© Springer International Publishing AG 2017
Sanjeev Sockalingam and Raed Hawa (eds.)Psychiatric Care in Severe Obesity10.1007/978-3-319-42536-8_99. Mood Disorders and Severe Obesity: A Case Study
(1)
Department of Psychiatry, Department of Molecular Medicine and Development, University of Siena School of Medicine, Viale Bracci, 1, Via XXIV Maggio, 23, Siena, 53100, Italy
(2)
Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, Canada, M5T 2S8
(3)
Department of Psychiatry and Pharmacology, University of Toronto, Toronto, ON, Canada
(4)
Brain and Cognition, Discovery Foundation (BCDF), University of Toronto, Toronto, ON, Canada
Case Vignettes
Lisa is a 28-year-old Caucasian female. She is single, unemployed and lives with her parents. She has been receiving long-term disability due to her severe depression. She is diagnosed with major depressive disorder (MDD) and she visits a mood disorder clinic for a comprehensive second opinion, as requested by her current psychiatrist. There is a history of mental health problems in her family. Lisa’s mother also suffered from MDD and her uncle died by suicide at the age of 33. Furthermore, her sister is diagnosed with generalized anxiety disorder. Lisa was first diagnosed with MDD in her early twenties, during the latter years of her undergraduate studies. She noted long periods of low energy, lack of pleasure in the activities she used to enjoy and inability to go to class and fulfill her course requirements . As a result of these symptoms, she discontinued enrollment at university.
Lisa currently weighs 120 kg, with a BMI of 32 kg/m2. She has been struggling with increased body weight throughout her life, which has been an enduring source of guilt and shame. Notwithstanding, Lisa finds food comforting when she is faced with the various challenges and notes it to temporarily reduce her anxiety. Lisa sleeps 10 hours per night and often finds that she needs to nap during the day. She reports having an insatiable appetite, often eating two dinners—one in the early evening and again before bed, in order to satisfy her hunger.
During her visit to the clinic, Lisa also reports having difficulty concentrating on her day-to-day tasks, such as difficulty focusing on what she is reading and holding conversations with others. She is a heavy smoker, consuming a more than half-a-pack per day for the past 5 years. Lisa also noted that she has sought treatment for her inflammatory bowel disorder.
At the present visit, she denies drug or alcohol misuse. She denies suicidal or homicidal ideation, although she reports that she has had suicidal ideation in the past. She is currently taking 150 mg of venlafaxine XR once daily.
9.1 Introduction
Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD) , have a high prevalence and morbidity. MDD has a 4.33 % overall global point prevalence [1], whereas BD has an estimated lifetime prevalence of 1.5 % [2]. Collectively, mood disorders are common and serious mental illnesses associated with substantial costs to individuals and society. “Burden of illness” studies provide replicated evidence that mood disorders are leading categories of the indicators of high disability-adjusted life years (DALYs) and years lived with disability (YLDs).
In addition to mood disorders, overweight and obesity are also a public health priority. Epidemiological studies have estimated that about 50 % of individuals in the Organization for Economic Co-operation and Development (OECD) countries are currently overweight and 18 % are affected by mild-to-severe obesity [3]. In addition, obesity is linked to numerous metabolic and physical health complications, such as type 2 diabetes, dyslipidemia, increased risk of cardiovascular events, diseases of the musculoskeletal system, and different forms of cancer [4].
As mentioned previously in this book, mood disorders and obesity frequently co-exist [148]. Individuals with MDD have an increased probability of obesity, notably abdominal obesity that is up to 50 % greater than the matched general population [5]. In addition to the extensive overlap of MDD and obesity, the prevalence of obesity is also increased in individuals with BD [6,144]. Conversely, obese patients also have a higher risk of incident depressive and manic symptoms/episodes [7–9]. Individually, both mood disorders and obesity have a high rate of morbidity and the co-occurrence often incurs a more severe and complicated illness presentation [10]. Consequently, comorbid obesity in persons with a mood disorder is not only a proxy of elevated risk of mortality and increased public health costs, but also a primary therapeutic target [11].
