Pharmacogenetics of Elavil (amitriptyline)

Pharmacogenetics of Elavil (amitriptyline)
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Elavil (amitriptyline) is metabolized through CYP2c19 and CYP2D6 and to a lesser extent CYP2C9. Pharmacogenetic testing of these pathways serves as an anchor for the intense personalization required to effectively prescribe Elavil and other antidepressant medicines. Prevalent polymorphisms in genes for the cytochromes responsible for first pass metabolism of these, and many other drugs, cause differences in rate of drug clearance that result in dramatic differences in safety and efficacy. Physicians who incorporate pharmacogenetic drug reaction testing into their practice don't know how they had managed without that knowledge.

Potential for drug drug interactions (DDIs)

CYP2D6 metabolizes virtually all of the anti depressants, many of which are also strong inhibitors of the enzyme. Adverse events driven by interactions between opioid analgesics and anti depressants can be greatly increased in patients with gene based decreased CYP2D6 functioning.

Individualized Patient Reports based on patient drug, herbal and diet regimens

DNA test reports can include patient specific information on potential drug drug interactions (DDIs) mediated by the tested polymorphic drug metabolizing enzymes, taking into account patient diet, OTC medicines, herbal preparations, recreational drugs and other factors. Testing patients for drug metabolizing enzyme genotypes can provide physicians with immediate insight into individual patient differences in drug processing ability and help decrease the time to safe and effective treatment. This information can be especially valuable when potential drug-drug interactions (DDIs) are a possibility.

Physician Potential Benefits and Applications

Diagnostic

Resolve adverse drug reaction caused medical conditions.
Determine the need for higher dose or more expensive drug.
Understand sudden changes in behavior triggered by adverse drug reactions induced by drugs of abuse.
Optimize drug therapy at an earlier stage in treatment, by narrowing the therapeutic options for the patient.
Help patient understand difficulties

Screening

Patients who have had therapeutic failures and need to receive a problem drug again.
Patients who have had adverse drug reactions or severe side effects in the past.
Family members of patients who have had an adverse drug reaction.
Patients who want to be prepared for emergent situations.

CYP metabolized drugs of abuse

Dextromethorphan (Nyquil etc.)
Oxycontin
Ketamine
Heroin

CYP Metabolized herbs and foods

St. John's wort
Ginko biloba
Garlic

Dosing Recommendations
The following charts and tables are adapted from Julia Kirchheiner, et al Molecular Psychiatry Feature Review, 9 442-473 (2004), "Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response," a meta analysis of published research from 1970-2003 on the relevance of pharmacogenetic effects of CYP 2D6 and CYP 2C19 on 36 antidepressants and 38 antipsychotics.

Chart 1: Dose Adjustment for CYP 2D6

Table 1: Dose Adjustment for CYP 2D6

	Drug	PM (%)	IM (%)	EM (%)	UM (%)
Tricyclic antidepressants	amitryptiline	73	92	111	130
	clomipramine	60	87	121	155
	desipramine	42	83	125	167
	doxepin	36	82	127	172
	imipramine	28	79	131	183
	nortriptyline	53	96	119	142
	trimipramine	32	76	141	206
SSRIs	citalopram	98	100	101	102
	fluoxetine	78	94	107	120
	fluvoxamine	69	93	112	131
	paroxetine	66	90	114	138
	sertraline	99	100	100	100
Other antidepressants	buproprion	90	97	104	111
	maprotiline	36	82	127	172
	mianserin	74	90	114	138
	mirtazapine	102	101	99	97
	moclobemide	121	107	92	77
	nefazadone	90	97	105	113
	trazadone	80	93	110	127
	venlafaxine	68	86	109	132
Antipsychotics	aripiprazole	70	92	113	134
	flupentixol	74	86	116	146
	haloperidol	76	97	107	126
	olanzapine	61	105	122	139
	perazine	86	91	110	117
	perphenazine	31	80	129	178
	risperidone	87	96	106	116
	thioridazine	40	85	126	140
	zuclopenthixol	63	90	116	142

Chart 2: Dose Adjustment for CYP 2C19

Table 2: Dose Adjustment for CYP 2C19

	Drug	PM (%)	IM (%)	EM (%)
Tricyclic antidepressants	amitryptiline	53	81	109
	clomipramine	62	79	110
	doxepin	48	91	105
	imipramine	58	83	108
	trimipramine	45	52	111
SSRIs	citalopram	61	84	108
	fluoxetine	70	86	107
	fluvoxamine	93	97	101
	sertraline	75	90	105
Other antidepressants	maprotiline	100	100	100
	mianserin	142	117	92
	moclobemide	54	82	110
Antipsychotics	clozapine	78	91	104
	zotepine	82	93	104

Ordering Tests
Now you can add another dimension to providing safer and more efficacious care to your patients by ordering DNA Drug Reaction Profiles for them. Click here for ordering instructions and requisition forms.

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