Clinical Utility of Pharmacogenomics of Psychotropic Medications

NCT03907124 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: STUDY00018828
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

While the scientific understanding of pharmacogenomics is quickly accelerating, its translation to clinical decision-making (especially in psychiatric practice) has progressed more slowly. In an effort to begin to bridge this translational gap, genetic testing has been developed for various and commonly existing psychiatric disorders, such as major depression, schizophrenia, bipolar disorder, and pain syndromes to improve the safety of prescribing psychotropic medications for these disorders. This genetic testing incudes several pharmacodynamics and pharmacokinetic genetic factors, such as the cytochrome P450 1A2 gene (CYP1A2); the cytochrome P450 2B6 (CYP2B6) gene; P450 2D6 gene (CYP2D6); the cytochrome P450 2C9 gene (CYP2C9); the cytochrome P450 2C19 gene (CYP2C19); uridine-glucoronyl-transferase 2B15 (UGT2B15) gene; the serotonin transporter gene (Solute Carrier Family 6 Member; SLC6A4); p-glycoprotein ( ATP-binding cassette sub-family B member 1; ABCB1) transporter gene; the serotonin 2A receptor gene (HTR2A); the serotonin 2C receptor (HTR2C) gene; serotonin 1a receptor (5HT1a) gene; dopamine 1 receptor (DRD1) gene; dopamine 2 receptor (DRD2) gene; adrenergic alpha-2A receptor (alpha-2A) gene; opioid mu (opioid receptor mu 1; OPRM1) receptor gene; dopamine synthesis gene (ankyrin repeat and kinase domain containing 1; ANKK1); dopamine metabolizing enzyme \[Catechol-o-methyltransferase (COMT\]) gene; kainite receptor gene (glutamate ionotropic receptor kainate type subunit 4; GRIK4); folate (methylenetetrahydrofolate reductase; MTHFR) gene; sodium channels (sodium voltage-gated channel alpha subunit 2; SCN2A) gene. The interpretive report is based on copies of these multiple informative genes. The investigators are proposing to utilize comprehensive genetic testing to select more genetically-informed psychotropic medications to enhance their effectiveness in real-world patients with psychiatric illnesses such as schizophrenia, major depression, bipolar affective disorder as well as pain in a state hospital setting. The investigators plan to use genetic testing offered by Admera® for major classes of psychotropic medications. The investigators hypothesize that genetic testing will demonstrate clinical benefits by improving state hospital patients' response and decreasing their adverse effects. The proposed study will be conducted in a total sample of 60 subjects diagnosed with schizophrenia, major depression, bipolar affective disorder as well as pain at the Oregon State Hospital, Salem Oregon over a total period of 24 months

Conditions

Psychiatric Disorders; Pain

Keywords

Utility; Pharmacogenomics; Psychotropic; Medications

Outcome Measures

Primary Outcomes (4)

• Positive Subscale of Positive and Negative Syndrome Scale (PANSS)

  PANSS is one of the most widely clinical scales to monitor positive and negative symptoms of schizophrenia. The scores range from 30 to 210. A score of 58 is considered mildly ill; 75 is moderately ill and 95 is markedly ill; and 116 is severely ill. This study will only use the scores from positive subscale (range 7 to 49) and the eligibility criteria will require a moderate score on 4 positive sub-scale items, including hallucinations, delusions, suspiciousness and conceptual disorganization to qualify for the study.

  15 minutes

• Behavioral Assessment of Pain Screening Instrument (BAPSI)

  This scale assesses level of pain-related disability, psychological distress, and pain intensity. 0 - 3 = minimal levels of average pain intensity; 4 - 6 = moderate levels of average pain intensity; 7 - 10 = severe levels of average pain intensity.

  10 minutes

• Generalized Anxiety Disorder-7 (GAD-7)

  This is a scale to assess severity of anxiety symptoms. Total score=21; 5-9 = Mild; 10-14 = Moderate; \>15 = Severe \*For Panic Disorder, Social Phobia, \& PTSD, cutoff score of 8 may be used for optimal sensitivity/specificity (see Evidence section). Critical Actions This tool should be used for screening and monitoring symptom severity and cannot replace a clinical assessment and diagnosis. Do not forget to rule out medical causes of anxiety before diagnosing an anxiety disorder (for example, EKG for arrhythmias, TSH for thyroid disease).

  10 minutes

• Public Health Questionnaire-9 (PHQ-9)

  This is a commonly used scale in clinical practice to assess depressive symptoms. The total score is 36. Score of 0-4 = Minimal or no depressive symptoms; 5-9 = Mild symptoms; 10-14 = moderate symptoms; 15-19 = Moderately severe symptoms; 20-27 = severe symptoms.