Although traditionally mood disorders and obesity have been considered as two separate entities, epidemiological, longitudinal, and clinical studies have shown that the co-occurrence of both conditions do bi-directionally influence each other and alter illness trajectory, presentation, and outcome. Although there may not yet be definitive evidence to support this view, some authors have proposed a “metabolic-mood syndrome, ” highlighting the relationship between these two diseases with features of bi-directionality and convergence [12, 13].
This chapter intends to provide an overview of both mood disorders and obesity, followed by studies examining the presence of obesity in mood disorders and mood disorders in obesity. The subsequent section will examine the emerging paradigm of the “metabolic-mood syndrome ” and the various factors that characterize this relationship between mood and metabolism, including genetic, and environment risk factors. An examination of antidepressants and their impact on obesity will also be provided, specifically examining the serotonin norepinephrine re-uptake inhibitors (SNRIs) and selective serotonin re-uptake inhibitors (SSRIs) . This chapter will conclude by revisiting the case study presented at the beginning of this chapter.
9.2 Mood Disorders
Mood disorders represent a category of illness characterized by pathological changes in mood, both positive (manic and hypomanic) and negative (depressive episodes). These changes in mood are also often accompanied by cognitive deficits, changes in neuro-vegetative function and physical health. A longstanding interest in psychiatry has been to sub-classify different subtypes of mood disorders with an overarching aim of providing prognostication and informing treatment selection. Achieving the foregoing goal, however, is belied by the clinical and patho-etiological heterogeneity of these disorders. Although the DSM-5 [14] has separate chapters for depressive disorders and bipolar disorders, recognition of overlap in both disorders is well established. Each mood disorder may be characterized by varying rates of severity, and specific features of onset (e.g., seasonal, postpartum), course (e.g., remitting, recurrent), and etiology (exogenous, endogenous) [15].
The etiology of mood disorders is polygenic and multifactorial. According to preclinical and clinical studies, data-driven hypothesis indicates that mood disorders are the result of multiple interacting risk factors (genetic, environmental, biological) [16–18, 147]. Given this heterogeneity, it is not surprising that patient response to existing multimodality therapies is variable and unpredictable [19–21].
9.3 Obesity
Overweight and obesity are defined as abnormal or excessive fat accumulation that represents a risk to health. The National Heart, Lung, and Blood Institute (NHLBI) guidelines define overweight as a body mass index (BMI) between 25.0 and 29.9 kg/m2, obesity as a BMI of ≥30 kg/m2, and extreme obesity as a BMI of ≥40 kg/m2. Most people develop obesity from a combination of excessive food intake and a sedentary lifestyle. However, risk factors, such as genetic and environmental factors, are involved in the regulation of body weight, appetite, adiposity, as well as levels of physical activity. As such, there are wide individual differences around the mechanism of weight gain [22–24, 143]. Furthermore, there is also ample evidence to demonstrate that hormonal pathways and insulin resistance are involved in the development of obesity [25, 26] (see Chapter 3).
Overweight and obesity are major risk factors for a number of chronic diseases, including type 2 diabetes, hypertension, dyslipidemia, cardiovascular diseases, and severe cancers. However, there seem to be specific subgroups of obese patients that are lacking these comorbidities, termed “Metabolically Healthy Obese ” (MHO), with a risk of cardiovascular disease similar to healthy subjects [27]. Conversely, individuals with healthy body weight can display obesity-associated illnesses, which have been called “Normal-Weight Obese ” (NWO) [28, 29]. Another interesting phenomenon is the “Obese Paradox, ” where several clinical trials have shown that in patients with type 2 diabetes, kidney failure or heart failure, increased body weight appeared to be a protective factor, decreasing the patients’ rate of mortality when compared with normal-weight subjects [30, 31]. There are divergent opinions about the validity of this paradox [32], but emerging data suggest that body weight is a correlate of metabolic abnormalities with tremendous variation between individuals in their metabolic signature .
