Psychiatric disorders in pregnancy and in the puerperium:

classification, diagnosis and treatment

 

Psychiatry disorders in pregnancy and puerperium: classification,

diagnosis and treatment

Renata Sciorilli Camacho I ; Fábio Scaramboni Cantinelli I ; Carmen Sylvia

Ribeiro I ; Amaury Cantilino II ; Bárbara Karina Gonsales III ; Érika
Braguittoni III ; Joel Rennó Jr. IV

I
 Psychiatrist. Collaborator of the Project of Attention to the Mental Health of the Woman
(Pro-Woman) of the Institute of Psychiatry of the Hospital das Clínicas of the Faculty of
Medicine of the University of São Paulo (IPq-HC-FMUSP) 
II
 Psychiatrist. Coordinator of the Women's Depression Program at the Hospital das Clínicas
of the Federal University of Pernambuco (HC-UFPE) 
III
 Clinical psychologist. Collaborator of the Pro-Woman of IPq-HC-FMUSP 
IV
 Physician psychiatrist. IPq-HC-FMUSP Pro-Woman Coordinator

mailing address

ABSTRACT

A number of questions are still open about such a broad subject as the mental health of
gestational and postpartum women. As contradictory as it may seem, many patients
experience sadness or anxiety rather than joy in those phases of their lives. The limits
between the physiological and the pathological may be narrow, which may generate doubts
in obstetricians, clinicians or psychiatrists. Many patients also feel guilty, impairing
adherence to treatment and acceptance of a pathology in a phase that, in theory, should be
joyful. 
In the last decades, studies have investigated a little more on the subject, but some
questions are still under debate: could puerperal disorders be a manifestation of a previous
disorder not adequately treated? Are gestation or puerperium protective or risk factors for
the onset of psychiatric disorders? Could the hormonal changes that occurred during this
period be involved in its etiology? What are the main risk factors? In what situations would
it be appropriate to use psychotropic drugs as a treatment measure? 
In this article, we will address some of these issues, on a topic that still needs to be
investigated for more accurate conclusions.
Key words: Gestation, puerperium, psychiatric disorders, risk factors, treatment

ABSTRACT

Several questions regarding mental health during the period of pregnancy and puerperium
are still open. Even this seems contradictory, many patient present sadness or anxiety
instead of joy in these phases of life. The limits between physiological and the pathological
one can be narrow, what it may generate doubts in obstetricians, physicians or
psychiatrists. Many patients also feel guilty, harming the treatment and the accessibility of
their pathology in a phase that theoretically would have to be of joy. 
Few decades ago till today, there are studies that investigate deeper on this topic, but some
questions are still in discussion: could puerperal diseases be a manifestation of a previous
disease not adequately treated? Would be the pregnancy or the puerperium protective
factors or risk factors for the psychiatric diseases development? Could it be involved in the
etiology of the hormonal alterations that occur in this period? What would be the main
factors of risk? In what situations would it be adjusted to use medications as treatment? 
This article has the proposal to discuss some of these questions that are immersed in a topic
that is still opening to investigation to let us with more accuracy conclusions.

Key-words: Psychiatric pregnancy, puerperium, diseases, risk factors, treatment.

Introduction

Gestation and the puerperium are periods of a woman's life that need to be evaluated with
special attention because they involve innumerable physical, hormonal, psychic and social
insertion changes that may directly reflect on the mental health of these patients.

Increasing importance has been given to the subject, and current studies have aimed to
delineate the risk factors for psychiatric disorders in these phases of life in order to be
diagnosed and treated as early as possible.

Recent studies have revealed that underdiagnosed and untreated psychiatric disorders in
pregnant women can lead to serious maternal-fetal consequences, even during labor
(Jablensky et al ., 2005; Seng et al ., 2001).

It is also known that the presence of anxiety or depression in pregnancy is associated with
depressive symptoms in the puerperium (Bloch et al ., 2003).

These themes have been more researched in recent decades and there is still no
specification for these pathologies in the International Classification of Diseases (ICD-10),
except as a diagnosis of exclusion in the case of puerperium-related disorders.
The Diagnostic and Statistical Manual of Mental Disorders, in its fourth edition and revised
text ( DSM-IV-TR ), does not distinguish postpartum mood disorders from those occurring in
other periods, except as a specifier "beginning in post -parto ", which is used when the
onset of symptoms occurs within four weeks after delivery (Cantilino, 2003).

