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Vol. 22, Issue 2, 2018 FDA Approves for Bipolar Depression in Children and Adolescents In March 2018, the US Food and In the study, lurasidone was delay between the emergence of symp- Drug Administration approved well-tolerated. Side effects included toms and the first treatment for bipolar the antipsychotic drug lurasidone nausea, sleepiness, minimal weight disorder is also a risk factor for more (Latuda) for the treatment of bipolar gain, and insomnia. Lurasidone did severe depression, more time depressed, depression in children and adoles- not seem to affect glucose, triglycer- and a poorer outcome in adulthood. cents aged 10–17 years. Lurasidone ides, cholesterol, or blood pressure. Parents of children aged 2-12 who was already approved for adults with have mood or behavioral problems are bipolar depression, as an add-on treat- Editor’s Note: This is the first drug encouraged to consider joining the Child ment to the mood stabilizers to be approved for bipolar depression in Network at our website, bipolarnews.org and , and for schizophre- this age range. This editor (Robert M. (click on the tab for the Child Network). nia in people aged 13 years and up. Post) has written extensively on the By participating in this research network, A 6-week clinical trial in 347 youth high incidence of childhood onset bipolar parents are able to make a weekly rating of compared lurasidone (in doses ranging disorder in the US, and especially in the the severity of their children’s symptoms of from 20 to 80 mg/day) to placebo offspring of parents with bipolar disorder. anxiety, depression, ADHD, oppositional and found that those who received It is important to be alert to the pos- behavior, and mania via the secure website. lurasidone showed significant im- sibilities of depression and bipolar disorder The ratings can then be shared with the provements in depression compared in children in the US (along with related child’s clinicians for easy visualization to those who received placebo. The illnesses such as anxiety, oppositional of the course of symptoms over time, average dose was below 40 mg/day. defiant disorder, and attention deficit which may help with treatment decisions. The research by Melissa P. DelBello hyperactivity disorder (ADHD)), as and colleagues was published in the early-onset illness tends to have a more Journal of the American Academy of severe long-term course than adult-onset Child and Adolescent Psychiatry in 2017. depression and bipolar disorder. A longer In This Issue:

Pediatric Bipolar Disorder Diagnoses Bullying Affects Kids’ Much More Common in US than England Mental Health p. 3 A 2014 article by Anthony James and US were diagnosed with bipolar dis- colleagues in the Journal of the American order, only 22.1 adults per 100,000 in New Treatment for Academy of Child and Adolescent England received such a diagnosis, Fragile X p. 3 Psychiatry reported that hospitalizations making the diagnosis of bipolar disor- for pediatric bipolar disorder are 72.1 der in adults 7.2 times more common times higher in the US than in England. in the US. Diagnoses of childhood Playing Football Before The researchers determined that attention-deficit hyperactivity disor- Age 12 May Be there were 100.9 diagnoses of pediatric der (ADHD) were 13.0 times more Bad for the Brain p. 3 bipolar disorder per 100,000 people in common in the US than in England, the US, but only 1.4 cases per 100,000 while cases of childhood depression people in England. The discrepancy were 4.2 times more common in the US. Treating a in diagnoses for adult bipolar disorder James and colleagues hypothesized Multi-Symptomatic and for other childhood psychiatry several potential reasons for the dra- Child p. 4-7 illnesses were smaller but still notable: matic difference in diagnosis rates at While 158.2 adults per 100,000 in the Continued on Page 2

An Independent Publication of Bipolar Disorder Investigators BNN V. 22, Iss. 2, 2018 bipolarnews.org

