INTEGRATIVE MEDICINE TREATMENTS FOR WOMEN

Excerpt from:

Sinha, P, Freeman M, Hill, R. Integrative Medicine Treatments for Women. In Lake, J and Spiegel, D (ed.), Clinical Manual of Complementary and Alternative Treatments in Mental Health. Washington, DC: American Psychiatric Press, Inc. 2006.

Depression During Pregnancy

Mood disorders are more common among women than men in general, and approximately ten% of women report depressed mood during pregnancy (Nonacs and Cohen, 2002). en complete suicide more often than women, although more women attempt suicide. Approximately one-third of depressed women experience their first episode of major depression during pregnancy (O'Hara, 1994). Pregnancy raises several important questions for women with major depression as well as their clinicians. Should a woman of child-bearing age with major depression discontinue conventional or non-conventional treatments prior to conception or after discovering she is pregnant? What is the risk of recurrent depression during pregnancy or following child-birth? What are the risks to the fetus and the pregnant woman if she chooses to discontinue or to continue treatment? What risks exist for a baby if the mother is depressed during pregnancy? Clinicians are often challenged by caring for a pregnant woman who is depressed while minimizing risks to both the woman and fetus and weighing the benefits and risks of psychiatric treatment.

Untreated depression is common in pregnancy and negatively affects pregnancy outcomes. Pregnancy does not protect against depression, as demonstrated by a prospective study (Evans et al 2001) that found a 13.5% incidence of depression at 32 weeks gestation. Diagnosing major depressive disorder during pregnancy is complicated by the fact that decreased energy, insomnia, appetite disturbances, and diminished libido are frequently reported by non-depressed pregnant women. Thyroid abnormalities, anemia, and diabetes associated with pregnancy may confound efforts to diagnose a psychiatric illness (Klein and Essex, 1995). It is always prudent to ask a pregnant woman about suicidality, hopelessness, guilt, and anhedonia-symptoms that are more specific indicators of major depression.

Psychiatric illness during pregnancy or the postpartum period carries significant risks for women and their children. Depression during pregnancy increases the risk of poor self-care, poor compliance with pre-natal care, decreased appetite, and lower weight gain, and is associated with negative pregnancy outcomes (Zuckerman et al, 1989). Antenatal depression is associated with lower birth weight, preterm birth, abnormal small head circumference, and low Apgar scores (Dayan et al, 2002). Animal studies show an association between maternal stress and fetal hypoxia, low birth weight and miscarriage (Wadwha et al, 1993). Antenatal depression increases the risk of postpartum depression and may interfere with mother-infant bonding. Infants of depressed mothers are more likely to exhibit behavioral, attachment, and cognitive problems (Weinberg and Tronick, 1998).

Clinicians and patients should ideally discuss the risks and benefits of both conventional and non-conventional treatment options (including psychotherapy) prior to conception. The clinician should inform the woman about the risk of teratogenesis, toxicity or withdrawal symptoms in the neonate, and possible neurobehavioral problems in the infant exposed to any proposed intervention (Wisner et al, 2000). To date, few studies have been done on the efficacy of antidepressants during pregnancy . The clinician should also discuss non-pharmacological treatment options for women who report depressed mood in the weeks before expected childbirth.

Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat major depression during pregnancy. Neither SSRIs nor tricyclic antidepressants increase the risk of major birth defects or intrauterine death (Wisner et al, 2000). SSRI withdrawal or toxicity syndromes have been reported in neonates exposed to antidepressants in late pregnancy. The Food and Drug Administration recently added warnings to SSRI and venlafaxine labels about signs of toxicity or withdrawal in newborns. Prospective studies and case reports point to respiratory distress, jitteriness, hypoglycemia, and hypotonia (Costei et al, 2002; Laine 2003; Nordeng et al, 2001; Zeskind and Stephens 2004). On the basis of these findings, SSRI withdrawal or toxicity syndromes appear to be transient however further studies are needed to assess longer-term risks to infants. Perinatal syndromes in infants exposed to TCAs in utero include transient symptoms such as jitteriness, irritability, urinary retention, and functional bowel obstruction. Neonatal withdrawal symptoms from TCAs are transient, and seizures have been reported with the use of clomipramine during pregnancy (Cowe et al, 1982).

