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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention 6 Treatment of Depression in Parents SUMMARY Treatment Rates Studies of community samples indicate that approximately 30 percent of depressed adults receive any treatment for their illness. Although limited, evidence suggests that treatment rates for mothers may be even lower than the general population. Treatment Tools Evidence shows that a variety of safe and effective tools exist for treating adults with depression, including pharmacotherapies, psychotherapies, behavioral therapies, and alternative medicines. Studies of depression treatment tools in adults rarely measure outcomes that specifically affect parents, including parenting quality and impact of therapeutic treatments on children. Quality studies documenting the safety and efficacy of therapeutic treatments for perinatal depression are limited as well, although preliminary evidence and observational data are generally favorable. Treatment Delivery Approaches A variety of approaches exist to deliver depression treatment in multiple settings, including primary and specialty care, web- and
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention community-based. Evidence from primary care settings suggests that models of care that integrate multiple interventions (e.g., education, care management, frequent telephone follow-up) are clinically effective in reducing depressive symptoms in adults. Existing studies are relatively short term, however, and the cost-effectiveness and exportability of these models are not usually considered. Studies of approaches to effectively deliver treatment and to prevent relapse in adults with depression rarely target parents, especially in settings in which traditionally underserved populations of parents or their children are seen. Treatments that address individual patient preferences, concurrent conditions (such as medical comorbidities and substance abuse), overcoming depression-related stigma and mistrust, and health disparities tend to be better received and more effective than approaches that rely on health provider experience alone. Depression is a common and recurrent disorder that can have profound effects on medical, social, and financial well-being, and a large body of literature documents safe and effective therapeutic strategies. In this chapter, we have divided these strategies into treatments (i.e., tools) and interventions (i.e., approaches). Standard treatments for depression include pharmacotherapy, psychotherapy and alternative remedies. Successful interventions have generally been more structured and comprehensive, often featuring multidisciplinary approaches that emphasize several treatment modalities (e.g., collaborative care). Although the evidence base is rich for depression treatments and interventions in the general adult population, far fewer studies have analyzed outcomes in parents or families. For this reason, we have chosen to proceed in this chapter with a brief summary of treatment rates, therapeutic options, and interventions in the general adult population before focusing more intently on the body of literature specific to parents. Chapter 7 addresses the approaches to prevent adverse outcomes in depressed parents and the children of depressed parents, including the impact of treatment on families. The committee reviewed the relevant literature in order to identify depression treatment rates, therapeutic options that are available to treat depression, and options for the delivery of depression treatment in the general adult population that address outcomes for depressed adults and then specifically in parents, as well as to identify areas in which relatively little research has been conducted. The committee did not seek to systematically
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention identify every study on the evaluation of existing therapeutic tools or delivery interventions for treating depression in adults (and parents); instead, whenever possible, the committee drew on existing meta-analyses and systematic reviews. Whenever possible, the committee limited its review to interventions that have been evaluated in at least one randomized trial and presents a summary of the methodological details, study population demographics, and outcome measures (i.e., depressive symptoms or depression diagnosis) that were used for studies of treatment delivery interventions in a table that is described in the second part of this chapter. TREATMENT RATES General Population More recent nationally representative work has illustrated that those in racial or ethnic minority populations with past-year depressive order are significantly more likely to go without mental health treatment than non-Hispanic whites (64 percent Hispanics, 69 percent Asians, 60 percent of African Americans, compared to 40 percent of non-Hispanic whites) Alegría et al., 2008). Disparities in the likelihood of both having access to and receiving adequate care for depression were significantly different for Asians and African Americans in contrast to non-Hispanic whites. Simply relying on present health care systems without consideration of the unique barriers to quality care that ethnic and racial minority populations face is unlikely to affect the pattern of disparities observed. Populations reluctant to visit a clinic for depression care may have correctly anticipated the limited quality of usual care. The close association of depression with certain medical conditions (e.g., neurological, cardiovascular, and endocrine disorders) has inspired researchers to explore the feasibility of addressing this mental illness in specialty medical clinics. For example, recent investigations document higher treatment rates and superior outcomes among depressed patients identified at diabetes clinics (Simon et al., 2007). Mothers with Depression At the present time, there are no epidemiological data documenting treatment rates among depressed parents, although indirect evidence suggests that these figures are even lower than in the general population. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial (a large national trial designed to identify depression treatment strategies), for example, only 22 percent of women seeking treatment had children living