More Childhood-Onset Illness in the US Than in Other Countries

Continued from Page 1 However, children in the US of adult males aged 55–64 in the US hospital discharge of bipolar disorder in may simply be more likely to have versus England. US men had a higher children in the US versus England. The a variety of childhood psychiatric incidence of virtually every common lower hospitalization rates for pediatric disorders than those from England. medical condition, including diabetes, bipolar disorder in England may reflect hypertension, heart disease, heart attack, the better availability of community Editor’s Note: A 2011 meta-analysis of stroke, lung disease, and cancer, and these or outpatient treatment options there. epidemiological studies by researcher Anna results held up even when the research- Diagnostic practices may also differ. R. Van Meter in the Journal of Clinical ers controlled for socio-economic status James and colleagues suggested that in Psychiatry supports the view that bipolar and access to health care. Banks and col- the US, pediatric diagnoses of bipolar disorder not otherwise specified (BP-NOS), leagues concluded that American men are disorder are often used to describe which is often the earliest manifestation in much worse health than British men. children and adolescents with irritabil- of bipolar disorder, is about twice as In a 2018 editorial in the journal ity and frequent mood shifts, whereas common in the US than in other countries. BMJ, Steven H. Woolf and Laudan English diagnostic practices rely more Even if there are some diagnostic dif- Aron further highlight that after on episodic bouts of euphoria to di- ferences that contribute to the immense losing ground for decades, US life agnose bipolar disorder in children. 72.1 fold higher rates of hospitalization for expectancy has now fallen below the childhood bipolar in the US compared to average for other developed countries. Britain, one cannot overlook the findings Bipolar Network News that these children are requiring hospital- It looks like in addition to Americans bipolarnews.org ization for something resembling bipolar suffering poorer general health than people Editor-in-Chief: Robert M. Post, MD disorder and are in need of treatment. in other developed countries, children in Managing Editor: Moira McCauley In England the researchers found America may also be psychiatrically much TheBNN is published 4–6 times a year by investigators no diagnoses of bipolar disorder in pre- sicker. The high rates of bipolar disorder working with patients with bipolar disorder to better adolescent children, whereas in the US, in US children are catastrophic, not to understand the long-term course of illness. The newsletter is available free of charge to all who request diagnoses in children under age 6 exceeded mention the toll of conditions that tend it. the rates of pediatric bipolar disorder in to accompany bipolar disorder and other

Although the editors of the BNN have made every 19-year-olds in England. In a 2017 review mood, anxiety, and behavioral disorders. effort to report accurate information, much of the article in the journal Neuroscience & Yet there does not appear to be any recogni- work detailed here is in abstract or pre-publication Biobehavioral Reviews, this editor tion of the magnitude of the problem or form, and therefore cannot be taken as verified data. The BNN can thus assume no liability for errors of Robert M. Post and colleagues reviewed public sector attempts to ameliorate it. fact or omission, or lack of balance. Patients should research on incidence of childhood onset Woolf and Aron end their BMJ editorial consult with their physicians, and physicians with the published literature, before making any treatment bipolar disorder and found higher rates on a pessimistic note: “Ironically, leaders decisions based on information given in this issue or in of the illness in the US than in Canada, are outspoken about ending the opioid BNN any issue of the . Argentina, and several European coun- epidemic and bemoan spiraling and unsus- Dr. Post has consulted on behalf of drug companies tries. Genetic and environmental factors tainable healthcare costs. Solutions to both including Abbott, Astra Zeneca, Bristol-Myers Squibb, Glaxo-SmithKline, Jansen, and Pfizer. contributed to this vulnerability in US problems—which involve investment to patients. Compared to Europeans in the support struggling families and communi- The opinions expressed in the BNN are solely those of Dr. Post, and do not represent the views of any Netherlands and Germany, those with ties and thereby improve public health—are scientific entity or foundation. bipolar disorder in the US have more often rejected, usually by leaders with Send any comments or suggestions to: family history of psychiatric illness and competing self-interests or ideological ob- [email protected] face more psychosocial stress in childhood. jections. The consequences of these choices BNN are dire: not only more deaths and illness 5415 W. Cedar Lane Suite 201B Several studies have also found that but also escalating healthcare costs, a sicker Bethesda, MD 20814 general medical health in adult males workforce, and a less competitive economy. To subscribe or unsubscribe, see our website is worse in the US than in other devel- Future generations may pay the great- or email us at: oped countries, as is life expectancy. est price.” This editor (Robert M. Post) [email protected]. A 2006 study by James Banks and would further emphasize that most adult Note that we do not accept requests to colleagues in JAMA, the Journal of psychiatric disorders begin in childhood, subscribe friends or family members. Please the American Medical Association, and our current generation of children have them contact us directly. reported a disparity in the medical health are already paying the greatest price.

