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Pharmacogenetic Testing

Rxight Is Now An Affiliate In The IGNITE Network

By | Announcements, Pharmacogenetic Testing, Pharmacogenomics, Precision Medicine | No Comments

Rxight Pharmacogenetics has become an affiliate member of the NIH-funded effort, IGNITE (Implementing GeNomics In pracTicE). IGNITE is a network dedicated to supporting and advancing the use of genetic information across clinical and diverse healthcare settings. It is comprised of a series of projects aiming to enhance translation of validated actionable genomic information into clinical settings and decision making, and includes educational initiatives for patients and providers. IGNITE is poised to have a significant impact on the acceleration of genomic information into medical practice, and Rxight Pharmacogenetics is proud to be a member of this step forward in clinical care.

The Pharmacogenetics of Antiplatelet Agent: Meta-Analyses of Aspirin and Clopidogrel Loss-of-Function Alleles

By | Anticoagulants, Pharmacogenetic Testing, Provider | No Comments

Antiplatelet agents combined with aspirin have been shown to play a significant role in mitigating the effects of coronary disease, and ample research has found that distinct genetic determine patients’ response to clinically significant antiplatelet agents.
 
Platelets play a decisive role during the formation of an initial hemostatic plug through their intricate response to injury. When inappropriately activated, platelets contribute to pathological thrombus formation. Arterial thrombus formation can then lead to tissue ischemia causing potentially fatal coronary and cerebrovascular events.
 

Interindividual Genetic Variation Impacts Aspirin Antiplatelet Efficacy

 
Aspirin is regarded as “the cornerstone for secondary cardiovascular prevention,” the efficacy of which has long been established. as noted in Current Pharmaceutical Design, “Pharmacogenetics of the Antiplatelet Effect of Aspirin” (2012).
 
The researchers aver that there is considerable interindividual variation in response to aspirin, thus reducing its efficacy in treating heart disease in some patients.
 

P1A2 and P2Y1 Association with Decreased Aspirin Antiplatelet Efficacy

 
Specifically, the review conducted by Current Pharmaceutical Design examined polymorphisms of genes that contributed highly to antiplatelet responses. These were P1A2 from glycoprotein GP IIb/IIIa, and the P2Y1 polymorphism from AD receptor (ADP) genes.
 
P1A2 was characterized as having an association with coronary thrombus formation. One study showed P1A2 allele was related with a shorter baseline bleeding time in comparison to a wild type allele. After measuring bleeding after aspirin ingestion, there was a a reduced antiplatelet effect.
 
Another study supported this finding by discovering an enhanced thrombin formation in P1A2 carriers compared to P1A1/A1 homozygotes before and after aspirin ingestion. The review concluded that P1/A2 polymorphism is a prothrombotic platelet phenotype responding inadequately to aspirin.
 
Polymorphism P2Y1 was utilized in an arachidonic acid-induced optical platelet aggregometry to assess its antiplatelet effect of aspirin. The results showed that the T allele of the C893T P2Y1 polymorphism was substantially linked with a decreased antiplatelet effect of aspirin.
 

CYP2C19 Mediates Clopidogrel Non-Response

 
Evidence for association of CYP2C19 with clopidogrel response was investigated in the Journal of Human Genetics “Pharmacogenomics of Anti-Platelet Therapy: How Much Evidence is Enough for Clinical Implementation?” (June 2013).
 
The study established CYP2C19 as a genetic factor contributing to the creation of the active metabolite of clopidogrel. A corresponding analysis detailing the associations of CYP2C19 alleles and increasing residual on-treatment platelet reactivity corroborated this finding. The study concluded that patients with even one reduced function of CYP2C19 and taking clopidogrel as treatment for percutaneous coronary intervention may be “associated with increased risk of major adverse cardiovascular events as a consequence of aspirin antiplatelet inefficacy.
 
The International Journal of Environmental Research and Public Health “Pharmacokinetic and Pharmacodynamics Responses to Clopidogrel” (February 2017) also reviewed the connection between CYP2C19 and clopidogrel. The review was based on the authors’ argument that genetic polymorphisms impact the absorbtion and metabolism of clopidogrel and that the P2Y12 receptor may interfere with its antiplatelet activity.
 
In one meta-analysis, it was found there was a critical relation between CYPC219 loss-of-function in diverse patients with frequent cardiovascular events. In another meta-analysis, CYPC219 was identified as having a having a crucial part in reducing the active metabolite of clopidogrel.
 

CYP3A4/5 Mediates Clopidogrel Non-Response

 
In addition to analyzing clopidogrel, the review also analyzed CYP3A4/5. The authors found that the CYP3A5*3 allele has an influence on clopidogrel metabolism because of its possible dependence on CYP2C19 and CYP3A4 inhibitors. In the study, the patients with a CYP3A5*3/3 genotype displayed enhanced platelet reactivity compared to those with a CYP3A5*1 allele in CYP2C19 poor metabolizers. An additional study reported CYP3A5*3 on clopidogrel response is prominently in patients with the CYP2C19 loss-of-function.
 

Benefits of Individualizing Antiplatelet Therapy with Pharmacogenetic Testing

 
Research has been conclusive in identifying potential antiplatelet pharmacogenetic applications pointing to effective individualized treatments, according to the studies.
 