9.4 Clinical Studies of Obesity in Mood Disorders
Community studies have been conducted with an aim of exploring the correlation between mood disorders and obesity. Kendler et al. [33] performed a community retrospective study using the data from 1,029 pairs of female twins, assessing depressive symptoms and BMI values. They concluded that a high percentage (28.9 %) of individuals with atypical depressive symptoms also had a higher BMI (>28.6 kg/m2) than individuals with typical or severe depressive symptoms [33]. A prospective community study performed in adolescents investigated the relationship between mood disorders in youth and obesity in early adulthood. Patients were evaluated first in 1983 (adolescence) and again in 1992 (young adulthood). The authors described a correlation between those with a high BMI in adolescence and incident depression in adulthood (p<0.01). Furthermore, there was also a significant correlation between women with obesity in adulthood with an increased prevalence of depression symptoms in youth [34]. In another study, Roberts et al. [35] evaluated 1,886 patients (≥50 years of age) in 1994 (MDD = 7.3 %), with a repeat evaluation in 1999. They reported a 65 % higher rate of obesity when compared to those without depression. Moreover, the presence of depression at index evaluation also predicted obesity at the follow-up visit 5 years later (OR = 1.92; 95 % CI = 1.31–2.80) [35]. Another community study was performed in 591 young adults (292 males, 299 females) between the ages of 18 and 19 years, comparing those with mood disorders to their healthy peers, and then following them until the age of 40 years. At the first assessment, 19 % of the sample was defined as overweight. The results show a significant association between atypical depression and overweight in both men and women (OR = 2.8, 95 % CI = 1.6, 4.8; p<0.01). Specifically, women with a history of childhood depressive symptoms had higher mean BMI (21.9 %; 95 % CI = 0.5, 2.0; p<0.01) and higher average weight gain between the ages of 20 and 40 years than women without childhood depressive symptoms. It was further noted that hypomanic symptoms were associated with weight gain only in men [36].
A cross-sectional study with a sample of 49 patients with mood disorders (29 BD) treated with long-term lithium had a higher rate of severe obesity (12 %) than the general population (5.7 %) [37]. In addition, there are large differences in the reported correlation of obesity and mood disorders as a function of gender. For instance, McElroy et al. [38] assessed a sample of 644 individuals with BD (type I and II) across the United States and Europe and found that 57 % of patients were overweight or obese (31 % overweight, 21 % obese, and5 % severely obese). When compared with the healthy population, this sample showed that BD females have a high rate of obesity or severe obesity (BMI >40 kg/m2). Males with BD instead showed a high rate of overweight and obesity but not an elevated rate of severe obesity [38]. With a large sample (n = 175), Fagiolini et al. [39] demonstrated that, compared with non-obese BD patients, obese BD patients had fewer years of schooling, earlier depressive and manic episodes, higher depressive symptoms at baseline, and required a longer course of treatment during the acute phase to achieve remission. Furthermore, obese patients experienced a relapse (n = 25, 54 %) at a higher rate than non-obese patients and the time-to-relapse was shorter than among patients who were not obese at baseline. Specifically, recurrences of depressive symptoms were significantly greater for obese patients (n = 15, 33 %) than for non-obese patients (n = 11, 14 %) [39]. In an analysis of data from a Canadian community survey (n = 36,984), McIntyre et al. [40] reported that individuals with a lifetime history of a mood disorder were more likely to be obese (19 %) than those without a mood disorder (15 %, p<0.05). The age-adjusted rate of overweight or obesity (BMI ≥25 kg/m2) in persons with BD I was significantly higher than that of the general population (55 % vs. 48 %, p<0.01) [40].
In an analysis of data from 9,125 respondents in the National Comorbidity Survey-Replication (NCS-R) , obesity was significantly associated with a lifetime diagnosis of BD (OR = 1.47; 95 % CI: 1.12–1.93) and this association was greater for BD present in the last 12 months (OR = 1.61; 95 % CI: 1.07–2.43) [41]. Furthermore, evaluating data from 43,093 respondents in the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) revealed that adults with lifetime BD had a significantly greater age-, race-, and sex-adjusted prevalence of obesity compared to control subjects (OR = 1.65, 95 % CI:1.45–1.89; p<0.01) [42]. Conversely, in the same dataset, obesity was associated with any mood disorder, including a manic episode (OR = 1.55; 95 % CI: 1.29–1.86 for obesity and OR = 2.70; 95 % CI: 2.00–3.66 for severe obesity ) [43].