Page 2 BNN V. 22, Iss. 2, 2018 bipolarnews.org

Children Who Are Bullied Playing Tackle Football Have Poorer Mental Health Before Age 12 May Be A 2017 study of twins between the ages of 11 and 16 found that being bullied around age 11 caused anxiety, depression, hyper- Bad for the Brain activity and impulsivity, inattention, and conduct problems, A 2017 study found that men who some of which lasted for years. Participants recorded their expe- began playing American tackle football riences with physical or verbal bullying, social manipulation, and before age 12 were more likely to have property attacks (trying to break one’s belongings, for example). depression, apathy, problems with execu- The effects of bullying decreased over time. The bullied children tive functioning, and behavioral issues in were still significantly more anxious than their non-bullied twins two adulthood than their peers who began years later, but this difference faded by the five-year mark. However, playing football after age 12. Duration of paranoid thoughts and cognitive disorganization did persist for 5 years. football play did not seem to matter—those The twin study design helped researchers zone in on the causal men who stopped playing football after effect bullying might have on the children’s mental health, rather than high school were just as likely to be af- other factors the twins shared, such as genetics or family environ- fected in adulthood as those who went on ment. The study included 11,108 twins born in England and Wales. to play football in college or professionally. The research by Timothy Singham and colleagues was pub- The study by Michael L. Alosco and lished in the journal JAMA Psychiatry. Interestingly, the researchers colleagues was published in the journal found that prior mental health difficulties increased children’s Translational Psychiatry. It included 214 likelihood of being bullied, such that being bullied could be con- men (average age 51) who had played sidered a symptom of preexisting vulnerabilities. Singham and football in their youth, but not other colleagues suggest that in addition to interventions to reduce contact sports. The men reported their bullying and address familial factors that might make children sus- own experiences with depression, apathy, ceptible to bullying, children should also be taught resilience skills. cognitive function, and behavioral regula- tion. Those who began football before age 12 were twice as likely to report Cannabinoid Gel Treats Fragile X Syndrome impairment in behavioral regulation, Fragile X syndrome is a genetic disorder characterized by de- apathy, and executive function than those velopmental problems such as intellectual disabilities, cognitive who began playing later. Those who impairment, and behavioral and learning challenges. Zynerba started younger were also three times Pharmaceuticals announced in 2017 that a cannabinoid gel they more likely to have clinical depression in have produced improved symptoms of fragile x syndrome in adulthood than those who started older. children and adolescents when applied daily to the upper arm. According to Alosco and colleagues, Multiple cannabinoids are derived from cannabis plants, and between ages 9 and 12, the brain reaches include cannabidiol, which likely conveys some of the plant’s peak maturation of gray and white matter positive effects, and tetrahydrocannabinol (THC), which lends volume, and synapse and neurotransmitter marijuana its psychoactive or psychomimetic effects, such as delu- density also increases. The repeated head sion or delirium. Cannabidiol is the active ingredient in the gel, and injuries that can occur during youth football no THC was found in participants’ blood tests after using the gel. play during this time may disrupt neurode- The open study of 20 patients aged 6 to 17 years found that the partici- velopment, with lasting negative effects. pants showed improvement on a scale measuring anxiety, depression, One drawback to the study was that and mood after 12 weeks of using the gel. The gel also appeared to recruitment was not random—men who improve aberrant behaviors including social avoidance, temper tantrums, volunteered for the study might have repetitive movements, and hyperactivity. Treatment began at a dose of done so due to a recognition of their 50mg per day, and could be increased up to 250 mg per day within the first own cognitive problems. However, the six weeks of the study. The dose then remained stable for the next six weeks. results suggest more study is needed, Zynerba Pharmaceuticals hope to begin controlled clinical trials in 2018, and caution is encouraged when making with the goal of attaining approval for the drug from the US Food and Drug decisions about youth football participa- Administration. Other companies are also competing to garner the first tion. Some youth football leagues have FDA approval of a cannabis-based drug. Many of the drugs currently in begun placing greater limits on the development are intended to target neurological or behavioral conditions. type of contact allowed during play.

