bipolar disorder case study child

• Case report
• Open access
• Published: 11 September 2017

A case of a four-year-old child adopted at eight months with unusual mood patterns and significant polypharmacy

• Magdalena Romanowicz   ORCID: orcid.org/0000-0002-4916-0625 1 ,
• Alastair J. McKean 1 &
• Jennifer Vande Voort 1  

BMC Psychiatry volume  17 , Article number:  330 ( 2017 ) Cite this article

45k Accesses

2 Citations

1 Altmetric

Metrics details

Long-term effects of neglect in early life are still widely unknown. Diversity of outcomes can be explained by differences in genetic risk, epigenetics, prenatal factors, exposure to stress and/or substances, and parent-child interactions. Very common sub-threshold presentations of children with history of early trauma are challenging not only to diagnose but also in treatment.

Case presentation

A Caucasian 4-year-old, adopted at 8 months, male patient with early history of neglect presented to pediatrician with symptoms of behavioral dyscontrol, emotional dysregulation, anxiety, hyperactivity and inattention, obsessions with food, and attachment issues. He was subsequently seen by two different child psychiatrists. Pharmacotherapy treatment attempted included guanfacine, fluoxetine and amphetamine salts as well as quetiapine, aripiprazole and thioridazine without much improvement. Risperidone initiated by primary care seemed to help with his symptoms of dyscontrol initially but later the dose had to be escalated to 6 mg total for the same result. After an episode of significant aggression, the patient was admitted to inpatient child psychiatric unit for stabilization and taper of the medicine.

Conclusions

The case illustrates difficulties in management of children with early history of neglect. A particular danger in this patient population is polypharmacy, which is often used to manage transdiagnostic symptoms that significantly impacts functioning with long term consequences.

Peer Review reports

There is a paucity of studies that address long-term effects of deprivation, trauma and neglect in early life, with what little data is available coming from institutionalized children [ 1 ]. Rutter [ 2 ], who studied formerly-institutionalized Romanian children adopted into UK families, found that this group exhibited prominent attachment disturbances, attention-deficit/hyperactivity disorder (ADHD), quasi-autistic features and cognitive delays. Interestingly, no other increases in psychopathology were noted [ 2 ].

Even more challenging to properly diagnose and treat are so called sub-threshold presentations of children with histories of early trauma [ 3 ]. Pincus, McQueen, & Elinson [ 4 ] described a group of children who presented with a combination of co-morbid symptoms of various diagnoses such as conduct disorder, ADHD, post-traumatic stress disorder (PTSD), depression and anxiety. As per Shankman et al. [ 5 ], these patients may escalate to fulfill the criteria for these disorders. The lack of proper diagnosis imposes significant challenges in terms of management [ 3 ].

J is a 4-year-old adopted Caucasian male who at the age of 2 years and 4 months was brought by his adoptive mother to primary care with symptoms of behavioral dyscontrol, emotional dysregulation, anxiety, hyperactivity and inattention, obsessions with food, and attachment issues. J was given diagnoses of reactive attachment disorder (RAD) and ADHD. No medications were recommended at that time and a referral was made for behavioral therapy.

She subsequently took him to two different child psychiatrists who diagnosed disruptive mood dysregulation disorder (DMDD), PTSD, anxiety and a mood disorder. To help with mood and inattention symptoms, guanfacine, fluoxetine, methylphenidate and amphetamine salts were all prescribed without significant improvement. Later quetiapine, aripiprazole and thioridazine were tried consecutively without behavioral improvement (please see Table  1 for details).

No significant drug/substance interactions were noted (Table 1 ). There were no concerns regarding adherence and serum drug concentrations were not ordered. On review of patient’s history of medication trials guanfacine and methylphenidate seemed to have no effect on J’s hyperactive and impulsive behavior as well as his lack of focus. Amphetamine salts that were initiated during hospitalization were stopped by the patient’s mother due to significant increase in aggressive behaviors and irritability. Aripiprazole was tried for a brief period of time and seemed to have no effect. Quetiapine was initially helpful at 150 mg (50 mg three times a day), unfortunately its effects wore off quickly and increase in dose to 300 mg (100 mg three times a day) did not seem to make a difference. Fluoxetine that was tried for anxiety did not seem to improve the behaviors and was stopped after less than a month on mother’s request.

J’s condition continued to deteriorate and his primary care provider started risperidone. While initially helpful, escalating doses were required until he was on 6 mg daily. In spite of this treatment, J attempted to stab a girl at preschool with scissors necessitating emergent evaluation, whereupon he was admitted to inpatient care for safety and observation. Risperidone was discontinued and J was referred to outpatient psychiatry for continuing medical monitoring and therapy.

