Clinical Question: Topamax and Seroquel in a Woman with Bipolar Disorder Planning to

Breastfeed

Published: December 1, 2009

A clinician asks: “I am a psychiatrist treating a patient with Bipolar Disorder on Seroquel and
Topamax. I would like to know what information is available regarding the safety of these
medications to the infant if used during breastfeeding.”

With regard to topiramate (Topamax), there is relatively little information on breastfeeding. One
case series included five women with epilepsy treated with topiramate during pregnancy and
lactation. Breastfed infants had very low topiramate concentrations, and no adverse effects were
observed in the infants.
The literature includes a handful of case reports assessing the use of quetiapine (Seroquel) in
breastfeeding women. The largest series included six women treated with multiple medications,
including quetiapine. Levels of quetiapine were typically low in the breast milk and infant
serum. Four of the six infants showed normal development; two of the children had mild
developmental delays. It is not clear if these delays were a result of exposure; however, it is
reassuring to note that in the two children showing mild delays, estimated levels of quetiapine
exposure through breast milk were not higher than in the children with no delays. Based on the
limited number of case reported in the literature (a total of 8 mother-infant pairs), there appears
to be low levels of infant exposure to quetiapine through the breast milk, and no clear association
between adverse outcome and exposure has been observed.
Clearly more research is required to assess the safety of these drugs in nursing infants, and
decisions regarding the use of these drugs in breastfeeding women involve a careful
consideration of the risks and benefits. For women with bipolar disorder, breastfeeding raises
concerns for another reason. The sleep deprivation associated with exclusively breastfeeding a
new infant may be destabilizing for those with bipolar disorder and may precipitate a relapse
during this vulnerable time.

Ruta Nonacs, MD PhD

Generic Medications
Published: August 10, 2009
Many patients ask questions about generic medications, wondering how they differ and if they’re
as safe and as effective as the more expensive brand name versions. To better understand this
concept, we’ll discuss an example.

Many patients have heard of the medication, Prozac, a selective serotonin reuptake inhibitor
antidepressant, generically known as fluoxetine. The company, Eli Lilly & Co., researched and
developed this medication, which received Food and Drug Administration (FDA) approval in
1987. Eli Lilly was allowed to be the sole manufacturer until the patent for Prozac expired in
2001, at which point other drug manufacturers were able to apply to the FDA to be able to sell
generic versions of this medication. Because the manufacturers of generic medications did not
have the initial start up costs of researching, developing, and marketing the medication, they are
able to sell fluoxetine more cheaply. One example of a company which produces generic
fluoxetine is Teva Pharmaceuticals Industries, which was granted FDA approval for fluoxetine in
January of 2002.

Companies producing generic versions of medication, such as Teva, must demonstrate to the
FDA that their product has the same active ingredient, in this case fluoxetine hydrochloride,
dosage, efficacy, performance, and strength of Prozac. The fluoxetine hydrochloride product
they produce must also be cleared by the body in the same method and time frame as the brand
name product; the risks and benefits also need to be the same.

While the active ingredient is the same, generic medications may have different inactive
ingredients. Generic fluoxetine will look different from brand-name Prozac because the FDA
does not allow generic medications to look identical to brand-name versions. For example, the
20mg pulvule (capsule) by Eli Lilly has an opaque green cap and off-white body, while generic
fluoxetine capsules comes in various colors including blue, green and white, green and purple,
and blue and turquoise, for example.

The vast majority of patients will be able to take generic medications without difficulty and
without any noticeable change in effectiveness or side effects. Occasionally, patients notice a
difference between a generic version and a brand name version or sometimes between generic
medications by different manufacturers. These may be due to differences in the inactive
ingredients, fillers, or binders.

All generic medications must meet the same manufacturing standards as brand-name
medications and the FDA makes thousands of inspections per year to manufacturing companies
producing brand-name and/ or generic medications to ensure that guide lines are being met.
Generic medications are a safe and cost effective treatment option and should be considered first
line, when a generic version of the medication is available.

