The following is derived from numerous symposia and posters at the American Psychiatric Association annual meetings, plus a lecture given at the 2002 DRADA conference. Although I have made every effort to organize the material, no attempt has been made to craft it into a cohesive whole. What we know represents at best a work-in-progress, as this article reflects:

Gender

At a symposium on age and gender, Kimberly Yonkers MD of Yale reported these statistics:

The lifetime prevalence of major depression in women is 21 percent, eight percent for dysthymia, four percent for premenstrual dysphoric disorder (PMDD), and 15 percent for postpartum depression. Women suffer depression in twice the numbers as men, a ratio that plays out across the nationalities surveyed in a classic 1993 study. For example, for US women aged 26-64 the rate of lifetime depression is eight percent vs 3.5 percent for men while in Edmonton the corresponding numbers are 13.2 and 7.5, and in New Zealand the numbers stack up at 17 and 9.6. Girls and boys have the same rates of depression until about puberty, when the female rates suddenly double, which lasts until about age 50, after which by around age 60 the women’s numbers fall back into line with the men’s.

Most of the information on how men and women respond to antidepressants is based on secondary analysis of the data rather than direct testing. What these investigations have revealed is that males with both typical and atypical depression respond better than females to tricyclics, and that females with atypical depression respond better than males to MAOIs. Females also preferentially respond to SSRIs and placebos. Young women did better on SSRIs, suggesting estrogen is a necessary component for SSRI response.

Standard depression treatments may not apply to postpartum depression, Dr Yonkers advised, owing to its very acute onset. Short-term cognitive-behavioral therapy and SSRIs work quite well. Eleven of 12 women who failed to respond to tricyclics responded to an SSRI. An open label study of Effexor showed nearly 70 percent remission by week eight.

For PMDD, women need not take an SSRI continuously. One week before menses is fine, but two weeks seems to work better, according to one study.

Women at Risk

At the 2000 APA meeting, the Harvard Study of Moods and Cycles reported its initial findings from its population of 4,161 women aged 36-44. That study found significant depressive symptoms in 22.4 percent of the sample, suggesting a prevalence of 7.4 percent. Women most at risk were widowed, divorced, or separated, high tobacco users, and with significant premenstrual symptoms. Considerable variability was noted with regard to reproductive endocrine function.

Birth Risks

According to a Norwegian study of 33,260 women, psychiatric symptoms in pregnant women increase the risk of some birth complications. A Massachusetts General Hospital study of 1,917 women, however, concluded depressive symptoms in pregnancy were not associated with adverse neonatal outcomes. However, women who reported either a current or past history of medication treatment of mood/anxiety may be at increased risk for adverse neonatal outcome. Another Mass Gen study of 25 subjects found that poor psychosocial functioning at baseline predicts high risk for relapse during pregnancy.

Depression and Bipolar Disorder in Pregnancy

A number of commentators buried the myth that pregnancy provides some sort of protection against mood disturbances. Another part of the Mass Gen study above of 1,917 pregnant women in the second trimester found 16 percent reported CES-D scores of 16 or greater while 4.4 percent reported more severe depression. Those with scores of 16 or greater were more often younger than 30, non-caucasian, and unmarried. Significant depressive symptoms during pregnancy was most strongly associated with a past history of mood disturbance or previous use of antidepressants.

Another Mass Gen study found risk for relapse after lithium discontinuation to be similar in pregnant and nonpregnant women, with 50 percent relapsing within six months.

Yet another Mass Gen study followed 44 pregnant women during their pregnancy and the year postpartum. Among the 33 subjects who discontinued their mood stabilizer during pregnancy, 26 relapsed (78.8 percent). The ten patients who abruptly discontinued their maintenance mood stabilizer appeared at highest risk of relapse (100 percent) compared to subjects who gradually weaned off over more than two weeks ( 62 percent).

