Utility of the Pharmacogenetic Information Provided by NEUROPHARMAGEN in the Treatment of Bipolar Depressionwith Bipolar Depression

Study Overview
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Brief Summary
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Evaluation of the impact of the genetic variation of individual genes on the therapeutic response and side effects profile in a cohort of well-characterized patients with bipolar depression, using NEUROPHARMAGEN.

Detailed Description
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Bipolar disorder (BD) is a severe psychiatric condition characterized by mood swings between (hypo)mania and depression, with a total lifetime prevalence of 2.4%. An early and effective therapeutic approach is key for the patient prognosis, being the pharmacotherapy the main therapeutic tool for its management. Treatment guidelines for BD include a variety of psychotropic medications, including lithium, anticonvulsants, antipsychotics, antidepressants, anxiolytics, and combinations of these medications. However, treatment response is often inadequate and poor tolerability is frequently observed. Variability in treatment efficacy and tolerability has been shown to be influenced by several factors, including the inherited genetic variation. Several meta-analyses have shown that some genetic variants influence the probability of response to selective serotonin reuptake inhibitors (SSRIs) in patients with depression. Similarly, specific genetic polymorphisms have been associated with the risk of certain antipsychotic-induced adverse effects in patients with schizophrenia. However, the impact of many these variants has not been studied in the context of bipolar disorder. NEUROPHARMAGEN is a pharmacogenomic-based decision support tool that helps clinicians in the selection and dosing of psychoactive drugs based on the integration of pharmacogenetic information, among other patient's characteristics that influence the medication success. The clinical utility of NEUROPHARMAGEN has been evaluated in major depression disorder (MDD) through randomized clinical trials with hundreds of patients. Two small pilot trials in bipolar patients have suggested a potential clinical utility of this tool in this patient population. However, the output of pharmacogenomic-based tools such as NEUROPHARMAGEN is based in the analysis of several genes, which could differ in their individual clinical utility in a disorder-related manner. This observational, retrospective, epidemiological study includes 76 patients who attended the Bipolar Disorder Program of the Psychiatry Service of the Hospital Clinic de Barcelona (Spain) with the aim of objectively evaluate the impact of the genetic variation in individual genes on the therapeutic response and side effects profile in this cohort, using NEUROPHARMAGEN.

Official Title
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Genetic Variations Associated With the Therapeutic Response and Profile of Adverse Effects in the Treatment of Bipolar Depression

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Diagnostic Test: Pharmacogenomic-testing with NEUROPHARMAGEN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years and older Diagnosis of bipolar disorder with an index episode (IE) of depression with or without associated psychotic symptoms, according to the Diagnostic Manual of Mental Disorder 4th Edition Text Revision (DSM-IV-TR) Written informed consent to participate in the study Attending the Bipolar Disorder Program of the Psychiatry Service of the Hospital Clinic de Barcelona (Spain) for at least 6 months since the beginning of the index episode of the bipolar depression. Exclusion Criteria: Any serious or terminal medical organic disease Mental retardation (defined as an intelligence quotient <85) Electroconvulsive therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bipolar depression pharmacogenetics<br>Patients 18 years and older, with a diagnosis of bipolar disorder with an index episode of depression with or without associated psychotic symptoms (according to the Diagnostic Manual of Mental Disorder 4th Edition Text Revision, DSM-IV-TR), who attended the Bipolar Disorder Program of the Psychiatry Service of the Hospital Clínic de Barcelona (Spain). | Diagnostic Test: Pharmacogenomic-testing with NEUROPHARMAGEN<br>* This observational retrospective study aims at evaluating the impact of the genetic variation in individual genes on the therapeutic response and side effects profile in a bipolar disorder cohort, using NEUROPHARMAGEN. NEUROPHARMAGEN is a pharmacogenomic-based decision support tool that helps clinicians in the selection and dosing of psychoactive drugs based on the integration of pharmacogenetic information.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression for Bipolar Disorder (CGI-BP-M) | The CGI-BP-M is a modified version of the Clinical Global Impression for Bipolar Disorder for the assessment of manic, hypomanic, depressive or mixed symptoms, long-term outcome of bipolar disorder, and the assessment of the efficacy of several treatments. It consists of three subdomains (depression, mania, and overall), each of them with scoring from 1 (normal) to 7 (extremely ill patients). | At the time of enrollment (current status after end of index episode) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression Rating Scale (HAM-D) | HAM-D rates the clinical severity of depression. It has 17 questions, each with three to five possible answers, with scores ranging from 0 to 2 or from 0 to 4, respectively. The total score ranges from 0 to 52 and cut-off scores can be used to classify the depressive disorder. | At the time of enrollment (current status after end of index episode) | 
| Functioning Assessment Short Test (FAST) | FAST is a brief instrument designed to assess the main functioning problems experienced by psychiatric patients, particularly bipolar patients. It comprises 24 items that assess impairment or disability in six specific areas of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time. All of items are rated using a 4-point scale (0 = no difficulty, 1 = mild difficulty, 2 = moderate difficulty and 3 = severe difficulty). The global score is obtained by adding up the scores of each item. The higher the score, the more serious the difficulties are. | At the time of enrollment (current status after end of index episode) | 
| Clinical Global Impression for Bipolar Disorder (CGI-BP-M) | The CGI-BP-M is a modified version of the Clinical Global Impression for Bipolar Disorder for the assessment of manic, hypomanic, depressive or mixed symptoms, long-term outcome of bipolar disorder, and the assessment of the efficacy of several treatments. It consists of three subdomains (depression, mania, and overall), each of them with scoring from 1 (normal) to 7 (extremely ill patients). | At onset of index episode (baseline) | 
| Presence of mood switch | Sudden transition from a depressive mood episode to an episode of mania or hypomania. | Baseline (onset of index episode) to 6 months (or end of the episode) | 
| Number and type of adverse effects | Sociodemographic and clinical data, including the pharmacological treatment in the index episode (IE) and mood switch (the latter for those patients applicable), and the presence and type of side effect associated with the pharmacological treatment in the IE were extracted from all enrolled subjects. The adverse events recorded were as follows: weight gain, dyslipidemia (cholesterol, LDL, HDL, triglycerides), glucose, sedation, extrapyramidal symptoms, seizures, neuroleptic malignant syndrome, corrected QT interval prolongation, sexual dysfunction, and hyperprolactinemia. | Baseline (onset of index episode) to 6 months (or end of the episode) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mood disorders, Pharmacogenomic Testing, Precision Medicine, Adverse events, Treatment response