Childhood abuse and treatment response in patients with irritable bowel syndrome: a post-hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release.

OBJECTIVE: Although irritable bowel syndrome (IBS) is frequently comorbid with childhood trauma, information on the clinical implications of this comorbidity is limited. We investigated whether a history of abuse was associated with response to treatment in a double blind, randomized, placebo controlled trial of paroxetine controlled release (CR) in IBS. METHODS: Seventy-two IBS subjects were randomized to receive paroxetine CR (dose 12.5-50 mg/day) or placebo for 12 weeks. Subject selection was independent of abuse history. Sixty-one subjects completed the Sexual and Physical Abuse Questionnaire about their childhood abuse history. IBS symptoms were recorded using the Interactive Voice Response System (IVRS). Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS) and Clinical Global Impression (CGI) were also measured. The primary outcome was treatment response defined as > or =25% reduction in composite pain scores (CPS) on the IVRS from randomization to end of treatment. RESULTS: The rate of abuse history was 50.8% (n = 31/61). Baseline demographic clinical characteristics (CPS, BDI, BAI, PSS, CGI scores) were not associated with abuse history. After 12 weeks of treatment, subjects with abuse history showed significantly higher CPS (t = 2.422, P = 0.018) than subjects without a history and less mean change of CPS (t = 3.506, P = 0.001). In a logistic regression analysis, history of abuse did not predict treatment response as measured by > or =25% reduction in CPS (OR = 0.481, CI = 0.164-1.406, P = 0.181), while the drug status (paroxetine CR) was significantly associated with treatment response as defined by a CGI improvement score of 1-2 (OR = 12.121, CI = 2.923-50.271, P = 0.001). Abuse history did not predict CGI-I (Fisher's exact, P = 0.500) improvements during the trial. CONCLUSIONS: History of abuse did not appear to have any significant clinical correlates at baseline and did not predict treatment response. Further studies are needed to confirm whether SSRIs are effective in IBS patients irrespective of their abuse history.

Serum valproate levels in 6 breastfeeding mother-infant pairs.

BACKGROUND: Women with bipolar disorder are at high risk for recurrence of an affective episode in the postpartum period, and treatment with a mood stabilizer may be indicated. Few data are available to inform the risk-benefit decision regarding the use of valproate for women with bipolar disorder who elect to breast-feed. METHOD: Serum valproate levels were obtained from 6 breastfeeding mother-infant pairs. All mothers had a diagnosis of bipolar disorder (Research Diagnostic Criteria) and were taking divalproex sodium as prophylaxis for or treatment of a recurrent affective episode. None of the mothers received valproate during pregnancy. RESULTS: The mothers had serum valproate levels near or within the therapeutic range (39.4 to 79.0 microg/mL). Infant serum levels were low, ranging from 0.7 to 1.5 microg/mL (0.9%-2.3% of maternal serum levels). No adverse clinical effects were observed in the infants. CONCLUSION: Serum valproate levels were low in nurslings of mothers treated with valproate. These data can be used to inform clinical decisions regarding the use of valproate during breastfeeding.

Obsessions and compulsions in women with postpartum depression.

OBJECTIVE: The quantity, content, and intensity of the obsessions and compulsions of women with postpartum onset major depressive disorder were compared with those of women with major depressive disorder with non-postpartum onset. METHOD: Sequential cases of women with postpartum onset major depression (N = 37) and major depression (N = 28) who presented to our Women's Mood Disorders program were included. Psychiatric examination using DSM-IV criteria and the Inventory to Diagnose Depression established the diagnosis of major depression. Obsessive thoughts and compulsions were reported on the Yale-Brown Obsessive Compulsive Scale and reviewed during the psychiatric examination. Comparisons between groups were performed with chi-square statistics, Fisher exact test and its extensions, and Mann-Whitney U test. RESULTS: Although more women with postpartum onset major depression (N = 21, 57%) than major depression (N = 10, 36%) reported obsessional thoughts, the difference between the groups was not significant (p = .13). However, for women who endorsed obsessions, those with postpartum onset had a higher median number (median = 7) than women without postpartum onset (median = 2, p = .00). Most of the difference in frequency of thoughts was owing to more women with postpartum onset major depression having aggressive thoughts (N = 20, 95%) than women with major depression (N = 6, 60%, Fisher exact p = .03). The most frequent content of the aggressive thoughts for women with postpartum onset major depression was causing harm to their newborns or infants. The presence or number of obsessional thoughts or compulsions was not related to severity of the depressive episode. CONCLUSION: Childbearing-aged women commonly experience obsessional thoughts or compulsions in the context of major depressive episodes. Women with postpartum onset major depression experience disturbing aggressive obsessional thoughts more frequently than women with non-postpartum major depression.

Serum fluvoxamine levels in breastfed infants.