This article aims to review the literature, presenting the main epidemiological aspects,
classification, diagnosis and treatment of psychiatric disorders related to pregnancy and
puerperium.

Epidemiology

Although gestation is typically considered a period of emotional well-being and if the arrival
of motherhood is expected to be a joyful moment in a woman's life, the perinatal period
does not protect her from mood disorders.

A prevalence of depression in pregnancy is estimated at 7.4% in the first, 12.8% in the

second and 12% in the third trimester (Bennett et al ., 2004).

In adolescents, prevalence was between 16% and 44%, almost twice as high as in adult
pregnant women, which may be related to the lack of affective maturity and relationships of
these patients, as well as the fact that a large part of them have to abandon her studies on
motherhood (Szigethy and Ruiz, 2001).

Dysphoria postpartum ( blues maternity ) includes mild depressive symptoms and can be
identified in 50% to 85% of mothers, depending on the diagnostic criteria used (Cantilino,
2003).

A study of 1,558 women detected 17% of pregnant women with significant symptoms for
depression in late pregnancy, 18% in the immediate puerperium and 13% in the sixth and
eighth weeks of the puerperium. The same value (13%) was found in the sixth month of
puerperium (Josefsson et al ., 2001).

Another study found values ranging from 8.6% to 10.1% for the diagnosis of depression
between the 6th and 24th weeks of the puerperium (Boyce and Hickey, 2005).

A meta-analysis of 59 studies showed an estimated prevalence of postpartum depression on

the order of 13% (O ?? Hara and Swain, 1996).

The puerperal psychosis is a rarer picture, and the incidence found was between 1.1 and 4
for every 1,000 births (Bloch et al ., 2003).

Risk factors

The main psychosocial risk factors related to major depression in the puerperium are: age
under 16 years, history of previous psychiatric disorder, stressful events experienced in the
last 12 months, marital conflicts, being single or divorced, being unemployed (the patient or
her spouse) and show little social support.

Other risk factors identified were: vulnerable personality (poorly organized or organized
women), expecting a baby of the opposite sex, having few satisfactory affective
relationships and poor emotional support (Boyce and Hickey, 2005). Spontaneous or
repetitive aborts were also indicated as risk factors (Botega, 2006).

Women more susceptible to mood disorders in the puerperium also had a diagnosis of
premenstrual dysphoric disorder or had depressive symptoms on the second or fourth day
after delivery. Patients who have a history of increased sensitivity to oral contraceptive use
would also be more vulnerable (Bloch et al ., 2005).

Another study attempted to find a link between unwanted pregnancy and risk for
depression, but the results were inconclusive. It was only found that women with higher
education and better financial performance presented lower risk, whereas women from
populous families presented a high risk for depression. It was also hypothesized that the
prior existence of mental disorder may be the most important factor associated with the risk
of developing new episodes in the puerperium (Schmiege and Russo, 2005).

Women with bipolar affective disorder had a high risk of puerperal psychosis (260/1000)
when compared to healthy women, who had 1 to 2 cases per 1,000 puerperal women
(Chaudron and Pies, 2003).

Etiology

The etiology of puerperal depression is not yet fully understood, but it is believed that, in
addition to the aforementioned risk factors, hormonal and hereditary factors are also
involved.

In pregnancy, estrogen and progesterone levels are higher than those seen in women
outside the gestational period, and this factor may be involved in mood changes that occur
in this phase. The abrupt drop of these hormones in the postpartum period would be
involved in the etiology of puerperal depression. Bloch et al.. (2003) conducted a review of
the literature in order to correlate endocrine and hereditary factors with the etiology of this
disorder. There was no genetic relationship different from that already expected in non-
puerperal conditions. It was hypothesized that some women would be more sensitive to
hormonal variations at any point in their lives, including premenstrual period, menarche,
gestation, puerperium, menopause, and even while using contraceptives.

Panic Disorder

One study compared symptomatology in women with previously diagnosed panic disorder
and found that 43% of these patients had improved anxiety during pregnancy, 33% had
worsened, and 24% did not present any changes. Already in the sixth month of puerperium,
63% had worse symptoms of panic (Northcott and Stein, 1994).
 