Little is known about J’s early history. There is suspicion that his mother was neglectful with feeding and frequently left him crying, unattended or with strangers. He was taken away from his mother’s care at 7 months due to neglect and placed with his aunt. After 1 month, his aunt declined to collect him from daycare, deciding she was unable to manage him. The owner of the daycare called Child Services and offered to care for J, eventually becoming his present adoptive parent.

J was a very needy baby who would wake screaming and was hard to console. More recently he wakes in the mornings anxious and agitated. He is often indiscriminate and inappropriate interpersonally, unable to play with other children. When in significant distress he regresses, and behaves as a cat, meowing and scratching the floor. Though J bonded with his adoptive mother well and was able to express affection towards her, his affection is frequently indiscriminate and he rarely shows any signs of separation anxiety.

At the age of 2 years and 8 months there was a suspicion for speech delay and J was evaluated by a speech pathologist who concluded that J was exhibiting speech and language skills that were solidly in the average range for age, with developmental speech errors that should be monitored over time. They did not think that issues with communication contributed significantly to his behavioral difficulties. Assessment of intellectual functioning was performed at the age of 2 years and 5 months by a special education teacher. Based on Bailey Infant and Toddler Development Scale, fine and gross motor, cognitive and social communication were all within normal range.

J’s adoptive mother and in-home therapist expressed significant concerns in regards to his appetite. She reports that J’s biological father would come and visit him infrequently, but always with food and sweets. J often eats to the point of throwing up and there have been occasions where he has eaten his own vomit and dog feces. Mother noticed there is an association between his mood and eating behaviors. J’s episodes of insatiable and indiscriminate hunger frequently co-occur with increased energy, diminished need for sleep, and increased speech. This typically lasts a few days to a week and is followed by a period of reduced appetite, low energy, hypersomnia, tearfulness, sadness, rocking behavior and slurred speech. Those episodes last for one to 3 days. Additionally, there are times when his symptomatology seems to be more manageable with fewer outbursts and less difficulty regarding food behaviors.

J’s family history is poorly understood, with his biological mother having a personality disorder and ADHD, and a biological father with substance abuse. Both maternally and paternally there is concern for bipolar disorder.

J has a clear history of disrupted attachment. He is somewhat indiscriminate in his relationship to strangers and struggles with impulsivity, aggression, sleep and feeding issues. In addition to early life neglect and possible trauma, J has a strong family history of psychiatric illness. His mood, anxiety and sleep issues might suggest underlying PTSD. His prominent hyperactivity could be due to trauma or related to ADHD. With his history of neglect, indiscrimination towards strangers, mood liability, attention difficulties, and heightened emotional state, the possibility of Disinhibited Social Engagement Disorder (DSED) is likely. J’s prominent mood lability, irritability and family history of bipolar disorder, are concerning for what future mood diagnosis this portends.

As evidenced above, J presents as a diagnostic conundrum suffering from a combination of transdiagnostic symptoms that broadly impact his functioning. Unfortunately, although various diagnoses such as ADHD, PTSD, Depression, DMDD or DSED may be entertained, the patient does not fall neatly into any of the categories.

This is a case report that describes a diagnostic conundrum in a young boy with prominent early life deprivation who presented with multidimensional symptoms managed with polypharmacy.

A sub-threshold presentation in this patient partially explains difficulties with diagnosis. There is no doubt that negative effects of early childhood deprivation had significant impact on developmental outcomes in this patient, but the mechanisms that could explain the associations are still widely unknown. Significant family history of mental illness also predisposes him to early challenges. The clinical picture is further complicated by the potential dynamic factors that could explain some of the patient’s behaviors. Careful examination of J’s early life history would suggest such a pattern of being able to engage with his biological caregivers, being given food, being tended to; followed by periods of neglect where he would withdraw, regress and engage in rocking as a self-soothing behavior. His adoptive mother observed that visitations with his biological father were accompanied by being given a lot of food. It is also possible that when he was under the care of his biological mother, he was either attended to with access to food or neglected, left hungry and screaming for hours.

The current healthcare model, being centered on obtaining accurate diagnosis, poses difficulties for treatment in these patients. Given the complicated transdiagnostic symptomatology, clear guidelines surrounding treatment are unavailable. To date, there have been no psychopharmacological intervention trials for attachment issues. In patients with disordered attachment, pharmacologic treatment is typically focused on co-morbid disorders, even with sub-threshold presentations, with the goal of symptom reduction [ 6 ]. A study by dosReis [ 7 ] found that psychotropic usage in community foster care patients ranged from 14% to 30%, going to 67% in therapeutic foster care and as high as 77% in group homes. Another study by Breland-Noble [ 8 ] showed that many children receive more than one psychotropic medication, with 22% using two medications from the same class.

