Advanced Pediatric Psychopharmacology
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 25, Number 5, 2015 ª Mary Ann Liebert, Inc. Pp. 444–447 DOI: 10.1089/cap.2015.29006.bjc
Pharmacotherapeutic Considerations in the Treatment of an Adolescent with Anorexia Nervosa and Obsessive Compulsive Disorder Presenters: Timothy Rice, MD Discussant: Barbara J. Coffey, MD, MS
Chief Complaint and Presenting Problem
V
. was a 17-year-old girl, the third of six children, referred following an inpatient hospitalization for medication management of anorexia nervosa (AN) and obsessive compulsive disorder (OCD). History of Present Illness V. reported onset of anxiety at age 5 or 6 years, characterized by worries about her weight and appearance, school performance and peer interactions, and perfectionistic tendencies. By age 12 V. began to restrict eating. This significantly worsened around age 15, when V. reported eating one or fewer meals a day and engaging in occasional binge eating and purging. Her periods became irregular and she began experiencing significant palpitations when anxious. At age 16, V. was referred to an eating disorder specialty clinic where a trial of cognitive behavioral therapy (CBT) and familybased therapy (FBT) was initiated. This eight-session treatment failed to improve her disordered eating or weight loss. She notably went from 125.8 pounds to 113 pounds during the eight weeks she was in treatment; her periods completely ceased. By the eighth session, at the age of 16, V. was 5¢9† and weighed only 108 pounds, with a body mass index (BMI) of 15.9; V. was subsequently admitted to an inpatient unit specialized in eating disorders and weight restitution. She was hospitalized for 16 weeks. On the 13th week of her hospitalization, following significant weight reconstitution, fluoxetine was initiated, which was titrated each week to a discharge dose of 30 mg daily. On discharge her weight was 149 pounds and BMI 22.0. She was discharged to follow-up in a community clinic associated with an academic medical center to manage treatment adherence and anger difficulties. Anger problems included screaming at her mother during family sessions and having a dismissive attitude towards therapists, which made treatment difficult. Four days after discharge from the inpatient service V. initiated treatment at the community clinic, and reported stuttering and an inability to speak coherently with friends or at school due to her anxiety. She experienced frequent intrusive thoughts, such as ‘‘I’m not smart,’’ and ‘‘I’m not pretty.’’ Additionally, V. was excessively concerned about contamination and cleaned compulsively, washing her hands over 30 times a day. She reported that cleaning, organizing, and her academic work significantly reduced her anx-
iety. She reported fears of saying the wrong things and losing things, and repeating and checking compulsions. V. reported that her fluoxetine had significantly improved her mood. She felt that the medication helped her to ‘‘look people more in the eye,’’ a level of assertiveness that previously made her uncomfortable. However, V. questioned the medication, and reported that she did not feel she deserved to be happy. She reported a ‘‘hyper’’ mood, stating ‘‘I get up in the morning and dance around,’’ and ‘‘I feel more alive.’’ She reported that she was nervous about becoming ‘‘manic.’’ On review of other symptoms, V. denied significant sadness, irritability, loss of interest, suicidal ideation, homicidal ideation, or self-injury; she denied auditory or visual hallucinations. She denied history of alcohol or illicit drug use. She denied purging with diet pills or laxatives. She reported adhering to a 3,000 kCal diet, but admitted to having concerns that she would ‘‘slip back into my disordered ways.’’ Past Psychiatric History V. had had no formal previous psychiatric treatment. Developmental History V. was the product of an uneventful pregnancy with full prenatal care and no maternal use of alcohol, tobacco, or narcotics. Delivery was uncomplicated and birth weight was 8 lbs., 9 oz. Postnatal history was uneventful. V. was described as a ‘‘perfect’’ infant, ‘‘chubby,’’ to have ‘‘loved food,’’ and been without any feeding difficulties. Mother reported that V. met all milestones early. There was notably a significant period of separation from mother at seven months of age when her older sister was diagnosed with leukemia and V. was cared for by her maternal aunt for six months. V. was reported to have not shown any signs of separation anxiety nor oppositional behavior as a toddler. Subsequently, in her schoolage years, V. was reported to become anxious with separation. She was reported to be very attentive to her studies and meticulous. In her late school-age years and early adolescence, V. reportedly became ‘‘whiney,’’ competitive with her sisters for maternal attention, and reportedly felt that her sisters ‘‘took mother away from her’’ during her first year of life. V. developed bursts of anger directed at her family, occurring side-by-side with reports of excellent behavior at school.
Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, New York.
444
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY Educational History V. entered day care at age four years. She was reported to be a socially well-related child, but exhibited significant anxiety. V. entered mainstream kindergarten and attended public schools. She performed well academically and maintained an A average throughout her educational course. She had no behavioral problems at school. Social History V. lived in a two-bedroom apartment in an inner-city neighborhood with her mother, father, older sister, age 19, two younger sisters, ages 15 and 10, and a brother, age 3. Her older brother, age 22, lived nearby. Father had worked full time since V.’s birth at a self-owned company, and mother raised the children. V.’s eldest sister was the first of her family to go to college. Overall, V. reported feeling distant from most of her family members. Mother reported significant competition between sisters. V.’s sisters were noted to often comment on her height or ‘‘how big she was getting’’ when she would eat. Pertinent Family History There was no known family history of psychiatric illness. Perfectionistic traits were reported in all of V.’s sisters. Medical History V. had no history of major medical problems, hearing, or visual impairments. She had not experienced any serious physical injuries. Her only hospitalization was for weight restoration and psychiatric treatment at age 16. V.’s teeth were eroded, but she had no formal dental history. Age at menarche was 13; she experienced two months of amenorrhea when at her lowest weight at age 16. At the time of her intake to the outpatient clinic she had resumed regular menstruation. There were no known abnormalities to her growth and development. She had no allergies. Medication History V.’s first trial of psychotropic medication took place during her inpatient hospitalization at age 17. She was discharged on fluoxetine 30 mg daily. Laboratory Results V.’s Children’s Yale Brown Obsessive Compulsive Scale (CYBOCS) score was 33, signifying extreme severity of obsessive compulsive disorder (OCD) symptomatology. At intake to the outpatient clinic, laboratory values, including a complete blood count with differential, chemistry screen, thyroid stimulating hormone, hepatic function panel, and lipid panel, were within normal limits. Mental Status Exam At the beginning of treatment, V. appeared to be an anxious 17year-old girl, requesting the door be left open and shaking her leg violently. V. wore large, bulky clothing that hid her frame, and maintained poor eye contact. She engaged in compulsions throughout much of the interview, including using the portable hand sanitizer she carried. Speech was well-developed at an appropriate volume and rate. Vocabulary and semantics were advanced, sentence structure was complex, and speech was spontaneous and productive.
445 V. was tense, with restricted anxious affect, but became more comfortable and pleasant throughout the interview. There was no evidence of thought disorder, suicidal, or homicidal ideation. Although she could recognize that her obsessions were ‘‘stupid,’’ she remained fearful and avoided direct discussion of her OCD symptoms. Her insight and judgment were fair. Treatment Course Following her intake at the community clinic, V. expressed a desire to stop her medication. When an increased dose was recommended for her OCD symptoms she politely disagreed, and subsequently became angry; with an attacking posture, she defiantly taunted, ‘‘you can’t make me it take, I will stop it.I will weigh nothing, and I will die.’’ Her food intake had dropped to no more than 200 kCal a day, including black coffee in the morning, a hard-boiled egg and more black coffee at lunch, and tidbits of dry toast in the evening. V. was told that she could not be forced to take medication, but agreed to speak with her nutritionist and pediatrician to understand the factors that influenced her wish to refuse the medication. As a result, V. decided to continue to take medication; her dose was raised to 40 mg and she agreed to a titration up to 80 mg, increased each week by 10 mg. She acknowledged that it reduced her anxiety, intrusive thoughts, and panic-like attacks when she felt she would otherwise go