Adele C. Viguera

Episodes of Mood Disorders in 2,252 Pregnancies and Postpartum Periods

OBJECTIVE The risks of major affective episodes during pregnancy and during the postpartum period have rarely been compared in large samples across diagnoses. The authors hypothesized that perinatal episodes would mainly be depressive, would occur more in the postpartum than the prenatal period, and would be more prevalent with bipolar than unipolar depressive disorders. METHOD The authors pooled clinical information on 2,252 pregnancies of 1,162 women with clinically treated DSM-IV bipolar I disorder (479 pregnancies/283 women), bipolar II disorder (641/338), or recurrent major depressive disorder (1,132/541) to compare rates of affective episode types by diagnosis during pregnancy and the postpartum period and to identify risk factors. RESULTS Among women with bipolar disorder, 23% had illness episodes during pregnancy and 52% during the postpartum period. Among women with unipolar depression, 4.6% had illness episodes during pregnancy and 30% during the postpartum period. Based on exposure-adjusted risk per pregnancy, episodes were 3.5 times more prevalent during the postpartum period than during pregnancy, and the risk was consistently higher with bipolar disorder. Depression was the most frequent morbidity during and following pregnancy. In multivariate modeling, factors associated with affective episodes in pregnancy, in descending order, were younger age at onset, previous postpartum episodes, fewer years of illness, bipolar disorder, fewer children, and not being married. Postpartum episodes were associated with younger age at onset, illness during pregnancy, bipolar disorder, fewer children, and more education. Moreover, pregnancy was less likely and perinatal episodes more likely if diagnosis preceded a first pregnancy. First lifetime episodes occurred in the perinatal period in 7.6% of cases. CONCLUSIONS Among women with major affective disorders, illness risk was much greater during the postpartum period than during pregnancy. Illness mainly involved depression and was strongly associated with younger age at illness onset, bipolar disorder, and high lifetime occurrence rates. The relative risk during pregnancy compared with nonpregnant periods remains uncertain.

Discontinuing antidepressant treatment in major depression

&NA; Maintenance treatments in bipolar disorders and schizophrenia are securely established, and their discontinuation is associated with high but modifiable risk of early relapse. The benefits of long‐term antidepressant treatment in major depression and the risks of discontinuing medication at various times after clinical recovery from acute depression are not as well defined. Computerized searching found 27 studies with data on depression risk over time including a total of 3037 depressive patients treated for 5.78 (0‐48) months and then followed for 16.6 (5‐66) months with antidepressants continued or discontinued. Compared with patients whose antidepressants were discontinued, those with continued treatment showed much lower relapse rates (1.85 vs. 6.24%/month), longer time to 50% relapse (48.0 vs. 14.2 months), and lower 12‐month relapse risk (19.5 vs. 44.8%) (all p < 0.001). However, longer prior treatment did not yield lower postdiscontinuation relapse risk, and differences in relapses off versus on antidepressants fell markedly with longer follow‐up. Contrary to prediction, gradual discontinuation (dose‐tapering or use of long‐acting agents) did not yield lower relapse rates. Relapse risk was not associated with diagnostic criteria. More previous illness (particularly three or more prior episodes or a chronic course) was strongly associated with higher relapse risk after discontinuation of antidepressants but had no effect on response to continued treatment; patients with infrequent prior illness showed only minor relapse differences between drug and placebo treatment.

The association of depressive, anxiety, and stress symptoms and postpartum relapse to smoking: A longitudinal study

INTRODUCTION The aim of this prospective repeated measures, mixed-methods observational study was to assess whether depressive, anxiety, and stress symptoms are associated with postpartum relapse to smoking. METHODS A total of 65 women who smoked prior to pregnancy and had not smoked during the last month of pregnancy were recruited at delivery and followed for 24 weeks. Surveys administered at baseline and at 2, 6, 12, and 24 weeks postpartum assessed smoking status and symptoms of depression (Beck Depression Inventory [BDI]), anxiety (Beck Anxiety Inventory [BAI]), and stress (Perceived Stress Scale [PSS]). In-depth interviews were conducted with women who reported smoking. RESULTS Although 92% of the participants reported a strong desire to stay quit, 47% resumed smoking by 24 weeks postpartum. Baseline factors associated with smoking at 24 weeks were having had a prior delivery, not being happy about the pregnancy, undergoing counseling for depression or anxiety during pregnancy, and ever having struggled with depression (p < .05). In a repeated measures regression model, the slope of BDI scores from baseline to the 12-week follow-up differed between nonsmokers and smokers (-0.12 vs. +0.11 units/week, p = .03). The slope of PSS scores also differed between nonsmokers and smokers (-0.05 vs. +0.08 units/week, p = .04). In qualitative interviews, most women who relapsed attributed their relapse and continued smoking to negative emotions. DISCUSSION Among women who quit smoking during pregnancy, a worsening of depressive and stress symptoms over 12 weeks postpartum was associated with an increased risk of smoking by 24 weeks.