It is important to note that our patient received four different neuroleptic medications (quetiapine, aripiprazole, risperidone and thioridazine) for disruptive behaviors and impulsivity at a very young age. Olfson et al. [ 9 ] noted that between 1999 and 2007 there has been a significant increase in the use of neuroleptics for very young children who present with difficult behaviors. A preliminary study by Ercan et al. [ 10 ] showed promising results with the use of risperidone in preschool children with behavioral dyscontrol. Review by Memarzia et al. [ 11 ] suggested that risperidone decreased behavioral problems and improved cognitive-motor functions in preschoolers. The study also raised concerns in regards to side effects from neuroleptic medications in such a vulnerable patient population. Younger children seemed to be much more susceptible to side effects in comparison to older children and adults with weight gain being the most common. Weight gain associated with risperidone was most pronounced in pre-adolescents (Safer) [ 12 ]. Quetiapine and aripiprazole were also associated with higher rates of weight gain (Correll et al.) [ 13 ].

Pharmacokinetics of medications is difficult to assess in very young children with ongoing development of the liver and the kidneys. It has been observed that psychotropic medications in children have shorter half-lives (Kearns et al.) [ 14 ], which would require use of higher doses for body weight in comparison to adults for same plasma level. Unfortunately, that in turn significantly increases the likelihood and severity of potential side effects.

There is also a question on effects of early exposure to antipsychotics on neurodevelopment. In particular in the first 3 years of life there are many changes in developing brains, such as increase in synaptic density, pruning and increase in neuronal myelination to list just a few [ 11 ]. Unfortunately at this point in time there is a significant paucity of data that would allow drawing any conclusions.

Our case report presents a preschool patient with history of adoption, early life abuse and neglect who exhibited significant behavioral challenges and was treated with various psychotropic medications with limited results. It is important to emphasize that subthreshold presentation and poor diagnostic clarity leads to dangerous and excessive medication regimens that, as evidenced above is fairly common in this patient population.

Neglect and/or abuse experienced early in life is a risk factor for mental health problems even after adoption. Differences in genetic risk, epigenetics, prenatal factors (e.g., malnutrition or poor nutrition), exposure to stress and/or substances, and parent-child interactions may explain the diversity of outcomes among these individuals, both in terms of mood and behavioral patterns [ 15 , 16 , 17 ]. Considering that these children often present with significant functional impairment and a wide variety of symptoms, further studies are needed regarding diagnosis and treatment.

Abbreviations

Attention-Deficit/Hyperactivity Disorder

Disruptive Mood Dysregulation Disorder

Disinhibited Social Engagement Disorder

Post-Traumatic Stress Disorder

Reactive Attachment disorder

Norman RE, Byambaa M, De R, Butchart A, Scott J, Vos T. The long-term health consequences of child physical abuse, emotional abuse, and neglect: a systematic review and meta-analysis. PLoS Med. 2012;9(11):e1001349. https://doi.org/10.1371/journal.pmed.1001349 . Epub 2012 Nov 27

Article   PubMed   PubMed Central   Google Scholar  

Kreppner JM, O'Connor TG, Rutter M, English and Romanian Adoptees Study Team. Can inattention/overactivity be an institutional deprivation syndrome? J Abnorm Child Psychol. 2001;29(6):513–28. PMID: 11761285

Article   CAS   PubMed   Google Scholar  

Dejong M. Some reflections on the use of psychiatric diagnosis in the looked after or “in care” child population. Clin Child Psychol Psychiatry. 2010;15(4):589–99. https://doi.org/10.1177/1359104510377705 .

Article   PubMed   Google Scholar  

Pincus HA, McQueen LE, Elinson L. Subthreshold mental disorders: Nosological and research recommendations. In: Phillips KA, First MB, Pincus HA, editors. Advancing DSM: dilemmas in psychiatric diagnosis. Washington, DC: American Psychiatric Association; 2003. p. 129–44.

Google Scholar  

Shankman SA, Lewinsohn PM, Klein DN, Small JW, Seeley JR, Altman SE. Subthreshold conditions as precursors for full syndrome disorders: a 15-year longitudinal study of multiple diagnostic classes. J Child Psychol Psychiatry. 2009;50:1485–94.

AACAP. Practice parameter for the assessment and treatment of children and adolescents with reactive attachment disorder of infancy and early childhood. J Am Acad Child Adolesc Psychiatry. 2005;44:1206–18.

Article   Google Scholar  

dosReis S, Zito JM, Safer DJ, Soeken KL. Mental health services for youths in foster care and disabled youths. Am J Public Health. 2001;91(7):1094–9.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Breland-Noble AM, Elbogen EB, Farmer EMZ, Wagner HR, Burns BJ. Use of psychotropic medications by youths in therapeutic foster care and group homes. Psychiatr Serv. 2004;55(6):706–8.

Olfson M, Crystal S, Huang C. Trends in antipsychotic drug use by very young, privately insured children. J Am Acad Child Adolesc Psychiatry. 2010;49:13–23.

PubMed   Google Scholar  

Ercan ES, Basay BK, Basay O. Risperidone in the treatment of conduct disorder in preschool children without intellectual disability. Child Adolesc Psychiatry Ment Health. 2011;5:10.

