Topiramate for Posttraumatic Symptoms in an Obese Adolescent Girl

Abstract

Chief Complaint and Presenting Problem

D. was a 16-year-old adopted adolescent girl admitted to a child and adolescent psychiatry inpatient service for a 2-month history of suicidal ideation (SI) and recurrent running away from home.

History of Present Illness

D. reports that she left home three times (1 month, 2 weeks, and 2 days before her admission) in the month preceding her admission. When she ran away 2 days before admission, she had been taken to an Emergency Department (ED) and then discharged to police custody, as she had refused to return home. Police brought her to a shelter for homeless and runaway youth after deliberation with the Administration for Children's Services (ACS) and her mother. She stayed there overnight, and the next afternoon, she took an ornament and crushed it, with the intention of using a shard to cut herself and commit suicide. Staff at the organization called Emergency Medical Services who brought her to an alternate local ED.

D. reported that she had been depressed for around 2 years. D. had become more emotionally and behaviorally dysregulated in the preceding 2 months in the context of adoptive mother having had three cerebrovascular accidents (CVAs) in the past 6 months; two occurred in the 2 months preceding D.'s admission. D. had difficulty coping with her mother's sudden impairments and seizures after the CVAs. Other stressors included the impact of subsequent frequent arguments with mother, of feeling unloved by her biological and adoptive parents, and of significant academic difficulties.

D. had had three ED visits in the past 2 months; in one visit, she was initiated on escitalopram 5 mg, but she did not take the medication or attend an arranged crisis aftercare visit. On one of these visits, D. was unaccompanied by a parent, and ACS was contacted by ED staff; mother had had COVID-19 exposure-related concerns in the setting of her health condition. In addition, D. had stopped going to school in the past month.

In the ED in the hospital system where she was admitted, she expressed passive suicidal thoughts that she wished she was dead because she felt that no one loved her. She stated that she felt “helpless” and requested hospitalization, saying that she did not want to return to the homeless organization or to her mother's house. She could be reassured with supportive interventions, and she reported that she was easily overwhelmed by thinking of her mother's deteriorating health. The decision was made to admit D. to the child and adolescent inpatient psychiatry unit for safety and stabilization.

Past Psychiatric History

D. had no prior psychiatric diagnoses, suicidal thoughts, episodes of self-injury or violence, or prior hospitalizations. She had never received formal psychotherapy; she had only met with her school's guidance counselor sporadically.

D. and her family reported that she started having increased moodiness when she underwent menarche at age 9. At that time she became increasingly self-conscious about her skin color, weight, and physical development. Her adoptive mother believes that their relationship changed when D. entered junior high school at 14. D. started challenging authority and fighting in school and with her brothers. Mother was called to the school almost weekly. Mother also received a report that D. was leaving school with a male member of the staff; he was reassigned, but her mother was suspicious that he had made further attempts to contact D. At this age, mother noticed that she started telling lies to friends and family to “look better in other people's eyes,” and she began becoming involved with older men. Mother confiscated her phone to prevent her from being in contact with these older men.

Developmental History

Adoptive mother did not know whether D.'s biological mother received prenatal care or used substances during pregnancy. According to adoptive mother, D. was born full term with no pregnancy/delivery complications, to her knowledge. D. met all of her developmental milestones on time.

Educational History

D. attended 10th grade regular education at a local public high school; she currently had low grades and had not attended school for 1 month. She had no past history of repeating grades or learning disorders. Mother denied any history of bullying.

Social History

D. lived with her birth mother, grandmother, and two older half brothers at birth. The family was evicted when D. was 8 months old, whereupon mother and the three children moved to a family shelter. Birth mother abandoned the children, and in the week until staff realized that the children were unattended, D. was cared for by her older half brother.

D. was placed in foster care at age 9 months along with her two older half brothers. D.'s foster mother formally adopted them when D. was 8 years old.

Adoptive parents work in education and business. D. was the youngest of eight children in the adoptive family, which included her two half brothers and a mix of adopted and biological children of her adoptive mother. Adoptive mother reported an indulgent upbringing, as D. was the “baby of the family,” with many extracurricular activities, vacations, and a luxuriously designed bedroom. D. was involved in a religious community and enjoyed praying for congregants and helping seniors. D. denied substance use or sexual activity.