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention with them, implying that depressed mothers were underrepresented in this sample, perhaps owing to the perception of stigma or domestic responsibilities discouraging travel (Pilowsky et al., 2006). It is also documented that depressed people in the general population are at higher risk of having complex comorbid illnesses, including substance abuse and domestic violence (Regier et al., 1990). Exposure to interpersonal violence, for example, has been associated with poorer outcomes in mothers with substance use and mental health disorders (Amaro et al., 2005). Mothers with Antepartum Depression Treatment rates for pregnant women are believed to be considerably lower than the rest of the adult population, despite the fact that the risks of untreated antepartum depression usually outweigh any risks posed by psychotherapy or commonly prescribed antidepressants (see the discussion of the safety and efficacy of pharmacotherapy below). For example, Marcus et al. conducted a prospective study examining the incidence of antepartum depression in obstetric settings (Marcus et al., 2003). They reported that 20 percent of the women met a conventional threshold for significant depressive illness (they scored higher than 16 on the Center for Epidemiologic Studies Depression Scale, CESD), yet only 14 percent of these women ultimately received any treatment. Another study screened pregnant women and proceeded to conduct structured interviews to confirm the diagnosis and severity (Flynn, Blow, and Marcus, 2006). Among the pregnant women with a confirmed diagnosis of acute major depression, only 33 percent received any treatment. Another investigation was conducted using a large patient database in Canada (119,547 mothers; Oberlander et al., 2006). Approximately 15 percent of the population received a diagnostic code for depression within 4 months of delivery, yet less than 10 percent of this subset received a prescription for an antidepressant. Mothers with Postpartum Depression Data for the frequency of depression treatment during the postpartum period are scarce. One of the few investigations examined a secondary analysis of a mother-infant study that followed 117 mothers who were identified as depressed between 2 and 4 weeks postpartum. Three months after screening, only 14 women (12 percent) had received psychotherapy, and only 4 (3.4 percent) had received pharmacotherapy (Horowitz and Cousins, 2006). Even when depression is addressed, the initiation of medication or counseling does not guarantee success. Insurance data claims and health maintenance organization (HMO) refill records suggest that approximately
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention half of patients will stop their antidepressants during the first 3 months, and a vast majority do not complete the minimum recommended duration of 6 months. These figures are slightly higher among privately insured beneficiaries and somewhat lower in the public sector (National Committee on Quality Assurance, 2005). Data describing the percentage of parents who receive adequate treatment are not currently available. There is a growing awareness of the undertreatment of depression, including government efforts to improve medication adherence and treatment follow-up through such measures as Healthcare Effectiveness Data and Information Set (HEDIS), a tool created by the National Committee for Quality Assurance, to collect data about the quality of care, including depression care, provided by health plans. However, data from health care organizations do not indicate that significant improvement has transpired during the past decade (National Committee on Quality Assurance, 2008). Although depression treatment rates are low, there remains available a variety of safe and effective therapeutic interventions. PHARMACOTHERAPY General Population Antidepressants are among the most commonly prescribed medications in health care today. Much of this popularity can be traced to the development of newer medications such as selective serotonin reuptake inhibitors (SSRI: fluoxetine, sertraline, paroxetine, citalopram), serotonin norepinephrine reuptake inhibitors (SNRI: venlafaxine, duloxetine), and norepinephrine reuptake inhibitors (NRI: bupropion), which are perceived to be safer than older antidepressants (Barbui et al., 2007). The enhanced utility of newer antidepressants may also add to their popularity as serotonergic agents (SSRI and SNRI) as they have proven to be very effective for anxiety disorders. For the treatment of major depression, it is widely believed that roughly two-thirds of patients will respond to the first antidepressant that is initiated (Fava and Davidson, 1996). Data to support these response rates, however, have been gathered historically from randomized controlled trials conducted by pharmaceutical companies to demonstrate drug efficacy for regulatory bodies. Depressed subjects enrolled in such trials were usually young men with minimal medical and psychiatric comorbidity and do not necessarily represent the demographic characteristics of depressed parents. In the STAR*D trial, which attempted to examine antidepressant effects in a real-world setting, fewer than half of the subjects exhibited a clinical response after a full therapeutic trial of an SSRI (Trivedi et al., 2006). Another notable development in research and clinical antidepressant