Is Lithium Still Worth Using? An Update of Selected Recent Research

The treatment of bipolar disorder has seen greater innovation in the past decade than at any other time since the introduction of lithium and the neuroleptics a half-century ago. The place of lithium in contemporary psychiatric therapeutics has become controversial, calling for the present overview of research findings pertaining to its use in treating patients with bipolar disorder. Lithium, by itself, typically is inadequate for rapid control of acute mania; antipsychotics, divalproex, or potent sedatives are commonly used, with or without lithium, for this purpose. The special usefulness of lithium lies in long-term prevention of recurrences of mania and bipolar depression and in reducing risk of suicidal behavior. Lithium also may be beneficial in recurrent unipolar depression and is an effective adjunct for treatment-resistant depression. Expectations that prolonged untreated bipolar illness, multiple episodes, rapid cycling, or retreatment following discontinuation might routinely lead to lithium nonresponsiveness, and the belief that lithium is too toxic for use during pregnancy, have not been borne out by research. Lithium retains a substantial share of prescriptions for bipolar disorder and is inexpensive. No other treatment has performed as well as lithium in as many aspects of long-term care of bipolar disorder patients, and despite some risks and limitations, lithium remains the standard against which all proposed alternatives are compared.

Lamotrigine in Breast Milk and Nursing Infants: Determination of Exposure

OBJECTIVE. Although lamotrigine use during pregnancy has substantially increased over the past decade secondary to accumulated reproductive safety data, systematic data on lamotrigine during breastfeeding remains sparse. We sought to characterize the determinants of lamotrigine concentrations in breast milk and nursing-infant plasma. PATIENTS AND METHODS. Women who enrolled in a prospective investigation of perinatal medication pharmacokinetics, were treated with lamotrigine, and chose to continue lamotrigine while breastfeeding were included in the analysis. Breast milk samples were collected via breast pump from foremilk to hindmilk from a single breast to determine the excretion gradient and serial samples over 24 hours to determine the time course of excretion. Paired maternal/infant plasma samples were also collected. Lamotrigine concentrations in all of the samples were determined by using high-performance liquid chromatography with ultraviolet detection. Statistical analyses of breast milk and infant plasma concentrations and their determinants were conducted. RESULTS. Thirty women and their nursing infants participated in the study, providing a total of 210 breast milk samples. The mean milk/plasma ratio was 41.3%. There was a nonsignificant trend for higher lamotrigine concentrations in breast milk 4 hours after the maternal dose. Infant plasma concentrations were 18.3% of maternal plasma concentrations. The theoretical infant lamotrigine dose was 0.51 mg/kg per day, and the relative infant lamotrigine dose was 9.2%. Mild thrombocytosis was present in 7 of 8 infants at the time of serum sampling. No other adverse events were observed or reported in the breastfed infants. CONCLUSIONS. Consistent with previous investigations of medications in breast milk, the lamotrigine milk/plasma ratio is highly variable. The rate of lamotrigine excretion into human breast milk is similar to that observed with other antiepileptic drugs. These data expand the extant literature on lamotrigine in breastfeeding and demonstrate relatively comparable nursing-infant exposure to lamotrigine compared with other antiepileptic drugs.

