Management of Antidepressant-coincident Manic Episodea in a Nine-year-old Child Presenting with Obsessive-compulsive and Related Disorders: A Case Report

Abstract

Obsessive-compulsive and related disorders are less prevalent among children, and the recommended treatment involves high doses of antidepressants along with non-pharmacological management. Existing evidence suggests that the risk of inducing mania with antidepressants is comparatively high in children and adolescents aged 14 years and younger. Here, we discuss a case of a 9-year-old girl diagnosed with trichotillomania, obsessive-compulsive disorder, excoriation disorder, and onychophagia who developed a manic episode after starting escitalopram and was later managed on aripiprazole.

Introduction

Trichotillomania (TTM), excoriation, and onychophagia are classified with obsessive-compulsive disorder (OCD) as obsessive-compulsive and related disorders (OCRDs) in the International Classification of Diseases, 11th Revision (ICD-11). ¹ About 25% of OCD cases begin by age 14, while OCRDs are less common in children. The global OCD prevalence among children and adolescents ranges from 0.25% to 3%, with Indian studies showing 0.1%-0.8%. ² A multicenter Indian outpatient study of children and adolescents (≤18 years) found that about 10% had at least one comorbid obsessive-compulsive related disorder, such as hoarding, TTM, or body dysmorphic disorder. ³

Diagnosing bipolar disorder (BD) in young people poses challenges due to various differentials and comorbidities. Patients with OCD and BD often show poor insight, a chronic course, high comorbidity, reduced treatment response, and worse prognosis than those with OCD alone. This comorbidity is particularly relevant in the context of antidepressant treatment, as such patients are at an increased risk not only for antidepressant-induced mania but also for antidepressant-coincident mania, wherein manic symptoms emerge during antidepressant therapy due to the natural course of BD rather than being directly precipitated by the medication itself, and symptoms persisted even after stopping antidepressants. Distinguishing between these two phenomena is crucial. ⁴ The risk of inducing mania with antidepressants is high in children under 14. ⁵ This report discusses a 9-year-old girl who developed a manic episode after starting treatment for OCRDs, highlighting management challenges.

Case Summary

A 9-year-old girl in the fifth grade, with normal developmental and an easy temperament, with no family history of psychiatric illness, presented with a psychiatric condition lasting one year. Symptoms included hair-pulling, nail-biting, skin picking, hand washing for 3-4 hours daily, and chewing clothes for 8 months. She was diagnosed with OCD with poor insight, TTM, excoriation disorder, and onychophagia. An abdominal ultrasound ruled out trichobezoars. Initially, she was prescribed fluoxetine 10 mg from the psychiatry department for two days, and she was switched to escitalopram 5 mg by the pediatric neurology team. Over the next week, she experienced irritability, excessive talking, distractibility, and less sleep, impacting her social and educational functioning. Two weeks later, she was admitted for management. Mental status examination revealed she was conscious but uncooperative, with increased psychomotor activity and distractibility, and elevated self-esteem. Her medical history was normal, with a body mass index (BMI) of 14.16 kg/m².

Baseline investigations, including a complete hemogram, liver function tests, kidney function tests, electrolytes, fasting blood sugar, vitamin B12, and lipid profile, were performed and found to be within normal limits. A comprehensive neurological evaluation was done in consultation with the pediatric neurology team. Differential diagnoses, including Klüver-Bucy syndrome, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), and pica, were carefully considered and ruled out. Investigations, including an antistreptolysin O (ASO) titer, magnetic resonance imaging (MRI) of the brain, electroencephalogram, antinuclear antibody test, serum iron level, total iron-binding capacity, and serum ferritin, were performed, and all results were normal. She was ultimately diagnosed with OCD with poor insight, TTM, excoriation disorder, onychophagia, and SSRI-induced manic symptoms, while considering bipolar type I disorder as a differential.

The Child Mania Rating Scale-Parent Version (CMRS) score was 34. The Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), Trichotillomania Scale for Children (TSC), and Repetitive Body-Focused Behavior Scale-Parent Version (RBFB-P) were administered, yielding scores of 22, 18, and 14, respectively. After stopping escitalopram, she was treated with clonazepam to assess symptom persistence. Persistent manic symptoms led to the initiation of aripiprazole 2.5 mg, resulting in improved response within five days, with CMRS decreasing to 20. Hair-pulling has decreased, and social engagement has begun. During the admission, psychoeducation was provided to the patient’s family members regarding the nature of her illness and its management. Over three weeks, aripiprazole was gradually increased to 7.5 mg.