Pregnancy and Meds

A Stanford study of the newborns of mothers who took antidepressants had similar APGAR and other scores to the controls, confirming the relative safety of antidepressants during pregnancy.
At last year’s APA meeting, a Mass Gen study using APGAR tests and other measures of 70 infants whose mothers took SSRIs or TCAs during pregnancy found no "readily apparent treatment-emergent adverse effects," though "long-term neurobehavioral effects of fetal exposure to these medications remain unknown." Nevertheless, in light of the risk of postpartum depression associated with antidepressant discontinuation, the authors recommend "clinicians may be best advised to continue antidepressant medication."
At last year’s APA meeting, an Emory University study using APGAR tests and other measures of 95 newborns whose mothers either took or did not take antidepressants found "no significant differences in obstetric outcomes between nonmedicated and medicated groups in each trimester." Also there were no differences in the different types of antidepressants with respect to obstetric outcomes.
From the Lamictal patient database: The number of patients with major birth defects following Lamictal monotherapy was 3 in 168 (2.5 percent) and following Lamictal polytherapy (without Depakote) was 2 in 116 (4.3 percent)

Postpartum Depression

A Case Western Reserve University study of 51 nondepressed pregnant women who had at least one past episode of postpartum depression were assessed 20 weeks postpartum and followed up at intervals till 52 weeks postpartum. One year recurrence was 21 in 51, or 41 percent. Five of the 21 (24 percent) recurrences were in the first two weeks, 13 (67 percent) in 19 (90 percent) recurrences were in first 20 and 28 weeks following birth. All recurrences except two occurred by 28 weeks postpartum.

Menopause

The Harvard Study of Moods and Cycles released a number of findings:

An earlier study found women who underwent menopause prior to age 48 were twice as likely to self-report a history of depression that required treatment for a year or longer vs women who were still premenopausal at age 49 or later.

Data available from the Harvard Study of Moods and Cycles suggest that depression may exert an influence on endocrine function and further development of early ovarian failure. The authors hypothesize that depression may permanently alter hypothalamic-pituitary-gonadal axis regulation. Earlier exposure to perimenopause (and ultimately an earlier menopause) may result in a prolonged exposure to a hypo-estrogenic state, which has been associated with loss of bone density, sexual dysfunction, and a decline in cognitive function. If an earlier transition to perimenopause would not, in fact, result in an earlier menopause, women with a history of depression could face a longer period of menopausal transition before reaching menopause. Under this scenario, the authors suggest those women would be exposed to a more prolonged period of hormonal variability - a period shown to be associated with greater vulnerability for new or recurrent depression.

More from Moods and Cycles: 1) Age of menarche and other events in early reproductive life are associated with risk of depression. 2) Women with a lifetime history of major depression are at a greater risk of developing menstrual cycle changes consistent with those that signal an earlier transition into the perimenopause compared with women with no depression history. 3) Early follicular phase FSH (ovarian hormone activity) and LH (luteinizing hormone) are higher and estradiol levels are lower in depressed vs nondepressed late reproductive-aged women. 4) Women with no prior history of depression who develop new onset of depression during their late reproductive years have a greater cycle-to-cycle variability in FSH and LH compared with those who stay nondepressed.

A Harvard Study of Moods and Cycles published at the 2004 APA meeting prospectively tracked 644 women in the sample with no history of depression, finding that this population had a three times greater risk of developing depressive symptoms entering perimenopause than premenopausal women of the same age. The strength of the association increased with greater numbers of adverse life events. Perimenopausal women with significant vasomotor symptoms (that cause blood vessels to restrict or widen) had more than six times the normal risk.