Treatment of Mood Disorders During Pregnancy and Postpartum

Studies suggest that pregnancy does not protect women from the emergence or persistence of mood disorders. Mood and anxiety disorders are prevalent in women during the childbearing years and, for many women, these mood disorders are chronic or recurrent. Maintenance antidepressant therapy is often indicated during the reproductive years and women face difficult treatment decisions regarding psychotropic medications and pregnancy. Treatment of psychiatric disorders during pregnancy involves a thoughtful weighing of the risks and benefits of proposed interventions and the documented and theoretical risks associated with untreated psychiatric disorders such as depression. Collaborative decision-making that incorporates patient treatment preferences is optimal for women trying to conceive or who are pregnant. This article reviews the diagnosis and treatment guidelines of mood disorders during pregnancy and postpartum, with specific reference to the use of psychotropic medications during this critical time.

Lamotrigine in bipolar disorder: efficacy during pregnancy

OBJECTIVE Clinical management of bipolar disorder (BPD) patients during pregnancy is a major challenge. The high risk of bipolar depression during pregnancy encourages consideration of lamotrigine (LTG). We therefore compared recurrence risks among pregnant women with BPD treated with LTG to those discontinuing mood stabilizer therapies. METHODS We compared risks and weeks to new DSM-IV illness-episodes among 26 initially clinically stable pregnant women diagnosed with DSM-IV BPD who continued LTG treatment to those discontinuing all mood stabilizer treatment during pregnancy. RESULTS The risk of new illness-episodes with LTG was 30% versus 100% after discontinuing mood stabilizers, and survival-computed time-to-25%-recurrence was 28.0 versus 2.0 weeks (chi(2 )=17.3, p < 0.0001; hazard ratio = 12.1; 95% confidence interval = 1.6-91.7). CONCLUSIONS Discontinuing mood stabilizer treatment presents high risks of illness-recurrence among pregnant women diagnosed with BPD. LTG may afford protective effects in pregnancy, and its reported fetal safety compares favorably to other agents used to manage BPD.

Prophylaxis Latency and Outcome in Bipolar Disorders

Objective: To analyze new and reviewed findings to evaluate relations between treatment response and latency from onset of bipolar disorder (BD) to the start of mood-stabilizer prophylaxis. Method: We analyzed our own new data and added findings from research reports identified by computerized searching. Results: We found 11 relevant studies, involving 1485 adult patients diagnosed primarily with BD. Reported latency to prophylaxis averaged 9.6 years (SD 1.3), and follow-up in treatment averaged 5.4 years (SD 3.1). Greater illness intensity and shorter treatment latency were closely associated, resulting in a greater apparent reduction in morbidity with earlier treatment. However, this finding was not sustained after correction for pretreatment morbidity, and treatment latency did not predict morbidity during treatment. Therefore, assessments based on improvement with treatment, or without correction for pretreatment morbidity, can be misleading. Conclusions: Available evidence does not support the proposal that delayed prophylaxis may limit response to prophylactic treatment in BD and related disorders.

Increased Estradiol and Improved Sleep, But Not Hot Flashes, Predict Enhanced Mood during the Menopausal Transition

BACKGROUND The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression. METHODS Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17β-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Åsberg Depression Rating Scale (MADRS)] using multivariate linear regression. RESULTS Seventy-two peri/postmenopausal women with depression disorders were randomized to 17β-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 ± 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women. CONCLUSIONS For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression.

Bupropion SR for the treatment of postpartum depression: a pilot study.

Despite the prevalence of postpartum depression, few studies have assessed the efficacy of antidepressants for the treatment of this disorder. Failure to treat postpartum depression (PPD) places the woman at risk for chronic depression and may have adverse effects on child wellbeing and development. Eight female outpatients aged 18-45 yr were enrolled in an 8-wk open-label trial of bupropion SR for PPD. All patients met DSM-IV criteria for major depression with onset within 3 months of delivery and scored 17 or greater on the Hamilton Depression Rating Scale (HAMD) at baseline. Those with onset of depressive symptoms during pregnancy, psychotic symptoms, or significant medical illness were excluded. Median scores on the HAMD declined from 20.5 (range 15-38) at baseline to 10.0 (range 1-20) at end-point (p<0.05, Wilcoxon signed-ranks test; LOCF). Six out of the eight subjects demonstrated a > or =50% decrease in HAMD scores from baseline; three subjects achieved remission (HAMD score of < or =7) at week 8. Median final dosage of bupropion SR was 262.5 (range 37.5-300). Bupropion SR was well tolerated, and no subjects discontinued treatment as a result of medication side-effects. Bupropion SR represents an effective and well-tolerated antidepressant for the treatment of PPD.