Another study found that the puerperium would be a period of greater vulnerability to the
onset of the first episode of panic. Among the women studied, 10.9% presented onset of
symptoms in the puerperium (in this case, up to 12 weeks of the puerperium), a higher
than expected number, which is 0.92% (Sholomskas et al ., 1993).

Obsessive-compulsive disorder (OCD)

Of the pregnant women with OCD, 46% presented worsening symptoms in the first
gestation and 50% in the second gestation. Symptoms of OCD are frequent in postpartum
and include thoughts and obsessions related to possible infant contamination and negative
obsessive thoughts about labor (Labad et al ., 2005).

Gestation is also associated with the onset of OCD in 13% of the women and worsening of
the symptomatology was observed in 29% of the puerperae. Women with OCD also have a
high risk for the development of postpartum depression (Williams and Koran, 1997).

 
Postpartum Disorders

Postpartum psychiatric disorders are characterized as postpartum dysphoria (puerperal

blues), postpartum depression and puerperal psychosis (Chaudron and Pies, 2003).

The blues puerperal typically affects women in the early days after the baby's birth, peaking
in the fourth or fifth day after delivery and remitting spontaneously at most in two weeks. It
includes easy crying, humor lability, irritability, and hostile behavior toward family members
and companions. These frameworks do not normally require pharmacological intervention,
and the approach is to maintain emotional support, understanding, and assistance in caring
for the baby (Cantilino, 2003). Evidence suggests that postpartum depression may be part
of or continuation of depression started during gestation (Ryan et al ., 2005).

The signs and symptoms of perinatal depression are little different from those of the major
non-psychotic depressive disorder that develop in women in other times of life. Patients
present with depressed mood, easy crying, affective lability, irritability, loss of interest in
usual activities, feelings of guilt, and impaired concentration. Neurovegetative symptoms,
including insomnia and loss of appetite, are frequently described (Nonacs and Cohen, 1998;
Gold, 2002). However, some somatic symptoms may be confused with normal conditions of
this period. Thus, symptoms such as hypersomnia, increased appetite, easy fadigability,

It is important to note that many women with perinatal depression do not reveal their
symptoms of depression for fear of possible stigmatization (Epperson, 1999). Women feel
that their social expectations are that they are satisfied and end up feeling guilty that they
are experiencing depressive symptoms at a time that should be joyful.

Some clinical features are described in postpartum depression. There is a suggestion of a

more prominent anxious component (Ross et al ., 2003), as well as recurrent thoughts of
damaging the baby (Jennings et al ., 1999). Wisner et al . (1999) examined obsessive
thoughts in depressed women and found that women with postpartum depression had more
aggressive thoughts about their offspring than depressed women outside the postpartum
period, regardless of the severity of the condition. Godfroid et al. (1997), in a
polysomnographic study in women with depression, showed that women with postpartum
depression had a significant increase in phase IV sleep and a shorter I stage time when
compared to women with depression of similar severity outside the postpartum
period. Hendrick et al. (2000), also in a comparison between women with postpartum and
postpartum depression, have found that postpartum depression requires more time to
respond to pharmacotherapy and tends to require more antidepressant agents for remission
of symptoms. In addition, there is frequent reporting of ambivalent feelings about the baby
and of oppression for the responsibility of caring for children (Beck, 1996; Nonacs and
Cohen, 2000). These data are in favor of the specificity of the concept of postpartum
depression.

Puerperal psychosis usually begins more abruptly. Studies have found that 2/3 of the
women who presented with puerperal psychosis began symptomatology in the first two
weeks after the birth of their children. A picture with presence of delusions, hallucinations
and confusional state is described that seems peculiar to the pictures of puerperal
psychosis. There may be associated depressive, manic or mixed symptoms. No typical
presentation has been established. However, these women often exhibit disorganized
behavior and delusions involving their children, with thoughts of causing them some kind of
harm. Although suicide is rare in the puerperal period in general, the incidence of suicide in
patients with psychotic disorders in this period is high, often requiring hospital intervention
for this reason, as well as for the risk of infanticide. Depressive symptoms, more than
manic, are usually associated with pictures of infanticide or suicide (Chaudron and Pies,
2003).

Recent neuroscientific studies support the hypothesis that a woman with puerperal
psychosis who commits infanticide requires more treatment and rehabilitation than legal
punishment, in order to avoid other fatalities due to the severity of the condition; currently,
some countries already support this hypothesis. Family education would also be present in
this type of intervention (Spinelli, 2004).

