3 Effect Of Pregnancy On Drug Metabolism
Physiological changes in pregnancy can affect serum concentrations of psychiatric medications (Table 4). Some of these changes may increase or decrease the dose necessary for some medications. The blood level of nortriptyline, a tricyclic antidepressant, has been found to drop below the therapeutic range as women reach the fifth month of pregnancy (12). Certain hepatic enzymes in the cytochrome P450 system are induced by high levels of estradiol and progesterone during pregnancy (13-16). These include 3A4, which breaks down quetiapine and clozapine, and 2D6, which metabolizes risperidone. Cytochrome 1A2, on the other hand, becomes less active during pregnancy (17). Because 1A2 is the main metabolizing enzyme for olanzapine, blood levels ofthis medication may increase during pregnancy.
Wide interindividual variations exist in the degree ofmedication clearance present during pregnancy (18). For medications that must remain within a specific therapeutic window (e.g., lithium, tricyclic antidepressants, antiepileptic drugs), it is advisable to increase the monitoring frequency ofblood levels ofmedications. Although the optimal frequency
Table 3
FDA Use-in-Pregnancy Ratings for Specific Medications
Medication FDA Use-in-Pregnancy Rating
Anxiolytics and sedatives
Alprazolam (Xanax) D
Buspirone (Buspar) B
Clonazepam (Klonopin) D
Diazepam (Valium) D
Flurazepam (Dalmane) X
Lorazepam (Ativan) D
Temazepam (Restoril) X
Zolpidem (Ambien) B
Antidepressants
Amitriptyline (Elavil, Endep) D
Bupropion (Wellbutrin) B
Citalopram (Celexa, Lexapro) C
Clomipramine (Anafranil) C
Desipramine (Norpramin, Pertofrane) C
Doxepin (Adapin, Sinequan) C
Fluoxetine (Prozac, Sarafem) C
Fluvoxamine (Luvox) C
Imipramine (Tofranil) D
Mirtazapine (Remeron) C
Nefazodone (Serzone) C
Nortriptyline (Aventyl, Pamelor) D
Paroxetine (Paxil) C
Sertraline (Zoloft) C
Trazodone (Desyrel) C
Venlafaxine (Effexor) C
Mood stabilizers
Lithium (Lithobid, Eskalith) D
Valproate (Depakote, Depakene) D
Carbamazepine (Tegretol) D
Gabapentin (Neurontin) C
Lamotrigine (Lamictal) C
Oxcarbazepine (Trileptal) C
Antipsychotics
Aripiprazole (Abilify) C
Clozapine (Clozaril) B
Fluphenazine (Prolixin) C
Haloperidol (Haldol) C
Olanzapine (Zyprexa) C
Table 3 (Continued)
Medication
FDA Use-in-Pregnancy Rating
Risperidone (Risperdal) C
Quetiapine (Seroquel) C
Trifluoperazine (Stelazine) C
Ziprasidone (Geodon) C
Stimulants
Dextroamphetamine (Adderall, Dexedrine) C
Methylphenidate (Ritalin) C
Anticholinergic agents
Diphenhydramine (Benadryl) B
Hydroxyzine (Atarax) C
Trihexyphenidyl (Artane) C
Antihypertensive agents
Propanolol (Inderal) C
Clonidine (Catapres) C
Hormone supplements
Levothyroxine A
Oral contraceptives X
Analgesics
Acetaminophen (Tylenol) B
Ibuprofen (Motrin) B
Naproxen (Naprosyn) B
Sumatriptan (Imitrex) C
of monitoring has not been established, a wise rule would be to check medication blood levels at least monthly during the second and third trimesters of pregnancy. Ifa medication dosage is increased during pregnancy, it should probably be reduced following delivery to avoid the possibility of toxicity in the mother following the birth.
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