Summary of Clinical Studies

“The clinical benefit of Neuropharmagen® has been evaluated in various clinical studies published in reputable journals edited by experts. In fact, this is the only pharmacogenetic test in the field of psychiatry supported by in-depth clinical research.

Moreover, we continue to rely on personalized medicine in psychiatry, relying on the ongoing clinical research on new pathologies.

You can learn about the results of trials below:”

Randomized clinical trial, double-blind, controlled, naturalistic, multicenter and prospective, enrolling 316 patients with major depressive disorder

The largest randomized clinical trial (RCT) conducted to date using a pharmacogenetic test in patients with major depressive disorder in 18 hospitals in Spain.

Developed to evaluate the effectiveness of Neurofarmagen in the choice of pharmacological treatment, with improvement measured by the Patient Global Impression of Improvement (PGI-I) scale.

The main purpose: The basic study variable was the number of patients who showed a response to treatment, which was defined as “mild improvement” or “significant improvement” on the Patient Global Impression of Improvement (PGI-I) scale. Minor variables such as the Hamilton Depression Rating Scale (HDRS-17) or FIBSER (Frequency, Intensity, Burden of Side Effects Rating) were also analyzed to assess treatment tolerability.

Results

The use of Neurofarmagen® helped to increase the rate of response to ongoing therapy among patients from 1 to 3 failures in the previous treatment by 67% in 12 weeks. OR: 2.39 [CI: 1.28–4.44).

The response rate to treatment increased significantly after 12 weeks in patients treated according to the recommendations of the Neurofarmagen® test, compared with patients who received conventional treatment (control group).

The burden of adverse effects decreased significantly among patients who were treated according to the recommendations of the Neurofarmagen® test, compared with patients who received conventional treatment.

54% reduction in burden
of adverse effects in 12 weeks

This is an analysis of clinical data obtained in a randomized clinical trial AB-GEN (retrospective analysis) to assess the clinical benefit of drug therapy based on the recommendations of the Neuropharmagen® test in certain subgroups of patients by age, basic severity and duration of depressive episodes.

Design:  Clinical prospective, double-blind and randomized study in patients with major depressive disorder (MDD). Read the AB-GEN Study.

The core target: To study the impact of factors considered to be determinants of clinical response to antidepressants (such as age, main severity, and duration of a depressive episode) on the clinical benefit of Neurofarmagen®. The end points considered were PGI-I response rates (rate ≤ 2), change in HDRS rates, and HDRS response (change ≥ 50%).

Objects:  the study group was described in the basic publication of the results of the AB-GEN study [1]. The following subgroups of patients were examined in this data analysis: Age (< 60 years; 60 years and more), main severity (HDRS main score < 18; HDRS baseline score ≥ 18; HDRS main score ≥ 25); time since diagnosis (up to 1 year; up to 5 years; more than 5 years).

Results: Treatment based on recommendations in accordance with the PGx pharmacogenetic technology produced a significant improvement in response rates in middle-aged patients compared with the conventional group (under 60 years of age; obtained the same results with a cutoff of < 65 years), in patients with moderate and severe depression, in patients with a diagnosis time of up to 1 and up to 5 years. The subgroups in the analysis were reasonably adjusted to the general data in terms of demographic and clinical indicators, with the even distribution of the number of patients between the PGx group and the treatment as usual group (TAU).

The use of Neuropharmagen® helped to improve the indicators response to therapy in middle-aged patients with moderate to severe depression, as well as in patients with the diagnosis up to 5 years ago.

PGI-I results according to patient age
(<60 years, p=0.015; >o=60 years, p=0.813)

PGI-I results according to main severity
(mild, HDRS < 18, p=0.638; moderate+severe, HDRS>o= 18, p=0.031)

PGI-I results according to time since diagnosis of MDD
(under 1 year, p=0.043; under 5 years, p=0.019; over 5 years, p=0.891)

Design: Observational, naturalistic, universal, multicentre, retrospective study. All patients were initially prescribed medication according to standard medical protocols, and the Neurofarmagen® test was performed on all the patients.

Main purpose: To determine the association of a pharmacogenetic profile (as determined by Neuropharmagen®)with changes in the clinical performance over 3 months by comparing patients treated based on test results and patients treated independently of test results. Change in clinical performance was measured by the Clinical Global Impressions – Severity scale (CGI-S). Stabilization was taken as CGI-S ≤3 for 3 months.

Patients:  191 DSM-IV emotional and psychotic patients with previous treatment failure with a CGI-S assessment ≥ 3 (92% had a CGI-S assessment ≥ 4) at baseline and with detailed information about their therapy mode included to analysis (see STROBE2007 compatible patient movement below).

Results

The use of Neuropharmagen@ helped to reduce the percentage of non-stabilized patients by 40% compared to patients who were treated in accordance with the traditional course, regardless of the psychiatric diagnosis.