Premenstrual Dysphoric Disorder - PMDD

A Turkish study found bipolar women taking mood stabilizers experienced fewer mood fluctuations during menstrual cycles than healthy subjects, suggesting mood stabilizers may protect bipolar women against premenstrual complaints.
A Butler Hospital study (Providence) of 276 women found the day of onset for severe PMDD symptoms highly variable, differing from cycle-to-cycle by three days or more in more than 60 percent of women. Duration of symptoms varied by three or more days in more than 50 percent of women, leading the authors to conclude: "Care must be taken when utilizing luteal phase dosing to ensure adequate pharmacologic coverage of cycle-to-cycle episodes."
Another Butler Hospital study found no difference in PMDD patients receiving intermittent luteal phase Zoloft vs continuous Zoloft. A Virginia Commonwealth University study found that 50 mg of Zoloft had no advantage over 25 mg of Zoloft, either taken continuously or intermittently.
A Swedish/GSK study of 186 women found that 68.1 percent responded to 20 mg of Paxil administered the last 14 days of the cycle vs 84.8 percent on continuous Paxil vs 29.8 for a placebo.
At last year’s APA meeting, an open label Canadian study of Topamax on 30 women with PMDD who had tried SSRIs and other treatments found there was relief from premenstrual dysphoria. Seven dropped out of the study due to side effects.

SSRIs work well for premenstrual dysphoric disorder (PMDD), according to Karen Schwartz MD, assistant professor at Johns Hopkins, talking to the 2002 DRADA conference, and they work faster than for classic depression, suggesting different mechanisms at play. Women with PMDD may limit their SSRI medication to the week before their period rather than remaining on the drug constantly. SSRIs work "significantly better" for PMDD than TCAs.

PMDD is a distinct clinical syndrome, first described by Hippocrates and finally receiving recognition in the DSM III under the name Late Luteal Phase Dysphoric Disorder, and more recently in the 1994 DSM-IV by its present name. The symptoms are similar to depression, but with breast tenderness, headaches, and bloating and with symptoms remitting in the week post menses. Women with dysthymia or major depression may also have symptoms that worsen.

Dr Schwartz stressed the need for a complete psychiatric evaluation. She displayed an ad for Serafem (Prozac with a Barbie color scheme, as she described it) that ran in a women’s magazine with a symptom checklist to take to one’s doctor, symptoms that hardly mean one has PMDD, she pointed out. One of her patients, she learned, had earlier hypomanic episodes, so she gave her a mood stabilizer instead of an antidepressant. "Had I just checked for depression symptoms," she concluded, "I could have switched her into mania."

Bipolar Women

An analysis of the first 500 patients of the STEP-BD database found women were significantly more likely to have a lifetime diagnosis of bipolar II, thyroid disease, suicide attempts, antidepressant treatment, and possibly greater antidepressant-induced hypomanic switch. Men were more likely to have a history of violence and legal problems and a history of head trauma. No gender differences were found in age of onset, polarity of onset of illness, episode pattern, number of lifetime episodes of mania or depression, or quality of mania, or (surprisingly) lifetime history of rapid cycling.

Treatment for Bipolar Women

At last year’s APA meeting, a Case Western Reserve University study of 28 women on the beta blocker verapamil found the overall response rate 57 percent, seven of nine who responded to mixed, five to mania only, two to both depression and mania.

SSRI Sexual Dysfunction

Break out the Viagra. A University of New Mexico study of 150 women with SSRI-associated sexual dysfunction found those receiving Viagra demonstrated 70 percent improvement. in sexual dysfunction.

Partnership and Violence

A Harvard study of 181 Chinese-American women found partner violence is strongly associated with increased risk of major depression.
A University of Texas study of 1,440 white, black, and Hispanic couples found partner violence highest among black couples, followed by Hispanics, then whites. Between 27 and 41 percent of the men and four and 24 percent of the women were drinking at the time of the violent incident. As well as alcohol, depression was also associated with partner violence.

Compulsive Buying

A presentation by Michel Lejoyeaux MD of H Louis Mourier (France) reported that the prevalence compulsive buying in depression at 31.9 percent. Compulsive buyers were younger, more often women, and unmarried.

Talking Therapy

A University of Pittsburgh study of women treated with acute interpersonal therapy (IPT) followed by maintenance IPT found the majority who achieve remission with IPT alone are protected for two years against new episodes of major depression. In contrast, patients who require the addition of SSRIs to achieve remission are highly vulnerable to relapse and recurrence.

Neurobiology of Female Depression

A multi-center study of 86 elderly men and women found that after adjusting for height and other factors, depressed women had a significantly smaller hippocampus-amygdala complex than depressed men. Amongst normal controls, there was no difference.

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Updated July 15, 2004

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