BACKGROUND: Between 10% and 15% of new mothers will experience an episode of postpartum depression. Although antidepressants are effective agents for the treatment of postpartum depression, minimal data are available to support their safety in infants of breastfeeding mothers. METHOD: In this article, we present 2 cases of nursing mother-infant pairs in which the mother was treated with fluvoxamine and in which infant serum fluvoxamine levels were obtained. Both mothers began the fluvoxamine treatment postpartum, and serum levels were obtained from mothers and infants after a minimum of 7 days on a stable maternal dose. One level was obtained from the infant in case 1, and 2 levels were obtained from the infant in case 2. RESULTS: Each of the infant serum fluvoxamine levels obtained was too low to quantify (at a limit of detection of 2.5 ng/mL). Neither of the infants experienced adverse events related to the mother's treatment with fluvoxamine. Each of the infants is reportedly healthy 2 to 3 years after the exposure. CONCLUSION: While these results are encouraging, they are limited and cannot be generalized to all cases of infants exposed to fluvoxamine. Additional mother-infant serum fluvoxamine levels and infant behavioral observations will facilitate the risk-benefit decision-making process for women who choose to breast-feed while taking fluvoxamine.

Prevention of recurrent postpartum depression: a randomized clinical trial.

BACKGROUND: Women who have suffered one episode of postpartum-onset major depression (PPMD) comprise a high-risk group for subsequent episodes. We conducted a double-blind, randomized clinical trial to test the efficacy of nortriptyline in the prevention of recurrent PPMD. METHOD: Nondepressed women who had at least one past episode of PPMD (Research Diagnostic Criteria) were recruited during pregnancy. Subjects were randomly assigned to nortriptyline or placebo. Treatment began immediately postpartum. Each subject was assessed for 20 sequential weeks with the Hamilton Rating Scale for Depression and Research Diagnostic Criteria for recurrence of major depression. RESULTS: No difference was found in the rate of recurrence in women treated with nortriptyline compared with those treated with placebo. Of 26 subjects who took nortriptyline preventively, 6 (0.23, 95% exact confidence interval [CI] = 0.09 to 0.44) suffered recurrences. Of 25 subjects who took placebo, 6 (0.24, 95% exact CI = 0.09 to 0.45) suffered recurrence (Fisher exact p = 1.00). CONCLUSION: Nortriptyline did not confer additional preventive efficacy beyond that of placebo. The rate of recurrence of PPMD (one fourth of women) was unacceptably high.

Antigens and surface components associated with virulence of Actinomyces viscosus.

We have isolated a specific cell wall antigen of high molecular weight which appears to be unique to virulent strains of A viscosus and A naeslundii. The antigen is composed of two parts: a polysaccharide moiety containing 6-DOT as the major sugar and determinant of serologic specificity, and a small peptide bearing some resemblance to the peptidoglycan. Other data indicate a positive correlation between the presence of this antigen and an extrachromosomal piece of DNA having most of the properties of a bacterial plasmid. The specific function of the 6-DOT antigen in disease production is not known, but its clear association with virulent strains suggests the possibility of monitoring specific populations of oral actinomycetes.

Relationship of psychiatric illness to childbearing status: a hospital-based epidemiologic study.

Women who presented to a University psychiatric hospital were categorized into those with childbearing-related onset illness (CBROI, n = 168) and compared to those with non-childbearing-related onset illness (NCBROI, n = 1004). Women with CBROI were an average of five years younger. The two groups did not differ in membership across five major psychiatric diagnostic categories. However, women with CBROI were given the specific diagnosis adjustment disorder with depressed mood more frequently. Anxiety disorders were also common in women with CBROI. Most women with CBROI had the onset of illness during the postpartum period compared to during pregnancy or after pregnancy loss.

Symptomatology of affective and psychotic illnesses related to childbearing.

Symptom patterns in women with childbearing-related onset illnesses (CBROI) and nonchildbearing-related onset illnesses (NCBROI) were compared. Women with diagnoses of Affective Disorders and Psychoses (n = 762) were divided into four groups: CBROI with psychosis, CBROI with non-psychotic affective illnesses, NCBROI with psychosis, and NCBROI with non-psychotic affective illness. Principal components analysis of 64 symptoms revealed 9 factors. The most dramatic result was the high score for psychotic women with CBROI on the factor cognitive disorganization/psychosis. Psychotic women with CBROI also reported homicidal ideation more frequently. Symptoms of non-psychotic women with CBROI and NCBROI did not differ.

Effects of childbearing on the natural history of panic disorder with comorbid mood disorder.

This historical prospective study included 22 women with panic disorder. They experienced 45 pregnancies associated with or after their first lifetime episode of panic disorder. Mood disorder predated or was associated with 32 of these pregnancies. The most common effect of pregnancy was No Change in symptoms from baseline during pregnancy and continued No Change postnatally for both panic attacks (n = 22; 49%) and depression (n = 19; 59%). The pattern of panic attack across gestations was consistent for only 5 of 14 multiparae. An interesting observation was that first lifetime onset of panic disorder was common postpartum (n = 4) or post-miscarriage (n = 2). First-onset depression was also common postpartum (n = 4).