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention trials has been a change in what is considered the ideal therapeutic endpoint. While a therapeutic response was the historic goal—defined as a greater than 50 percent decline on a given depression severity scale—experts have realized that patients who satisfied this criterion often had significant residual symptoms and fairly high relapse rates. Remission is now regarded as the desired therapeutic endpoint. In practical terms, remission is achieved when virtually all depressive symptoms are absent. Operationally, remission is usually defined as a depression severity score below an established threshold (e.g., a score of less than 7 on the Hamilton Depression Rating Scale). From recent research trials, the remission rates for antidepressants range from 30 to 40 percent (Thase, Entsuah, and Rudolph, 2001). Higher remission rates may be achieved through the addition of other antidepressant medications (i.e., augmentation) or concurrent psychotherapy (Keller et al., 2000). Mothers with Antepartum Depression The safety and efficacy of antidepressants during the antepartum period are a major concern from maternal, scientific, and health policy perspectives. Mothers, fathers, and health care providers must weigh the substantial risks of untreated antepartum depression against the potential risks of antidepressant exposure. When faced with this dilemma, many women have historically discontinued medications as soon as their pregnancy was confirmed, although a naturalistic investigation recently reported that women who stopped their antidepressants during the first trimester were much more likely to relapse before delivery than those who continued (68 versus 26 percent) (Cohen et al., 2006). And over half of these relapses actually occurred during the first trimester. Prospective randomized studies of medications are rarely conducted on pregnant women in part because of ethical concerns. As a result, we have only retrospective or naturalistic data to consider when evaluating the efficacy and safety of antidepressants in the antepartum period. Since the effectiveness of antidepressants can be accurately assessed only through blinded, controlled trials, the literature summarizing the efficacy of antidepressants during pregnancy is nonexistent. The relative safety, however, can be inferred from a body of evidence that has grown remarkably in recent years. As the SSRIs are currently the most popular class of antidepressants, most of the recent investigations have examined their relative safety. For the most part, it appears that SSRIs do not carry a significant risk for major congenital malformations. The only potential exception can be found in data suggesting that paroxetine may be associated with cardiovascular defects. A recent analysis of the Swedish Medical Birth Registry confirmed
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention previous reports of this risk, citing an odds ratio of 1.81 (95 percent confidence interval, CI = 0.96–3.09) for ventricular and atrial defects (Kallen and Olausson, 2007). This finding was based on 13 cases among 959 exposures. A subsequent analysis of data pertaining to over 3,000 exposures was performed by the Motherisk Program in Canada, which found that paroxetine was associated with a decreased risk of malformations (0.7 percent versus an established population risk of 1.0 percent) (Einarson et al., 2008). On the basis of previous reports, however, the U.S. Food and Drug Administration (FDA) chose to demote paroxetine to Category D1 status in pregnancy, discouraging its use unless absolutely necessary. Other adverse outcomes associated with SSRI in pregnancy are worth considering, including persistent pulmonary hypertension, preterm labor, and neonatal adaptation syndrome. Persistent pulmonary hypertension (PPHN) is a relatively rare complication occurring shortly after delivery that has been associated with a 20 percent mortality rate (Hageman, Adams, and Gardner, 1984). Results of a case-control study identified 14 cases of SSRI-induced PPHN in the case group (n = 377) and 6 cases of PPHN among controls (n = 836) (Chambers et al., 2006). The risk appeared to be highest with exposure after 20 weeks gestation. While the SSRIs were associated with a sixfold increase in the relative risk of this serious phenomenon, it should also be remembered that the absolute risk remains quite low (6–12 cases per 1,000 exposures) and is probably not as serious as the risks posed by untreated depression on the mother and the infant alike. Several studies have noted that SSRIs are associated with a decrease in gestational age, birth weight, or both. Although depression itself has been associated with these two effects, comparisons between SSRIs and other antidepressants and between SSRIs and matched controls appear to confirm these findings. For example, Suri et al. followed the outcomes of three different cohorts (antidepressants, depressed without antidepressants, nondepressed controls; n = 90) and reported significant differences in gestational age (38.5, 39.4, and 39.7 weeks, respectively), rates of preterm birth (14, 0, and 5 percent, respectively) and special care nursery admissions (21, 9, and 0 percent, respectively) (Suri et al., 2007). Results of this investigation were confirmed in the large retrospective study by Oberlander cited above. In comparison to depressed mothers not receiving pharmacotherapy, mothers who were prescribed SSRIs were much more likely to give birth before 37 weeks gestation (6 percent versus 9 percent; 95 percent CI = –0.009 to –0.04), and their infants were more likely to suffer respiratory distress 1 For detailed description of U.S. Food and Drug Administration risk categories for drug use in pregnancy, see http://www.fda.gov/fdac/features/2001/301_preg.html#categories. Categories depend on the type of studies available and the risk of fetal abnormalities and include: A, B, C, D, and X.