Adoptive mother tried to keep D.'s birth parents in D.'s life, but she had had very sporadic and erratic contact with her biological parents. Birth mother reportedly speaks to D. for a few minutes at a time, and ends phone calls by telling D. that she does not have more time. Birth mother also had had a baby 2 years ago that she was currently raising. Adoptive mother reports that this triggered insecurity in D. and questions as to why she was not kept by her birth mother. Birth father had reportedly promised many times to keep in contact, visit, and buy her things, but these promises had always been broken.

Family History

There is no history of self-harm or suicide in her biological or adoptive families. However, both birth mother and father had a history of mood disorders. Birth father also had a history of alcohol and cannabis use, attention-deficit/hyperactivity disorder, and multiple psychiatric hospitalizations. Birth father also reported a possible manic episode as a teenager with lack of sleep and racing thoughts, for which he was treated with fluoxetine and chlorpromazine.

Medical History

D. had a history of mild intermittent asthma. Otherwise, she had normal growth and development in the time that she was with adoptive mother; prior information was unknown. Menarche occurred early at age 9. Weight is consistent with the 99th percentile for girls of her age.

Medication History

D. had been prescribed escitalopram 5 mg for 2 weeks, but had been nonadherent. She took fluticasone 1 puff every morning for asthma.

Mental Status Examination

On initial examination, D. was a well-groomed adolescent girl appearing her stated age. She was co-operative and engaged in the interview with good eye contact and a child-like demeanor. There was moderate psychomotor agitation associated with affect-laden thought content. Speech was spontaneous and full with normal volume, rate, tone, and prosody. No psychomotor retardation was noted.

D. described her mood as “depressed.” Her affect was euthymic, pleasant/friendly, full range, and somewhat incongruent with mood. Her thought process was linear, organized, and goal directed. Her thought content was significant for passive SI with no definitive plan. She denied homicidal ideation.

There was no evidence of perceptual disturbances. Cognition was normal with alertness, good attention, and memory. Her insight was fair as she required guided questions as to her reasons for needing admission. Judgment was fair; she was help-seeking and demonstrated interest in improving problems.

Physical Examination

Physical examination and vital signs were within normal limits. She had old scars on bilateral forearms and significant obesity. Her body mass index (BMI) was 43, which classified her as having morbid obesity.

Hospital Course

D. was admitted voluntarily to the child and adolescent psychiatry inpatient service to address SI, self-harm, and worsening depression. She contracted for safety on the unit. Routine admission laboratory screening, including complete blood count, complete metabolic profile, alcohol level, urine toxicology, urinalysis, and lipid panel were unremarkable except for low high-density lipoprotein. D.'s morbid obesity did not warrant a more extensive medical work-up, as she was observed to increase her caloric intake as a means of coping with emotional stressors.

The decision was made to restart escitalopram 5 mg po q am as previously prescribed. Guanfacine 1 mg po qhs was added on the fourth day of admission to attempt to reduce D.'s self-injurious impulsive behaviors (Table 1). D. required as needed oral chlorpromazine 50 mg and/or lorazepam 2 mg almost every day for aggressive behavior and agitation. She occasionally required intramuscular (IM) injections of chlorpromazine 50 mg for aggression and severe agitation, usually after arguments with other patients or upsetting conversations with family. D. required trazodone 25 mg or diphenhydramine 50 mg on many nights for insomnia; she experienced recurring nightmares in which a man who tried to speak with her in the park was trying to kill her.

Table 1.