Betty Wang, MD

http://www.fda.gov/Drugs/EmergencyPreparedness/BioterrorismandDrugPreparedness/ucm1344
51.htm

Depression and Menopausal Symptoms Go Together

Published: August 17, 2009
It is well established that women are at increased risk for developing depression compared to
men. It has been hypothesized that this vulnerability to depression may be hormonally mediated,
and several longitudinal studies have documented an increased risk of depressive symptoms
during perimenopause or the menopausal transition. Based on the results of two prospective
cohort studies, approximately one-third of women will develop their first episode of depression
during the menopausal transition. (Cohen LS et al 2006, Freeman EW et al 2006).
Studies investigating the relationship between hot flashes, a hallmark vasomotor symptom of the
menopause transition, and depression have indicated that hot flushes and night sweats are
associated with depression in perimenopausal women. A recent large cross-sectional population-
based survey of midlife women has attempted to better understand the impact of depression on
menopausal symptoms.
This study included a sample of women (ages 45-70), who were obtained randomly from two
large health plans, one in Washington State and the other in Massachusetts. The majority of the
2530 eligible women had previously taken hormone replacement therapy and had since
discontinued it. Women who were taking SSRI or SNRI antidepressants were included. Of the
2530 eligible women, 1358 women completed the telephone survey examining depressive
symptoms using the Patient Health Questionnaire (PHQ-8) and the Wiklund Menopause
Symptom Checklist. 580 of these women were taking hormone replacement therapy and were
excluded from the analysis, as were another 8 women with unknown menopausal status.

A total of 770 women were included in the analysis, and it was observed that 98 (12.7%) of the
women reported moderate to severe depressive symptoms. After adjusting for age and body
mass index, those women with moderate to severe depressive symptoms were almost twice as
likely to report recent vasomotor symptoms (hot flashes or night sweats) than the women with no
or mild depressive symptoms.

Women with severe depression were also more likely to report their vasomotor symptoms as
severe, despite the fact that 20% of those women were also taking either an SSRI or SNRI,
agents which have been shown to improve vasomotor symptoms. The women who experienced
moderate to severe depression were also more likely to experience feeling anxious at least 50%
of the time.

This study is the first to demonstrate a correlation between the severity of depressive symptoms
and the intensity of menopausal symptoms. The authors concluded that depressive symptoms
“amplified” or were associated with more severe vasomotor symptoms, but they also noted that
this study could not rule out the possibility that more severe vasomotor symptoms were in fact
worsening the depressive symptoms.
This study has a few limitations including the fact that all the information was based on self
report and some women were taking SSRI or SNRI antidepressants. (The brands and dosages
were not included in the results). Also because women who were on hormone therapy were
excluded, it is not known what impact hormonal replacement therapy may have on depressive
symptoms. Longitudinal studies comparing depressed and non-depressed women as they
transition into menopause may help to further delineate the relationship between menopausal
symptoms and depression.
While some questions remain, these findings underscore the importance of screening for
depressive symptoms in perimenopausal women. Depression is a relatively common problem in
this population, particularly in those with more severe vasomotor symptoms. The authors point
out that recognition and treatment of depression in women during the menopause transition may
reduce the burden of menopausal or vasomotor symptoms.

April Hirschberg, MD

Cohen LS, Soares CN, Vitonis AF et al. Risk for new onset of depression during the menopausal
transition: the Harvard study of moods and cycles. Arch Gen Psychiatry 2006; 63: 385-90.

Freeman EW, Sammel MD, Lin H et al. Associations of hormones and menopausal status with
depressed mood in women with no history of depression. Arch Gen Psychiatry 2006; 63:375-82.

Reed SR, Ludman EJ, Newton KM et al. Depressive symptoms and menopausal burden in the
midlife. Maturitas 2009; 62: 306-310.