9.5 Clinical Studies of Mood Disorders in Obesity
There are also numerous studies assessing mood disorders in patients with severe obesity. However, most of these studies have reported mood disorders based on informal clinical interview, self-report scales, and/or psychological tests. Only a few studies have used clinician-administered structured diagnostic interviews, such as the Mini International Neuropsychiatric Interview (M.I.N.I.) , to diagnose mood disorders in study participants. Several studies have assessed symptoms of depression, anxiety, distress , or stress among obese patients and individuals seeking treatment for obesity (e.g., ileal bypass, gastric bypass operations, bariatric surgery, and other forms of anti-obesity treatments). A review of 11 studies, with a combined sample of 837 obese patients, found that mood disorders were assessed with DSM criteria (any edition) among ten studies. The review demonstrated that a large percentage (32 %, n = 294) of obese patients met DSM criteria for lifetime mood disorders (MDD, BD I, BD II, dysthymia). Specifically, among studies that used structured clinical interviews to assess syndromal mood disorders, 41 % of patients had a mood disorder in their lifetime, compared with 24 % of patients in studies that did not use structured clinical interviews [44].
Similarly, Black et al. [45] reported a significantly high proportion of MDD (19 % vs. 5 %) and other mood disorders (31 % vs. 9 %) among a sample of 88 obese patients undergoing bariatric surgery, compared to individuals of normal weight. Furthermore, a clinical study performed on a sample of 47 adolescents and young adult patients receiving inpatient treatment for severe obesity (mean BMI = 42.2 kg/m2) found that 19 obese adolescents (43 %) met DSM-IV criteria for mood disorders (14 MDD, 5 BD) compared with 8 (17 %) out of the 47 mild obese patients (mean BMI = 29.8 kg/m2) and 247 (15 %) of 1,608 healthy control subjects [46].
9.6 The Metabolic-Mood Syndrome
Taken together, the overlap of mood disorders and obesity provides the basis for proposing a patho-etiological framework that has both discrete and shared pathophysiological substrates that subserve both phenotypes. Herein, we describe the features of this bidirectional and convergent relationship.
9.6.1 Phenomenology
The presentation and the clinical features of mood disorders are frequently different and more complicated when a patient is obese. Overweight or obese patients tend to present atypical depressive symptoms with greater frequency (e.g., reactive mood, increased appetite, hypersomnia, leaden paralysis) when compared to depressed patients of normal weight. Conversely, depression with melancholic features, depression that is not meeting criteria for any existing DSM5-defined specifier, has a prevalence of association with obesity similar to the general population [5, 47–50]. Although it could be postulated that obesity is a mere consequence of the food intake and lack of physical activity associated with atypical depression, results described above indicate that obesity in itself subsequently increases the risk of developing depressive symptoms as well the risk of suicide and cognitive impairment [51–53].
Furthermore, when obesity co-occurs with depression, it usually has a more chronic course [54]. Similarly, the co-occurrence of obesity with BD is linked to a predominance of depressive symptoms and need for hospitalization, with longer depressive phases when compared to BD patients with normal body weight [42]. Obesity also adversely affects the response to pharmacological treatment of mood disorders. Clinical trials have shown that obese patients with BD have a reduced probability of response to antidepressants and to lithium/valproate, respectively [55–60]. In addition, comorbid mood disorders have a negative impact on both the pharmacological and surgical interventions of obesity [61].
9.6.2 Genetic Factors
Genetic factors are involved in both mood disorders and obesity. Major depressive disorder and BD are illnesses with elevated rates of heritability (30–50 % and 50–70 %, respectively) [62, 63]. The genetics of both mood disorders and obesity are considered polygenic, with alterations being described in a large number of genes [64–66]. Surprisingly, there are specific genes that are involved in both diseases and, in some instances, there is evidence of interactions. For example, the FTO (fat mass and obesity-associated) gene is related to the development of obesity, and a recent study has shown that this correlation is mitigated by the presence of depressive symptoms [67].