into a rage. After five months of treatment with fluoxetine 80 mg daily, V.’s weight loss had stabilized to a final weight of 137 pounds and a BMI of 20.2, which remained stable for over two months. She had no medical symptoms related to malnutrition, and endorsed far less academic and social impairment. She agreed to continue treatment, and retained medication adherence. Brief Formulation In summary, V. was a 17-year-old adolescent girl referred for psychotherapy and medication treatment of anorexia nervosa following failed outpatient family based therapy, ultimately necessitating hospitalization for weight restitution and introduction of a selective serotonin reuptake inhibitor (SSRI). V.’s childhood development was characterized by early-onset social anxiety and OCD. From a biological perspective, V. may have been vulnerable to anorexia nervosa (AN) and OCD, as her family history was notable for significant perfectionistic traits. V.’s history of purging and severe malnourishment placed her at risk for medical complications, such as cardiac dysfunction, which she developed at her lowest weight. Dental enamel erosion and amenorrhea, often observed in adolescents with AN, had also occurred. From a psychosocial perspective, psychological and developmental factors played a strong role, as is often the case in AN. Given early-onset history of anxiety, V.’s OCD symptoms were significantly exacerbated at the onset of adolescence. Her shift from ordering and cleaning compulsions to food restriction undoubtedly had underlying developmental foundations, as teenage girls at this stage often become more focused on their appearance and body image. Additionally, a major task of emotional development in early adolescence is a move toward separation-individuation, which may have been particularly frightening for V. as she had long struggled with anger toward her mother and more recently, her therapists. The early period of separation between mother and V. at the time of the older sibling’s diagnosis with
446
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY
leukemia may have rendered V. more vulnerable to anxiety and affective dysregulation. Modulation and management of angry affect also had negatively impacted her family based and individual previous treatment, which made her current treatment more challenging. Multi-Axial Diagnoses Axis I: Axis II: Axis III: Axis IV: Axis V:
Anorexia nervosa Obsessive compulsive disorder Social phobia None Amenorrhea related to malnourishment, past Level of psychosocial stress: Moderate, social isolation Global Assessment of Functioning score: 50
Discussion This illustration of V.’s symptoms and clinical course represents a common but challenging dilemma in the treatment of AN. In adolescents with AN, social phobia, OCD, and other anxiety disorders are frequently present prior to onset of eating disorder symptoms. Of the many associations between anxiety disorders and AN, only OCD is a significant predictor of later-onset AN (Buckner et al. 2010). About one in five adolescent women with AN meet criteria for overt OCD (Salbach-Andrae et al. 2008); genetic linkage (Mas et al. 2013) and family studies (Bienvenu et al. 2012) suggest a common genetic background between the two disorders. One conceptualization of this phenotype is an underlying inherited deficit in habit formation processes, with specific developmental courses for each set of symptoms. As such the psychopharmacologist must be attentive to the presence of comorbid OCD in adolescents with AN in order to optimize treatment. An additional transdiagnostic concept underlying AN and OCD is compulsivity (Godier & Park 2014), which has a defined anatomic correlate within the cortico-striatal circuitry. In this circuit, initially rewarding weight loss behavior in AN may become compulsive over time through excessive habit formation. The reward system is very important in AN (O’Hara et al. 2015), knowledge of which may inform treatment (Park et al. 2014). Given these neurobiological considerations, what is the appropriate role for a serotonergic agent in the treatment of anorexia with comorbid OCD? A recent naturalistic study of inpatient treatment of individuals with comorbid anorexia and OCD (Simpson et al. 2013) did not specifically address medication management