The review by the International Journal of Environmental Research and Public Health asserted there is an “inter-individual variability” in clopidogrel’s antiplatelet effects. They concluded inadequate platelet responsiveness to clopidogrel has a role in accumulating the risk of cardiovascular events, and therefore increasing drug dosage or switching to alternative drug medications may be more beneficial for patients. Similarly, the review published in Current Pharmaceutical Design concludes by recommending utilization of antiplatelet pharmacogenetics in clinical practice. “The promise of pharmacogenetics lies in the prospect of improving treatment efficacy and safety.”

The Prospect of Pharmacogenetics in Pediatrics

By | Opioids, Other, Pharmacogenetic Testing, Provider | No Comments

Pharmacogenetics of Opioids as a Potential Alternative in Pediatric Pain Management

 
Opioid and codeine treatment in pain management for children has been a primary concern in clinical settings, specifically for surgical pain management. The concerns are the adverse reactions caused by the opioids, such as respiratory depression. Current Opinion in Anesthesiology, “Codeine and Opioid Metabolism: Implications and Alternatives for Pediatric Pain Management” (2017), reviews how important clinical factors and genetic polymorphisms affect the metabolism of opioids after surgical operations.

 

Adverse Side Effects of Codeine

 
Codeine’s efficacy has been questioned in the pain management of children. Current Opinion in Anesthesiology identifies the adverse reactions of it. The prominent ones are respiratory depression, anoxic brain injuries, and even death occurring in children. With reported doses of codeine, significant respiratory depression was found in newborns in a report by Canadian Pharmacists Journal “Pain Management in Children: A Transition from Codeine to Morphine for Moderate to Severe Pain in Children” (2012).

 
Opioids in Pain Management

 
Opioids are the cornerstone of pain and chronic pain management. “Successful pain management provides adequate analgesia without excessive adverse reactions affirms Clinical Biochemistry “Pharmacogenetics of Chronic Pain Management” (2014). Drug metabolism and responses are influenced by numerous factors, including pharmacogenetics. Genetic variations contribute to the distinct inter individual responses to pain medications.

 
Involvement of CYP2D6 in Codeine

 
Those with two nonfunctional alleles of CYP2D6 are considered poor metabolizers. Extensive metabolizers have one or two effective CYP2D6 alleles and those with duplicated CYP2D6 alleles are ultra rapid metabolizers. Canadian Pharmacists Journal indicates the functions of CYP2D6 are similar in both children and adults.

 
The review also acknowledges the safety concerns of CYP2D6 ultra rapid metabolizers from several studies. One study demonstrated how a breastfed newborn infant died after his mother consumed Tylenol #3 for postpartum pain. Toxicology testing found the mother had abnormally high concentration levels of morphine in her breast milk. Genotype testing found the mother was an ultra rapid metabolizer of codeine. The study concluded since the mother was an ultra rapid metabolizer, higher than normal morphine levels crossed into the breast milk and resulted in the infant dying from morphine intoxication.

 
Another study found a two-year-old child who also died of morphine intoxication. The child was prescribed codeine in recommended dosages after having his tonsils removed. Genotype testing revealed the child was an ultra rapid metabolizer of codeine. However, there were also other contributing factors; the child had bronchopneumonia and sleep apnea. The study concluded these factors “may have increased his risk of hypoxemia, leading to alterations in opioid receptors and increased sensitivity to morphine.”

 
Canadian Pharmacists Journal concludes these studies show ultra rapid metabolizers of codeine are correlated with a higher risk of morphine intoxication among children.

 

Alternatives to Prevent Adverse Drug Reactions

 
Canadian Pharmacists Journal argues morphine as a safer alternative compared to codeine. They argue morphine has “demonstrated efficacy and relative safety when used appropriately in pain management in both adults and children.” A study they analyzed found morphine treatment more effective than a placebo for children in postoperative pain.

 
Current Opinion in Anesthesiology also outlines the possible alternatives to prevent the risks of opioids, such as pharmacogenetics. They indicate personalized opioid therapy for pain management is “distant from reality”, but current CYP2D6 pharmacogenetic research on codeine is hopeful. The review summarizes, “pharmacogenetics has the potential to guide anesthesia providers on perioperative opioid selection and dosing to maximize efficacy and safety.”

Related Post

Pharmacogenetics Emerging as a Method to Guide Medication Therapy

By | Gene Panel, Opioids, Other, Pharmacogenetic Testing, Provider | No Comments

According to a recent article published in American Family Physician “Pharmacogenetics: Using Genetic Data to Guide Drug Therapy (2015), pharmacogenetics is being more widely used by family physicians and the number of patients who are interested in acquiring genetic information is growing.

 

The Components of Pharmacogenetics Testing

 
Pharmacogenetics involves genetic variations that code for drug metabolizing enzymes. It also involves how a medication breaks down in the body and how the body responds to the medication. The most common forms of genetic variations are single nucleotide polymorphisms.

 
The differences in single nucleotide polymorphisms or other polymorphisms result in diverse types of genes or alleles, the American Family Physician explains. Individuals inherit these alleles that “govern expression of the gene and the cor¬responding enzyme or protein.” As a result, these genetic differences influence how the drug reacts in the body and how the body metabolizes the drug.

 

Genetic Variability Can Alter the Effects of Drugs

 
Studies have demonstrated there is a connection between genetic variations and changes in drug levels and effects.