9.6.3 Environmental Risk Factors
Obesity and mood disorders have several environmental risk factors (i.e., social determinants of health) in common and the bi-directionality between the two clinical entities is evident. Generally, psychosocial stress is considered to be one of the biggest risk factors for developing a mood disorder and consequential emotional eating behaviors, leading to overweight and obesity [68–70]. Sedentary lifestyle and unhealthy diet can also lead to the development of obesity, but recent results have proffered a possible causative role of mood disorders [71, 72]. However, the most replicated epidemiological factor that precedes a mood disorder is childhood trauma (sexual, emotional, or physical) [73]. Emerging data have underscored the involvement of this risk factor in obesity [74].
9.6.4 Metabolic Systems
Endocrinological and inflammatory mechanisms have been recognized as factors that contribute to the development of both obesity and mood disorders. The hypothalamic–pituitary–adrenal (HPA) axis is involved in the mobilization of energy reserves to restore energy homeostasis through its hormonal action on various regions of the body, including adipose tissue. Obese individuals often have a dysfunctional HPA axis, which can lead to increased food intake and lack of hunger satisfaction. Individuals with mood disorders also have alterations in the HPA axis. In fact, BD patients have an increased secretion of cortisol during euthymic, depressive, and manic periods, and show a reduced response and reactivity to stress. The relationship between mood disorders and inflammatory disorders has been a significant focus of research during the last decade. Several meta-analyses have shown high levels of pro-inflammatory cytokines (e.g. TNF-α, IL-6) in the blood of patients with MDD and BD [75–77]. Excess adipose tissue can lead to inflammatory dysregulation, with the body being in a chronic and persistent low-grade inflammatory state, with select studies noting persistently high levels of C-reactive protein (CRP) in obese patients [78]. Interestingly, Milaneschi et al. [79] found a relationship between leptin, an adipose-derived hormone involved in the regulation of food intake and energy expenditure, and depressive symptoms. In particular, they found that elevated levels of leptin secretion by central adiposity could facilitate the development of depressive mood over a 9-year follow-up period [79].
9.6.5 Brain Substrates
Mood disorders are clinical conditions associated with alterations in brain structures and functions. It has been shown that MDD and BD are subserved by abnormalities in the structure and function of neural circuits that govern reward/emotion regulation and cognitive functions. For example, neuroimaging studies have reported alterations in functional connectivity at different levels of brain networks, such as frontal-occipital, frontal-amygdala, and subcortical regions [80–82]. Recently, it has been suggested that obesity could have pathological brain biomarkers involved in the regulation of motivation and reward (e.g. in fronto-occipital and fronto-amygdala networks) both at resting-state and in response to food and non-food rewarding stimuli, indicating that abnormalities extend beyond appetite regulation [83, 84]. Furthermore, data from neuroimaging studies have shown that a reduction in white matter, often present in MDD, is significantly linked to a higher BMI value [85]. More prominent alterations of temporal, parietal, and occipital structures were also found in patients with depression and higher BMIs [86].
