The Effects of CYP2C19 Genotype on Proxies of SSRI Antidepressant Response in the UK Biobank.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used psychopharmaceutical treatment for major depressive disorder (MDD), but individual responses to SSRIs vary greatly. CYP2C19 is a key enzyme involved in the metabolism of several drugs, including SSRIs. Variations in the CYP2C19 gene are associated with differential metabolic activity, and thus differential SSRI exposure; accordingly, the CYP2C19 genotype may affect the therapeutic response and clinical outcomes, though existing evidence of this link is not entirely consistent. Therefore, we analysed data from the UK Biobank, a large, deeply phenotyped prospective study, to investigate the effects of CYP2C19 metaboliser phenotypes on several clinical outcomes derived from primary care records, including multiple measures of antidepressant switching, discontinuation, duration, and side effects. In this dataset, 24,729 individuals were prescribed citalopram, 3012 individuals were prescribed escitalopram, and 12,544 individuals were prescribed sertraline. Consistent with pharmacological expectations, CYP2C19 poor metabolisers on escitalopram were more likely to switch antidepressants, have side effects following first prescription, and be on escitalopram for a shorter duration compared to normal metabolisers. CYP2C19 poor and intermediate metabolisers on citalopram also exhibited increased odds of discontinuation and shorter durations relative to normal metabolisers. Generally, no associations were found between metabolic phenotypes and proxies of response to sertraline. Sensitivity analyses in a depression subgroup and metabolic activity scores corroborated results from the primary analysis. In summary, our findings suggest that CYP2C19 genotypes, and thus metabolic phenotypes, may have utility in determining clinical responses to SSRIs, particularly escitalopram and citalopram, though further investigation of such a relationship is warranted.

Predictors of clinical response after rTMS treatment of patients suffering from drug-resistant depression.

Repeated transcranial magnetic stimulation (rTMS) is a therapeutic brain-stimulation technique that is particularly used for drug-resistant depressive disorders. European recommendations mention the effectiveness of 30 to 64%. The failure rate of treatment is high and clinical improvement is visible only after a certain period of time. It would thus be useful to have indicators that could anticipate the success of treatment and more effectively guide therapeutic choices. We aimed to find predictive indicators of clinical improvement at 1 month after the start of rTMS treatment among the data collected during the care of patients with drug-resistant depression included in the Neuromodulation Unit of the Esquirol Hospital in Limoges since 2007. In total, 290 patients with a pharmaco-resistant depressive episode, according to the Hamilton Depression Rating Scale (HDRS) (score ≥8), before treatment who underwent a complete course of rTMS treatment and did not object to the use of their collected data were included. The clinical response in routine practice, corresponding to a decrease in the HDRS score of at least 50% from inclusion, was determined and complemented by interquartile analysis. A combination of factors predictive of clinical response during care, such as a short duration of the current depressive episode associated with a higher HDRS agitation item value (or a lower perceived sleepiness value) and a higher number of previous rTMS treatments, were identified as being useful in predicting the efficacy of rTMS treatment in routine clinical practice, thus facilitating the therapeutic choice for patients with drug-resistant depression.

Acceptability of Pharmacogenetic Testing among French Psychiatrists, a National Survey.

Psychiatric disorder management is based on the prescription of psychotropic drugs. Response to them remains often insufficient and varies from one patient to another. Pharmacogenetics explain part of this variability. Pharmacogenetic testing is likely to optimize the choice of treatment and thus improve patients' care, even if concerns and limitations persist. This practice of personalized medicine is not very widespread in France. We conducted a national survey to evaluate the acceptability of this tool by psychiatrists and psychiatry residents in France, and to identify factors associated with acceptability and previous use. The analysis included 397 observations. The mean acceptability score was 10.70, on a scale from 4 to 16. Overall acceptability score was considered as low for 3.0% of responders, intermediate for 80.1% and high for 16.9%. After regression, the remaining factors influencing acceptability independently of the others were prescription and training history and theoretical approach. The attitude of our population seems to be rather favorable, however, obvious deficiencies have emerged regarding perceived skills and received training. Concerns about the cost and delays of tests results also emerged. According to our survey, one of the keys to overcoming the barriers encountered in the integration of pharmacogenetics seems to be the improvement of training and the provision of information to practitioners.