1 1 Emotional Brain BV, Almere, The Netherlands.
2 2 Chemistry and Life Sciences, V.O. Patients & Trademarks, Amsterdam, The Netherlands.
3 3 Alan Turing Institute Almere, Almere, The Netherlands.
4 4 Department of Experimental Psychology, Utrecht University, Utrecht, The Netherlands.
5 5 Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa.
6 6 Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
7 7 Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands.
8 8 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
9 9 Department of Central Hospital Pharmacy, Viecuri Hospital, Venlo, The Netherlands.
10 10 Exelion Bio-Pharmaceutical Consultancy B.V., Waddinxveen, The Netherlands.
11 11 Department of Information and Computing Sciences, Utrecht University, Utrecht, The Netherlands.
12 12 Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
13 13 Research Group of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherland.
14 14 Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
15 15 Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.
16 16 Department of Psychology, Centre for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada.

Genotype scores predict drug efficacy in subtypes of female sexual interest/arousal disorder: A double-blind, randomized, placebo-controlled cross-over trial.

Womens Health (Lond). 2018 Jan-Dec;14:1745506518788970

Authors: Tuiten A, Michiels F, Böcker KB, Höhle D, van Honk J, de Lange RP, van Rooij K, Kessels R, Bloemers J, Gerritsen J, Janssen P, de Leede L, Meyer JJ, Everaerd W, Frijlink HW, Koppeschaar HP, Olivier B, Pfaus JG

Abstract

Attempts to develop a drug treatment for female sexual interest/arousal disorder have so far been guided by the principle of 'one size fits all', and have failed to acknowledge the complexity of female sexuality. Guided by personalized medicine, we designed two on-demand drugs targeting two distinct hypothesized causal mechanisms for this sexual disorder. The objective of this study was to design and test a novel procedure, based on genotyping, that predicts which of the two on-demand drugs will yield a positive treatment response. In a double-blind, randomized, placebo-controlled cross-over experiment, 139 women with female sexual interest/arousal disorder received three different on-demand drug-combination treatments during three 2-week periods: testosterone 0.5?mg?+?sildenafil 50?mg, testosterone 0.5?mg?+?buspirone 10?mg, and matching placebo. The primary endpoint was change in satisfactory sexual events. Subjects' genetic profile was assessed using a microarray chip that measures 300,000 single-nucleotide polymorphisms. A preselection of single-nucleotide polymorphisms associated with genes that are shown to be involved in sexual behaviour were combined into a Phenotype Prediction Score. The Phenotype Prediction Score demarcation formula was developed and subsequently validated on separate data sets. Prediction of drug-responders with the Phenotype Prediction Score demarcation formula gave large effect sizes (d?=?0.66 through 1.06) in the true drug-responders, and medium effect sizes (d?=?0.51 and d?=?0.47) in all patients (including identified double, and non-responders). Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the Phenotype Prediction Score demarcation formula were all between 0.78 and 0.79, and thus sufficient. The resulting Phenotype Prediction Score was validated and shown to effectively and reliably predict which women would benefit from which on-demand drug, and could therefore also be useful in clinical practice, as a companion diagnostic establishing the way to a true personalized medicine approach.

PMID: 30016917 [PubMed - indexed for MEDLINE]