About depression scales for use in pregnancy

As far as we know, there are no scales specifically designed for the detection of depression
during pregnancy. Authors have used the Edinburgh Postnatal Depression Scale (EPDS) for
this purpose (Clark, 2000; Areias et al ., 1996). An American study tested the Beck
Depression Inventory (BDI) - a scale for general depression - during pregnancy and
obtained the following cutoff result at 16: 83% sensitivity, 89% specificity, positive
predictive value of 50% and negative predictive value of 98% (Holcomb et al ., 1996). The
author probably had a low positive predictive value because the BDI contained items of
physical symptoms that were confused with a normal pregnancy picture.

Scales that address predictors of postpartum depression have also been used in
pregnancy. The Pregnancy Risk Questionnaire is an 18-item scale that lists psychosocial risk
factors for postpartum depression. In an original validation study, it obtained a sensitivity of
44% and a positive predictive value of 23% (Austin et al ., 2005). These values seem quite
reasonable for a prediction instrument. Another instrument for the same purpose is the
Postpartum Depression Predictors Inventory, a checklist that ideally must be completed in
each of the three trimesters of pregnancy and which also accesses psychosocial risk factors
(Beck, 1998).

Detection of women with postpartum depression

Women in the puerperium are often examined by their obstetricians or general practitioners
in consultations focused on physical recovery after childbirth. In addition, they are seen by
their pediatricians four to six times during the year following the birth of their baby. When
they have depression, although they seek help more commonly from these physicians than
from mental health professionals (Gold, 2002), they are often not diagnosed or recognized
as adequately depressed. Recent studies have shown the usefulness of using self-
assessment scales for screening women with postpartum depression in primary care
services (Buist et al., 2002). The possibility of detecting postpartum depression with these
scales has been shown to be significantly greater than spontaneous detection during routine
clinical evaluations by physicians in these services (Fergerson et al ., 2002). Scales would
alert clinicians, obstetricians, and pediatricians to those women who might need further
evaluation and treatment.

In Brazil, where physicians are increasingly obliged to take care of a large number of
patients with a short time available, such instruments end up having considerable value. In
addition, these scales are self-applicable and easy to use by non-medical professionals and
without specialization in mental health. These characteristics make the application
procedure of these are, in addition to practical, considered low cost, which makes feasible
its use in primary health care services.

Thinking about this practicality, two scales designed specifically for postpartum depression
screening were created: the EPDS in 1987 and the Postpartum Depression Screening Scale
(PDSS) in 2000. Both have a translation into Portuguese and validation in Brazil. the study
of the PDSS performed by one of the authors of this article (Cantilino, 2003).

EPDS (Cox et al ., 1987) was the first instrument found in the literature developed to
specifically screen for postpartum depression. The EPDS is a self-enrollment tool that
contains 10 common symptom questions of depression and uses Likert type responses. The
mother chooses the answers that best describe how she has felt in the past week.

Carrying out a phenomenological study of postpartum depression, Beck (1992) perceived

themes that described more about the essence of this experience. These themes were
related to unbearable loneliness, obsessive thoughts, feeling of being out of mind,
suffocating guilt, cognitive difficulties, loss of prior interests, uncontrollable anxiety,
insecurity, loss of control of emotions and ideas related to death. Another phenomenological
study conducted by Beck (1996) specifically investigated the significance of experiences of
mothers with postpartum depression who had interacted with their infants and older
children. In a study evaluating instruments for depression in postpartum women, Ugariza
(2000) pointed out the need for an evaluation scale that could measure specific symptoms
of postpartum depression. Considering the observations made in the studies and seeking a
better accuracy in the screening of patients with postpartum depression, it was conceived
the creation of a new scale that would cover these concepts.

PDSS, developed by Beck and Gable (2000) in the United States, is a Likert type self-rating
scale. The instrument has 35 items that assess seven dimensions: sleep / appetite
disorders, anxiety / insecurity, emotional lability, cognitive impairment, loss of self, guilt /
shame, and intent to harm oneself. Each dimension is composed of five items that describe
how a mother may be feeling after the birth of her baby (Beck and Gable, 2000).