Memarzia J, Tracy D, Giaroli G. The use of antipsychotics in preschoolers: a veto or a sensible last option? J Psychopharmacol. 2014;28(4):303–19.

Safer DJ. A comparison of risperidone-induced weight gain across the age span. J Clin Psychopharmacol. 2004;24:429–36.

Correll CU, Manu P, Olshanskiy V. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009;302:1765–73.

Kearns GL, Abdel-Rahman SM, Alander SW. Developmental pharmacology – drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349:1157–67.

Monk C, Spicer J, Champagne FA. Linking prenatal maternal adversity to developmental outcomes in infants: the role of epigenetic pathways. Dev Psychopathol. 2012;24(4):1361–76. https://doi.org/10.1017/S0954579412000764 . Review. PMID: 23062303

Cecil CA, Viding E, Fearon P, Glaser D, McCrory EJ. Disentangling the mental health impact of childhood abuse and neglect. Child Abuse Negl. 2016;63:106–19. https://doi.org/10.1016/j.chiabu.2016.11.024 . [Epub ahead of print] PMID: 27914236

Nemeroff CB. Paradise lost: the neurobiological and clinical consequences of child abuse and neglect. Neuron. 2016;89(5):892–909. https://doi.org/10.1016/j.neuron.2016.01.019 . Review. PMID: 26938439

Download references

Acknowledgements

We are also grateful to patient’s legal guardian for their support in writing this manuscript.

Availability of data and materials

Not applicable.

Author information

Authors and affiliations.

Mayo Clinic, Department of Psychiatry and Psychology, 200 1st SW, Rochester, MN, 55901, USA

Magdalena Romanowicz, Alastair J. McKean & Jennifer Vande Voort

You can also search for this author in PubMed   Google Scholar

Contributions

MR, AJM, JVV conceptualized and followed up the patient. MR, AJM, JVV did literature survey and wrote the report and took part in the scientific discussion and in finalizing the manuscript. All the authors read and approved the final document.

Corresponding author

Correspondence to Magdalena Romanowicz .

Ethics declarations

Ethics approval and consent to participate, consent for publication.

Written consent was obtained from the patient’s legal guardian for publication of the patient’s details.

Competing interests

The author(s) declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Cite this article.

Romanowicz, M., McKean, A.J. & Vande Voort, J. A case of a four-year-old child adopted at eight months with unusual mood patterns and significant polypharmacy. BMC Psychiatry 17 , 330 (2017). https://doi.org/10.1186/s12888-017-1492-y

Download citation

Received : 20 December 2016

Accepted : 01 September 2017

Published : 11 September 2017

DOI : https://doi.org/10.1186/s12888-017-1492-y

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Polypharmacy
• Disinhibited social engagement disorder

BMC Psychiatry

ISSN: 1471-244X

• General enquiries: [email protected]

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

The PMC website is updating on October 15, 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Medicina (Kaunas)

The Challenges of Children with Bipolar Disorder

Robert m. post.

1 School of Medicine, George Washington University, Washington, DC 20052, USA

2 Bipolar Collaborative Network, 5415 W. Cedar Lane, Suite 201-B, Bethesda, MD 20814, USA

Heinz Grunze

3 Psychiatrie Schwäbisch Hall, Campus ZfPG, 74523 Schwäbisch Hall, Germany; [email protected]

4 Campus Nuremberg-Nord, Paracelsus Medical University, 90419 Nuremberg, Germany

Associated Data

All data given in this review have been previously published and are in the public domain.

Childhood onset bipolar disorder (CO-BD) presents a panoply of difficulties associated with early recognition and treatment. CO-BD is associated with a variety of precursors and comorbidities that have been inadequately studied, so treatment remains obscure. The earlier the onset, the longer is the delay to first treatment, and both early onset and treatment delay are associated with more depressive episodes and a poor prognosis in adulthood. Ultra-rapid and ultradian cycling, consistent with a diagnosis of BP-NOS, are highly prevalent in the youngest children and take long periods of time and complex treatment regimens to achieve euthymia. Lithium and atypical antipsychotics are effective in mania, but treatment of depression remains obscure, with the exception of lurasidone, for children ages 10-17. Treatment of the common comorbid anxiety disorders, oppositional defiant disorders, pathological habits, and substance abuse are all poorly studied and are off-label. Cognitive dysfunction after a first manic hospitalization improves over the next year only on the condition that no further episodes occur. Yet comprehensive expert treatment after an initial manic hospitalization results in many fewer relapses than traditional treatment as usual, emphasizing the need for combined pharmacological, psychosocial, and psycho-educational approaches to this difficult and highly recurrent illness.