strategies, only noting proportion of patients receiving medication, types of medication used, and changes made (additions and removal) during treatment. Given research on the responsiveness of OCD to SSRIs via action on cortico-striatal-thalamic circuits and the apparent overlap of these circuits in AN, the use of SSRIs may be particularly appropriate. However, to date no clinical trials have defined the riskbenefit ratio of fluoxetine pharmacotherapy in patients with AN, so practice relies still on clinical judgment (Sebaaly et al. 2013). Treatment response may be moderated by weight restoration status, which was a factor in V.’s fluoxetine initiation in week 13 of her 16 week inpatient hospitalization. Clinicians’ ongoing need to rely on clinical judgment highlights the value of V.’s case history, which is replete with difficulties in
treatment adherence. This demonstrates the value of understanding the meaning behind intermittent medication refusals, so as to avoid being trapped in a coercive battle with an ambivalent patient. Patients with AN have been understood to communicate through action patterns rather than words, especially around issues concerning intake. Provision of medication and individual psychotherapy may have helped V. to remain treatment adherent and sustain weight gains. Psychotherapeutic approaches should be informed by CBT, with exposure and response prevention to address OCD. In fact, some of the efficacy of FBT for AN is related to the use of exposures surrounding issues of food and nutrition (Hildebrandt et al. 2012). In this case, however, V. had a suboptimal response to FBT related to frequent non-adherence and anger. V.’s case demonstrates that a multimodal treatment approach, including behavioral techniques and pharmacotherapy, in patients with comorbid AN and OCD may be of high value in generating positive outcome for individuals with these comorbid diagnoses. Acknowledgments We would like to acknowledge and thank Zoey Shaw for her assistance in review and preparation of the manuscript. Disclosures Dr. Rice has no conflicts of interest or financial ties to disclose. Dr. Coffey has received research support from Eli Lily Pharmaceutical, NIMH, NINDS, Tourette Syndrome Association, Otsuka, Shire, Bristol-Myers, Pfizer, and Boehringer Ingelheim. References Bienvenu OJ, Samuels JF, Wuyek LA, Liang KY, Wang Y, Grados MA, Cullen BA, Riddle MA, Greenberg BD, Rasmussen SA, Fyer AJ, Pinto A, Rauch SL, Pauls DL, McCracken JT, Piacentini J, Murphy DL, Knowles JA, Nestadt, G: Is obsessive–compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med 42:1-–13, 2012. Buckner JD, Silgado J, Lewinsohn PM: Delineation of differential temporal relations between specific eating and anxiety disorders. J Psychiat Res 44) 781-–787, 2010. Godier LR, Park RJ: Compulsivity in anorexia nervosa: a transdiagnostic concept. Front Psychol 5:778, 2014. Hildebrandt T, Bacow T, Markella M, Loeb KL: Anxiety in anorexia nervosa and its management using family-based treatment. Eur Eat Disord Rev 20:e1–16, 2012. Mas S, Plana MT, Castro-Fornieles J, Gasso P, Lafuente A, Moreno E, Martinez E, Mila M, Lazaro L: Common genetic background in anorexia nervosa and obsessive compulsive disorder: Preliminary results from an association study. J Psychiatr Res 47:747-–754, 2013. O’Hara CB, Campbell IC, Schmidt U: A reward-centred model of anorexia nervosa: A focussed narrative review of the neurological and psychophysiological literature. Neurosci Biobehav Rev 52: 131–152, 2015. Park RJ, Godier LR, Cowdrey FA: Hungry for reward: How can neuroscience inform the development of treatment for anorexia nervosa? Behav Res Ther 62:47–59, 2014. Salbach-Andrae H, Lenz K, Simmendinger N, Klinkowski N, Lehmkuhl U, Pfeiffer E: Psychiatric comorbidities among female adolescents with anorexia nervosa. Child Psychiatry Hum Dev 39:261–272, 2008.
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY Sebaaly JC, Cox S, Hughes CM, Kennedy ML, Garris SS: Use of fluoxetine in anorexia nervosa before and after weight restoration. Ann Pharmacother 47:1201–1205, 2013. Simpson HB, Wetterneck CT, Cahill SP, Steinglass JE, Franklin ME, Leonard RC, Weltzin TE, Riemann BC: Treatment of obsessivecompulsive disorder complicated by comorbid eating disorders. Cogn Behav Ther 42:64–-76, 2013.