As symptoms persisted after stopping escitalopram, a diagnosis of bipolar type I disorder, current episode manic without psychotic symptoms, and comorbid OCRDs was made. After increasing aripiprazole to 7.5 mg for 14 days, her manic symptoms resolved, and CMRS reached 0. Skin picking and hand washing behaviors had completely resolved. The CY-BOCS, TSC, and RBFB-P scores decreased to 2, 8, and 6, respectively. Following the resolution of manic symptoms, her nail-biting and hair-pulling behaviors were addressed through habit reversal therapy over four sessions. She maintained well on aripiprazole 7.5 mg for 9 months. The patient was closely monitored for side effects of aripiprazole, and no side effects were observed.

Discussion

This case is unique due to the limited literature on comorbid OCRDs and BD in children. Diagnosing BD in this age group is challenging, as many differentials must be excluded. In our patient, we ruled out ADHD, oppositional defiant disorder (ODD), disruptive mood dysregulation disorder, PANDAS, and Klüver-Bucy syndrome. Apart from the hyperorality, other core features such as visual agnosia, hypermetamorphosis, altered dietary habits, and disinhibited sexual behavior were absent. Additionally, the MRI of the brain was normal, making KBS unlikely. Insidious and continuous course rather than abrupt onset, with no temporal relation between symptom onset and streptococcal infection (ASO titer negative) ruled out PANDAS.

Patients with comorbid OCD and BD often have an earlier onset (around 10 years), increased severity of symptoms, higher hospitalization rates, poorer treatment response, frequent hoarding obsessions, and more comorbid ADHD and ODD.^4,6 Our patient showed early OC symptoms at 8 years, required hospitalization, but responded well to aripiprazole without having comorbid ADHD or ODD. Other studies suggest that hoarding symptoms with comorbid ADHD and ODD correlate with poorer responses. ⁴

According to ICD-11, ¹ BD cannot be diagnosed solely based on antidepressant-induced manic symptoms. We need to verify whether any prescribed medications cause manic symptoms at specific doses and durations, and confirm the timing between medication use and the onset of mood symptoms. In this case, BD was diagnosed because manic symptoms continued after the discontinuation of antidepressants.

SSRIs and clomipramine are first-line treatments for TTM and OCD. ⁷ Psychotherapy is first-line for nail-biting, with pharmacotherapy as a second-line option. ⁷ Currently, no FDA-approved drugs exist for body-focused repetitive behaviors. Both first and second-generation mood stabilizers are FDA-approved for treating manic episodes in adolescents with BD. ⁸ Most patients with comorbid OCD and BD require combinations of mood stabilizers or mood stabilizers with atypical antipsychotics like aripiprazole. ⁶ Adding antidepressants often results in poor responses and higher rates of manic or hypomanic switches compared to non-comorbid patients. ⁶

Research indicates that mania is associated with elevated levels of 5-HIAA, the primary serotonin metabolite, and increased serotonin reuptake in platelets. Studies also indicate that serotonin receptors (5-HT1D, 5-HT1A) are connected to hypomanic and manic episodes. The mechanisms for the manic transition phase remain unknown. ⁹

Aripiprazole, an atypical antipsychotic, features a unique action mechanism. It partially agonizes dopamine D2 receptors and serotonin 5-HT1A receptors, while antagonizing serotonin 5-HT2A receptors. At D2 receptors, it stimulates and inhibits dopamine activity based on concentration. This stabilizes dopaminergic activity, potentially lessening mania symptoms and the risk of switch. ¹⁰ Aripiprazole, through its partial agonist action at dopamine D2/D3 and serotonin 5-HT1A receptors and antagonist effect at 5-HT2A receptors, modulates fronto-striatal circuits implicated in TTM, thereby reducing compulsive hair-pulling behavior. Literature supports the efficacy of low-dose aripiprazole, especially in low-BMI, as seen in our case.^11,12

The biggest challenge was selecting a medication while considering the comorbid OCRDs and BD. Currently, no atypical antipsychotics, including aripiprazole, are FDA-approved for children under 10 for BD. In children aged 6 years and above, aripiprazole is approved for irritability associated with autism spectrum disorder. ¹³ In pediatric BD, aripiprazole has shown efficacy in reducing manic symptoms, with favorable tolerability profiles reported in randomized controlled trials involving children and adolescents aged 10 years and older. ¹⁴ Although data in children under 10 years are sparse, it is generally well tolerated, especially when carefully titrated and monitored. Current guidelines recommend aripiprazole monotherapy as the first-line treatment for acute mania, and it is also effective as an augmenting agent for refractory OCD.^15-17 Many studies have shown aripiprazole’s effectiveness in treating OCD in patients with comorbid BD. ¹⁸

Conclusion

Aripiprazole may be considered, along with non-pharmacological management, for the treatment of OCRDs and comorbid BD.

Data Availability Statement

There is no data set associated with this submission. Any desired information will be available from the corresponding author upon reasonable request.