1. Introduction

Epidemiological data by Merikangas et al., (2010) indicated that 2.2% of adolescents in the US have a bipolar spectrum disorder, including BP-NOS, but disappointedly only 20% are in any kind of treatment [ 1 ]. Other data indicate a similar percentage of bipolar I children in other countries, but if those with BP-NOS are considered, the incidence may be considerably higher, perhaps around 5%. Childhood onsets of bipolar disorders are more common in the US than in many European countries with one quarter of onsets in adults with bipolar disorder occurring before age 13 and two thirds before age 19 [ 2 , 3 , 4 , 5 ] Multiple factors account for this; among the most prominent are an increased incidence of a positive family history of mood disorders and substance abuse disorders in patients’ parents and grandparents [ 6 , 7 , 8 ] and an increased incidence of multiple psychosocial adversities (different types of abuse) in childhood [ 9 ]. There are additive effects on earlier age on onset when there is the combined presence of both a high loading of family history and incidence of childhood adversity [ 7 ]. Other risk factors in the US include obesity, an inflammatory diet, and poor access to health care yielding longer delays to diagnosis and first treatment.

2. Transgenerational Transmission and Illness Evolution

Not only does bipolar disorder in adults in the US compared to Europeans appear to be a more pernicious illness [ 2 ], but compared to the Europeans, the children of US adults with bipolar disorder likely have an increased incidence of bipolar disorder, depression, substance abuse, suicidality, and other psychiatric illnesses [ 3 ]. The data are convergent with those of Axelson et al. [ 4 ], indicating that upon a systematic 8 years of follow up, children of a bipolar parent compared to a control parent in the community are at increased risk (in descending order) for an anxiety disorder, depression, disruptive behavioral disorder, ADHD, and substance abuse, each more than the approximately 20% who will develop a bipolar disorder diagnosis.

Considerable data also suggest that there may be an evolution in illness manifestations in those at high risk because of a parent with bipolar disorder from the initial appearance of an anxiety disorder to a depression and then to bipolar disorder [ 5 ]. In US cohorts this may be associated with a high risk of multiple early prodromes, including anxiety, ADHD, ODD, as well as depression and then bipolar disorder [ 10 ], and each of these may show an increasing incidence from a cohort effect [ 6 ].

3. Early Recognition and Treatment

Early recognition and treatment are critical as childhood onset illness as compared to adult onset is associated with a problematic course of increased substance abuse, suicide, and episodes of mood disorder in adulthood [ 7 , 8 ]. Lack of aggressive comprehensive treatment is associated with increase in risk not only of relapses [ 9 ] and social and educational dysfunction, but also of cognitive dysfunction if further episodes occur in the year after a first mania [ 11 , 12 ]. Attempts to enhance cognitive reserve deserve further study and consideration.

However, the ideal treatment of childhood onset bipolar disorder is compromised by a lack of systematic clinical trials, and current guidelines that are largely based on expert opinion. Children are being treated with a high incidence of atypical antipsychotics, but lesser degrees of lithium and mood stabilizing anticonvulsants, such as valproate, lamotrigine, or carbamazepine. Yet naturalistic follow up studies suggest that those treated with lithium have better long-term outcomes and more euthymic days [ 13 ] or fewer days of feeling depressed and less suicidality [ 14 ] than other treatment and mood stabilizer approaches.

3.1. The Case for Lithium Treatment of Children

Lithium has positive controlled data for treatment of acute mania [ 15 ] and prevention [ 16 ]. After a first manic hospitalization, Berk et al. [ 17 ] reported that one year of randomized treatment with lithium was superior to that of quetiapine on measures of mania, depression, functioning, cognition, and brain imaging. In addition, lithium has multiple assets that have not yet been systematically addressed in children [ 18 ]. Lithium increases hippocampal volume in adults, likely based on its ability to increase BDNF and neurogenesis. It also increases white matter integrity in children who have been shown to have these deficits. In adults, lithium helps prevent cognitive deterioration in patients with mild cognitive impairment and it reduces the incidence of a diagnosis of dementia in old age [ 19 , 20 ]. Based on its ability to stimulate the enzyme telomerase, lithium protects the length of telomeres, which are reduced in length by stress and depression [ 21 ]. This and other diverse mechanisms could account for the data suggesting that lithium could help prevent a variety of medical illnesses including cancer [ 22 ].

Lithium appears most effective in those with a positive family history of mood disorders and especially if there is a positive family history of response to lithium. In addition, those with classic presentations of euphoric mania, clear well-intervals between episodes, a lack of anxiety or substance abuse comorbidity, and non-rapid cycling are more likely to respond [ 23 ]. Initiating lithium treatment early in the course of illness is also more productive than latter treatment after multiple episodes or rapid cycling has occurred [ 24 , 25 , 26 ]. Lithium is FDA- and EMA-approved for children over 12 years of age.

