Pharmacogenomics-Guided Pharmacotherapy in Patients with Major Depressive Disorder or Bipolar Disorder Affected by Treatment-Resistant Depressive Episodes: A Long-Term Follow-Up Study

Abstract

Treatment-resistant depression (TRD) reduces affected patients’ quality of life and leads to important social health care costs. Pharmacogenomics-guided treatment (PGT) may be effective in the cure of TRD. The main aim of this study was to evaluate the clinical changes after PGT in patients with TRD (two or more recent failed psychopharmacological trials) affected by bipolar disorder (BD) or major depressive disorder (MDD) compared to a control group with treatment as usual (TAU). We based the PGT on assessing different gene polymorphisms involved in the pharmacodynamics and pharmacokinetics of drugs. We analyzed, with a repeated-measure ANOVA, the changes between the baseline and a 6 month follow-up of the efficacy index assessed through the Clinical Global Impression (CGI) scale, and depressive symptoms through the Hamilton Depression Rating Scale (HDRS). The PGT sample included 53 patients (26 BD and 27 MDD), and the TAU group included 52 patients (31 BD and 21 MDD). We found a significant within-subject effect of treatment time on symptoms and efficacy index for the whole sample, with significant improvements in the efficacy index (F = 8.544; partial η² = 0.077, p < 0.004) and clinical global impression of severity of illness (F = 6.818; partial η² = 0.062, p < 0.01) in the PGT vs. the TAU group. We also found a significantly better follow-up response (χ² = 5.479; p = 0.019) and remission (χ² = 10.351; p = 0.001) rates in the PGT vs. the TAU group. PGT may be an important option for the long-term treatment of patients with TRD affected by mood disorders, providing information that can better define drug treatment strategies and increase therapeutic improvement.

Frequencies of Combined Dysfunction of Cytochromes P450 2C9, 2C19, and 2D6 in an Italian Cohort: Suggestions for a More Appropriate Medication Prescribing Process

“…About one-third of these patients experience severe side effects [ 39 ]. The optimization of drug cocktails in these patients according to PGXs and DDIs has been proven to be effective in ameliorating the treatment outcomes [ 41 , 42 , 43 ].…”

The Role of Pharmacogenetics in Personalizing the Antidepressant and Anxiolytic Therapy

“…The CYP450 family is a large group of enzymes responsible for the metabolism of various drugs and xenobiotics, including antidepressant drugs. Among the many identified CYP450 enzymes, the most important ones involved in the metabolism of a variety of psychotropic drugs are CYP2D6, CYP2C19, CYP3A4, CYP1A2, CYP2B6, CYP2C8, and CYP2C9 [9,37]. Various CYP450 enzymes are capable of metabolizing more than one drug, and a single drug can be metabolized by multiple CYP enzymes [15].…”

“…In addition to various environmental, physiological, and psychological factors, these individual differences might be largely due to genetic factors [3,4]. Therefore, various pharmacogenetic studies have been conducted to identify genetic variants that can predict patients who may optimally benefit from specific, individually tailored treatments [5][6][7][8][9] (Figure 1).…”

“…Pharmacogenetic studies have focused primarily on candidate genes involved in drug metabolism and transport (pharmacokinetics) as well as drug action (pharmacodynamics), which can influence both treatment efficacy and the development of adverse drug effects [9][10][11]. Pharmacokinetics addresses the variability in the drug's absorption, distri- The molecules involved in ADME processes include enzymes responsible for drug metabolism and drug transport molecules that mediate drug uptake and efflux [4].…”