Psychiatric episodes in women with young children.

An historical cohort study was performed. Subjects were 118 pregnant women or mothers of children of < 3 years who were assessed at presentation to a psychiatric hospital and 5 years later. The relationship of episode onset to childbearing (during pregnancy or within 3 months of birth) was derived from psychiatric records at presentation and retrospectively determined by interview and life-event charting at follow-up. Determining childbearing status from records yielded an error rate of 30% compared with the status derived from direct interview. A change in diagnosis in the ChildBearing-Related Onset Illness (CBROI) category occurred in 50% of subjects. When Research Diagnostic Criteria were applied retrospectively to the presenting episodes, 95% of women with CBROI had affective disorder diagnoses. Clinicians in our intake setting often missed episodes of mania or hypomania in our subjects' histories.

Effects of postpartum psychiatric illnesses on family planning.

OBJECTIVE: We investigated the relationship between postpartum psychiatric episodes and subsequent family planning. Our hypothesis was that women who had a postpartum illness would plan to have fewer children. METHOD: We conducted a mail survey of members of the self-help group Depression After Delivery (DAD). The membership was asked about changes in family planning after a postpartum illness. Two groups were defined: women who took action to prevent further pregnancies after the illness (CHANGE) and women who did not take action to prevent future pregnancies (NO CHANGE). RESULTS: Among respondents 32 percent changed their family plans after suffering a postpartum illness. Fear of recurrence, effects on the family, treatment costs and severity of the episode manifested by suicide or infanticide attempt, hospitalization, and prescribed medication were reasons given for altering plans. CONCLUSIONS: The postpartum illness dramatically changed some women's reproductive plans. Prevention strategies for these illnesses need to be addressed when women are making decisions about having other children.

PIP: 268 women who had suffered from postpartum psychiatric illness and lived in Pennsylvania completed a questionnaire designed to allow researchers examine how these women's experience of postpartum psychiatric illness affected family plans. These women comprised 40% of those who responded to a mail-in survey. The researchers also aimed to determine what factors influenced change in the number of children desired. They identified two groups: women who claimed that postpartum psychiatric illness did not affect their family planning decisions (NO CHANGE) and those who took action after the postpartum episode to prevent future pregnancies (CHANGE). The CHANGE group comprised 32% of the respondents. In both groups, the leading psychiatric diagnosis by far was depression. Women in the CHANGE group were significantly more likely to be hospitalized for the postpartum episode than those in the NO CHANGE group (28% vs. 14%; p = 0.006). Hospitalized women were more likely to suffer impairment in functioning than non-hospitalized women (p = 0.0001). Women who had received psychopharmacological treatment were less likely to suffer impairment in functioning than those who did not receive this treatment (p = 0.0001). Women in the CHANGE group were more likely to have attempted suicide or infanticide than those in the NO CHANGE group (11% vs. 3%; p = 0.009). They were less likely to be prescribed medication than the NO CHANGE group (27% vs. 54%; p = 0.002), suggesting that the medication may have decreased the intensity of the episode and therefore contributed to the NO CHANGE group's willingness to plan other pregnancies. Other factors influencing changes in family planning decisions were treatment costs (19% for CHANGE vs. 8% for NO CHANGE; p = 0.019), fear of recurrence (79% vs. 68%; p = 0.048), family anguish (58% vs. 37%; p = 0.003), and being worried about the effects on the mother/baby relationship (30% vs. 15%; p = 0.006). 85% of the women did not receive any recommendations from health providers on how to prevent recurrence of subsequent postpartum episodes.

Effects of the postpartum period on nortriptyline pharmacokinetics.

The objective of this research was to investigate sequential serum levels and level/dose ratios of the tricyclic antidepressant nortriptyline (NTP) through the first 17 postpartum weeks. The initial NTP dose was given immediately postpartum to 16 mothers and increased gradually to 70 mg over the first week. A dose of 75 mg was prescribed until adjustment according to serum levels. Serum levels of NTP and its metabolites Z- and E-OH-NTP were determined. At postpartum Week 2, the women developed a mean level/dose (L/D) ratio for NTP of 1.11 (range 0.37 to 3.23), and subsequently experienced an increase in the L/D ratios which continued through Week 6. At Week 8, the NTP L/D ratios declined, and became relatively stable at Week 11 and beyond. For postpartum women treated with NTP, side effect profiles should be carefully followed during the first 6 weeks after delivery as a clinical marker for elevation of serum levels. Since our highest L/D ratios for NTP occurred at Week 6, a serum level is recommended at this time. If the dose needs to be lowered to maintain a nontoxic level, a repeat serum level should be obtained at Week 11, at which time an increase in dose may be required.