3.2. Atypical Antipsychotics

While some atypical antipsychotics are FDA-approved for preventing mania and total episodes, some, such as aripiprazole, have not shown significant efficacy in preventing depressions. Ziprasidone is effective in mania, but it failed in depression in adults. Olanzapine has efficacy in mania and depression, but issues of weight gain and metabolic tolerability make it a third line option [ 27 ]. Those with a parental history of non-response to lithium maybe more likely to respond to atypicals [ 28 ].

Lurasidone has efficacy in bipolar depression in children aged 10–17 years as well as in adults, but long-term preventive data are mixed [ 29 ]. It is of interest that in studies of bipolar depression in both children and adults, lurasidone was more effective and had a bigger effect size in those with baseline elevations in the inflammatory marker C-reactive protein (CRP) [ 30 , 31 ].

3.3. Mood Stabilizing Anticonvulsants

As opposed to robust data in adults with mania, data on valproate and carbamazepine in mania in children are more mixed and equivocal. Valproate is widely used in mania in children, although several placebo-controlled trials failed to show efficacy in acute mania. It should not be used in women of childbearing age [ 32 ]. Oxcarbazepine (OXC) was not effective in the whole group of children with bipolar disorder, while the youngest compared to the oldest did significantly better on OXC than placebo [ 33 ]. Data showed the opposite pattern on lamotrigine where older patients fared better than younger children [ 34 ]. As noted above, in the long-term naturalistic studies those treated with lithium performed better than those treated with atypicals and anticonvulsants [ 14 ].

3.4. Family History Is Useful in the Choice of Mood Stabilizing Treatment

Considerable evidence indicates that a positive family history of mood disorders is a predictor of response to lithium [ 23 ]. Conversely, those without a family history of bipolar disorder are more likely to respond to carbamazepine (along with characteristics that are the mirror image of lithium non-response, such as more continuous cycling and the presence of anxiety and substance abuse comorbidity, and the presence of mood incongruent delusions). Interestingly, those with a personal or family history of anxiety disorders are more likely to respond to lamotrigine [ 35 ].

3.5. Combinations Are More Effective than Monotherapy

Findling et al. [ 36 ] reported that children stabilized on the combination of lithium and valproate relapsed at a very high rate when they were randomized to either monotherapy. They then rapidly re-responded when combination therapy was re-instituted indicating the need for combination therapy in the majority of children with bipolar disorder. Geller et al. [ 37 ] came to the same conclusion in her randomized study of lithium, valproate, and risperidone, in that most patients required a combination of the atypical with lithium or valproate (and often with adjunctive stimulants) to achieve adequate mood stabilization. Kowatch et al. [ 38 ] also concluded that combinations were ultimately needed in his randomized study of lithium, valproate, and carbamazepine in acute mania.

Given the high incidence of comorbid ADHD and bipolar disorder in children, most investigators recommend first achieving mood stabilization prior to the use of stimulants for residual symptoms of ADHD. Adding a stimulant in this fashion is not associated with exacerbation of the bipolar disorder [ 39 ]. First treating these comorbid patients with high dose stimulants or antidepressants prior to mood stabilization risks a high incidence of non-response or a worsening of symptoms [ 40 ].

3.6. Other Agents and Supplements for Comorbidities

Some drugs that are not effective antimanic agents, such as gabapentin, still have evidence of effectiveness in other syndromes and comorbidities, including alcohol use disorder (AUD), avoidance and anxiety disorders, and anxiety attacks, such as topiramate and zonisamide in AUD and bulimia [ 41 ]. Two supplements available without prescription have a wide range of potential benefits in bipolar disorder as listed in Table 1 . For example, N-acetylcysteine (NAC) has placebo-controlled data for effectiveness in depression and anxiety in adult bipolar patients, as well as the ability to limit multiple drugs of abuse and habits such as gambling, OCD, and trichotillomania [ 41 , 42 , 43 ]. There are three positive placebo-controlled trials of NAC for irritability in autism in children 4–17 years of age so that safety in children has been demonstrated.

Potential utility of supplements and drugs in the treatment of comorbidities of bipolar disorder. Note that all are off label in bipolar disorder except valproate *.

* References cited in [ 41 ].

Acetyl-L-carnitine (LAC) has been reported low in the blood of adult depressed patients, especially those with early onset, more severe and treatment refractory depression, and in those with histories of abuse in childhood [ 44 ]. It has antidepressant effects in patients and in animal models of depression, but effectiveness has not yet been demonstrated in children. However, the possibility of normalizing LAC blood levels in depressed patients with a history of adversity in childhood suggests the importance of studying this subgroup as patients with bipolar disorder have such a high incidence of histories of abuse in childhood which in turn is associated with relative treatment refractoriness. LAC also has anti-pain effects, sensitizes insulin receptors, and improves peripheral neuropathy [ 44 , 45 ].