Clinical, prospective, randomized, single-blind, controlled, multicenter study in 100 patients with major depressive disorder

  • Performed to evaluate the efficacy and tolerability of treatment based on pharmacogenetic information obtained using the Neurofarmagen® test in South Korean patients according to the change in indicators on the Hamilton Depression Rating Scale-17 (HAMD-17) and the change in indicators in the FIBSER questionnaire (Frequency, Intensity, Burden of Side Effects Rating), respectively.
  • Mean change in HAMD-17 assessment and mean change in FIBSER score were significant in the Neurofarmagen® test group compared to the conventional treatment group.
  • The use of Neurofarmagen® helped to improve response rates to therapy during 8 weeks of observation.

A meta-analysis of clinical trials has been performed investigating the effectiveness of Neuropharmagen® in improving the condition of adult patients with major depressive disorder.

Design: A total of 450 selected patients were examined in three clinical studies. A meta-analysis of random effects was performed. Standardized mean differences (SMDs) and their respective 95% confidence intervals were calculated from clinical data (change in CGI-S and HDRS-17 scores) for each individual study as well as data combinations. Odds ratios (ORs) were estimated based on standardized differences in the analyzed continuous variables (change in CGI-S and HDRS-17 scores) using the logical approximation method developed by Hasselblad and Hedges.

Results: A random effects model estimated the statistically significant magnitude of effects for a course of treatment based on pharmacogenetics (d = 0.34, 95% CI = 0.11-0.56, p -value = 0.004), which corresponded to an approximate increase in the chances of obtaining a clinical response by 1.8 times with the selection of medicines based on pharmacogenetics compared with its unavailability. After excluding patients with mild depression, the cumulative estimated effect size increased to 0.42 (95% CI = 0.19–0.65, p-value = 0.004, n = 287), with OR = 2.14 (95% CI = 1.40-3.27). These results reinforce the clinical utility of this pharmacogenetic tool in improving the health status of patients with depression, especially those with moderate to severe depression.

  • Performed to investigate the role of pharmacogenetic tests in the treatment of patients with bipolar disorder by comparing patients who receive a therapeutic substitution according to the PGx test with patients who receive treatment regardless of test results. The analysis was performed with the assessment of the clinical condition of patients using the CGI-S, HDRS-21 and YMRS scales, and adverse effects were recorded using the DOTES scale.
  • The change in severity was most favorable in patients whose treatment was modified based on the results of the test.
  • There was improvement of the number of adverse effects in the group that complied with the recommendations of the test.

Mirror analysis of costs for 2 years for 30 patients with bipolar disorder

  • Performed to assess potential cost savings associated with the use of pharmacogenetic analysis in patients with bipolar disorder.
  • Comparison of costs before and after changing therapy as recommended by the Neuropharmagen® test showed cost savings in terms of inpatient hospitalization as well as its average duration.

Design:A retrospective study of groups of children and adolescents with severe mental disorders who were treated and received PGx pharmacogenetic testing. The proportion of patients who achieved an improvement in the clinical performance (according to the CGI scale), a decrease in the severity of side effects (according to patients) and a change in the number of prescribed medications has been assessed.

Patients:  20 children and adolescents who applied for Neuropharmagen® pharmacogenetic tests (10 of them lived in charity schools; and 10 in families with parents) and taking several medications. All patients 17 years of age or younger.

Results:  Pharmacogenetic tests improved clinical outcome in almost all children (95%, 19/20 children). Improvement (CGI-I) was 2 (0.79) (range 1–4): 2.1 (0.56) (range 1–3) in children from the charity schools and 1.9 (0.99) ( in the range 1–4) in children from families. PGx pharmacogenetic tests helped to reduce patient-reported related side effects (p=0.006), the number of children with multiple medications (from 65% to 45%), and the average number of medications per child (from 3.3 to 2.4 medications, p=0.017).

Research

Population

N

Design

Exclusion criteria

Improved efficiency

Improved tolerability

Espadalier 2016

Various

182

Retrospective

Diag. < 1 year

Exposed

Yes

Not evaluated

Perez 2017

MDD

316

Double blind

Randomized

CGI-S < 4

Yes

Yes

1st multicenter randomized clinical trial of commercial pharmacogenomic technology

Menshon 2018

MDD

316

Double blind

Randomized

CGI-S < 4

Yes

Yes

1st investigation of the effect of patient characteristics on pharmacogenomics

Khan 2018

MDD

100

Without placebo control

Randomized

CGI-I ≥ 3

Continuous Therapy > 6 wk

Yes

Yes

1st multicenter randomized clinical trial of commercial pharmacogenomic technology on representatives of non-European race

Lelmini 2018

Bipolar

23

Prospective

Observational

CGI-S < 3

Continuous therapy ≥ 3 mo

Yes

Yes

1st study of commercial pharmacogenomic technology

on bipolar disorder

Blasco 2018

Various

(teenagers)

20

Retrospective

Without control group

CGI-S < 4

Yes

Yes

1st study of commercial pharmacogenomic technology

on adolescents

Vieta (unpublished)

Bipolar disorder

80

Retrospective

N/a

Continuous

Continuous

by Viete (unpublished)

Schizophrenia

200

Prospective

Observational

Taking medications for the treatment of adverse side reactions

Hospitalization < 15 d

Continuous

Continuous