These include desipramine, nortriptyline, and fluoxetine. The older antidepressants may have lower efficacy in women than the newer SSRI drugs. Women seem to respond better to fluoxetine, sertraline, and other SSRIs (Yonkers, 2003).

The usual starting dosages for imipramine, amitriptyline, and desipramine are 2550 mg daily at bedtime. The dose can be increased to 2550 mg daily every week, if warranted, to a maximum dose of 300 mg daily. The initial dosage for nortriptyline is 1025 mg PO q d and can be increased by 10 mg each week if necessary to a maximum dose of 150 mg daily (Bryant and Brown, 1986). However, if the pregnant patient's depression is not improved on these older drugs, it is recommended to use one of the SSRIs. In fact, it may be beneficial to begin therapy with a well-studied SSRI such as fluoxetine (Yonkers, 2003).

Therapeutic response usually occurs within 1014 days and includes improved sleep and appet.i.te, as well as return of normal routine activities and mood elevation (Bryant and Brown, 1986). If there is absolutely no response to therapy after 23 weeks, one should consider an alternative antidepressant. It is recommended that tapering of the antidepressant dose begin approximately 23 weeks prior to delivery, to minimize neonatal effects. To prevent anticholinergic withdrawal symptoms (chills, malaise, muscle aches, diarrhea, and nightmares) in the mother, the dose should be reduced by 50 mg every 34 days (Blackwell, 1981). The starting dose of fluoxetine is 1020 mg/day (Yonkers and Cunningham, 1993).

Psychosis Management of psychosis during pregnancy frequently requires hospitalization because of the patient's confusion, hostility, disorientation, anxiety, and possible suicidal tenden-cies. Psychiatric consultation and psychological evaluation are mandatory for patients with psychosis. Antipsychotic agents are frequently necessary in the treatment of psy-Key references 205.

chosis. The agent of choice for acute psychotic reactions is haloperidol 15 mg PO (or IM) every 68 h. Chlorpromazine is another agent that is used in the acutely psychotic patient with a starting dose of 100 mg PO every 812 h. Upon achievement of a stable dose, chlorpromazine can be administered once daily at bedtime. Some authorities recommend high-potency agents, haloperidol or trifluoperazine, over the low-potency neuroleptics (Miller, 1994a, 1996). The daily dose of haloperidol (Haldol) is 510 mg/day and of trifluoperazine (Stelazine), 1040 mg/day (Yonkers and Cunningham, 1993).

Lithium may be necessary for manic-depressive disorders or manic disorders. For acute mania, the initial dosage is 0.62.1 g/day in three divided doses. Monitoring of the serum levels is mandatory, with adjustments in the dosage as indicated to maintain serum levels of 0.81.5 mEq/L. Recently, reevaluation of lithium use during early pregnancy led to marked lower estimated risk for birth defects, specifically for Ebstein's anomaly. The drug is currently recommended for use during pregnancy, avoiding weeks 26 of embryonic development if possible (Yonkers et al et al., 1998, 2004).

Electroconvulsive therapy is warranted when all else fails. Although carbamazepine and valproic acid are used effectively to treat mania, these drugs are not recommended for use during pregnancy.

Key references Bupropion Pregnancy Registry. Interim Report. 1 September 1997 through 29 February 2004. Wilmington: Inveresk, June 2004.

Diav-Citrin O, Shechtman S, Weinbaum D, Arnon J, Wajnberg R, Ornoy A. Pregnancy outcome after gestational exposure to paroxetine. a prospective controlled cohort study.

Teratology 2002; 65 65: 298.

Einarson T, Einarson A. Newer antidepressants in pregnancy and rates of major malformations. A meta-a.n.a.lysis of prospective comparative studies. Pharmacoepidemiol Drug Saf 2005; 14 14: 823.

Hendrick V, Smith LM, Suri R, Hw.a.n.g S, Haynes D, Altshuler L. Birth outcomes after prenatal exposure to antidepressant medication. Am J Obstet Gynecol 2003; 188 188: 812.

Little BB. Pharmac.o.kinetics during pregnancy. Evidence-based maternal dose formulation.

Obstet Gynecol 1999; 93 93: 858.

Little BB, Yonkers KA. Epidemiology of psychiatric disorders and the importance of gender.

In: Yonkers KA, Little BB (eds). Treatment of Psychiatric Disorders in Pregnancy.

London: Arnold Publishers, 2001.

Rabheru K. The use of electroconvulsive therapy in special patient populations. Can J Psychiatry 2001; 46 46: 710.

Yolles JC. Psychotropics versus psychotherapy. an individualized plan for the pregnant patient. In: Yonkers KA, Little BB (eds). Treatment of Psychiatric Disorders in Pregnancy.

London: Arnold Publishers, 2001:1.

Yonkers KA. Special issues related to the treatment of depression in women. J Clin Psych 2003; 64 64 (Suppl. 18): 8. (Suppl. 18): 8.

Yonkers KA, Little BB, March D. Lithium during pregnancy. Drug effects and their therapeutic implications. CNS Drugs 1998; 9 9: 261.

Yonkers KA, Wisner KL, Stowe Z et al. Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry 2004; 161 161: 608.

Further references are available on the book's website at http://www.drugsandpregnancy.com 11.Antihistamines, decongestants, and expectorants during pregnancy Decongestants 206.

Expectorants and ant.i.tussives 212.

Antihistamines 209.

Special considerations 214.

Second-generation antihistamines 211.

Key references 215.

Upper respiratory infections, sinusitis, rhinitis, hay fever, nasal congestion, and a variety of 'allergic maladies' are frequent during pregnancy. The 'common cold' is the most frequent respiratory ailment encountered in pregnant women, and the most frequent indication for an antihistamine decongestant and/or expectorant regimen (Hornby and Abraham, 1996). There is no curative therapy against rhinoviruses, but the symptoms can be relieved until the illness runs its course.

