PSYCHIATRY / ADHD

Pharmacogenetic Psychiatry / ADHD Report
The Alpha Genomix Pharmacogenetic Psychiatry Report provides patient-specific, evidence-based information covering genes implicated in behavioral health. This report delivers dosing guidance for currently affected medications and a listing of all risk-related medications commonly used in behavioral health to assist clinicians in determining the most effective dose and medication, potentially eliminating multiple medication trials.

CYP1A2

The CYP1A2 is involved in the metabolism of 8-10% of commonly used drugs as well as natural compounds such as caffeine. A large number of CYP1A2 variants have been identified and have been shown to influence individual’s ability to metabolize psychotropic drugs including Clozaril, Cymbalta, Zanaflex, Zofran, Rozerm, Naropin, Cipro and Zyprexa. CYP1A2 has been shown to be important for dosing of several psychotropic drugs and can impact both drug efficacy and adverse drug reactions. CYP1A2 is the main CYP isoform involved in Clozapine (Clozaril) metabolism. Case studies have shown that ultrarapid metabolizers of clozapine who presented as resistant to treatment had improved response when Clozapine dose was increased and co-administrated with the CYP1A2 inhibitor fluvoxamine (Luvox). There has also been discussion of the interaction of smoking and drug response and the potential dangers of smoking cessation in the patients with schizophrenia. The CYP1A2 assay identifies some common variants associated with variability in CYP1A2 enzyme activity.

CYP2C9

The CYP2C9 is involved in the metabolism of 15% of clinically important medications including psychotropic drugs such as Prozac, Dilantin, Mysoline, Celebrex and Clinoril. To date 30 different variants of CYP2C9 have been identified. The CYP2C9 assay identifies some common variants associated with variability in CYP2C9 enzyme activity. For example, Patients who had adverse reactions to Phenytoin have been shown to harbor a variant of CYP2C9 with reduced to or no enzymatic activity. The CYP2C9 assay identifies some common variants associated with variability in CYP2C9 enzyme activity.

CYP2C19

The CYP2C19 is involved in the metabolism of approximately 10% of clinically relevant medications. There is substantial evidence linking the CYP2C19 polymorphisms to variability in the pharmacological and safety profiles of the following therapies used in the treatment of psychiatric conditions including Elavil, Zoloft, Onfi, Celexa, Lexapro and Toftanil. To date 30 different variants of CYP2C19 have been identified. The CYP2C9 assay identifies some common variants associated with variability in CYP2C9 enzyme activity.

CYP2D6

The CYP2D6 is involved in the metabolism of 25% of clinically important medications. Examples of CYP2D6 substrates can be found in antidepressants including amitriptyline, citalopram, clomipramine, desipramine, doxepin, fluvoxamine, imipramine, maprotiline, mianserin, nortriptyline, fluoxetine, paroxetine). Antipsychotics including chlorpromazine, clozapine, haloperidol, perphenazine, risperidone, thioridazine and zuclopenthixon.  The impact that a CYP2D6 polymorphism has on therapy with any of the aforementioned drugs is related to the resulting metabolizer status that the polymorphism(s) cause in the individual receiving therapy.To date more than a 100 different variants have been identified. The CYP2D6 assay identifies common variants associated with variability in CYP2D6 enzyme activity.

CYP3A

CYP3A4 and 3A5 are involved in the metabolism of approximately 50% of commonly used drugs. The following drugs used in the management of various psychiatric conditions are metabolized extensively by CYP3A including Duragesic, Suboxone, Tegretol, Seroquel, Geodon, Xanax, Versed, Halcion, Serzone, Oleptro, Vibryd, Sonata and Ambien. CYP 3A4 and CYP3A5 enzymes have overlapping substrate specificity and the contribution of CYP3A5 in the overall metabolism is smaller than the one for CYP3A4. The CYP3A assay tests for the presence of CYP3A genetic variants that can influence its activity.

ADRA2A

Alpha-2-adrenergic receptors 2 A (ADRA2A) is a G protein-coupled receptor that have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. Various variants of the ADRA2A gene have been reported to have varied responses to certain drugs. Pediatric patients with the CC genotype and attention deficit hyperactivity disorder may have a poorer response to methylphenidate treatment compared to pediatric patients with the CG or GG genotype. Other genetic and clinical factors may also influence response to methylphenidate.

COMT

Several complex associations between COMT the Val158Met Variant as a risk factor for numerous diseases have been found but they all seem to have a limited predictive value. However, the response to some psychotropic medications seems to be dependent to some extent upon COMT status. In general, the wild-type genotype predicts a good response to methylphenidate and amphetamines in the treatment of attention deficit hyperactivity disorder.