447 Address correspondence to: Barbara J. Coffey, MD, MS Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1230 New York, New York 10029 E-mail: [email protected]
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 25, Number 5, 2015 ª Mary Ann Liebert, Inc. Pp. 444–447 DOI: 10.1089/cap.2015.29006.bjc
Pharmacotherapeutic Considerations in the Treatment of an Adolescent with Anorexia Nervosa and Obsessive Compulsive Disorder Presenters: Timothy Rice, MD Discussant: Barbara J. Coffey, MD, MS
Chief Complaint and Presenting Problem
V
. was a 17-year-old girl, the third of six children, referred following an inpatient hospitalization for medication management of anorexia nervosa (AN) and obsessive compulsive disorder (OCD). History of Present Illness V. reported onset of anxiety at age 5 or 6 years, characterized by worries about her weight and appearance, school performance and peer interactions, and perfectionistic tendencies. By age 12 V. began to restrict eating. This significantly worsened around age 15, when V. reported eating one or fewer meals a day and engaging in occasional binge eating and purging. Her periods became irregular and she began experiencing significant palpitations when anxious. At age 16, V. was referred to an eating disorder specialty clinic where a trial of cognitive behavioral therapy (CBT) and familybased therapy (FBT) was initiated. This eight-session treatment failed to improve her disordered eating or weight loss. She notably went from 125.8 pounds to 113 pounds during the eight weeks she was in treatment; her periods completely ceased. By the eighth session, at the age of 16, V. was 5¢9† and weighed only 108 pounds, with a body mass index (BMI) of 15.9; V. was subsequently admitted to an inpatient unit specialized in eating disorders and weight restitution. She was hospitalized for 16 weeks. On the 13th week of her hospitalization, following significant weight reconstitution, fluoxetine was initiated, which was titrated each week to a discharge dose of 30 mg daily. On discharge her weight was 149 pounds and BMI 22.0. She was discharged to follow-up in a community clinic associated with an academic medical center to manage treatment adherence and anger difficulties. Anger problems included screaming at her mother during family sessions and having a dismissive attitude towards therapists, which made treatment difficult. Four days after discharge from the inpatient service V. initiated treatment at the community clinic, and reported stuttering and an inability to speak coherently with friends or at school due to her anxiety. She experienced frequent intrusive thoughts, such as ‘‘I’m not smart,’’ and ‘‘I’m not pretty.’’ Additionally, V. was excessively concerned about contamination and cleaned compulsively, washing her hands over 30 times a day. She reported that cleaning, organizing, and her academic work significantly reduced her anx-
iety. She reported fears of saying the wrong things and losing things, and repeating and checking compulsions. V. reported that her fluoxetine had significantly improved her mood. She felt that the medication helped her to ‘‘look people more in the eye,’’ a level of assertiveness that previously made her uncomfortable. However, V. questioned the medication, and reported that she did not feel she deserved to be happy. She reported a ‘‘hyper’’ mood, stating ‘‘I get up in the morning and dance around,’’ and ‘‘I feel more alive.’’ She reported that she was nervous about becoming ‘‘manic.’’ On review of other symptoms, V. denied significant sadness, irritability, loss of interest, suicidal ideation, homicidal ideation, or self-injury; she denied auditory or visual hallucinations. She denied history of alcohol or illicit drug use. She denied purging with diet pills or laxatives. She reported adhering to a 3,000 kCal diet, but admitted to having concerns that she would ‘‘slip back into my disordered ways.’’ Past Psychiatric History V. had had no formal previous psychiatric treatment. Developmental History V. was the product of an uneventful pregnancy with full prenatal care and no maternal use of alcohol, tobacco, or narcotics. Delivery was uncomplicated and birth weight was 8 lbs., 9 oz. Postnatal history was uneventful. V. was described as a ‘‘perfect’’ infant, ‘‘chubby,’’ to have ‘‘loved food,’’ and been without any feeding difficulties. Mother reported that V. met all milestones early. There was notably a significant period of separation from mother at seven months of age when her older sister was diagnosed with leukemia and V. was cared for by her maternal aunt for six months. V. was reported to have not shown any signs of separation anxiety nor oppositional behavior as a toddler. Subsequently, in her schoolage years, V. was reported to become anxious with separation. She was reported to be very attentive to her studies and meticulous. In her late school-age years and early adolescence, V. reportedly became ‘‘whiney,’’ competitive with her sisters for maternal attention, and reportedly felt that her sisters ‘‘took mother away from her’’ during her first year of life. V. developed bursts of anger directed at her family, occurring side-by-side with reports of excellent behavior at school.
Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, New York.
444
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY Educational History V. entered day care at age four years. She was reported to be a socially well-related child, but exhibited significant anxiety. V. entered mainstream kindergarten and attended public schools. She performed well academically and maintained an A average throughout her educational course. She had no behavioral problems at school. Social History V. lived in a two-bedroom apartment in an inner-city neighborhood with her mother, father, older sister, age 19, two younger sisters, ages 15 and 10, and a brother, age 3. Her older brother, age 22, lived nearby. Father had worked full time since V.’s birth at a self-owned company, and mother raised the children. V.’s eldest sister was the first of her family to go to college. Overall, V. reported feeling distant from most of her family members. Mother reported significant competition between sisters. V.’s sisters were noted to often comment on her height or ‘‘how big she was getting’’ when she would eat. Pertinent Family History There was no known family history of psychiatric illness. Perfectionistic traits were reported in all of V.’s sisters. Medical History V. had no history of major medical problems, hearing, or visual impairments. She had not experienced any serious physical injuries. Her only hospitalization was for weight restoration and psychiatric treatment at age 16. V.’s teeth were eroded, but she had no formal dental history. Age at menarche was 13; she experienced two months of amenorrhea when at her lowest weight at age 16. At the time of her intake to the outpatient clinic she had resumed regular menstruation. There were no known abnormalities to her growth and development. She had no allergies. Medication History V.’s first trial of psychotropic medication took place during her inpatient hospitalization at age 17. She was discharged on fluoxetine 30 mg daily. Laboratory Results V.’s Children’s Yale Brown Obsessive Compulsive Scale (CYBOCS) score was 33, signifying extreme severity of obsessive compulsive disorder (OCD) symptomatology. At intake to the outpatient clinic, laboratory values, including a complete blood count with differential, chemistry screen, thyroid stimulating hormone, hepatic function panel, and lipid panel, were within normal limits. Mental Status Exam At the beginning of treatment, V. appeared to be an anxious 17year-old girl, requesting the door be left open and shaking her leg violently. V. wore large, bulky clothing that hid her frame, and maintained poor eye contact. She engaged in compulsions throughout much of the interview, including using the portable hand sanitizer she carried. Speech was well-developed at an appropriate volume and rate. Vocabulary and semantics were advanced, sentence structure was complex, and speech was spontaneous and productive.
445 V. was tense, with restricted anxious affect, but became more comfortable and pleasant throughout the interview. There was no evidence of thought disorder, suicidal, or homicidal ideation. Although she could recognize that her obsessions were ‘‘stupid,’’ she remained fearful and avoided direct discussion of her OCD symptoms. Her insight and judgment were fair. Treatment Course Following her intake at the community clinic, V. expressed a desire to stop her medication. When an increased dose was recommended for her OCD symptoms she politely disagreed, and subsequently became angry; with an attacking posture, she defiantly taunted, ‘‘you can’t make me it take, I will stop it.I will weigh nothing, and I will die.’’ Her food intake had dropped to no more than 200 kCal a day, including black coffee in the morning, a hard-boiled egg and more black coffee at lunch, and tidbits of dry toast in the evening. V. was told that she could not be forced to take medication, but agreed to speak with her nutritionist and pediatrician to understand the factors that influenced her wish to refuse the medication. As a result, V. decided to continue to take medication; her dose was raised to 40 mg and she agreed to a titration up to 80 mg, increased each week by 10 mg. She acknowledged that it reduced her anxiety, intrusive thoughts, and panic-like attacks when she felt she would otherwise go into a rage. After five months of treatment with