A variety of antihistamines are available and most are used in combination with a sympathomimetic amine, such as pseudoephedrine with its decongestant activity. These agents are given for symptomatic relief in pregnant women. Dose and systemic effects are important considerations. Intranasal routes of administration are equally, if not more, effective than oral administration. Importantly, the nasal route reduces dose delivered to the fetus while adequately treating the patient's symptoms (Hornby and Abrahams, 1996).

DECONGESTANTS.

All the commonly used decongestants have been a.s.signed Food and Drug Administration (FDA) pregnancy risk rating (Table 11.1).

Pseudoephedrine Pseudoephedrine hydrochloride is the preferred agent for pregnant women who require a decongestant (Hornby and Abrahams, 1996). It is the most frequently used sympathomimetic and is usually taken as a decongestant. It is also frequently combined with different antihistamines in 'common cold' or 'sinus' medications. Epidemiological studies of more than 1000 first-trimester human pregnancies exposed to pseudoephedrine indicate no a.s.sociation with congenital anomalies (Aselton et al et al., 1985; Heinonen et al et al., 1977; Jick et al et al., 1981).

Decongestants 207.

Table 11.1 Some commonly used decongestants Some commonly used decongestants Drug FDA cla.s.s Decongestants Ephedrinea C.

Naphazoline C.

Oxymetazoline C.

Phenylephrine C.

Phenylpropanolamine C.

Pseudoephedrine C.

Tetrahydrozoline C.

Xylometazoline C.

Expectorants Guaifenesin None Iodinated glycerol X.

Pota.s.sium iodide D.

Terpin hydrate None Ant.i.tussives Benzonatate Ca Codeine C.

Dextromethorphan C.

FDA, Food and Drug Administration aSee Chapter 7.

Ephedrine (Ephedra, Ma Huang, over-the-counter weight loss/energy pill) used in large doses is a.s.sociated with sudden cardiac death in adults, and based upon anecdotal information should be avoided during pregnancy because of potential adverse maternal and fetal effects, including tachycardia and serious adverse cardiovascular events, such as heart attack, stroke, and fetal vascular disruption.

Phenylephrine and phenylpropranolamine Phenylephrine and phenylpropranolamine are decongestants in common use and are frequently combined with antihistamines in cold and flu remedies. Phenylephrine (Neo Synephrine) may also be used in nasal sprays. According to their manufacturer, these agents may interfere with uterine blood flow and thus should be used with caution in women with conditions already a.s.sociated with decreased uterine blood flow, such as hypertension. A weak, possible a.s.sociation of phenylephrine and phenylpropranolamine with congenital anomalies was found in the Collaborative Perinatal Project among 1249 and 726 pregnancies, respectively (Heinonen et al et al., 1977). It is unlikely that either agent is causally related to congenital malformations in first-trimester-exposed fetuses.

In another study of more than 225 infants exposed during the first trimester, no such a.s.sociation was found (Aselton et al et al., 1985; Jick et al et al., 1981). No adverse effects were found among offspring in animal studies regarding the teratogenicity of these two agents. Phenylephrine may also be used for the treatment of acute hypotension.

208.

Antihistamines, decongestants, and expectorants during pregnancy Oxymetazoline, xylometazoline, and naphazoline Oxymetazoline, xylometazoline, and naphazoline Oxymetazoline, xylometazoline, and naphazoline are sympathomimetic agents used as decongestants in long-acting nasal sprays (Afrin, Allerest, Dristan, 4-Way). The frequency of congenital anomalies was not increased among more than 250 infants whose mothers took oxymetazoline during the first trimester (Aselton et al et al., 1985; Jick et al et al., 1981). Similarly, among 432 infants whose mothers took xylometazoline in the first trimester, the frequency of congenital anomalies was not increased (Aselton et al et al., 1985; Jick et al et al., 1981). No studies have been published regarding naphazoline use during pregnancy.

Table 11.2 Antihistamines Antihistamines Generation FDA cla.s.s First generation Azatadine (Optimine) C.

Bromodiphenhydramine (Ambenyl) C.

Brompheniramine C.

Buclizine (Bucladin) C.

Carbinoxamine (Clistin) C.

Chlorpheniramine B.

Clemastine (Tavist) B.

Cyclizine (Marezine) C.

Cyproheptadine (Periactin) B.

Dexchlorpheniramine (Polaramine) B.

Dimenhydrinate C.

Diphenhydramine B.

Diphenylpyraline (Hispril) C.

Doxylamine (Unisom) B.

Meclizine (Antivert, Bonine) C.

Methdilazine B.

Phenindamine (Nolahist) C.

Promethazine C Pyrilamine (Dormarex, Sommicaps, Sominex) C.

Terfenadine (Seldane) C.

Trimeprazine C.

Tripelennamine (PBZ) B.

Triprolidine (Actidil, Bayidy) C.

Second generation Astemizole C.

Cetirizine B.

Cromolyn sodium B.

Desloratadine

Ebastine

Fexofenadine C.

Ipratropium B.

Loratadine B.

Antihistamines 209.

Table 11.3 Congenital anomalies and first-trimester antihistamine exposure Antihistamine Congenital anomalies and first-trimester antihistamine exposure Antihistamine Percent congenital n/N anomalies (%) First generation Azatadine 4.7.

6/127.

Brompheniramine 5.9.

16/271.

Chlorphenamine (chlorpheniramine) 6.9.

96/1388.

Clemastine 3.7.

110/2847.

Cyproheptadine 4.2.

12/285.

Dexchlorpheniramine 4.6.

50/1080.

Diphenhydramine 4.7.

154/3286.