title: Pharmacokinetic considerations in antipsychotic augmentation strategies: How to combine risperidone with low-potency antipsychotics.
abstract: To investigate in vivo the effect of low-potency antipsychotics on metabolism of risperidone (RIS).
  
  
  
  A therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-OH-RIS of 1584 patients was analyzed. Five groups were compared; a risperidone group (n=842) and four co- medication groups; a group co-medicated with chlorprothixene (n=67), a group with levomepromazine (n=32), a group with melperone (n=46), a group with pipamperone (n=63) and a group with prothipendyl (n=24). Plasma concentrations, dose-adjusted plasma concentrations (C/D) of RIS, 9-OH-RIS and active moiety (RIS+9-OH-RIS; AM) as well as the metabolic ratios (9-OH-RIS/RIS; MR) were computed.
  
  
  
  Differences in plasma concentrations were detected for AM and RIS. Pairwise comparisons revealed significant findings; RIS plasma concentrations were higher in co-medication groups than in monotherapy group. Chlorprothixene- and prothipendyl- medicated patients demonstrated no other differences. In the levomepromazine and melperone group plasma and C/D concentrations of AM and RIS were higher, while MRs were lower. For pipamperone, differences included higher C/D values of RIS and lower MRs.
  
  
  
  Alterations of risperidone metabolism suggest pharmacokinetic interactions for levomepromazine and melperone. In the pipamperone-group, lower MRs as well as higher plasma and C/D levels of RIS suggest potential interactions.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulzen
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Aachen, Germany; University Hospital of Psychiatry, Bern, Switzerland. Electronic address: george.schor@gmail.com.
authors.forename: Georgios
authors.initials: G
authors.lastname: Schoretsanitis
authors.affiliation: Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Stegmann
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
authors.forename: Koen R J
authors.initials: KRJ
authors.lastname: Schruers
authors.affiliation: University Hospital of Psychiatry, Bern, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Walther
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; JARA - Translational Brain Medicine, Aachen, Germany.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lammertz
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany; Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Haen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D062313:Databases, Pharmaceutical; D016903:Drug Monitoring; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D001523:Mental Disorders / Q000097:blood* / Q000188:drug therapy*; D018967:Risperidone / Q000493:pharmacokinetics*
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone
keywords: Antipsychotics; Pharmacokinetics; Psychopharmacology; Risperidone; Therapeutic drug monitoring