Medication Dosage and Administration Schedule

Hospital day	Escitalopram	Guanfacine	Lamotrigine	Topiramate	PRN lorazepam	PRN chlorpromazine	Other
1	5 mg	None	None	none			Trazodone 25 mg
2						50 mg IM	Trazodone 25 mg
3
4		1 mg			1 mg PO2 mg PO	50 mg PO
5		2 mg			2 mg PO	50 mg PO
6	10 mg				2 mg PO	50 mg PO50 mg IM
7	10 mg
8	15 mg	3 mg					Trazodone 25 mg
9					2 mg PO
10					2 mg PO		Trazodone 25 mg
11					2 mg PO	50 mg PO
12							Trazodone 25 mg
13							Trazodone 25 mg
14
15					2 mg PO	50 mg PO	Trazodone 25 mg
16					2 mg PO	50 mg PO × 2
17		4 mg			2 mg PO	50 mg PO
18					2 mg PO
19					1 mg PO × 2		Trazodone 25 mg
20					1 mg PO	25 mg PO	Trazodone 25 mg
21					1 mg IM	25 mg PO25 mg IM
22					2 mg IM	50 mg IM
23	10 mg		25 mg
24
25
26
27						50 mg PO
28			50 mg			50 mg PO
29	None					50 mg PO50 mg IM
30						50 mg PO
31					2 mg PO	50 mg PO
32					2 mg PO × 2	50 mg PO
33			75 mg		2 mg PO	50 mg PO
34						50 mg PO
35					2 mg PO × 3	50 mg PO × 2
36					2 mg PO × 2	50 mg PO
37				50 mg BID	2 mg IM		Diphenhydramine 50 mg IMHaloperidol 5 mg IM
38							Diphenhydramine 50 mg PO
39
40
41							Diphenhydramine 50 mg PO
42			100 mg		2 mg PO		Diphenhydramine 50 mg POHaloperidol 5 mg PO
43
44					2 mg PO		Haloperidol 5 mg PO
45					2 mg PO × 2		Diphenhydramine 50 mg PO
46				50 mg qam/75 mg qhs	2 mg PO		Haloperidol 5 mg PO
47				50 mg qam/100 mg qhs	2 mg PO		Diphenhydramine 50 mg POHaloperidol 5 mg PO
48							Hydroxyzine 25 mg POHaloperidol 5 mg PO
49			125 mg				Hydroxyzine 25 mg PO
50							Haloperidol 5 mg PO
51							Hydroxyzine 25 mg PODiphenhydramine 50 mg PO
52					2 mg PO		Hydroxyzine 25 mg POHaloperidol 5 mg PODiphenhydramine 50 mg PO
53					2 mg IM		Hydroxyzine 25 mg PODiphenhydramine 50 mg IMHaloperidol 5 mg IM
54							Hydroxyzine 25 mg PO × 2
55							Hydroxyzine 25 mg PO

IM, intramuscular; PO, by mouth; PRN, as needed.

Initially, D. was very aggressive, provocative, and labile, with multiple suicidal statements made to staff. She cut her forearms with her fingernails, greeting cards, and plastic. She was often upset by arguments with her mother and being told she was not wanted back home. Frequently, she laughed after the events, and gave some staff the impression that she was not taking these events seriously. Escitalopram was increased to 10 mg on day 6 of her admission and then 15 mg on day 8. Owing to concerns about escitalopram's activating effects on her behavior, the dose was decreased to 10 mg on day 23 of her admission and discontinued on day 29. Guanfacine was increased to 2 mg on day 5 of her admission, 3 mg on day 8, and finally increased to 4 mg on day 17.

One week after admission, D. reported that her mother had physically abused her before admission. Two weeks later, she disclosed for the first time that her adoptive father had been sexually abusing her since the age of 9. Adoptive mother adamantly denied these allegations, and a new ACS case was opened. D. consistently reported that she was afraid to return home due to physical abuse by her mother and constant fighting. She also reported she did not feel safe with transfer to a respite facility, stating that she would run away and attempt to harm herself.

After an episode of aggression during the third week requiring IM chlorpromazine 50 mg and IM lorazepam 2 mg, lamotrigine 25 mg was added for mood dysregulation and gradually increased to 125 mg. A formal multidisciplinary behavioral plan was simultaneously constructed. Her behavioral control quickly improved over 5 days.

Four weeks after admission, D. reported hearing voices commanding her to cut herself and kill her friends and family. She continued to hear voices for a week; through this time, she did not appear to be internally preoccupied.

During the fifth week D. pushed through the unit door and required staff and security to regain control to return to the unit. Topiramate 50 mg twice a day was started on day 37 of her admission, and gradually increased to address her mood dysregulation and lability. Potential weight loss was considered as an added benefit. Topiramate was increased to 50 mg q am and 75 mg qhs on day 46, and finally 50 mg q am and 100 mg qhs on day 47.

With addition of topiramate, D.'s mood and behavior greatly improved for a week, with no further aggression or as needed medications for agitation or sleep. She reported decreased voices, thoughts of self-harm, and SI. She interacted more appropriately with peers, even mentoring younger patients. These sustained improvements reversed, however, near the end of her hospitalization as plans were initiated for transfer to a long-term inpatient psychiatric facility.

D. attended individual and group psychotherapy sessions about half the time, with variability in level of participation. She had limited insight to her mood and behavior, although it improved throughout admission.

Medication at the time of discharge included guanfacine 4 mg, lamotrigine 125 mg, and topiramate 150 mg.

Brief Formulation

In summary, D. was a 16-year-old adolescent girl admitted for a history of SI, running from home, emotional lability, and lack of behavioral control in the context of her adoptive mother's health deterioration, and unstable relationships with her birth parents. Significant symptomatic improvement occurred after the introduction of topiramate.