 
CYP2D6 and Opioids

 
The enzyme activity of CYP2D6 is volatile because of single nucleotide polymorphisms and other variations of CYP2D6. American Family Physician indicates codeine metabolism occurs in 90% of patients and results in normal morphine formation. However, 1% to 2% of people are ultra rapid metabolizers of codeine signifying they have an increased risk of morphine toxicity.

 
American Family Physician analyzed a study involving the death of a breastfed infant and a mother who was an ultra rapid metabolizer of codeine. The study demonstrated the infant died of morphine intoxication. There was opioid toxicity in the breast milk, which passed onto the infant.

 
They recommend pharmacogenetic testing for patients who are possible poor or ultra rapid metabolizers of opioids.

 

CYP2C19 and Clopidrogrel

 
Clopidogrel is primarily metabolized in the enzyme CYP2C19. CYP2C19 is highly polymorphic and 80% of individuals metabolize clopidogrel normally. However, 18% to 45% of people have intermediate enzyme activity and 2% to 15% have poor enzyme activity.

 
American Family Physician presents meta-analyses of CYP2C19 poor metabolizers. Poor CYP2C19 metabolizers taking clopidogrel treatment and undergoing percutaneous coronary intervention have a higher risk of cardiovascular death, myocardial infraction, stroke, and stent thrombosis.

 
These results lead to the recommendation that clinicians should consider alternative treatments, such as pharmacogenetic testing of CYP2C19 to guide antiplatelet therapy.

 

The Benefits of Pharmacogenetics

 
American Family Physician examined the clinical implications of pharmacogenetic testing and the various resources available and developing to support the usage of pharmacogenetics in clinical settings. They conclude “pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects.”

Related Post

The Pharmacogenetics of Antiplatelet Agents: Meta-Analyses of Aspirin and Clopidogrel Loss-of-Function Alleles

By | Gene Panel, Other, Pharmacogenetic Testing | No Comments

 
Antiplatelet agents combined with aspirin have been shown to play a significant role in mitigating the effects of coronary disease, and ample research has found that distinct genetics determine patients’ response to clinically significant antiplatelet agents.

 

Platelets play a decisive role during the formation of an initial hemostatic plug through their intricate response to injury. When inappropriately activated, platelets contribute to pathological thrombus formation. Arterial thrombus formation can then lead to tissue ischemia causing potentially fatal coronary and cerebrovascular events.

 

Interindividual Genetic Variation Impacts Aspirin Antiplatelet Efficacy

 

Aspirin is regarded as “the cornerstone for secondary cardiovascular prevention,” the efficacy of it, which has long been established, as noted in Current Pharmaceutical Design, “Pharmacogenetics of the Antiplatelet Effect of Aspirin” (2012).

 

The researchers avert that there is considerable interindividual variation in response to aspirin, thus reducing its efficacy in treating heart disease in some patients.

 

P1A2 and P2Y1 Association with Decreased Aspirin Antiplatelet Efficacy

 

Specifically, the review conducted by Current Pharmaceutical Design examined polymorphisms of genes that contributed highly to antiplatelet responses. These were P1A2 from glycoprotein GP IIb/IIIa, and the P2Y1 polymorphism from AD receptor (ADP) genes.

 

P1A2 was characterized as having an association with coronary thrombus formation. One study showed P1A2 allele was related with a shorter baseline bleeding time in comparison to a wild type allele. After measuring bleeding after aspirin ingestion, there was a reduced antiplatelet effect.

 

Another study supported this finding by discovering an enhanced thrombin formation in P1A2 carriers compared to P1A1/A1 homozygotes before and after aspirin ingestion. The review concluded that P1/A2 polymorphism is a prothrombotic platelet phenotype responding inadequately to aspirin.

 

Polymorphism P2Y1 was utilized in an arachidonic acid-induced optical platelet aggregometry to assess its antiplatelet effect of aspirin. The results showed that the T allele of the C893T P2Y1 polymorphism was substantially linked with a decreased antiplatelet effect of aspirin.

 

CYP2C19 Mediates Clopidogrel Non-Response

 

Evidence for association of CYP2C19 with clopidogrel response was investigated in the Journal of Human Genetics “Pharmacogenomics of Anti-Platelet Therapy: How Much Evidence is Enough for Clinical Implementation?” (June 2013).

 

The study established CYP2C19 as a genetic factor contributing to the creation of the active metabolite of clopidogrel. A corresponding analysis detailing the associations of CYP2C19 alleles and increasing residual on-treatment platelet reactivity corroborated this finding. The study concluded that patients with even one reduced function of CYP2C19 and taking clopidogrel as treatment for percutaneous coronary intervention may be “associated with increased risk of major adverse cardiovascular events as a consequence of aspirin antiplatelet inefficacy.”

 

The International Journal of Environmental Research and Public Health “Pharmacokinetic and Pharmacodynamics Responses to Clopidogrel” (February 2017) also reviewed the connection between CYP2C19 and clopidogrel. The review was based on the authors’ argument that genetic polymorphisms impact the absorbtion and metabolism of clopidogrel and that the P2Y12 receptor may interfere with its antiplatelet activity.

 

In one meta-analysis, it was found there was a critical relation between CYPC219 loss-of-function in diverse patients with frequent cardiovascular events. In another meta-analysis, CYPC219 was identified as having a having a crucial part in reducing the active metabolite of clopidogrel.