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention (8 percent versus 14 percent; 95 percent CI = 0.042–0.079). These significant differences were upheld after propensity score matching as well. Neonatal adaptation syndrome is a constellation of symptoms that have been attributed to third-trimester exposure of the fetus to concurrent SSRI or SNRI use. Symptoms include high-pitched crying, decreased appetite, tremor, hypertonicity, and respiratory distress. A prospective study used a scale created by Finnegan (1990) to measure these symptoms and concluded that the SSRIs were much more likely to be associated with this syndrome (Levinson-Castiel et al., 2006). In general, the symptoms peaked by day 2 after delivery and had remitted by the end of day 4. As neonatal adaptation syndrome has been implicated in a potential increase in the risk of admissions, some experts have recommended tapering mothers off anti-depressants prior to delivery (U.S. Food and Drug Administration, 2004). This practice is somewhat controversial; however, opponents have pointed out that drug discontinuation would itself be associated with an increased risk for withdrawal symptoms in the mother, as well as an increased risk of relapse during the immediate postpartum period. Adverse effects of SSRI antidepressants are a major concern in the parent and should be factored into the decision-making process as well. For instance, SSRIs have been associated with a 30–50 percent incidence of sexual dysfunction, which can impart considerable strain on a relationship regardless of the parent’s reproductive status. Nausea is also common with SSRIs, which may diminish the mother’s appetite, and sleep disturbances are frequently reported as well. Data documenting the safety of other antidepressants in pregnancy is relatively limited. Bupropion was once considered the safest of the available antidepressants in pregnancy, but the FDA recently demoted it from Category B to Category C. This was based on a review of reproduction studies in rabbits, which found a slight increase in fetal malformations and skeletal variations with relatively low-dose exposure. Mirtazapine and venlafaxine have not been associated with major fetal malformations. As duloxetine was approved for use only recently, data regarding its safety in pregnancy are inconclusive. One theoretical concern found with duloxetine (as well as venlafaxine and bupropion) involves preeclampsia. As all three antidepressants have been shown to cause a small but significant increase in blood pressure and heart rate in adults, they may also predispose expectant mothers to this complication (Eli Lilly, 2009; GlaxoSmithKline, 2008; Wyeth Pharmaceuticals, 2008). The long-term effects of in utero antidepressant exposure on the developing child have not been rigorously explored. Early studies reporting abnormal psychomotor development lacked sufficient control groups to separate the effects of the antidepressant from depression itself (i.e., the control groups were not depressed) (Mortensen et al., 2003). As untreated
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention antepartum depression has been associated with deficits in IQ, language development, social functioning, and acceptable behavior, well-designed studies with matched controls would be required to distinguish the etiology of any detrimental effects. Two relatively small studies were unable to find an association between SSRI exposure and developmental abnormalities (Misri et al., 2006; Nulman et al., 2002). Another study concluded that externalizing behaviors in children were much more likely to be a reflection of the mother’s current mood than exposure to antidepressants (Oberlander et al., 2007). Mothers with Postpartum Depression Untreated postpartum depression has been associated with serious consequences, most notably impaired mother-infant bonding and long-term effects on emotional behavior and cognitive skills. Although the risks of antidepressant transmission through breast milk are a common concern, it should be remembered that the risks of untreated depression are also readily transmitted to infants. Studies examining the concentrations of antidepressants in breast milk have generally shown that the cumulative exposure of infants to antidepressants through lactation is low and the behavioral risks are minimal (Gentile, 2005). Until recently, the methodology employed in these investigations was quite diverse (or unknown), precluding any meaningful comparisons about the relative risk of various agents. In 2005, however, two comparative studies were published, both of which appeared to confirm that infant exposure was considerably lower than maternal exposure. In one study, the investigators compared the ratio of breast milk concentrations to maternal plasma concentrations among seven antidepressants, reporting values ranging from 0.021 (sertraline) to 0.33 (desipramine) (Whitby and Smith, 2005). In the other investigation, authors estimated the relative infant dose via breast milk for five antidepressants, with values ranging from 0.5 percent (sertraline) to 