fluoxetine 80 mg daily, V.’s weight loss had stabilized to a final weight of 137 pounds and a BMI of 20.2, which remained stable for over two months. She had no medical symptoms related to malnutrition, and endorsed far less academic and social impairment. She agreed to continue treatment, and retained medication adherence. Brief Formulation In summary, V. was a 17-year-old adolescent girl referred for psychotherapy and medication treatment of anorexia nervosa following failed outpatient family based therapy, ultimately necessitating hospitalization for weight restitution and introduction of a selective serotonin reuptake inhibitor (SSRI). V.’s childhood development was characterized by early-onset social anxiety and OCD. From a biological perspective, V. may have been vulnerable to anorexia nervosa (AN) and OCD, as her family history was notable for significant perfectionistic traits. V.’s history of purging and severe malnourishment placed her at risk for medical complications, such as cardiac dysfunction, which she developed at her lowest weight. Dental enamel erosion and amenorrhea, often observed in adolescents with AN, had also occurred. From a psychosocial perspective, psychological and developmental factors played a strong role, as is often the case in AN. Given early-onset history of anxiety, V.’s OCD symptoms were significantly exacerbated at the onset of adolescence. Her shift from ordering and cleaning compulsions to food restriction undoubtedly had underlying developmental foundations, as teenage girls at this stage often become more focused on their appearance and body image. Additionally, a major task of emotional development in early adolescence is a move toward separation-individuation, which may have been particularly frightening for V. as she had long struggled with anger toward her mother and more recently, her therapists. The early period of separation between mother and V. at the time of the older sibling’s diagnosis with
446
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY
leukemia may have rendered V. more vulnerable to anxiety and affective dysregulation. Modulation and management of angry affect also had negatively impacted her family based and individual previous treatment, which made her current treatment more challenging. Multi-Axial Diagnoses Axis I: Axis II: Axis III: Axis IV: Axis V:
Anorexia nervosa Obsessive compulsive disorder Social phobia None Amenorrhea related to malnourishment, past Level of psychosocial stress: Moderate, social isolation Global Assessment of Functioning score: 50
Discussion This illustration of V.’s symptoms and clinical course represents a common but challenging dilemma in the treatment of AN. In adolescents with AN, social phobia, OCD, and other anxiety disorders are frequently present prior to onset of eating disorder symptoms. Of the many associations between anxiety disorders and AN, only OCD is a significant predictor of later-onset AN (Buckner et al. 2010). About one in five adolescent women with AN meet criteria for overt OCD (Salbach-Andrae et al. 2008); genetic linkage (Mas et al. 2013) and family studies (Bienvenu et al. 2012) suggest a common genetic background between the two disorders. One conceptualization of this phenotype is an underlying inherited deficit in habit formation processes, with specific developmental courses for each set of symptoms. As such the psychopharmacologist must be attentive to the presence of comorbid OCD in adolescents with AN in order to optimize treatment. An additional transdiagnostic concept underlying AN and OCD is compulsivity (Godier & Park 2014), which has a defined anatomic correlate within the cortico-striatal circuitry. In this circuit, initially rewarding weight loss behavior in AN may become compulsive over time through excessive habit formation. The reward system is very important in AN (O’Hara et al. 2015), knowledge of which may inform treatment (Park et al. 2014). Given these neurobiological considerations, what is the appropriate role for a serotonergic agent in the treatment of anorexia with comorbid OCD? A recent naturalistic study of inpatient treatment of individuals with comorbid anorexia and OCD (Simpson et al. 2013) did not specifically address medication management strategies, only noting proportion of patients receiving medication, types of medication used, and