Page 3 BNN V. 22, Iss. 2, 2018 bipolarnews.org Treatment Approaches to Childhood-Onset Treatment-Resistant Bipolar Disorder Dear readers interested in the treatment of young children Mania with bipolar disorder and multiple other symptoms: In 2017, BNN Editor Robert M. Post and colleagues published an open access paper in the journal The Primary Care Companion for CNS Disorders titled “A Multi-Symptomatic Child: How Depression to Track and Sequence Treatment.” The article describes a single case of childhood-onset bipolar disorder shared with us via our Child Network, a research program in which parents can create weekly ratings of their children’s ADHD mood and behavioral symptoms, and share the long-term results in graphic form with their children’s physicians. Here we summarize potential treatment approaches for this child, which may be of use to other children with similar symptoms. Anxiety We present a 9-year-old girl whose symptoms of depres- sion, anxiety, attention-deficit hyperactivity disorder (ADHD), oppositional behavior, and mania were rated on a weekly basis in the Child Network under a protocol approved by Overall Illness the Johns Hopkins School of Medicine Institutional Review Board. The girl, whose symptoms were rated consistently for almost one year, remained inadequately responsive to lithium, , and several other medications. Oppositionality We describe a range of other treatment options that could be introduced. The references for the suggestions are available in the full manuscript cited above, and many quotes from the original article are reprinted here directly. Sep ‘15 Dec ‘15 Mar ‘16 Jun ‘16

As illustrated in the figure, after There was little change in her moderate necessary, and combined use of medi- many weeks of severe mania, depres- but fluctuating depression ratings, cations, family education, and therapy. sion, and ADHD, the child initially but her ADHD symptoms got worse. appeared to improve with the in- The patient had been previously Mood Stabilizers and troduction of 4,800 micrograms per diagnosed with bipolar II disorder Atypical Antipsychotics day of lithium orotate (a more potent and anxiety disorders including school to Maximize Antimanic alternative to lithium that is phobia, generalized anxiety disorder, Effects marketed as a dietary supplement), in and obsessive compulsive disorder. combination with 1 mg per day of guan- Given the six weeks of moderate None of the treatment options in facine, and 1 mg per day of melatonin. to severe mania that the patient ex- this section are approved by the US Despite continued treatment with perienced in October and November Food and Drug Administration for use lithium orotate (up to 9,800 micrograms 2015, she would meet criteria for in children under 10 years of age, so twice per day), the patient’s opposi- a diagnosis of bipolar I disorder. all of the suggestions are “off label.” tional behavior worsened during the Further, they may differ from what period from November 2015 to March Targeting Symptoms to other investigators in this area of medi- 2016, and moderate depression re- Achieve Remission cine would suggest, especially since emerged in April 2016. Anxiety was also evidence-based medicine’s traditional generally less severe from December General treatment goals would gold standard of randomized placebo- 2015 to July 2016, and weekly ratings of include: mood stabilization prior to use controlled clinical trials is impossible overall illness remained in the moder- of ADHD medications, a drug regimen to apply here, given the lack of research ate severity range (not illustrated). that maximizes tolerability and safety, in children with bipolar disorder. In June 2016, the patient began taking targeting of residual symptoms with As we share in the original article, risperidone (maximum dose 1.7 mg/ appropriate medications supplemented reintroducing lithium alongside day) instead of lithium, and her mania with nutraceuticals, recognition that risperidone could be effective, as improved from moderate to mild. complex combination treatment may be “combinations were more effective