 

CYP3A4/5 Mediates Clopidogrel Non-Response

 

In addition to analyzing clopidogrel, the review also analyzed CYP3A4/5. The authors found that the CYP3A5*3 allele has an influence on clopidogrel metabolism because of its possible dependence on CYP2C19 and CYP3A4 inhibitors. In the study, the patients with a CYP3A5*3/3 genotype displayed enhanced platelet reactivity compared to those with a CYP3A5*1 allele in CYP2C19 poor metabolizers. An additional study reported CYP3A5*3 on clopidogrel response is prominently in patients with the CYP2C19 loss-of-function.

 

 

Benefits of Individualizing Antiplatelet Therapy with Pharmacogenetic Testing

 

Research has been conclusive in identifying potential antiplatelet pharmacogenetic applications pointing to effective individualized treatments, according to the studies.

 
The review by the International Journal of Environmental Research and Public Health asserted there is an “inter-individual variability” in clopidogrel’s antiplatelet effects. They concluded inadequate platelet responsiveness to clopidogrel has a role in accumulating the risk of cardiovascular events, and therefore increasing drug dosage or switching to alternative drug medications may be more beneficial for patients.

 
Similarly, the review published in Current Pharmaceutical Design concludes by recommending utilization of antiplatelet pharmacogenetics in clinical practice. “The promise of pharmacogenetics lies in the prospect of improving treatment efficacy and safety.”

 

 

 

Related Post

Antipsychotic Medications in Schizophrenia

By | Antipsychotics, Pharmacogenetic Testing, Pharmacogenomics, Precision Medicine, Psychiatric Medications | No Comments

Medications are central to the treatment of schizophrenia and a number of drugs are used to treat this serious mental condition. Schizophrenia is a long-term mental disorder marked by psychosis- a breakdown in the relation between thought, emotion, and behavior, leading to errors in perception, inappropriate actions and feelings, withdrawal from reality, and a sense of mental fragmentation.

 

Most patients are now treated with antipsychotics that are thought to control symptoms through the brain chemical, dopamine. There are two types of antipsychotics used: first generation and second generation.

 

First Generation Antipsychotics

 
The first generation antipsychotics have more serious side effects and are used only when necessary. They include haloperidol (Haldol), chlorpromazine (Thorazine), and Fluphenazine (Prolixin). Side effects of first-generation antipsychotics include extrapyramidal side effects which is marked by rigidity, bradykinesia, dystonias, tremor, and akathisia. Tardive dyskinesia (TD)— a disorder marked by permanent involuntary movements in the limbs and face such as grimacing and lip-smacking – is another adverse effect that can occur with first-generation antipsychotics. Additionally. first-generation antipsychotics are known to cause cardiac rhythm abnormalities.

 

Second Generation Antipsychotics and Side Effects

 
The newer second generation antipsychotics have less side effects than the older drugs, and are preferred for treatment of schizophrenia. They include: aripiprazole (Abilify), asenapine (Saphris), brexipiprazole (Rexulti), clozapine (Clozaril), Iloperidone (Fanapt), Lurasidone (Latuda), Olanzapine (Zyprexa), Paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).

 
Abilify side effects include akathisia (agitation), restlessness, insomnia, constipation, fatigue and blurred vision. Most of the second-generation antipsychotics have similar side effects, as they are similar chemically. Geodon is one of the newer antipsychotics with extra-pyramidal side effects reported (drug induced movement disorders).

 
During initial phases of treatment with the second generation antipsychotics patients may experience side effects such as dry mouth, drowsiness, restlessness, muscle spasms, tremor or blurring of vision. The second generation antipsychotics have a much lower risk of tardive dyskinesia, a serious side effect of the older antipsychotics. It is possible to lessen side effects by either lowering the dose or by changing medications.

 

Antipsychotic Pharmacogenetics

 
Patients and physicians often work together to find a dose that results in the fewest side effects. Patients will often change medications if the side effects are severe and side effects lessen over time. One way to potentially avoid side effects for new medications and for newly prescribed schizophrenia medications is to have your drug metabolism genes tested. After the human genome was sequenced back in 2003, genome wide association studies showed that there is variation among the population in the genes that process medications. As a result, if there’s a drug-processing gene with variation, it may have trouble processing medications that are metabolized by that gene product.

 

Know Your Risks with the Rxight® DNA Test

 
The most state-of-the-art way to determine genetic variations is with the Rxight® pharmacogenetics test from MD Labs. This advance in pharmacogenetics means that a physician can determine beforehand what drugs may be safe to take and what drugs to avoid or require different doses than recommended. All that is required is a prescription from a physician and a cheek swab at a participating pharmacy.

 
You could benefit from this advance in precision medicine with the knowledge of your gene variations with your physician or other healthcare services. The Rxight® pharmacogenetics test determines your genetic susceptibilities for over 200 drugs on the market. You could also benefit from knowing how you might respond to drugs you may have to take in the future. Most importantly, you could get information that may change your current dosing and medication for fewer harmful side effects from your antipsychotic medication.

Related Post

Overview of the Dangers and Side Effects of Psychotropic Medications

By | ADHD Medications, Antianxiety Medications, Antidepressants, Antipsychotics, Pharmacogenetic Testing, Precision Medicine, Psychiatric Medications | No Comments

Get the Rxight® Genetic Test to Know Your Risks

Psychiatric medications (often called “psychotropics”) are routinely used to treat a variety of psychiatric disorders – ranging from ADHD (attention deficit hyperactive disorder) and depression to bipolar disorder and anxiety to schizophrenia – Psychiatric medications are generally jused as an adjunct to psychotherapy.