changes made (additions and removal) during treatment. Given research on the responsiveness of OCD to SSRIs via action on cortico-striatal-thalamic circuits and the apparent overlap of these circuits in AN, the use of SSRIs may be particularly appropriate. However, to date no clinical trials have defined the riskbenefit ratio of fluoxetine pharmacotherapy in patients with AN, so practice relies still on clinical judgment (Sebaaly et al. 2013). Treatment response may be moderated by weight restoration status, which was a factor in V.’s fluoxetine initiation in week 13 of her 16 week inpatient hospitalization. Clinicians’ ongoing need to rely on clinical judgment highlights the value of V.’s case history, which is replete with difficulties in
treatment adherence. This demonstrates the value of understanding the meaning behind intermittent medication refusals, so as to avoid being trapped in a coercive battle with an ambivalent patient. Patients with AN have been understood to communicate through action patterns rather than words, especially around issues concerning intake. Provision of medication and individual psychotherapy may have helped V. to remain treatment adherent and sustain weight gains. Psychotherapeutic approaches should be informed by CBT, with exposure and response prevention to address OCD. In fact, some of the efficacy of FBT for AN is related to the use of exposures surrounding issues of food and nutrition (Hildebrandt et al. 2012). In this case, however, V. had a suboptimal response to FBT related to frequent non-adherence and anger. V.’s case demonstrates that a multimodal treatment approach, including behavioral techniques and pharmacotherapy, in patients with comorbid AN and OCD may be of high value in generating positive outcome for individuals with these comorbid diagnoses. Acknowledgments We would like to acknowledge and thank Zoey Shaw for her assistance in review and preparation of the manuscript. Disclosures Dr. Rice has no conflicts of interest or financial ties to disclose. Dr. Coffey has received research support from Eli Lily Pharmaceutical, NIMH, NINDS, Tourette Syndrome Association, Otsuka, Shire, Bristol-Myers, Pfizer, and Boehringer Ingelheim. References Bienvenu OJ, Samuels JF, Wuyek LA, Liang KY, Wang Y, Grados MA, Cullen BA, Riddle MA, Greenberg BD, Rasmussen SA, Fyer AJ, Pinto A, Rauch SL, Pauls DL, McCracken JT, Piacentini J, Murphy DL, Knowles JA, Nestadt, G: Is obsessive–compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med 42:1-–13, 2012. Buckner JD, Silgado J, Lewinsohn PM: Delineation of differential temporal relations between specific eating and anxiety disorders. J Psychiat Res 44) 781-–787, 2010. Godier LR, Park RJ: Compulsivity in anorexia nervosa: a transdiagnostic concept. Front Psychol 5:778, 2014. Hildebrandt T, Bacow T, Markella M, Loeb KL: Anxiety in anorexia nervosa and its management using family-based treatment. Eur Eat Disord Rev 20:e1–16, 2012. Mas S, Plana MT, Castro-Fornieles J, Gasso P, Lafuente A, Moreno E, Martinez E, Mila M, Lazaro L: Common genetic background in anorexia nervosa and obsessive compulsive disorder: Preliminary results from an association study. J Psychiatr Res 47:747-–754, 2013. O’Hara CB, Campbell IC, Schmidt U: A reward-centred model of anorexia nervosa: A focussed narrative review of the neurological and psychophysiological literature. Neurosci Biobehav Rev 52: 131–152, 2015. Park RJ, Godier LR, Cowdrey FA: Hungry for reward: How can neuroscience inform the development of treatment for anorexia nervosa? Behav Res Ther 62:47–59, 2014. Salbach-Andrae H, Lenz K, Simmendinger N, Klinkowski N, Lehmkuhl U, Pfeiffer E: Psychiatric comorbidities among female adolescents with anorexia nervosa. Child Psychiatry Hum Dev 39:261–272, 2008.
ADVANCED PEDIATRIC PSYCHOPHARMACOLOGY Sebaaly JC, Cox S, Hughes CM, Kennedy ML, Garris SS: Use of fluoxetine in anorexia nervosa before and after weight restoration. Ann Pharmacother 47:1201–1205, 2013. Simpson HB, Wetterneck CT, Cahill SP, Steinglass JE, Franklin ME, Leonard RC, Weltzin TE, Riemann BC: Treatment of obsessivecompulsive disorder complicated by comorbid eating disorders. Cogn Behav Ther 42:64–-76, 2013.
447 Address correspondence to: Barbara J. Coffey, MD, MS Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1230 New York, New York 10029 E-mail: [email protected]