Page 4 BNN V. 22, Iss. 2, 2018 bipolarnews.org than monotherapy in a study [by] “The mood stabiliz- an effect on liver enzymes than car- Geller et al. (2012), especially when ers (, , and bamazepine. However, low blood they involved an atypical antipsy- valproate) each have considerable sodium levels are more frequent on chotic such as risperidone. This might mood stabilizing and anti-anxiety than carbamazepine. include the switch from lithium orotate effects, at least in adults with bipolar to ,” the typical disorder. With inadequate mood sta- Other Atypical treatment for bipolar disorder, on bilization of this patient on lithium Antipsychotics That May which more research has been done. and risperidone, we would consider Improve Depression “Combinations of lithium and val- the further addition of lamotrigine. proate were also more effective than Lamotrigine appears particularly ef- “[In a study by Geller et al., the either [drug alone]…in the studies fective in adults with bipolar disorder ] risperidone of Findling et al. (2006),” and many who have a personal history and a had more side effects than lithium patients needed stimulants in addition. family history of anxiety (as opposed or valproate, including more weight “Most children also needed combi- to mood disorders), and it has positive gain and prolactin elevations. These nations of mood stabilizers (lithium, open data in adolescents with bipolar findings, along with the fact that carbamazepine, valproate) in the depression and in a controlled study of risperidone is not FDA-approved study [by] Kowatch et al. (2000).” In maintenance (in teenagers 13–17, but for unipolar or bipolar depression a 2017 study by Berk et al. of patients not in preteens 10–12) (Findling et al. in adults, suggests the possibility of hospitalized for a first mania, ran- 2015). With better mood stabilization, switching this child to another atypical domization to lithium for one year anxiety symptoms usually diminish..., [antipsychotic] with better antide- was more effective than and we would pursue these strate- pressant and anti-anxiety effects.” on almost all outcome measures. gies [instead of using] antidepressants Lurasidone was recently approved for depression and anxiety in young for bipolar depression in young Targeting ADHD children with bipolar disorder.” people aged 10–17 years old, and “Carbamazepine appears to be more does not seem to cause much weight “[The increased] severity of [the effective in adults with bipolar who gain or other metabolic side effects. child’s] ADHD despite improv- have [no] family history of mood dis- has anti-manic effects ing mania speaks to the...utility of orders,” unlike lithium, which seems in adults and children, has the ad- adding a stimulant to the regimen to work better in people who do have vantage of being relatively weight that already includes…guanfacine,” a family history of mood disorders. neutral, and recent data indicate its which is a common non-stimulant “While the overall results of oxcar- effectiveness as an adjunctive treat- treatment for ADHD. “This would bazepine in childhood mania were ment in adults with mixed depression. be supported by the data of Scheffer negative, they did exceed placebo A widely used atypical antipsy- et al. (2005) that stimulant augmenta- in the youngest patients (aged 7–12) chotic, quetiapine, is approved for tion for residual ADHD symptoms as opposed to the older adoles- mania and bipolar depression in does not [worsen] mania, and that cents (13–18) (Wagner et al. 2006). adults, but not in children. Weight the combination of a stimulant and “There are long-acting preparations gain on quetiapine is about equal guanfacine may have more favor- of both carbamazepine (Equetro) and to that of risperidone, but a study able effects than stimulants alone.” oxcarbazepine (Oxtellar) that would of quetiapine in young people with However, the consensus in the field allow for all nighttime dosing to help bipolar depression was not successful. is that mood stabilization should be with sleep and reduce daytime side , a dopamine partial achieved first, before low to moderate effects and sedation. Although data agonist, is another atypical antip- (but not high) doses of stimulants [on] anti-manic and antidepressant sychotic option. In children, weight are added. “Thus, in the face of an effects in adults are stronger for car- gain on aripiprazole can range from inadequate response to the lithium- bamazepine than oxcarbazepine,” minimal to substantial, and aripipra- risperidone combination in this child, there are good reasons to consider ox- zole decreases the hormone prolactin. stimulants could be deferred until better carbazepine. First, there is the finding While aripiprazole failed to show ef- mood stabilization was achieved.” mentioned above that oxcarbazepine ficacy in bipolar depression in adults, it worked best in the youngest children. is FDA-approved for use alongside an- Other Approaches to Mood Second, there is a lower incidence of tidepressants for unipolar depression. Stabilization and Anxiety severe white count suppression on Reduction oxcarbazepine. Third, it has less of Continued on Page 6