Little is known regarding the long-term effects of in utero exposure to antidepressants. In children between the ages of 15 and 71 months, there were no reports of significant adverse effects on children's IQs, behavior, language and temperament following exposure to TCAs or fluoxetine during pregnancy (Nulman et al, 2002). However, in utero exposure to fluoxetine may increase the risk of low birth weight (Chambers et al, 1996; Hendrick et al, 2003). One study on SSRI use in pregnant women suggested an association with premature birth (Simon et al, 2002), however larger studies did not support this finding (Kulin et al, 1998; Erickson et al, 1999). Babies exposed to SSRIs in utero were born one week earlier on average compared to controls (Zeskind and Stephens, 2004). It is important for clinicians to inform their patients that the long-term effects of both conventional antidepressants and non-conventional treatments on the child are unknown. Further, patients should be informed of the risk of negative effects of untreated maternal depression on the course of the pregnancy and child development.

Postpartum Depression (PPD)

According to the DSM IV, postpartum depression (PPD) is defined as the onset of major depression within four weeks after delivery. Risk factors for PPD include a history of depression, previous postpartum depression, a family history of PPD, and depression during pregnancy. The Edinburgh Postnatal Depression Scale (EPDS) is a screening tool that has been utilized to increase the rate of detection of PPD in clinical settings (Cox et al., 1987).

PPD not only negatively impacts women, but also affects the safety and development of infants. Depressed women may neglect their basic needs, and those with PPD are less in tune with the needs of their newborns. Infants of mothers with untreated depression are more likely to develop attachment disorders, have poorer cognitive function, and exhibit behavioral problems compared to infants of mothers who respond to treatment (Cicchetti et al, 1988) In addition, women with PPD may fail to take measures to provide a safe environment for their babies, such as compliance with car seat use and “baby proofing” of homes (McLennan and Kotelchuck, 2000).

We strongly recommend that all clinicians discuss the risks and benefits of antidepressant treatment and breastfeeding for both the mother and her baby. Breastfeeding is associated with multiple health benefits for the infant (Rodriguez et al, 1999). For mothers, breastfeeding is associated with reduced postpartum blood loss, decreased risk of ovarian and pre-menopausal breast cancers, and it may enhance emotional attachment between the mother and her infant (Labbok, 1999). Unfortunately, few placebo-controlled studies have been done on conventional antidepressant treatments of PPD. One double-blind trial using fluoxetine (Prozac ™) (Appleby et al, 1997) and another double-blind study using estrogen (Gregoire et al, 1996) suggested efficacy for the treatment of PPD. Although high infant blood levels have been reported in infants whose mothers were treated with fluoxetine (Prozac ™), most findings suggest that infants who are breast-fed have low blood levels of tricyclics and SSRIs (Llewellyn and Stowe, 1998; Wisner et al, 1996). In one study, the growth curve of breastfed infants of mothers treated with fluoxetine during and after pregnancy was significantly lower compared to infants of nursing mothers who discontinued fluoxetine following childbirth (Chambers et al, 1999). A few case reports suggest possible adverse events in infants who are breastfed by mothers treated with antidepressants including doxepin (Frey et al, 1999), citalopram (Schmidt et al, 2000), estrogen (Ball and Morrison, 1999), and wellbutrin (Chaudon et al, 2004).

The findings of most studies indicate that infant exposure to maternal antidepressants via breast milk is low (Burt et al, 2001), however many women decline treatment with antidepressants if they are breastfeeding because long-term effects on the infant have not been determined. Psychotherapy is often a first-line treatment option for women with PPD because concerns over breastfeeding are avoided. Cognitive behavioral therapy and interpersonal psychotherapy are probably effective treatments of PPD (Chabrol et al, 2002; Klier et al, 2001; O'Hara et al, 2000; Cooper et al, 2003). Premenstrual Mood Disorders

In premenstrual syndrome (PMS) is characterized by behavioral, physical, and minor mood symptoms that remit after menses (Freeman, 2003). Premenstrual mood problems typically start between the late-20s and early 30s (Freeman et al, 1995). Risk factors include a previous history of major depression, postpartum depression, or bipolar affective disorder, a positive family history of premenstrual problems, and psychosocial stressors (Steiner et al, 2003). Approximately 8% of women experience PMS, and its risk is greater in African American and younger women as well as those who report alcohol consumption, longer menses, and high levels of perceived stress (Deuster et al, 1999).