From a biopsychosocial perspective, biological factors were notable for a history of mood disorder in both birth parents, with father reporting a possible adolescent manic episode. Bipolar disorder has a heritable component with an ∼5–10% risk for first-degree relatives (Craddock and Sklar 2013), although D. never demonstrated overt symptoms of mania. Sleep was consistently intact, and although her mood was labile and at times expansive around affect-laden topics, all other symptoms of mania were absent. D.'s tendency to increase her food intake to cope with emotional stressors, which likely led to her morbid obesity, could possibly reflect binge-eating disorder. D. also displayed cluster B personality traits, including efforts to avoid abandonment, a pattern of unstable interpersonal relationships, impulsivity, recurrent suicidal gestures, affective instability, and difficulty controlling anger.

Psychosocial factors may have also led to her current clinical picture. D. had experienced chronic trauma that started with neglect and abandonment by her birth parents in infancy, and had been continually reaffirmed by their inconsistent contact and lack of affection. Birth of her youngest half brother who lived with birth mother likely precipitated her depression, and adoptive mother's reports of her increased behavioral and emotional dysregulation. The acute episodes of SI and running away from home that resulted in admission were temporally related to adoptive mother's CVAs, which likely triggered additional feelings of loss and abandonment by another parental figure. D. did not persistently experience symptoms of intrusion and had not experienced a life-threatening event (Brewin et al. 2017), so posttraumatic stress disorder (PTSD) was unlikely. Complex PTSD, which describes disturbances in self-organization, including dysregulation of affect, belief that relationships are painful, and a negative view of the self in multiple contexts that results from chronic trauma in early life (Brewin et al. 2017), was likely.

Protective psychosocial factors included D.'s involved adoptive family and upbringing. However, the protective nature of her supportive family relationships was called into question by allegations of sexual abuse from adoptive father and physical abuse by her adoptive mother. In addition, despite her previous aptitude for school, D. had recently experienced academic difficulties and stopped attending school in the past month.

Multiaxial Diagnosis at Discharge

: Unspecified trauma- and stressor-related disorder

Parent child relational problem

I: Cluster B traits (efforts to avoid abandonment, pattern of unstable interpersonal relationships, impulsivity, recurrent suicidal gestures, affective instability, and difficulty controlling anger)

II: Morbid obesity (BMI 43)

V: Family and school stressors

: Global Assessment of Functioning: 40.

Discussion

D. was an adolescent with a trauma- and stressor-related disorder complicated by emotional lability and obesity. Trauma in early life has been associated with long-term consequences, such as the development of PTSD, disability, and premature mortality, including increased risk for death by suicide (de Moraes Costa et al. 2020). Although selective serotonin reuptake inhibitors are Food and Drug Administration (FDA)-approved for treatment of trauma- and stressor-related disorder, their questionable efficacy and known adverse effect of weight gain did not make them ideal options for D. (Varma et al. 2018). The risk of activation is also well known, and youth with significant impulsivity, aggression, and irritability may be at risk for worsening impairment when treated with them (Luft et al. 2018).

Anticonvulsants such as topiramate have shown efficacy in modulating fear circuitry in the amygdala and limbic nuclei that are sensitized after traumatic effects (Berlant and Kammen 2002; Berlant 2006). In the most recent meta-analysis comparing medications for adults with PTSD, topiramate was found to be the most effective treatment, and the authors highlighted its beneficial effect of weight loss and lack of abuse potential (de Moraes Costa et al. 2020). Most importantly, it has been found to have a significant specific effect in reducing hyperarousal symptoms in PTSD (Varma et al. 2018).

Topiramate has many reported mechanisms of action in the central nervous system, which include increasing cerebral gamma-aminobutyric acid (GABA) concentrations, binding GABA-A receptors through a non-benzodiazepine mechanism, inhibiting brain glutamate release by antagonizing alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate glutamate receptors, inhibition of voltage-gated Na and L-type Ca channel activity, and inhibition of specific isoforms of carbonic anhydrase (Mula et al. 2006).

Topiramate has also been utilized successfully to treat mood disorders. The pathophysiology of epilepsy and bipolar disease may have similar elements, which could help explain why anticonvulsants (i.e., valproic acid, lamotrigine, and carbamazepine) are successfully used as mood stabilizers to treat bipolar disorder (Mula et al. 2006). Studies have found significant improvement when topiramate is used as adjunctive therapy for refractory bipolar disorder (Mula et al. 2006). A small study found that adjunctive topiramate therapy for bipolar disorder type I/II in the pediatric population led to a 62% improvement (DelBello et al. 2002).