Other agents not listed in Table 1 also deserve consideration even though the data on effectiveness in children is not solid [ 41 , 46 ]. For example, there is a very high incidence of borderline or low levels of vitamin D3 in children with major psychiatric illness, so supplementation with this safe vitamin would appear worthy of consideration. Similarly folic acid has been reported to enhance the effectiveness of lithium and many antidepressants, and for those with a methylenetetrahydrofolate reductase (MTHFR) deficiency, supplementation with L-methylfolate is a necessity.

This and other suggestions for addressing some of the complexities of bipolar disorder are acknowledged to be inadequately supported in the literature sufficiently to merit routines use [ 46 ]. However, given the paucity of systematic studies in children and the wide range of impairing symptoms and syndromes seen in the illness [ 18 , 47 ], some consideration of using these agents on the basis of careful evaluation of their potential risk: benefit ratio may be a rational approach. The potential role of the calcium channel blocker nimodipine also deserves further evaluation and consideration [ 23 , 48 , 49 ].

4. Psychotherapy: The Case for Systematic Employment of Family Focused Therapy and Similar Therapies

While optimal pharmacological approaches to childhood onset bipolar disorder remain n controversial, there is much consensus about the importance of psycho-social therapies.

Recent meta-analyses document the benefit of family focused therapy (FFT) and related group therapies [ 50 ]. Miklowitz et al. [ 51 ] also found that FFT was effective for those with prodromal symptoms including bipolar disorder not otherwise specified (BP-NOS) for producing stabilization in depression, reducing recurrence risk, and increasing psychosocial functioning, each with moderate to large effect sizes. Pavuluri et al. [ 52 ] endorsed family focus cognitive behavioral therapy, and Fristad et al. [ 53 ] also found multifamily psychoeducational therapy highly effective.

In addition, a recent report indicates that cognitive behavioral therapy (CBT) can be modified for transdiagnostic use in children and is more effective that treatment as usual [ 54 ]. Together these data provide strong evidence for the utility of FFT and other family interventions, and CBT for those with early symptoms, prodromes, and more full-blown bipolar disorder. Given the efficacy and safety of these psychosocial approaches and the utility of psycho-educational efforts, it would appear imperative that these types of therapies be utilized adjunctively in the routine treatment of early affective disorders in children.

5. The Need of Psychological and Pharmacological Attempts to Head of Early Illness in Those at Highest Risk

Given the high risks for the onset of diverse childhood psychiatric diagnoses in children of a parent with bipolar disorder [ 4 ], attempting a primary prevention would appear indicated. Endorsing attempts to achieve a good diet, regular exercise, sports participation and sleep habits, and mindfulness/meditation have not only been proven to be effective, but their safety, practicality, and theoretical rationale make them highly recommended [ 43 ]. As noted above, family therapy and CBT have considerable support in systematic studies.

A variety of safe pharmacological interventions may have merit in primary and/or secondary prevention even if not fully validated by systematic studies [ 46 ]. Along with safety, the non-specificity of potential effectiveness across multiple symptoms and syndromes makes their early utilization in children worthy of consideration. These could include omega-3-fatty acids, N-acetylcysteine, minocycline, and other anti-inflammatory drugs (especially in the presence of positive markers of inflammation), deserving further study and perhaps individual clinical trials. In those with a history of adversity in childhood, one might even consider a clinical trial with acetyl-L-carnitine (LAC) since levels of LAC in the blood of adult depressed patients are especially low in those with a history of childhood adversity [ 44 , 45 ].

6. Conclusions

The majority of follow up studies indicate that childhood onset bipolar disorder is not a benign illness and patients remain ill some two thirds of the time and experience considerable dysfunction [ 13 , 55 , 56 ]. Suicide and substance abuse remain a too common liability. Given the fact that the number of prior episodes is associated with the degree of cognitive dysfunction and the development of treatment resistance, preventing episodes from the outset become a major goal of treatment [ 46 , 57 , 58 ]. However, given the paucity of systematic research to guide optimal therapeutics, the complexity of presentations, and the need for comprehensive pharmacological and psychosocial intervention, achieving a good long-term outcome is not readily accomplished. This is all-the-more an imposing task as the majority children treated for psychiatric illness in the US are primary care physicians who are typically not well versed in the nuances of diagnosis and treatment [ 59 ].

Thus, there is a major need for more treatment research to better guide both psychiatrists and primary care physicians. Psychotherapeutic and psycho-educational are a necessary part of treatment and the limited access to expert referral is an additional problem that must be overcome. Since there are so many obstacles to achieving excellent treatment outcomes, it behooves the clinician to request help from parents in facilitating the diagnosis and the assessment of response to treatment by getting weekly rating of their child’s symptoms [ 47 , 60 , 61 ]. Parents can receive confidential IRB-approved emails every Sunday for rating the severity of anxiety, depression, attention deficit hyperactivity disorder (ADHD), oppositional behavior, and mania which can then be printed out for ease of longitudinal assess by the physician. Informed consent, demographic assessment, and receiving the ratings can be acquired at http://bipolarnews.org/?page_id=2630 (last accessed on 10 June 2021). With creative comprehensive treatment, often involving lithium, multiple other agents, and adjunctive psychotherapy, life-saving outcomes can be achieved in even the very difficult occurrences of childhood onset bipolar disorder and its many comorbidities.