Several studies implicate the monoamine systems (e.g. dopamine and serotonin) in the regulation of reward mechanisms and control of food intake [87–89]. Mood disorders are characterized by dopamine dysfunction —induction of abnormal mood changes by manipulating dopamine and its receptors is well documented in animal and pharmacological studies [90]. In addition, medications targeting the dopamine receptors (e.g. antipsychotics or antidepressants) are effective in dealing with heterogeneous symptoms that characterize mood disorders [91]. Neuroimaging studies have shown an involvement of dopaminergic circuits in patients with MDD and BD [92–94]. Obese subjects, both in preclinical and clinical studies, have a reduced availability of dopamine receptors in direct proportion to their BMI value. In particular, dopamine receptors are highly sensitive to stimuli, such as high-calorie food, but they have poor sensitivity to reward and feelings of hunger satisfaction.An alteration in energy metabolism is also a common factor to mood disorders and obesity. The mitochondria system is the cellular network responsible for energy metabolism. Neuroimaging studies have shown that mitochondrial function is impaired in mood disorders, leading to altered concentrations of creatine, lactate, and n-acetyl-aspartate in the brain [95–99]. Studies in obese patients have demonstrated similar alterations in brain concentrations of these components [100–102]. An important factor involved in regulating energy metabolism is the neurotrophin Brain-Derived Neurotropic Factor (BDNF) . The dysregulation of BDNF plays a significant role in the etiopathogenesis of mood disorders. Multiple studies have illustrated that many antidepressants stimulate an increased production in BDNF that is involved in processes of neuroplasticity, such as dendritic arborization, axonal growth, neuronal differentiation mechanisms, and neurodegeneration functions [103, 104]. Patients with MDD and BD, in all phases, have reduced serum concentrations of BDNF compared to healthy individuals [105, 106]. BDNF is also involved in regulating energy metabolism by modulating neuronal transport of glucose, mitochondrial function, and by regulating the intercellular energy homeostasis [107, 108]. Preclinical studies have shown that a reduction in BDNF in the periphery produces hyperphagia and body weight gain. In contrast, BDNF appears to be inhibited in patients with severe anorexia or those with significant food restriction and enhanced by energy availability [109, 110].
Finally, it is also important to consider the role of the endocannabinoid system (ECS) , as it also seems to be involved in energy metabolism. Rimonabant, a medication with antagonistic action on the endocannabinoid type 1 receptor (CB1), has recently been discontinued as an anti-obesity agent due to the emergence of depressive and anxiety symptoms and suicidal ideation [111, 112]. Several animal studies demonstrated antidepressant-like and anxiolytic-like effects of endocannabinoids [113–115]. Furthermore, clinical studies indicate an endocannabinoid dysregulation in obesity, with altered concentrations of endocannabinoids in serum, saliva, and adipose tissue of obese patients [116–119].
9.7 Antidepressant Medications and Severe Obesity: An Overview
The FDA-approved drugs for the treatment of mood disorders are anticonvulsants, antipsychotics, and antidepressants. Many of these drugs are linked to weight gain, leading to severe obesity and contributing to the development of metabolic diseases by altering metabolic parameters (i.e. lipids, insulin-resistance, glucose). Antipsychotic agents can be classified based on their risk for weight gain and subsequent development of metabolic diseases. Different antipsychotics confer high (clozapine and olanzapine), medium (risperidone and quetiapine) or low (amisulpride, asenapine, aripiprazole, lurasidone, and ziprasidone) risk [120]. The treatment with lithium and valproate is also linked with weight gain/obesity and thus, may also influence metabolic parameters. Lamotrigine appears to have a low risk of inducing weight gain/obesity. In an 18-month, multicenter, placebo-controlled study where patients were treated with lamotrigine for the last 8 weeks of an open-label phase, obese patients with BD I (n = 155) had significant weight loss with lamotrigine when compared with the placebo group [121]. Weight gain associated with anticonvulsants and antipsychotics are discussed in detail in a subsequent chapter (Chap. 22).
The following section provides an overview of two classes of antidepressants used to treat MDD and BD: serotonin norepinephrine re-uptake inhibitors and selective serotonin re-uptake inhibitors as they relate to obesity. Generally, second-generation, atypical antidepressant medications have a neutral or a beneficial role in body weight, inducing weight loss. Herein, we provide evidence from clinical trials that have evaluated the most commonly used antidepressant medications, examining their potency to induce weight changes. Interestingly, most of these clinical trials have samples composed of overweight and obese patients who were affected by Binge Eating Disorder (BED) . At the moment, there are no studies that have evaluated antidepressants among participants who have a co-occurrence of both mood disorders and obesity. However, this type of evaluation is necessary in the future to have a comprehensive view of the relationship between body weight management and antidepressant drugs.