8.9 percent (fluoxetine) (Gentile, 2005), all of which were safely below the 10 percent threshold advocated by the American Academy of Pediatrics (Figure 6-1). Prospective studies of adverse effects in infants receiving antidepressants through breast milk have not been numerous but generally support the relative safety of this exposure (Burt et al., 2001; Eberhard-Gran, Eskild, and Opjordsmoen, 2006). A total of eight studies have been published, examining the impact of antidepressants on the treatment or prevention of postpartum depression. Only three of these investigations featured a randomized, double-blind design, but all reported positive findings. Appleby found that both fluoxetine and cognitive-behavioral therapy were significantly more effective than
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention FIGURE 6-1 The safety of newer antidepressants in pregnancy and breastfeeding. SOURCE: Adapted, with permission from data in Table II and Table III from Gentile (2005). Copyright (2005) by Wolters Kluwer. placebo and that the combined treatment did not confer any additional benefits (Appleby et al., 1997). Similarly, Misri et al. (2004) found that paroxetine was associated with a highly significant treatment effect and that the combination of paroxetine plus cognitive-behavioral therapy was equally efficacious (versus monotherapy). In the only head-to-head comparison of antidepressants, 95 women with postpartum depression were randomized to sertraline or nortriptyline (Wisner et al., 2006). Both medications improved psychosocial function, the only difference being an earlier separation of sertraline from baseline among responders (versus nortriptyline). Three small open-label trials with fluvoxamine, venlafaxine, and bupropion provide additional evidence for the effectiveness of antidepressants in relieving postpartum symptoms. The data supporting the prevention of relapse of depression in women postpartum is limited. Two small randomized trials on prevention of relapse have also been published (Wisner et al., 2001, 2004). Patients given sertraline were much less likely to relapse than those randomized to placebo among nondepressed women with a history of perinatal depression (a re-
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Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention lapse rate of 1 in 14 with active medication versus 4 in 8 with placebo). A similar investigation failed to find any difference between nortriptyline and placebo (a relapse rate of 6 in 26 versus 6 in 25 with placebo). INTERPERSONAL PSYCHOTHERAPY AND COGNITIVE-BEHAVIORAL THERAPY General Population Multiple studies and meta-analyses provide evidence that cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) are efficacious treatments for general depression (de Mello et al., 2005; Deckersbach, Gershuny, and Otto, 2000; Dobson, 1989). Cognitive-behavioral therapy is based on the idea that the way a person perceives an event determines how they will respond both affectively and behaviorally (Dennis and Hodnett, 2007). CBT helps patients identify and correct self-critical beliefs and distortions in thinking to reduce distress and enhance coping efforts. Interpersonal psychotherapy is a brief, highly structured, manual-based psychotherapy that addresses interpersonal issues in depression, such as role disputes, social isolation, or prolonged grief (Whooley and Simon, 2000). In summary, cognitive-behavioral therapy addresses distorted, negative thinking associated with depression, and interpersonal psychotherapy addresses stressful social and interpersonal relationships associated with the onset of depressive symptoms (Weissman, 2007). Interpersonal psychotherapy is an accepted treatment for depression and has been found to be effective in multiple studies. A recent meta-analysis concluded that it was superior to placebo, similar to medication, and, when combined with medication, did not show an adjunctive effect compared with medication alone for acute treatment, maintenance treatment, or prophylactic treatment (de Mello et al., 2005). Although the meta-analysis found that IPT was more efficacious than CBT, other studies suggest that IPT is comparable to CBT in terms of outcomes. A recent review by Parker stated that IPT is unlikely to be the universal therapy for depression, given the heterogeneity of depressive disorders, but it may be appropriate therapy under specific circumstances (Parker et al., 2006). Cognitive-behavioral therapy is widely used for the treatment of depression. Although earlier studies suggested that its use was less efficacious than medications for patients with severe depression (Elkin et al., 1995), more recent studies have found that CBT is as efficacious as medications for even severely depressed patients (DeRubeis et al., 2005). There is also evidence that the effects of CBT last beyond the end of treatment (Hollon, Stewart, and Strunk, 2006), and studies have shown that patients treated with CBT are less likely to relapse after treatment termination than are
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