Neuropsychiatric Medications in Pregnancy

1. See Also
   1. Medications in Pregnancy
   2. Antepartum Depression
   3. Postpartum Depression
   4. Substance Abuse in Pregnancy
   5. Cocaine Abuse in Pregnancy
   6. Fetal Alcohol Syndrome
2. Background
   1. Pregnancy Categories will be replaced on medication bottles with specific warnings and precautions by 2020 in U.S.
      1. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm425317.htm
      2. Although FDA Pregnancy Categories are no longer FDA designated, they are included here
         1. As of 2018, succinct guidance (to replace ABCDX) on specific drugs in pregnancy is lacking
3. Precautions
   1. SSRIs have shown mixed or weak associations with Autism (as one of many contributing factors)
      1. Boukhris (2016) JAMA Pediatr 170(2):117-2 +PMID:26660917 [PubMed]
      2. Harrington (2014) Pediatrics 133:e1241-8 +PMID:24733881 [PubMed]
      3. Hviid A (2013) N Engl J Med 369:2406-15 [PubMed]
      4. Rai (2013) BMJ 346:f2059 [PubMed]
   2. SSRI association with Persistent Pulmonary Hypertension
      1. Increased risk by 6 fold if SSRIs used after 20 weeks
      2. Number needed to harm: 286-351
      3. Grigoriadis (2014) BMJ 348:f6932 [PubMed]
4. Indications: Neuropsychiatric Medications in Pregnancy
   1. Moderate-high risk Mood Disorder relapse in pregnancy
      1. Major Depression onset in Pregnancy
         1. See Depression in Pregnancy
      2. Bipolar Disorder (30-50% risk off mood stabilizers)
      3. Puerperal Psychosis
      4. Severe Major Depression
      5. History of Postpartum Depression
      6. Cyclothymia
   2. Disorder with high morbidity on relapse
      1. Schizophrenia
      2. Bipolar Disorder
      3. Severe chronic depression
      4. Panic Disorder with Agoraphobia
5. Class B: No risk in controlled animal studies
   1. Antidepressants
      1. Sertraline (Zoloft) - some safety data available
      2. Bupropion (Wellbutrin) - based on little safety data
   2. Antipsychotics
      1. Clozapine (Clozaril)
   3. Sedatives
      1. Zolpidem (Ambien)
6. Class C: Small risk in controlled animal studies
   1. Anxiolytics (not recommended in pregnancy)
      1. See Class D for adverse effects in pregnancy
      2. Clonazepam (Klonopin)
   2. Anticonvulsants
      1. Carbamazepine (Tegretol, 1% Neural Tube Defect risk)
      2. Ethosuximide
   3. MAO inhibitors (not recommended in pregnancy)
      1. Isocarboxazid
      2. Phenelzine
      3. Tranylcypromine
   4. Other Antidepressants
      1. Trazodone (Desyrel)
      2. Venlafaxine (Effexor) - little data available
      3. Mirtazapine (Remeron)
      4. Desipramine
      5. Fluoxetine (Prozac)
         1. Well studied in pregnancy, but data in 2015 showed association with cardiac defects
         2. Berard (2015) Br J Clin Pharmacol +PMID:26613360 [PubMed]
   5. Antipsychotics
      1. Haloperidol (Haldol)
         1. Best studied of all Antipsychotics
         2. No known Teratogenicity (preferred in pregnancy)
   6. Drugs of Abuse
      1. Amphetamine
      2. Lysergic Acid (LSD)
      3. Marijuana
   7. Chemical Dependency Medications
      1. Antabuse - not in Briggs (1998)
7. Class D: Strong evidence of risk to the human fetus
   1. Anxiolytics
      1. Wean off prior to conception (10% per week)
      2. Teratogenicity: Increased orofacial cleft risk
      3. Perinatal affects: Hypotonia, Apnea, Hypothermia
      4. If used, avoid first trimester and perinatal use
      5. Agents
         1. Chlordiazepoxide (Librium)
         2. Diazepam (Valium)
         3. Lorazepam (Ativan)
         4. Midazolam (Versed)
   2. Anticonvulsants
      1. Valproic Acid (Depakote, 5% Neural Tube Defect risk)
      2. Phenytoin (Dilantin)
      3. Phenobarbital
      4. Primidone (Mysoline)
   3. Miscellaneous
      1. Lithium
         1. Teratogenicity: Ebstein's Anomaly (0.1% risk)
         2. Perinatal: Cyanosis, Hypotonicity
   4. Selective Serotonin Reuptake Inhibitors
      1. Paroxetine (Paxil)
   5. Tricyclic Antidepressants
      1. Amitriptyline (Elavil)
      2. Imipramine
      3. Nortriptyline (Pamelor)
8. Class X: Very high risk to the human fetus
   1. Anxiolytics
      1. Alprazolam (Xanax)
      2. Triazolam (Halcion)
      3. Flurazepam (Dalmane)
   2. Drugs of Abuse
      1. Phencyclidine
      2. Alcohol - not in Briggs (1998)
         1. See Fetal Alcohol Syndrome
9. Preparations: Other
   1. Pregabalin (Lyrica) in first trimester has been linked to possible birth defects
      1. Winterfeld (2016) Neurology 86(24): 2251-7 [PubMed]
10. References
    1. Briggs (1998) Drugs in Pregnancy and Lactation, 5th ed
    2. Larimore (2000) Prim Care 27(1):35-53 [PubMed]
    3. Ward (2002) Am Fam Physician 66:629-39 [PubMed]