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Patient: 12-year-old girl
Present illness: The patient had been a lively sixth grade pupil, with apparently normal conduct and no developmental problems, living with her biological parents, a sister younger by 3 years and her paternal grandmother, until she became increasingly irritable and noisy in the preceding few weeks. Her mother noted the patient's increased talkativeness and more frequent quarrels with her little sister recently, but did not consider it to be problematic, until the school teacher called her up and told her that her daughter was no longer ‘manageable’ at school. The mother had also noted that the patient had been sleepless for the past several days. She reported that the girl had had her menarche 6 months prior.
ARE THE RESULTS AT RISK OF BIAS?
Was the sample of patients representative?
REASONABLY YES. The cohort was obtained from designated outpatient child psychiatric and paediatric sites by consecutive new case ascertainment.
Were the patients sufficiently homogeneous with respect to prognostic risk?
Various prognostic factors were examined, including psychotic features (seen in 61% of the cohort). No prognostic factor was identified for recovery, and the only significant predictor for relapse was maternal warmth.
Was the follow-up adequate and sufficiently complete?
YES. Of the initial 115 children, 94% were seen through the 8-year follow-up.
Were outcome criteria objective and unbiased?
YES. Recovery was defined as eight consecutive weeks without meeting Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria for mania, and relapse was defined as two consecutive weeks of meeting DSM-IV criteria for mania with Children's Global Assessment Scale score of 60 or lower. Manic and other symptoms were rated by blinded, trained raters using the semistructured psychiatric interview called Washington University Kiddie Schedule for Affective Disorders and Schizophrenia, and excellent inter-rater reliability has been reported (κ=0.82–1.00).
WHAT ARE THE RESULTS?
How likely are the outcomes over time?
▸ According to the life-table survival analyses, the overall likelihood of recovery was 95% (95% CI 91% to 100%) through 8 years, and the median time to recovery was 12 months, with over 80% of participants recovering by 3 years. Altogether the participants spent 42% of the time in manic episodes and 23% in depressive episodes during the 9-year follow-up.
▸ However, once recovered, the overall likelihood of relapse was 78% (95% CI 69% to 87%), and the median time to relapse was approximately 24 months. For those with high maternal warmth, the median time was almost 48 months, whereas for those with low maternal warmth, it was around 15 months.
▸ Apparently no change in diagnosis to schizophrenia is reported.
How precise are the estimates of likelihood?
The estimates were reasonably narrow, as shown by their 95% CIs.
HOW CAN I APPLY THE RESULTS TO PATIENT CARE?
Were the study patients and their management similar to those in my practices?
In this study, all treatments were provided by the participants’ own community practitioners. An associated study1 reported, however, that only 63% received any antimanic medication (antipsychotic, anticonvulsant or lithium) at any time. Lithium predicted early recovery.
Can I use the results in the management of patients in my practice?
Present status: On entry into the consulting room, accompanied by her mother, the girl was restless, noisy and talkative. When told by her mother to sit, she suddenly burst into anger and physically attacked her. Her speech was incessant, and its content was grandiose but often incoherent. In the midst of her continuous babbles, she suddenly stopped motionless and appeared as if she was listening to someone. When asked if she heard any voices, she said she was talking with her dead grandfather. She did not admit to any other bizarre delusions. The family denied the patient's use of prescribed or illicit drugs, or possible signs of infection in the preceding days.
Course of illness: The patient was hospitalised. As the doctor in charge, recognising the difficulties of any definitive diagnosis at the first presentation in adolescence, your provisional diagnosis would be bipolar I disorder, with mood-congruent psychotic features. While ordering brain CT and EEG to be taken, you wonder what this patient's likely prognosis is, given her childhood onset and its psychotic features.
Formulate your clinical question
Patients: Children or early adolescents with mania with psychotic features
Outcomes: Likelihood of recovery, relapse and development into schizophrenia
The search for relevant literature for this clinical question was extremely difficult and time-consuming. One typical starting point for the search would be: ‘bipolar disorder’ [MeSH] in the Clinical Queries ‘Prognosis/Narrow’, with age limited to ‘Child: birth-18 years’. This retrieved 686 references.
Among them, an NIMH-funded study, Course and Outcome of Bipolar Youth (COBY), appeared to be most relevant. Reading the most recent report from this study, Birmaher B et al. Four-year longitudinal course of children and adolescents with bipolar spectrum disorders. Am J Psychiatry 2009;166:795–804, however, it was found that this study recruited patients irrespective of their mood state and the participants had been ill for 4.4 years when they were enrolled. In other words, this study did not constitute an inception cohort, that is, those at a similar stage of illness course, and was totally unfit to answer prognostic questions.
Then another article was found which, at first sight, looked very pertinent: Findling RL et al. The 24-month course of manic symptoms in children. Bipolar Disord 2013;15:669–679. However, this study focused on manic symptoms and included participants with various diagnoses (bipolar I disorder, bipolar spectrum disorder and no bipolar disorder) and was again unable to answer the clinical question.
In the end, another NIMH-funded study was found, Phenomenology and Course of Pediatric Bipolar Disorders. It recruited consecutive new cases, 7–16 years of age and with a diagnosis of current Diagnostic and Statistical Manual of Mental Disorders (DSM) IV bipolar I manic or mixed phase. The index episode was also the first such episode in the majority of the cohort. Its most recent report, after 8 years of follow-up was: Geller B et al. Child bipolar I disorder: prospective continuity with adult bipolar I disorder; characteristics of second and third episodes; predictors of 8-year outcome. Arch Gen Psychiatry 2008;65:1125–1133.
What will you do with your patient?
As would be expected of bipolar disorder, the cumulative recovery rate was high, and the cumulative relapse rate after recovery was also high. However, the median time to recovery was much longer than expected, and through the ensuing 8 years, almost two-thirds of the time was spent in mood episodes. This information, as well as the prognostic non-significance of psychotic features and significance of maternal warmth and use of lithium, can form the basis of the long collaborative treatments to come with this patient and with her family.
Competing interests TAF has received lecture fees from Eli Lilly, Meiji, Mochida, MSD, Pfizer and Tanabe-Mitsubishi, and consultancy fees from Sekisui and Takeda Science Foundation. He is diplomate of the Academy of Cognitive Therapy. He has received royalties from Igaku-Shoin, Seiwa-Shoten and Nihon Bunka Kagaku-sha. The Japanese Ministry of Education, Science, and Technology, the Japanese Ministry of Health, Labor and Welfare, the Japan Foundation for Neuroscience and Mental Health, Mochida and Tanabe-Mitsubishi have funded his research projects.
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