 
It is estimated that 17 percent (some 80 million people) in the United States are taking some form of psychiatric medication (Scientific American, “1 in 6 Americans Takes a Psychiatric Drug,”  Dec 13 2016) According to the article, an earlier government report, from 2011, found that just over 10% of adults are taking prescription drugs for “problems with emotions, nerves or mental health,” published in the journal JAMA Internal Medicine.

 
While the potential benefits of psychotropic medications have been demonstrated in research and clinical practice for decades, patients are cautioned to remain vigilant of the many side effects of psychiatric medications.

 
This article presents a detailed summary of the major types of mental health medications and their associated risks for side effects as reported by the U.S. Food and Drug Administration (FDA) and the National Institute of Mental Health (NIMH) and an overview of the benefits of the Rxight® genetic test for psychiatric medications in identifying your unique genetically determined risk for developing side effects or non-response to dozens of these psychiatric medications along with hundreds of other medications across 50 pharmacological classes.

Antidepressant Side Effects

What are antidepressants?
Antidepressants are commonly used to treat depressive disorders. They also are used for other conditions, such as pain, anxiety and insomnia. Although antidepressants are not FDA-approved specifically to treat ADHD, they are sometimes used “off-label” for ADHD treatment.

The most commonly prescribed types of antidepressants today are called . Examples of SSRIs include:

Other types of antidepressants are serotonin and norepinephrine reuptake inhibitors (SNRIs) .These are chemically similar to SSRIs and include and duloxetine (Cymbalta)  and venlafaxine (Effexor).

 
Another antidepressant that is commonly used is bupropion – a third sub-class of antidepressant which acts differently than either SSRIs or SNRIs.  Bupropion is also used to treat seasonal affective disorder (SAD) and for smoking cessation treatment.

SSRIs, SNRIs, and bupropion are commonly used today because they do not cause as many side effects as the older (“first generation”) classes of antidepressants, and moreover are effective in treating a broader range of depressive and anxiety disorders.

 
Older antidepressant medications include tricyclic antidepressants, tetracyclic antidepressants, and monoamine oxidase inhibitors (MAOIs).  These are less commonly prescribed since the development of the newer generation antidepressants.
 
What are the possible side effects of antidepressants?
Some antidepressants may cause more side effects than others. The most common side effects listed by the FDA include:

  • Sexual problems (impotence or inability to orgasm)
  • Nausea and vomiting
  • Weight gain
  • Sleepiness or fatigue
  • Diarrhea

In 2004, the FDA ordered a “black box” label – the most serious warning it issues – on all antidepressants to caution of psychiatric drugs’ increasing suicide risk in children and adolescents. In 2006, the FDA increased the age to include young adults up to age of 25. (FDA, Revision to Product Labeling, 2004)

 
Call your doctor immediately if you have any of the following symptoms, especially if they are new, worsening, or worry you (U.S. Food and Drug Administration, 2011):

  • Suicidal thoughts or actions
  • New or worsening depression
  • New or worsening anxiety
  • Feeling restless or agitated or
  • Panic attacks
  • Insomnia
  • New or worsening irritability
  • Acting aggressively, being angry, or violent
  • Acting on dangerous impulses
  • An increase in activity and talking (mania)

Additionally, drug interactions can occur.  Specifically, combining the newer SSRI or SNRI antidepressants with one of the commonly-used “triptan” medications for treating migraines can cause a life-threatening condition called “serotonin syndrome.” Serotonin syndrome is marked by agitation, hallucinations, high temperature, or unusual blood pressure changes. Serotonin syndrome is usually associated with the older antidepressants called MAOIs, but it can happen with the newer antidepressants as well.

 
Antidepressants may cause other side effects that were not included in this list, as determined by individual genetics and ability to metabolize the drug in the liver.

 
How do patients respond to antidepressants?
Some people respond better to some antidepressant medications than to others.  It is critical to know that some people may not feel better with the first medicine they try. Additionally, sometimes people taking antidepressants feel better and stop taking the medication too soon, and the depression may return.

 
These inter-individual differences are based in genetics, and the Rxight® genetic test will indicate which antidepressants may not work for you right from the start instead of having to go through trial and error with your doctor  With Rxight results, you your doctor can work together to find the best and most effective antidepressant treatment tailored to your unique genetics.

 

Antipsychotic Side Effects

What are antipsychotics?
Antipsychotic medicines are primarily used to manage psychosis, a condition that affects the mind. Psychosis is characterized by some loss of contact with reality, often including or hallucinations (hearing or seeing things that are not really there), or delusions (false, fixed beliefs). It can also be a symptom of a physical condition such as drug abuse or a mental disorder such as schizophrenia, very severe depression (also known as “psychotic depression”), or bipolar disorder.

 
Antipsychotic medications are frequently used in combination with other drugs to treat delirium, dementia, and mental health conditions, including:

The older antipsychotic medications are conventionally referred to as “typical” antipsychotics or “neuroleptics”. Some of the common typical antipsychotics include:

Second generation antipsychotic medications are also called “atypical” antipsychotics. Some of the most common atypical antipsychotics are:

According to a 2013 research review by the Agency for Healthcare Research and Quality , typical and atypical antipsychotics both work to treat of bipolar disorder (preventing mania) and symptoms of schizophrenia Additionally, some atypical antipsychotics have wider applications and are used for treating bipolar depression or general depression.