Page 5 BNN V. 22, Iss. 2, 2018 bipolarnews.org

Two new drugs that are also do- inhibitor antidepressants (SSRIs) in There are several psychotherapeu- pamine partial agonists may be of obsessive compulsive disorder (OCD). tic approaches that can help children some use. Brexpiprazole was recently It can also improve a variety of habit- manage their illness, particularly those approved by the FDA for adults with based behaviors such as addictions. that involve the family as a whole and schizophrenia and as an adjunct to In children with autism, three focus on illness education, improved antidepressants in unipolar depres- placebo-controlled studies found communication, mood and behavioral sion. is FDA-approved that NAC reduced irritability. (One charting, cognitive behavioral therapy, for adults with schizophrenia and study looked at NAC by itself, and problem solving, and alternatives to mania, was superior to placebo in the other two used the supplement punitive discipline. Family-focused three studies of bipolar depression, and as an adjunct to risperidone.) NAC is therapy, an approach developed has been successful as an adjunctive sold without a prescription in health by researcher David Miklowitz treatment for unipolar depression. food stores, and doses of 500mg twice and colleagues, is one good option. and are less per day can slowly be increased (on a It may be difficult to find a therapist appealing options because they cause weekly basis) to 2,000–2,700mg/day. trained in such techniques, but the more weight gain than most other atyp- There is some support for the use of efforts are likely worthwhile. Research ical antipsychotics, and clozapine also omega-3 fatty acids to target depression by Lars Kessing has shown that patients requires weekly monitoring of white and ADHD, and their safety suggests hospitalized for the first time with blood cell count. However, among there is little risk in trying them for mania who were randomized to two atypical antipsychotics clozapine has patients who have symptoms of both. years of treatment at a specialty clinic the highest rate of anti-manic response Many children with serious psy- fared better than those who received in adults, and has been used success- chiatric illness have deficiencies in treatment as usual. They had fewer fully in childhood-onset schizophrenia. vitamin D3, and open data in 6–17- relapses and did better even years It is clear that comparative studies year-old patients with bipolar disorder after the specialty treatment ended, of the efficacy and tolerability of suggests that taking vitamn D3 sup- suggesting that a good initial inter- atypical antipsychotics in children with plements can improve symptoms. vention that includes education may bipolar disorder are sorely needed. In children who have undergone improve the long-term course of illness. In a patient like the one we’ve genetic testing that identified a methyl- Researcher Lakshmi Latham and discussed, if an excellent mood and tetrahydrofolate reductase (MTHFR) colleagues have found that that cog- anxiety response is achieved using deficiency, supplementation with l- nition returns to normal after a first mood stabilizers and atypical antip- methylfolate should be used (rather manic episode only if there are no sychotics, but substantial residual than folate itself) and could also recurrences over the following year, symptoms of ADHD and oppositional improve depression, as it seems to in suggesting the importance of initiating behavior remain, a stimulant could adults (when taken alongside SSRIs). intensive treatment that incorporates then be added, as noted above. For children with oppositional be- both medication and therapy aimed at havior that persists despite multiple prevention after a first manic episode. Nutraceutical Approaches attempts at mood stabilization and to Depression, Anxiety, and stimulant augmentation, there are Mood Charting Oppositional Behavior complex combinations of vitamins and minerals that may have some Since systematic treatment data For children like the one in our effect. EMPowerplus is one branded in children are so lacking, the best case study, who have shown some supplement designed to support chil- guidance for treatment is the in- improvement but still have residual dren’s mental health that has been dividual child’s actual response. symptoms, we would add a series of found to be safe and effective in small Charting the child’s improvement adjunctive treatments to the combi- open trials with children with bipolar or deterioration after trying a given nation of an atypical antipsychotic, disorder and behavioral dyscontrol. treatment can facilitate parental lithium, and another . It may have some interactions with and clinical decision-making. An excellent option for re- other drugs, especially lithium, doses We thus encourage parents to sidual anxiety and depression is of which would need to be reduced. provide this type of input and N-acetylcysteine (NAC). In studies in feedback to physicians in a format adults, this antioxidant has performed Psychotherapeutic such as the one used in our Child better than placebo at reducing bipolar approaches Network, which can be accessed at depression, and it can also improve the our website, bipolarnews.org (click effects of selective serotonin reuptake on the tab for the Child Network).