Unlike premenstrual syndrome, the diagnosis of premenstrual dysphoric disorder (PMDD) signifies significant psychiatric morbidity and impairment in work, school, or other activities. According to the DSM-IV-TR, women experience marked symptoms including 5 or more of the following: depression, anxiety; lability; irritability; poor concentration; diminished motivation; feelings of overwhelm; changes in appetite and sleep; and physical complaints. These symptoms must take place on a regular basis for at least one year during the last week of the luteal phase . The most frequently occurring symptoms of PMDD include anxiety, irritability and mood lability (Bloch et al, 1997). These symptoms generally remit within a few days of the follicular phase or the onset of menses, and are absent for one week following the end of menses.

Women with PMDD have higher rates of mood and anxiety disorders, previously diagnosed PPD (if they have children), and more obsessional personality traits in contrast to women who do not suffer from PMDD (Critchlow et al, 2001). A thorough psychiatric history is necessary to clearly differentiate PMDD from other mood or anxiety disorders. Documenting daily mood ratings and menses for at least two months is a practical way to confirm the diagnosis.

The first line conventional treatment of PMDD is SSRIs. At the time of writing the U.S. FDA has approved sertraline (Zoloft ™), fluoxetine (Prozac ™) and paroxetine (Paxil ™) for the treatment of PMDD for continuous use or administration during the luteal phase only (last 2 weeks of menses). In clinical trials of SSRIs for PMDD, symptoms are reduced with either continuous or luteal phase administration (Freeman, 2004). Estrogen probably ameliorates premenstrual symptoms, (Smith et al, 1995) however progesterone is ineffective and may worsen symptoms (Tiemstra and Patel, 1998). The evidence for beneficial effects of oral contraceptives on premenstrual mood symptoms is inconclusive (Andersch, 1982; Joffe et al, 2003).

Perimenopause and Menopause

Researchers have proposed that the decrease in estrogen during the menstrual cycle, the immediate postpartum period, and in the perimenopause is correlated with depressive mood symptoms (Schmidt and Rubinow, 1991). This is called the “estrogen withdrawal theory.” Perimenopause is associated with changes in the menstrual pattern that typically occur in women between the ages of 40 to 55 years (Soares and Cohen, 2001).Women in the perimenopause may be especially vulnerable to depressive symptoms due to declining estrogen levels.

Estrogen has been demonstrated to have antidepressant effects (Klaiber et al, 1979; Gregoire et al, 1996). However, the risk/benefit analysis for hormone replacement therapy (HRT) has recently become more complicated. In the Women's Health Initiative study, coronary artery disease, stroke, pulmonary emboli, and invasive breast cancer were reported more frequently in women who received both estrogen and progestin than in women who received placebo (Rossouw et al, 2002). The use of HRT remains controversial and it is unclear whether this approach is a viable treatment option for perimenopausal depression. The findings of double-blind studies show that SSRIs reduce the severity of vasomotor symptoms in the perimenopause. Fluoxetine, paroxetine, and venlafaxine (Effexor ™) are more effective for the management of hot flashes than placebo (Loprinzi et al, 2002; Stearns et al, 2003; Loprinzi et al, 2000). The findings of an open-label study suggest that citalopram (Celexa ™) improves both depressed mood and vasomotor symptoms in the perimenopause (Soares et al, 2003). Additional research on conventional treatments for perimenopausal and menopausal depression and vasomotor symptoms is needed.

Efficacy of selected complementary and alternative medication treatments for depression in women
Treatment modality	Efficacy*	Dose range	Safe in pregnancy	Safe in breastfeeding	Interactions with OCPs**
Bright light therapy	Positive	30-60 min/day	Yes	Yes	No
Omega 3-fatty acids	Positive, as adjunctive treatment	1-3g.day;up to 3g/day	Yes	Yes	No
St. John's Wort	Positive	900mg/day (divided doses, tid or bid)	Not established	Not established	Yes
SAM-e	Positive	200mg bid 2-7days, then 400mg bid if needed	Not established	Not established	None reported
Exercise	Positive	30 min/day	Yes	Yes	No
Folate	Positive as augmentation of antidepressant	0.4-1 mg/day	Yes	Yes	No
5-HTP	Positive	50 mg tid to 150mg qid	Unknown	Unknown	Unknown
Acupuncture	Positive	30-45 min/weekly, 6-8 weeks	Not established	Yes	No
*As shown in randomized controlled trials **Oral contraceptive pills Source.<m#>From Freeman et al, 2004; Copyright permission pending