A study was conducted with a comparative performance analysisof PDSS with EPDS (Beck

and Gable, 2001). A total of 150 postpartum mothers completed the two instruments and
then underwent the DSM-IV diagnostic interview. Eighteen of these women (12%) were
diagnosed as having major depression, 28 (19%) had minor depression and 104 (69%) had
no depression. Using the cut-off scores for major depression recommended in the
publications of the two instruments, PDSS achieved the best combination of sensitivity,
94%, and specificity, 91%, among the three scales. The PDSS identified 17 of the women
(94%) diagnosed with postpartum depression and the EPDS, 14 of these women
(78%). The observed sensitivity differential may be due to the fact that PDSS addresses
other components of this mood disorder.

In Brazil, the EPDS was translated into Portuguese and validated by Santos et
al. (2000). Sixty-nine puerperae were selected from a larger sample to fill out the
instrument and to be interviewed. Using the recommended cut-off point of 11/12, sensitivity
of 72%, specificity of 88%, and positive predictive value of 78% were obtained. The
instrument was validated in Brasília - which, according to the United Nations Development
Program (2003), is one of the highest human development indices in Brazil - and the
majority of the sample (72%) was composed of women with middle-high or high family
income. As the low development indices of some Brazilian regions imply low schooling, a
fact also common in the periphery of the great metropolises,

Thus, a validation study of the EPDS was carried out in Recife, with 120 puerperal women,
60 of them from a public service and 60 from a private service. The sensitivity was 94%,
the specificity was 85%, the negative predictive value was 99%, but the positive predictive
value was low, 48% (Cantilino et al ., 2003).

The PDSS also had a systematized translation and was submitted to a validation study in
Brazil. In this study, 120 puerperae were evaluated (60 in a public service and 60 in a
private service). PDSS showed sensitivity of 94%, specificity of 95%, positive predictive
value of 75% and negative predictive value of 99%. The present results confirm the validity
of PDSS in the Brazilian population to track postpartum depression (Cantilino, 2003;
Cantilino et al ., In press).

Importance of early diagnosis and treatment

Infanticide and suicide are among the most serious complications arising from postpartum
disorders without adequate intervention. However, the existence of psychiatric disorders not
only in the puerperium, but also in gestation, can lead to other serious consequences.

Women diagnosed with schizophrenia or major depression were at high risk for
complications during pregnancy, labor and the neonatal period. Among these complications,
there are placental abnormalities, hemorrhages and fetal distress. Women with
schizophrenia are at high risk for placental abruption and, more frequently, have low birth
weight babies. These children also had cardiovascular malformations and lower brain
circumference than the children of healthy mothers (Jablensky et al ., 2005).

Seng et al . (2001) found that women with posttraumatic stress disorder were at high risk
for ectopic pregnancy, spontaneous abortion, hyperemesis gravidarum, premature uterine
contractions and excessive fetal growth.

The mother-child relationship was also impaired when 507 mothers and their children, at 3
months of age, were evaluated. The children of mothers who had a diagnosis of postpartum
depression had difficulty sleeping and eating. They also presented losses of corporal
interaction with the environment and diminished social smile. These patients often
complained of excessive tiredness, which ended up negatively reflecting their relationship
with their children and, consequently, their development (Riguetti-Veltema et al ., 2002).

Therefore, each case should be assessed with particular attention in order to establish the
best treatment strategy for each particular situation, as early as possible.

Treatment Options

Researches have used techniques of psychopharmacological treatment, psychosocial,

psychotherapeutic and hormonal treatments, besides electroconvulsive therapy (ECT),
indicated for more severe cases or refractory to other forms of treatment. Most psychosocial
and hormonal interventions have been shown to be ineffective. However, results of studies
focused on interpersonal psychotherapy, cognitive-behavioral strategies and
pharmacological interventions have proven to be efficient.

Use of psychoactive drugs during gestation and lactation

The decision to offer biological treatments to pregnant women is a complex decision process
that involves a constant interaction between patient, family, obstetrician and
psychiatrist. Establishing a therapeutic alliance is critical. The confidence that the pregnant
woman deposits in her doctors will certainly minimize any mishap, especially the side effects
that may occur during treatment. This decision must always take into account, as its
mainspring, the risk-benefit ratio.

Wisner et al . (2000) published an important review highlighting the theme. Among the

various concepts raised by this team were the essentiality of informed consent and respect
for the patient's values and preferences on the part of the physician, who will always clearly
put his experience in the discussion, that is, the doctor offers support and solutions to the
problems the patient is summoned to participate in the best possible way of the decision,
which, in general, leaves entirely to the doctor.