 
What are the possible side effects of antipsychotics?

Antipsychotics are known to have a large number of side effects (also called adverse events) and risks, including potentially fatal complications.

 
The FDA lists the following side effects of antipsychotic medicines:

  • Constipation
  • Nausea
  • Vomiting
  • Uncontrollable movements, such as tics and tremors (the risk is higher with typical antipsychotic medicines)
  • Seizures Drowsiness
  • Blurred vision
  • Low blood pressure
  • Dizziness
  • Restlessness
  • Weight gain (the risk is higher with some atypical antipsychotic medicines)
  • Dry mouth
  • A low number of white blood cells, which fight infections

Typical antipsychotic medications can also cause additional side effects related to physical movement, such as:

  • Tremors
  • Restlessness
  • Rigidity
  • Muscle spasms

Long-term use of antipsychotic medications may lead to a condition called tardive dyskinesia (TD). Tardive dyskinesia causes uncontrolled muscle movements, commonly around the mouth. TD can range from mild to very severe, and in some people, the problem cannot be cured and becomes disfiguring.

 
Avoid the Risk of Antipsychotic Side Effects with Rxight®

The Rxight® medication panel includes 18 popular antipsychotics on the market. Because the potential side effects of both typical and atypical antipsychotics can be very serious and potentially fatal, knowing your risks ahead of time with Rxight® can be an invaluable test for you and your prescriber.

 

Mood Stabilizer Side Effects

What are mood stabilizers?
Mood stabilizers work by decreasing abnormal brain activity. They are used mainly to treat bipolar disorder and the mood swings associated with other mental conditions including:

  • Depression (usually in conjunction with an antidepressant)
  • Disorders of impulse control
  • Schizoaffective Disorder

Anticonvulsant (anti-seizure) medications are most frequently used as mood stabilizers. They were originally developed for treatment of seizures, but they were found to help control mood swings as well. One anticonvulsant commonly used as a mood stabilizer especially in patients with symptoms of both mania and depression, or those with rapid-cycling bipolar disorder, is valproic acid (sold as Depakote). Anticonvulsants used as mood stabilizers include:

Lithium is a non-anticonvulsant mood stabilizer approved for the treatment of mania and the maintenance treatment of bipolar disorder.

 
What are the potential side effects of mood stabilizers?

Mood stabilizers can cause several side effects, some of which may be serious, especially at high dosages. These side effects include:

  • Potentially fatal rash (Stevens-Johnson Syndrome)
  • Itching
  • Extreme thirst
  • Tremor
  • Nausea and vomiting
  • Fast, slow, or irregular heartbeat
  • Slurred speech
  • Blackouts
  • Changes in vision
  • Hallucinations
  • Loss of coordination
  • Swelling

Mood stabilizers may cause other side effects that are not included in this list. Your unique reaction to anticonvulsants is based in genetics, and the Rxight® genetic test will indicate which mood stabilizer not work for you may right from the start instead of having to go through trial and error with your doctor – a process which can be expensive, lengthy and dangerous.  With Rxight® results, you your doctor can work together to find the best and most effective antidepressant treatment tailored to your genotype, preferably before treatment begins.

 

Anti-Anxiety Medication Side Effects

What are anti-anxiety medications?
Anti-anxiety medications (also called “anxiolytics”) work by reducing the symptoms of anxiety, such as that seen in panic attacks, or extreme worry and fear. The most commonly prescribed anti-anxiety medications are called “benzodiazepines.” Benzodiazepines are most frequently used to treat a condition called generalized anxiety disorder, while in cases of social phobia (social anxiety disorder) or panic disorder (panic attacks). Benzodiazepines are usually second-line treatments, behind antidepressants such as SSRIS.

Benzodiazepines used to treat anxiety disorders – all of which are tested in the Rxight® panel – include:

Short-acting benzodiazepines such as Lorazepam and another class of medication known as beta-blockers are used to treat non-persistent symptoms of anxiety. Beta-blockers are used primarily to manage physical symptoms of anxiety (e.g., shaking, rapid heartrate, and sweating).

 
Buspirone  (which is chemically unrelated to the benzodiazepine family) is sometimes indicated for the long-term treatment of chronic anxiety. It is not effective to use on an “as-needed” basis like the benzodiazepines.

 
How common is addiction to benzodiazepines?
One of the serious risks of anti-anxiety medications is that you can build up a tolerance to benzodiazepines if they are taken over a long period of time and may need increasingly higher doses to get the same effect. There is a serious risk of addiction and dependence. To avoid these problems, doctors usually prescribe benzodiazepines for short periods, particularly in the elderly (NIMH, “Despite Risks, Benzodiazepine Use Highest in Older People”), and people with addiction tendencies. If people suddenly stop taking benzodiazepines, they may have withdrawal symptoms or their anxiety may return.