Topiramate has also shown effectiveness in treating emotional lability, interpersonal problems, impulsivity, anger, and aggression/hostility in patients with borderline personality disorder (BPD) (Nickel et al. 2004; Loew et al. 2006; Lieb et al. 2018). In a meta-analysis of treatments for BPD, mood stabilizers, including topiramate, were recommended as first-line treatments for the affective and impulsive-behavioral dysregulation seen in BPD (Lieb et al. 2018). Topiramate was also successfully used to treat self-mutilating behavior in a patient with BPD (Cassano et al. 2001). In addition to reducing negative symptoms of BPD, topiramate also significantly improved the patients' emotional health, improved their ability to participate in social and vocational activities, and improved their view on their own health (Loew et al. 2006). In addition, small studies have shown that topiramate improves disruptive behavior, aggression, and mood symptoms in children with pervasive developmental disorders (Doyle and McDougle 2012).

The property that most distinguishes topiramate from other psychotropic medications is its clear and consistent ability to promote weight loss. This attribute is especially useful, as other psychotropic drugs prescribed to manage mood and behavior dysregulation in children and adolescents cause significant weight gain (Arnone 2005; Kahathuduwa et al. 2019). In fact, topiramate was originally designed as an oral hypoglycemic medication, and the FDA approved it in combination with phentermine to treat obesity in adults in 2012 (Arnone 2005; Narayanaswami et al. 2017). This combination medication has been shown to be safe and effective in adolescents (Hsia et al. 2020). Appetite suppression caused by topiramate may be due to activation of the GABA-A receptor as well as antagonism of the kainite/AMPA glutamate receptors that stimulate appetite in the lateral hypothalamus (Arnone 2005; Czepiel et al. 2020). Topiramate has also been shown to inhibit fat deposition by modulation of lipoprotein lipase (Richard et al. 2000). Weight loss also secondarily improves patient outcomes by reducing blood pressure and lipid levels (Arnone 2005).

A recent meta-analysis including 1349 patients showed that topiramate is the most effective medication to facilitate BMI reduction on antipsychotic medications (Zhuo et al. 2018). In fact, topiramate is the most commonly prescribed off-label medication for young adults, and second most commonly prescribed medication, after metformin, for obesity in the pediatric population (Czepiel et al. 2020). In pediatric weight management programs, topiramate overtook metformin as the most commonly prescribed medication in 2017, especially when another indication such as headache was present (Borzutzky et al. 2021). Clinicians feel relatively comfortable using topiramate in the pediatric population, as it is FDA approved as monotherapy in children ≥2 years for multiple forms of epilepsy, including Lennox–Gastaut syndrome (Arnone 2005; FDA 2012).

D.'s morbid obesity created several psychosocial problems, impacting her self-esteem, and self-control. For example, D.'s weight contributed to her ability to break through the doors of the unit, contributing to a sense that staff were not capable of preserving the safety of her environment. Physical redirection was difficult; with her strength her impulses could cause significant harm, contributing to a fear that her actions could be destructive. Thus, addition of topiramate was a rational choice to target her emotional lability, impulsivity, and obesity.

Given that D. was taking several psychotropic medications, it was not possible to conclude that her symptomatic improvement was related only to the addition of topiramate. We have previously commented on guanfacine's beneficial effect on PTSD symptoms (Anderson et al. 2020) and facilitation of psychological therapy (Rice et al. 2018). Of course, comprehensive psychosocial interventions in both attachment and trauma-focused insight-oriented therapy coupled with behavioral and cognitive-behavioral treatment were simultaneously administered, and likely contributed to her improvement. However, significant improvement after the addition of topiramate is supportive of its effectiveness.

Future studies are needed to explore topiramate's role in treatment of children with obesity, trauma, and reactive hyperarousal and impulsivity.

Footnotes

Acknowledgment

We thank Maria Cruz for her editorial assistance.

Disclosures

B.J.C. is on the Scientific Advisory Board of Abide Therapeutics and Teva/Nuvelution, received honoraria from the American Academy of Child and Adolescent Psychiatry, and received research support from Neurocrine Biosciences and NIMH/UCSF. She is cochair of the Medical Advisory Board of the Tourette Association of America (TAA), and on the speakers' bureau for the TAA-CDC Partnership. The other authors have no other disclosures.

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