9.7.1 Serotonin Norepinephrine Re-Uptake Inhibitors
9.7.1.1 Venlafaxine
A 4-month retrospective clinical study involving 35 obese patients with BED found that venlafaxine (from 75 to 300 mg/day) is able to induce changes in body weight. The patients had significant reduction in their BMI values (M=2.00 kg/m2; range: −2.75–1.25 kg/m2) and body weight (M= −10.90 kg; range −15.18 to −6.62 kg) [122]. On the contrary, a recent clinical trial, investigating the relationship of long-term antidepressant use with weight gain/obesity, found that a high percentage of patients in treatment with venlafaxine (67 %) experienced a 7 % increase in body weight from baseline [123]. It is likely that the difference in body weight outcomes is correlated with other factors, such as age of onset, environmental risk factors, and gender.
9.7.1.2 Duloxetine
A 12-week open-label study involving 45 patients with a diagnosis of BED and obesity treated with flexible doses of duloxetine (30–90 mg/day) showed a statistically significant reduction in weight [124]. Recently, a 12-week randomized-controlled trial (RCT) by Guerdjikova et al. [125] assessed the efficacy of a flexible dose of duloxetine vs. placebo in 40 patients with a diagnosis of BED according to the DSM–IV–TR criteria and a concurrent comorbid depressive disorder. In their initial longitudinal analysis, duloxetine was found to be superior to the placebo in reducing weight (p = 0.04). However, the endpoint analysis results did not confirm these findings .
9.7.2 Selective Serotonin Re-Uptake Inhibitors
9.7.2.1 Fluvoxamine
Gardiner et al. [126] conducted a 9-week open-label study involving five patients with BED treated with fluvoxamine at 100–200 mg/day and reported significant weight loss and BMI reductions. Hudson et al. [127] found similar results in a study with 85 obese BED patients, who were randomized to receive either placebo or fluvoxamine at 300 mg/day (starting dose 50 mg/day). Results show a statistically significant reduction in BMI (M = −0.167 kg/m2; SD = 0.08). The estimated mean weight loss after 9 weeks of fluvoxamine treatment was 2.7 lbs, compared with 0.3 lbs for placebo (p<0.04). Notwithstanding, both studies have methodological limitations, such as small sample sizes and short treatment durations. However, a longer-term (12-week) double-blind, placebo-controlled trial (n = 20) performed by Pearlstein et al. [128] found no statistical differences in weight change between fluvoxamine at 150 mg/day and a placebo.
9.7.2.2 Sertraline
McElroy et al. [129] conducted a 6-week clinical trial, with 34 patients affected by obesity and BED using sertraline at 50 mg/day. A statistically significant reduction in BMI (M = 0.596 kg/m2; SD = 0.189) was observed at the end of the trial. Similar results were found in a 12-week RCT (n = 20) 5 years later [130]. Patients who received sertraline at 100 mg/day showed a 9 % reduction in body weight after 2 weeks of treatment [130]. In another 24-week study with a sample of 32 obese patients with BED, sertraline was administered in doses ranging from 100 to 200 mg/day [131]. At the 12-week follow-up, a reduction of more than 5 % in body weight was recorded in 64 % of the sample. These intermediate results were confirmed at the conclusion of the study, after 24 weeks .
9.7.2.3 Fluoxetine
In 1996, Greeno and Wing [132] conducted a study on 79 patients with a BMI between 30 and 45 kg/m2, who were assigned to treatment with a placebo or fluoxetine at 60 mg/day. After 6 days of treatment, the subjects receiving fluoxetine showed a significant reduction in their caloric intake from baseline compared to those treated with placebo. Similar results were found by Arnold et al. [133] after a 6-week RCT of 60 patients with BED and obesity comparing fluoxetine at 20–80 mg/day to a placebo. A significant reduction in BMI and weight was reported at the endpoint analysis, but not a reduction in the number of binge eating episodes.
Related posts:
Sleep and Severe Obesity
Motivational Interviewing for Severe Obesity
Psychiatric Suitability Assessment for Bariatric Surgery
Overview of Medical and Surgical Treatment of Severe Obesity
Young Adulthood and Obesity Management: Developmental Issues and Transition of Care
Addictive Disorders in Severe Obesity and After Bariatric Surgery
Full access? Get Clinical Tree