 
What are the possible side effects of anti-anxiety medications?
Like other medications, anti-anxiety medications may cause side effects, many of which are serious. The most common side effects of benzodiazepines are sleepiness and dizziness. Other possible side effects include:

  • Headache
  • Confusion
  • Tiredness
  • Nausea
  • Blurred vision
  • Nightmares

Tell your doctor immediately if any of these symptoms are severe or do not go away:

  • Drowsiness
  • Difficulty thinking or remembering
  • Increased saliva
  • Dizziness
  • Unsteadiness
  • Problems with coordination
  • Blurred vision

If you experience any of the symptoms below, call your doctor immediately:

  • Swelling of the eyes, face, lips, tongue, or throat
  • Difficulty breathing or swallowing
  • Rash
  • Hives
  • Hoarseness
  • Seizures
  • Yellowing of the skin or eyes (jaundice)
  • Depression
  • Difficulty speaking
  • Difficulty breathing

Common side effects of beta-blockers include:

  • Fatigue
  • Dizziness
  • Weakness
  • Cold hands

 

Stimulant Side Effects

What are Stimulants?
Stimulants increase alertness, attention, and energy, as well as elevate blood pressure, heart rate, and respiration. Stimulant medications are generally prescribed to treat individuals diagnosed with ADHD (attention-deficit hyperactivity disorder). People with ADHD who take prescription stimulants describe a calming and “focusing” effect from the medication.  This is due to its effects on the brain chemical dopamine.

Stimulants used to treat ADHD – all of which are analyzed in the Rxight® DNA test – include:

In 2002, the FDA approved non-stimulant medication atomoxetine (Strattera) for use as a treatment for ADHD. Additional non-stimulant antihypertensive medications, clonidine  and guanfacine, are also approved for treatment of ADHD.

In addition to treating ADHD, stimulants are prescribed to treat other health conditions, including narcolepsy, and occasionally depression.

 
What are the possible side effects of stimulants?
Stimulants may cause side effects, most of which are relatively minor and disappear when dosage levels are lowered. The most common side effects include:

  • Loss of appetite
  • Insomnia
  • Stomach pain
  • Headache

Less common side effects include:

  • Motor tics or verbal tics
  • Personality changes

What are serious side effects of stimulant medications?
While side effects of stimulant medications tend to be minimal, patients and parents of patients are cautioned that serious adverse effects may occur, as reported by the FDA Drug Safety Communication in 2013. Also see
FDA Warns of Psychiatric Adverse Events from ADHD Medications
.

 
Heart-related problems:

  • Sudden death in patients who have heart problems or heart defects
  • Stroke
  • Myocardial infarction (heart attack)
  • Increased blood pressure and heart rate

Mental (Psychiatric) problems:

  • Behavior and thought problems
  • New or worse aggressive behavior or hostility
  • New or worse bipolar illness
  • New psychotic symptoms (or new manic symptoms)
  • Physical or psychological dependence

For additional details on the FDA warnings and manufacturer labeling for medications covered in the Rxight® panel, please refer to our list of medications covered.

 

About Rxight® Pharmacogenetic Testing

The Rxight® genetic test analyzes your risks based on your unique genetic makeup through a process called “SNP genotyping.” The report which will be shared with you in a personal consultation with a pharmacist. The report “red-flags” medications which may cause you to have issues, or conversely highlight medications which may not be effective for you.

 
Rxight® is based on pharmacogenetics — the study of how genes affect a person’s response to medicines. Our panel of over 200 clinically significant medications includes dozens of commonly prescribed psychiatric medications, including antidepressants across five sub-classes, mood stabilizers used in bipolar disorder and schizoaffective disorder, antipsychotics, ADHD medications (stimulant and non-stimulant), and anti-anxiety medications.

 
Based on how well you metabolize those particular medications, which is determined by your genes that encode liver enzymes that break down drugs, you will be at risk for developing side effects or the medication not working well or at all. With the results of the Rxight® test you and your prescriber can find the right medication for you, preferably before treatment begins.

 
Contact us today by phone 1 (888) 888-1932 or email to learn more about how Rxight® pharmacogenetic testing can help you find the right medication, right from the start.

statins side effects

Statin Side Effects in Women

By | Drug Metabolism, Pharmacogenetic Testing, Pharmacogenomics, Precision Medicine, Statins | No Comments

Statin treatment in women without cardiovascular disease is controversial. Research has found that for women with elevated LDL levels as their only cardiovascular risk factor, the benefit of lowering LDL cholesterol with a statin drug might not outweigh the risks.
 
According to an article in Circulation “Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia” (March 2010) many women take statins and suffer side effects similar to those experienced by men. Statin side effects range from mild to severe and include liver damage, myopathy, and behavioral and cognitive problems.
 

Revised Treatment Guidelines Push for Increasing Statin Use

 
Treatment guidelines issued in 2014 in the New England Journal of Medicine suggest that up to 13 million more adults should be taking statins. The revised guidelines changed the focus from specific cholesterol levels to a wider assessment of heart attack and stroke risk.
 

Opponents Claim Too Many Women Prescribed Statins

 
Not everyone agrees with these new treatment guidelines, as reported in the New York Times, also in 2014: “Among men 60 to 75, the percentage would jump to 87 percent from 30 percent; among older women, it would increase to 54 percent from 21 percent.” In that New York Times article, the chief of cardiovascular medicine at the Cleveland Clinic said the report confirmed his concerns that the new guidelines “don’t target the right patients for treatment.” He faulted the study for not taking into account the family history of cardiovascular disease: “Should so many women be taking statins? Far too many healthy women are taking statins, they say, though some research indicates the drugs will do them little good and may be more likely to cause serious side effects in women.”
 