Faced with the most complete medical history possible, treatment options are offered,
including non-treatment. Among the options are biological treatments (drugs are described
taking into account their efficacy and the particular risks to mother and fetus). Possible risks
involve fetal toxicity, considering intrauterine death, physical malformations, growth
impairment, behavioral teratogenicity, and neonatal toxicity.

Something that must be mentioned with vehemence to the pregnant woman is that the fact
of not treating can bring much more damages to the fetus, reason why there will be, due to
the stress, effect on the hypothalamus-pituitary-adrenal axis, with increase of
corticosteroids and damages to the product conceptual.

Extreme situations, such as attempted or high risk of suicide or a psychotic state in which
the patient does not respond, even from the legal point of view, by their acts, will tend to
the decision of compulsory medication.

As the risk of teratogenicity is the main concern of the pregnant woman, the Food and Drug
Administration (FDA), the US agency that controls food and drugs, established a
classification, according to this risk, for each psychoactive drug:

 Risk A: Controlled studies do not demonstrate risk. Adequate and well-controlled

studies in pregnant women have not shown or demonstrated any risk to the fetus.
 Risk B: no evidence of risk in humans. Or the findings in animals show risk, but the
findings in humans do not, or if adequate studies in humans have not been
performed, findings in animals are negative.
 Risk C: Risk can not be excluded. Studies in humans are lacking, and animal studies
are positive for fetal risk or absent as well. However, potential benefits may justify
the potential risk.
 Risk D: positive evidence of risk. Research data or subsequently reported risk to the
fetus. Still, potential benefits may outweigh potential risk.
  Risk X: absolute contraindication in pregnancy. Studies in animal or human research,
or later reported, show a fetal risk that clearly outweighs any potential benefit to the
patient.

In this way, it is easy to conclude that the time a particular medication has in the market,
that is, the experience associated with it, is fundamental in this classification, and the safety
offered by the newer medications often still can not be translated in relation to its use in
pregnancy.

Particularities of each class of psychoactive drugs

Describing the inherent risk of each drug from each psychopharmaceutical group would be
long and would elapse in part from the context of this article. Attention is focused on the
most known and used. The data used below are from the Commitee on Drugs of American
Academy of Pediatrics (2000) and from Bazire (2002).

Antidepressants

Tricyclic antidepressants have long been in use and therefore their safety has been
established over the years, particularly amitriptyline (risk B). The issue may be due to
hypotensive effects on the mother, which would indicate preference for desipramine (risk
C ),since nortriptyline has a D-risk. Selective serotonin reuptake inhibitors (SSRIs) in
general have also been well established over time, though they obviously have less market
time than tricyclics. The "older sister", fluoxetine, is widely used and has risk B; some
restriction would be due to its rather long half-life, that is, in an eventual need for
withdrawal, the drug would still remain some time in the body. Paroxetine, which until
recently was widely used in pregnant women, had its safety contested in an article by
Williams and Wooltorton (2005), who pointed out a very important teratogenic risk for this
drug, which is being reclassified as risk D, used in the latter case. Particularly safe and
increasingly used are sertraline and citalopram, with the establishment of their increasing
safety (risk B). Fluvoxamine has a C-risk, as does escitalopram, although there is no report
of teratogenicity for this drug.

Monoamine oxidase inhibitors (MAOIs) also have assigned B-risk, their hypotensive effects,
particularly of tranylcypromine, in addition to the dietary question itself, would be
restrictive. Venlafaxine, mirtazapine and reboxetine are C-rated, and their use in pregnancy
has also increased. Duloxetine is a very recent drug and would not find a classification yet
appropriate. The antidepressive risk option A would be the use of tryptophan, of
questionable efficacy.

Mood stabilizers and anticonvulsants

Lithium carbonate (risk D) is well associated with malformations, in particular cardiovascular

- especially Ebstein's anomaly -, and its use is prohibited in the first trimester. Can be used
in the second and third quarters with great indication, exhausted other
possibilities. Carbamazepine and oxcarbazepine have associated C-risk, but appear to be
the best option, particularly for the first trimester, since valproate / divalproate crosses the
placenta easily and has been linked to some malformations, in particular spina bifida (risk
D). Phenytoin also has D-risk, as it also crosses the fetal membrane and is associated with
fetal hydantoin syndrome, characterized by growth retardation, mental retardation, facial
defects, hirsutism, cardiovascular anomalies, genitourinary and gastrointestinal
disorders. Phenobarbital has clear teratogenic implication (risk D). Lamotrigine and
vigabatrin have relatively little time to use, and the classification is C. Topiramate is also C,
although it does show some teratogenicity in rats.

