, notably those taking drugs for mental or behavioral disorder, circulatory diseases, immunological diseases, pain-related diseases, and patients experiencing polypharmacy.

Background Pharmacogenetic (PGx) testing and counselling (short: PGx service) in the community pharmacy is not routinely practiced. We propose a comprehensive pharmacist-led service where PGx information is integrated into medication reviews. Aim To evaluate the pharmacist-led service comprising PGx testing and counselling (PGx service) from the perspective of patients. Method For this mixed-methods study, we conducted two follow-up interviews F 1 and F 2 with patients recruited for the PGx service in a community pharmacy after 1st of January 2020. The semi-structured interviews were held by phone call and covered understanding of PGx, the implementation of recommendations, handling of PGx documents (list of concerned substances and PGx recommendation), gain in medication knowledge, and willingness to pay for the PGx service. Results We interviewed 25 patients in F 1 and 42 patients in F 2. Patients were generally able to understand and use results of the PGx service. At least one PGx recommendation was implemented for 69% of the patients. Handling of PGx documents ranged from patients having forgotten about the PGx results to patients consulting the list for every medication-related decision; the latter often expecting negative effects. Finally, 62% of the patients were willing to pay for the PGx service. Conclusion For future PGx testing and counselling, HCPs should consider the patients’ health literacy in a standardized way and use adequate communication skills to enhance the patient's understanding in PGx and to attenuate potential negative expectations.

We report the case of a 50-year-old male with major depressive disorder (MDD) to illustrate the challenge of finding effective antidepressant pharmacotherapy and the role that the patient's genetic makeup may play. Recent treatment attempts before clinic admission included venlafaxine and fluoxetine. Venlafaxine was discontinued due to lack of response, and subsequently switched to fluoxetine based on pharmacogenotyping of the P-glycoprotein transporter (P-gp, encoded by ABCB1) by the outpatient psychiatrist. Despite steady state serum levels within the therapeutic range, the patient did not benefit from fluoxetine either, necessitating admission to our clinic. Here a clinical pharmacist-led medication review including additional pharmacogenetic (PGx) analysis resulted in the change of the antidepressant therapy to bupropion. Under the new regimen, established in the in-patient-setting, the patient remitted. However, based on the assessed pharmacokinetics-related gene variants, including CYPs and ABCB1, non-response to fluoxetine could not be conclusively explained. Therefore, we retrospectively selected the serotonin transporter (SERT1, encoded by SLC6A4) for further genetic analysis of pharmacodynamic variability. The patient presented to be a homozygous carrier of the short allele variant in the 5-HTTLPR (S/S) located within the SLC6A4 promoter region, which has been associated with a reduced expression of the SERT1. This case points out the potential relevance of panel PGx testing considering polymorphisms in genes of pharmacokinetic as well as pharmacodynamic relevance.