CLINICAL UPDATE:

BIOLOGICAL PSYCHIATRYBy ALAN J. GELENBERG, M.D.

Pregnancy, psychotropic drugs,and psychiatric disordersBoth at our hospital and in my consulting practice, I havebeen impressed with the increasing number of questionsabout appropriate treatment for psychiatric illness duringpregnancy. The dilemma is obvious: how to treat the wom­an's suffering and possible behavioral disruptions whileprotecting a second (and involuntary) patient, her fetus? In­creasingly, health professionals and the public are sensitiveto risks from drug exposure in pregnant women. At the sametime, symptoms often cry out for treatment, and uncheckedpsychopathology is not healthful to the pregnancy either.

The risks associated with drug use during pregnancy canbe broadly lumped into three categories: teratogenesis, be­havioralteratogenesis, and side effects in the newborn. Ter­atogenesis refers to gross organ malformations, a risk usual­ly associated with drug exposure during the first trimesterand typified by the tragedy of thalidomide. Among psycho­tropic drugs, lithium is most probably incriminated as a te­ratogen, being associated with an apparently increased riskof anomalies of the heart and great vessels-in particular,Ebstein's anomaly. I Some reports had suggested a possibleassociation of benzodiazepine use with cleft lip/cleft palate,but more recent surveys question this association.' Similar­Iy, some surveys have suggested an increased risk of mal­formations in babies born to women who took neurolepticagents, but this association is not clear-cut either.'

A major problem in trying to establish whether a drug is ateratogen lies in the sensitivity of detection techniques.When the incidence of abnormalities is high, and particular­ly where an anomaly is consistent and readily detectable,the association can be established early and with a high de­gree of certainty. Among psychotropics, however, there isno firm evidence incriminating antipsychotic agents, anti­depressants, or anxiolytics as teratogens. But that does notmean they are safe. Rather, it means these drugs are unlike­ly to cause a high frequency of gross malformations. Thequestion of infrequent, variable, or subtle abnormalities re­mains open.

For a woman on maintenance lithium therapy who wishesto become pregnant, the safest course is to withdraw lithiumabout the time of menstruation prior to the cycle when shehopes to con(~eive.' It is wise to counsel the woman and herhusband on means to increase the probability of rapid con­ception, in order to shorten the period during which she is toremain free of lithium. The psychiatrist may also wish to

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discuss with the couple treatment options should she be­come manic early in her pregnancy: for instance, no medi­cation, electroconvulsive therapy (ECT), or low doses ofantipsychotic drugs. If lithium is used during the first tri­mester, ultrasound techniques may detect cardiac abnor­malities during the second trimester, and the woman and herhusband can decide about continuation of the pregnancy.(Ebstein's anomaly is difficult to treat and associated with areduced life span.)

Behavioral teratogenesis is, at this time, purely a theoret­ical construct in humans. In experimental animals, prenataland neonatal exposure to psychoactive drugs can lead tolong-lasting neurochemical, behavioral, and developmen­tal alterations in the young.' What this means in humans isunknown at present, but it adds to our desire to protect thedeveloping brain from unnecessary exposure to psychoac­tive compounds. Virtually all psychotropic drugs cross theplacental membrane as well as appearing in human milk.Hence, we seek to avoid exposure where possible, or tominimize the dose and shorten the length of treatment.

The third broad category is side effects in the newborn, aconcern when drugs are administered late in pregnancy.Adverse reactions and toxicity in the neonate usually aretypical of the drug. For example, neuroleptic agents maycause extrapyramidal reactions, cardiovascular instability,or temperature dysregulation; antidepressants might engen­der anticholinergic effects; benzodiazepines can producediminished muscle tone; and lithium could precipitate hy­pothyroidism. The best plan is to warn the pediatrician inadvance about what the mother has been taking.

Ideally, every pregnant woman would remain free ofdrugs for the entirety of her pregnancy. When circum­stances dictate otherwise, however, we need to balance rel­ative risks. Sometimes, nonbiological treatments will suf­fice for a while. In some cases of depression, mania, or psy­chosis, ECT may be helpful.· When drugs are required, thephysician should seek to use the lowest possible dose for theshortest required period, maintaining a collaboration withthe obstetrician and, especially toward the end of pregnan­cy, with the pediatrician. Informed consent is crucial.which usually requires a close working relationshipbetween the physician. patient. and her husband. Relevantdiscussions should be outlined in the clinical record.

Confronted with this clinical dilemma you will, at times.feel like Ulysses. seeking to navigate the straits betweenScylla and Charybdis. But with adequate time, sensitivity.

PSYCHOSOMATICS

and knowledge. the skilled clinical pilot usually will be ableto guide his or her patient through a safe passage. 0

REFERENCES1 Nora JJ. Nora HA, Toews WH Lithium. Ebslein's anomaly. and other con­

genital heart defects Lancet 2594-595.19742 Gelenberg AJ Diazepam (Valium) and oral Clefts A followup BioI Ther

Psych/air 747-48. 1984

3 Goldberg HL. DiMascio A: PsyChotropIc drugs in pregnancy. in LiptonMA, DiMascio A. Killam KF (eds): Psychopharmacology: AGeneration ofProgress. New York. Raven Press. 1978. pp 1047·1055.

4. Gelenberg AJ: When a woman taking lithium wants to have a baby. BioITher Psychiatr 6: 19-20. 1983

5. Vorhees CV. Brunner RL. Butcher RE: Psychotropic drugs as behavioralteratogens. Science 205: 1220-1225. 1979

6 Consensus Conference on Electroconvulsive Therapy JAMA 254:2103­2108.1985

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