Antipsychotics

Antipsychotics of more recent generations generally have a preference for treatment, in

particular for their efficacy in negative symptoms. Of these, risperidone enjoys more time in
the market, and risks have not been attributed to it, although it still presents a risk C.
Quetiapina and olanzapine also have some associated safety (risk C), as no association of
teratogenicity has yet been made. Quetiapine is the least studied to date, but may be
interesting because of its lack of action on prolactin, as well as clozapine (risk B),
particularly safe but with the limitation of pharmacovigilance related to agranulocytosis, as
well as hypotensive effects and great sedation. Haloperidol and phenothiazines
(levomepromazine, chlorpromazine) have relatively well established safety, by market time
(risk B). Haloperidol has been used in low doses as an alternative for hyperemesis
gravidarum. Possible limitations may lie in the side effects.

Benzodiazepines

They have had some associated teratogenicity, although the data are controversial because
of their frequent association with alcohol and illicit drugs. Alprazolam does not contain
formal reports of teratogenicity (risk C). Chlordiazepoxide (risk D) crosses the placenta and
has been related to teratogenicity, particularly if used within the first 42 days of
gestation. Diazepam and lorazepam are commonly associated, when used in the last
trimester, to hypotonic or delayed newborns, including the reflex to suckle; therefore, would
be classified as risk D. Clonazepam is relatively safe and receives the C classification. Of the
other benzodiazepines, there is not much information established.

Use of psychoactive drugs during lactation

Currently, many antidepressants are being studied in relation to lactation, and SSRIs were
the least present in breast milk. Among them, sertraline and paroxetine appear to be the
best alternatives (Haberg and Matheson, 1997). The following drugs were also considered
safe (sulpiride), most tricyclics, tryptophan, moclobemide, low and single dose
benzodiazepines, zolpidem, carbamazepine, low dose valproate and phenytoin.

Drugs such as haloperidol, low dose phenothiazines, MAOIs, mirtazapine, SSRIs, trazodone,
benzodiazepines and beta-blockers were considered moderate risk.

Clozapine is contraindicated for the risk of agranulocytosis, and studies in animals have
detected it in milk. Last generation antipsychotics still have few studies and should not be
used. The use of lithium carbonate should also be avoided because of the risk of toxicity in
the baby. There are still few studies related to the new antidepressants so that they can be
safely used (Botega et al ., 2006).

 
Hormone treatment

Hormonal treatment in mood disorders is very old, and currently the use of sublingual and
transdermal estrogens, such as 17-B estradiol, has been tested in the treatment of
postpartum depression (Murray, 1996). Although these reports suggest that estrogen use
has good results, only modest numbers of symptomatic improvement have been
reported. Estrogens are believed to act by interaction with core receptors and cell
membranes (McEwen, 1999). The action of these hormones on membrane receptors would
play an important role in the synthesis, release and metabolism of neurotransmitters, such
as noradrenaline, dopamine, serotonin and acetylcholine (Stahl, 2001). Estrogens would
also act on neuropeptides (eg, corticotrophin releasing factor [CRF], neuropeptide Y [NPY]),
also influencing the modulation of other activities, such as thermoregulation in hypothalamic
centers, and the control of satiety, appetite and blood pressure. Thus, in periods of abrupt
changes in circulating estrogen levels, there would be greater vulnerability to the
development of psychic disorders in women, particularly cognition and mood.

Regarding the use of supraphysiological doses of estrogens, more studies are needed to
prove their efficacy in women who are breastfeeding. This modality of treatment is not the
first choice when considering the risks and benefits of estrogen treatment for women in the
reproductive phase.

Psychotherapy

Many women quit or do not accept pharmacological treatment when they discover they are
pregnant, and according to the history of evolution and less seriousness of the disease,
psychotherapy may be a good treatment option.