  10 minutes

Secondary Outcomes (5)

• Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I)

  5 minutes

• Self-Report Quality of Life Scale (SQLS)

  5 minutes

• Social & Occupational Functional Assessment Scale (SOFAS)

  7 minutes

• Abnormal Involuntary Movement Scale (AIMS)

  7 minutes

• UKU Side Effect Rating Scale (USERS)

  10 minutes

Study Arms (2)

Genetically-guided treatment arm

EXPERIMENTAL

The active arm - where patients will receive genetically-guided treatment

Drug: Genetically-guided treatment with FDA-approved psychotropic drugs; Drug: Treatment as usual (TAU)

Treatment as usual (TAU) control arm

NO INTERVENTION

TAU is the control arm - where patients will continue to receive their usual treatment as before.

Interventions

Genetically-guided treatment with FDA-approved psychotropic drugs DRUG

Psychiatric patients in this experimental arm will receive genetically-guided treatment with psychotropic medications

Genetically-guided treatment arm

Treatment as usual (TAU) DRUG

All subjects assigned to TAU group, which is the control arm, will continue to receive FDA-approved psychotropic medications for psychiatric indications investigated in this study

Also known as: standard of care treatment with FDA-approved psychotropic drugs

Genetically-guided treatment arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is between the ages of 18 and 80
• Schizophrenia or schizoaffective disorder, major depressive disorder, bipolar affective disorder as ascertained by a qualified physician or mental health professional licensed to diagnose based on DSM-V criteria.
• Patients using antidepressants, anxiolytics, mood stabilizers, and sedative/hypnotics will be allowed
• Patients on clozapine treatment will be allowed.
• Study subjects with a score of at least 12 on the scale to assess capacity to consent i.e., UBACC.

You may not qualify if:

• Patients who are court-committed for involuntary medications
• Uncontrolled and/or serious medical illness (as ascertained at admission screening process)
• Pregnant patients
• Patients who cannot communicate in English.

Sponsors & Collaborators

• Oregon Health and Science University: lead

Study Sites (1)

Mujeeb Uddin Shad

Salem, Oregon, 97301, United States

Location

Related Publications (12)

• Kemp AH, Gordon E, Rush AJ, Williams LM. Improving the prediction of treatment response in depression: integration of clinical, cognitive, psychophysiological, neuroimaging, and genetic measures. CNS Spectr. 2008 Dec;13(12):1066-86; quiz 1087-8. doi: 10.1017/s1092852900017120.

  PMID: 19179943 BACKGROUND

• Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1231-42. doi: 10.1056/NEJMoa052963.

  PMID: 16554525 BACKGROUND

• Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.

  PMID: 17074942 BACKGROUND

• Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005 Sep 22;353(12):1209-23. doi: 10.1056/NEJMoa051688. Epub 2005 Sep 19.

  PMID: 16172203 BACKGROUND

• Thase ME. STEP-BD and bipolar depression: what have we learned? Curr Psychiatry Rep. 2007 Dec;9(6):497-503. doi: 10.1007/s11920-007-0068-9.

  PMID: 18221631 BACKGROUND

• Simon GE, Perlis RH. Personalized medicine for depression: can we match patients with treatments? Am J Psychiatry. 2010 Dec;167(12):1445-55. doi: 10.1176/appi.ajp.2010.09111680. Epub 2010 Sep 15.

  PMID: 20843873 BACKGROUND

• Perlis RH. Pharmacogenetic studies of antidepressant response: how far from the clinic? Psychiatr Clin North Am. 2007 Mar;30(1):125-38. doi: 10.1016/j.psc.2006.12.004.

  PMID: 17362808 BACKGROUND

• Mrazek DA. Psychiatric Pharmacogenomics. New York, NY: Oxford University Press; 2010.

  BACKGROUND

• Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmoller J. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry. 2004 May;9(5):442-73. doi: 10.1038/sj.mp.4001494.

  PMID: 15037866 BACKGROUND

• Mrazek DA, Biernacka JM, O'Kane DJ, Black JL, Cunningham JM, Drews MS, Snyder KA, Stevens SR, Rush AJ, Weinshilboum RM. CYP2C19 variation and citalopram response. Pharmacogenet Genomics. 2011 Jan;21(1):1-9. doi: 10.1097/fpc.0b013e328340bc5a.

  PMID: 21192344 BACKGROUND

• Licinio J, Wong ML. Pharmacogenomics of antidepressant treatment effects. Dialogues Clin Neurosci. 2011;13(1):63-71. doi: 10.31887/DCNS.2011.13.1/jlicinio.

  PMID: 21485747 BACKGROUND

• Rundell JR, Shinozaki G. Pharmacogenomic considerations in patients with both comorbid medical and psychiatric illness. Prim Psychiatry 2010; 17:33-38

  BACKGROUND

MeSH Terms

Conditions

Mental Disorders; Pain

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Mujeeb U Shad, MD, MSCS

  Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study raters will be kept blinded to the two arms of the study to avoid assessment bias.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a randomized prospective cohort study which will compare the utility of an interpretive report based on pharmacogenomic testing between study subjects receiving psychotropic medication with guidance from an interpretive report (i.e., Genetically-Guided Group) and those receiving psychotropic medications without the implementation of the interpretive report (Genetically-Unguided Group).

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: April 8, 2019
• Study Start: June 3, 2019
• Primary Completion: July 9, 2021
• Study Completion: July 9, 2021
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)