Acknowledgments

The authors acknowledge the support of the Stanley Foundation Medical Institute for generating data on transgenerational transmission as part of the Stanley Foundation Bipolar Network research activities.

Author Contributions

R.M.P. completed the first draft of the manuscript which was amended by H.G. Both authors read and approved the final manuscript. All authors have read and agreed to the published version of the manuscript.

This research received no external funding.

Institutional Review Board Statement

Not applicable as this is a review of published studies that have received individual IRB approval.

Informed Consent Statement

Not applicable as this is a review of published data not of new original research.

Data Availability Statement

Conflicts of interest.

The authors declare that this review was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. RMP has received speaker’s honoraria over the past 3 years from AstraZeneca, Validus, Sunovion, Takeda, and Pamlabs. H.G. received grants/research support, consulting fees and honoraria within the last 3 years from Gedeon Richter, Janssen-Cilag, and Sanofi-Aventis.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• My Bibliography
• Collections
• Citation manager

Save citation to file

Email citation, add to collections.

• Create a new collection
• Add to an existing collection

Add to My Bibliography

Your saved search, create a file for external citation management software, your rss feed.

• Search in PubMed
• Search in NLM Catalog
• Add to Search

[Pediatric bipolar disorder - case report of a bipolar patient with disease onset in childhood and adolescence: implications for diagnosis and therapy]

Affiliations.

• 1 Psychiatrie, Medizinische Universität Graz.
• 2 Therapiezentrum Justuspark, BVA, Bad Hall.
• PMID: 25383932
• DOI: 10.1055/s-0034-1385271

In recent years, intense controversies have evolved about the existence and exact diagnostic criteria of pediatric bipolar affective disorder. The present study aims to discuss pediatric bipolar affective disorder based on the current literature focussing on the diagnostic prospects. Based on a case study, a process of bipolar disorder developed in childhood is depicted exemplarily. Because of the high comorbidity and overlapping symptoms of paediatric bipolar affective disorder and other psychiatric disorders, the major impact of the differential diagnosis has to be stressed. An early diagnosis and the treatment possibilities are discussed.

© Georg Thieme Verlag KG Stuttgart · New York.

PubMed Disclaimer

Similar articles

• Self-medication, bipolar disorders, and stimulant dependence. Khantzian EJ, Albanese MJ. Khantzian EJ, et al. J Clin Psychiatry. 2009 Jun;70(6):935-6; author reply 936-7. doi: 10.4088/jcp.08lr04878. J Clin Psychiatry. 2009. PMID: 19573490 No abstract available.
• Effects of atypical antipsychotics on neurocognition in euthymic bipolar patients. Torrent C, Martinez-Arán A, Daban C, Amann B, Balanzá-Martínez V, del Mar Bonnín C, Cruz N, Franco C, Tabarés-Seisdedos R, Vieta E. Torrent C, et al. Compr Psychiatry. 2011 Nov-Dec;52(6):613-22. doi: 10.1016/j.comppsych.2010.12.009. Epub 2011 Feb 4. Compr Psychiatry. 2011. PMID: 21295774
• Severe creatine kinase increase during quetiapine and mirtazapine treatment. Apikoglu Rabus S, Izzettin F, Rabus M, Bilici M. Apikoglu Rabus S, et al. Psychopharmacology (Berl). 2006 Apr;185(2):263-4. doi: 10.1007/s00213-005-0273-3. Epub 2005 Dec 23. Psychopharmacology (Berl). 2006. PMID: 16374598 No abstract available.
• Quetiapine fumarate for schizophrenia and bipolar disorder in young patients. Ribolsi M, Magni V, Rubino IA. Ribolsi M, et al. Drugs Today (Barc). 2010 Aug;46(8):581-7. doi: 10.1358/dot.2010.46.8.1500050. Drugs Today (Barc). 2010. PMID: 20830318 Review.
• [Schizoaffective disorder: clinical symptoms and present-day approach to treatment]. Danileviciūte V. Danileviciūte V. Medicina (Kaunas). 2002;38(11):1057-65. Medicina (Kaunas). 2002. PMID: 12532717 Review. Lithuanian.

Publication types

• Search in MeSH

Related information

• PubChem Compound (MeSH Keyword)

LinkOut - more resources

Full text sources.

• Georg Thieme Verlag Stuttgart, New York

Other Literature Sources

• scite Smart Citations
• MedlinePlus Consumer Health Information
• MedlinePlus Health Information

• Citation Manager

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.