Psychotherapy may also be an ally with regard to discontinuation or dose reduction

measures in pharmacological treatment, decreasing the risk of relapse or depressive
symptoms during pregnancy. However, it is important to note that it is not appropriate to
discontinue pharmacotherapy in more severe or recurrent cases. Mild depressive episodes
or minor depression may have a good response to psychotherapeutic treatment, and it is
beneficial for the patients and the fetus to initially try non-pharmacological treatment in
these cases.

Newport et al . (2002) conducted a study with 576 postpartum women. The most significant
psychotherapeutic approaches to reduce symptomatology in these cases were studied and
two more effective modalities were found: interpersonal psychotherapy, which focuses on
the patient's depressive symptoms and their relationship with the world, as well as breaking
the barrier interpersonal; and cognitive-behavioral therapy (CBT), which aims to help the
patient solve dysfunctional behaviors and cognitions through learning and cognitive
restructuring.

CBT is based on assessing what ideas, thoughts and emotions the person has about
themselves and that they are distorted, causing a chain of dysfunctional behavioral
reactions.

In depressed patients, it is common to see reports of ideas, thoughts and feelings that end
up leaving the patient with mood altered, reflecting directly on his life and those around
him. These so-called automatic thoughts are at the heart of cognitive-behavioral
theory. The change in these thoughts, often distorted by reality, causes the depressed
patient to reevaluate his condition and restructure his daily life.

In the case of women who have postpartum depression, it is extremely common to present
thoughts and feelings related to baby care issues and their current situation. In this way,
the performance of CBT aims to evaluate and restructure such cognitions that reflect in their
behavior.

Meager (1996) found significant improvement in pregnant and postpartum women who
underwent CBT in therapy groups, based on the Edinburgh scales, the Beck Inventory for
Depression and the Profile of Mood States.

Spinelli and Endicott (2003) conducted a study with pregnant women comparing two
different groups: the first was submitted to family education techniques and the second to
interpersonal psychotherapy. The women in the second group underwent weekly 45-minute
sessions for 16 weeks. The following results were obtained: based on the Edinburgh scale,
11.8% of the patients submitted to family education techniques and 33.3% of the women
submitted to interpersonal psychotherapy were improved. In relation to the Hamilton scale,
improvement was observed in 29.4% in the first and 52.4% in the second group,
respectively. Based on the Beck Depression Inventory, there was improvement in 23.5% of
the patients in the first group, while 52.4% of the patients submitted to interpersonal
psychotherapy improved.

Electroconvulsive therapy (ECT)

Severely depressed women with suicidal thoughts, pictures of mania, catatonia or psychosis
may require hospitalization, and often the treatment of choice in these cases is ECT. Two
recent reviews have found that its use is safe and effective during gestation. In a review of
300 cases treated with ECT during gestation, published in the last 50 years, there were
reports of four preterm labor only. There were no cases of premature placental rupture
(Nonacs and Cohen, 2002).

Recent research suggests that risk is minimal during pregnancy, both in relation to the ECT
itself and the medications used during the procedure, making ECT a useful resource in the
treatment of psychiatric disorders in pregnant women. Maletzky (2004) performed a review
of 27 cases, describing that in 4 of these, the condition of the pregnant woman was the
main indication for the choice of ECT as a therapeutic measure, choosing this performed
according to the safety of the method in relation to the risks which may occur when
depressive disorders occur at this stage. ECT would also be an appropriate procedure as an
alternative to conventional pharmacotherapy for women who could not be exposed to
certain types of medications during pregnancy or those who did not respond to
pharmacological treatment.

Conclusion
Psychiatric disorders in gestation and in the puerperium are more common than imagined,
and many cases are still underdiagnosed. Increasing importance has been given to the
subject, and recent research has also focused on the damage that these pathologies can
cause not only to the mother's health, but also to fetal development, labor, and baby
health. Multiple risk factors are involved, but the exact etiology has not yet been
established. These disorders usually affect patients who already have a history of previous
psychiatric pathology, so a good preventive measure is the adequate treatment of these
episodes. Treatment measures are still widely discussed, and the risk-benefit ratio should be
taken into account,

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 Address for correspondence: 

Renata Sciorilli Camacho 
Rua Atlântica, 400, Jardim do Mar 
09750-480 - São Bernardo do Campo (SP) 
Phone: (11) 4330-4487 
E-mail: sc_camacho@hotmail.com

Received: 03/20/2006 - Accepted: 03/27/2006