Page 6 BNN V. 22, Iss. 2, 2018 bipolarnews.org

Is Your Child at Risk for a Mood Disorder? Join the Child Network!

74% of children who have a parent with bipolar disorder (Axelson et al. 2015) and 80% of those who have a parent with unipolar depression (Weissman et al. 2006) will develop a major psychiatric illness upon long-term follow up. These illnesses, including depression, anxiety, oppositional behavior, substance abuse, often go unrecognized for long periods of time. Joining the Child Network could help families and doctors identify these illnesses earlier.

The Child Network is specifically for parents of children ages 2 to 12 who are at high risk for a mood disorder or have symptoms of a mood disorder. Parents assess their child weekly using a secure website. There is also a short demographic questionnaire and a more detailed symptom checklist to be filled out once a year. The network will collect information about which treatments children are already taking, how effective they are, and for which children.

We believe that this network will be helpful to its participants. Parents will be able to print out the ongoing weekly ratings in a graphic form so that the child’s symptoms and respons- es to any treatments they receive over time can easily be visualized (as illustrated below).

Weekly Mood and Medication Chart

Fluoxetine

Lithium

Mar 2 Mar 9 Mar 16 Mar 23 Mar 30 Apr 6 Apr 13 Apr 20 Apr 27 May 4 May 11 May 18 May 25 Jun 1 Jun 8 Jun 15 Jun 22 Jun 29

Weekly Severity of Depression/Mania

3 2 1 r i t y 0 v e s i o n / M a s e 1 2 D e p r 3 Apr 2014 May 2014 June 2014

0 - Severity None: None 1 - Severity Mild/Infrequent: Minimal impact on usual roles 2 - Moderate Symptoms/Often: Definitely some dysfunction in usual roles 3 - Severe Symptoms/Much of the Time: Major dysfunctions in usual roles

We hope that this brief description of the Child Network study helps to orient you to its purpose. Please urge parents to use this new tool. Visit bipolarnews.org and click on the tab for the Child Network or go directly to http://bipolarnews.org/?page_id=2630 to learn more about the Child Network and to access the informed consent documents. Thank you for your time and interest in the Child Network. Robert M. Post, MD and Michael Rowe, PhD Bipolar Collaborative Network, and Robert L. Findling, MD, MBA, Principal Investigator This research study is IRB approved by the Johns Hopkins University School of Medicine Research Study, Principal Investigator: Robert L. Findling, MD, MBA , IRB Study #00026940

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