Women Found to Suffer More Side Effects from Statins Than Men

 
These studies highlight the fact that fewer women take statins than men, and that women suffer more side effects from statins than men. Although women represent about half the population, they are enormously under-represented in clinical trials of statins. It follows that the evidence on the benefits and risks for women is scarce. In one of the studies American Journal of Cardiology “Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)” (Jan 2006), there was no significant reduction in heart attacks, strokes and deaths among the women while the male participants on statins had fewer heart attacks and strokes.
 

Weigh the Risks and Benefits with Genetic Testing

 
Some side effects of statins and other drugs may be reduced by either altering the dose or by changing the particular statin prescribed. Side effects in general may be reduced by taking into account the variation in your drug metabolism genes. The study of variation in the drug metabolism genes defines the field of Pharmacogenetics. This advanced genomics field emerged after the human genome was sequenced and has become an important field of its own.
 

Rxight® Pharmacogenetic Testing for Statin Side Effects

 
Pharmacogenetics research showed there is variation in the genes that are responsible for processing drugs. That means that if a particular gene has variations it may result in a gene product (protein or enzyme) that is non-functional or has reduced function. This altered function, which can sometimes mean an inability to process a medication or a reduced ability to process a medication, may result in adverse side effects. Side effects may be lessened by avoiding those drugs that you don’t have the ability to process normally.

 
Once you and your physSician have these results you can use them for your lifetime. The results allow your physician to interpret your ability to metabolize over 200 drugs on the market. Your physician will then have at hand the predictive ability to prescribe drugs that are safer for you and to possibly avoid side effects with any new medication. With the Rxight® pharmacogenetic test from MD Labs you can bring precision medicine home to your personalized medical care.

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Research Shows Ultrarapid Metabolizers of CYP2D6 Face Increased Risk of Hospitalization

By | Adverse Drug Reactions, Pharmacogenetic Testing, Pharmacogenomics, Precision Medicine, Provider | No Comments

The cytochrome P450 2D6 (CYP2D6) hepatic enzyme is responsible for the metabolism a wide range of medications and other substances. For example, opioids such as codeine, morphine and tramadol are activated by CYP2D6, while several classes of antidepressants and antipsychotics are in made inactive by the CYP2D6 enzyme. While it has been shown extensively that variation within the genes controlling drug metabolism has been associated with toxicity/adverse drug reactions or conversely drug inefficacy, there is a dearth of data on the adverse health outcomes of the potential impact of extreme metabolism phenotypes (ultrarapid / poor metabolism of CYP2D6) on hospitalization and emergency department (ER) visits.
 
A recent study published in Pharmacogenomics and Personalized Medicine “Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6” (Jun 2016) found a patient’s CYP2D6 phenotype has a statistically significant impact on the rate of hospitalization from adverse drug effects for ultra-rapid metabolizers in comparison to extensive metabolizers. The hypothesis was that participants with ultra-rapid and poor metabolism would have higher rates of hospitalization.
 
The investigators examined hospital records over a 9-year period, employed data from the Mayo Clinic Biobank on patients enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT) protocol, which sequenced 86 pharmacogenomics genes for clinical use. For the study, a cohort of 929 adult patients underwent CYP2D6 testing. CYP2D6 clinical phenotypes ranged from ultrarapid to poor metabolizer, with extensive metabolizer being the reference group. There was no statistically significant difference between other CYP2D6 phenotypes and controls.
“Precision medicine within pharmacogenomics can be used to predict adverse health outcomes such as hospitalization,” the study’s authors concluded. “There may be clinical utility in pre-emptively genotyping patients to decrease health care use.”

pgx testing

Researchers at Vanderbilt University Call for Pre-emptive Genetic Testing in CVD Patients

By | Other, Pharmacogenetic Testing, Pharmacogenomics, Precision Medicine, Provider, Statins | No Comments

Cancer and cardiac patients are typically prescribed multiple medications due to the severity and clinical complexity of their illness. It has been proposed in numerous studies citing relevant data on statistically significant adverse medication reactions in this population that pharmacogenetic testing should be conducted pre-emptively on such groups to prevent adverse clinical outcomes.
 
Researchers at Vanderbilt University Medical Center’s Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment (PREDICT) investigated gene variants that were deemed clinically actionable based on institutionally approved clinical decision support advisors for five common DGIs (drug-gene interactions) in a clinical group of 10,044 cardiovascular disease (CVD) patients, as detailed in a January 2017 article in Pharmacogenomics and Personalized Medicine “Prevalence of clinically actionable genotypes and medication exposure of older adults in the community.”
 
The study analyzed clinically actionable pharmacogenotypes for clopidogrel, warfarin, statins, thiopurines, and tacrolimus. The researchers reported that 91% of patients had at least one actionable gene and more than 5% of patients were at high risk of suffering strong adverse reactions. Similar studies corroborate the PREDICT researchers’ findings, according to the article.
 
Pre-emptive genetic testing should therefore be integrated into standard care models, the researchers concluded. Given the preponderance of data on DGIs such as these, the investigators called for prescribers to give greater consideration to the possibility of clinically relevant drug-gene interactions in the older adult group. “Our findings affirm that pre-emptive genotyping is likely to have strong potential to improve medication safety, efficacy, and health outcomes,” the article stated. “Further investigations correlating genotypes and medication exposures to adverse reactions and other outcomes in older people appear justified.”

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