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Prospective studies of bipolar disorders (BDs) in children and adolescents are few and the findings conflict. While some studies report excellent recovery rates from index bipolar episodes (1,2), other studies report low recovery rates, ranging from 14% to 65% (3–6). No predictors of recovery were identified in any of these studies, with the exception of 1 study that reported longer episodes in those with comorbid attention-deficit hyperactivity disorder (ADHD) (3). This study examined the recovery pattern over a period of 6 months in subjects with index manic or mixed affective episodes, assessed their level of global functioning, and attempted to identify predictors of recovery and functioning. MethodsThe sample comprised all the consecutively presenting children and adolescents aged under 16 years who satisfied DSM-III-R criteria for manic or mixed-affective episode. The sample was recruited from the Child and Adolescent Psychiatry (CAP) Services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India, between January 1, 1998, and May 31, 1999. This was a protocol-driven study, and all subjects followed the stated protocol. After we obtained informed consent, we evaluated the subjects and their parents or guardians. Subjects were evaluated initially using a topical format (7) and subsequently using the Diagnostic Interview for Children and Adolescents-Revised (DICA-R) (unpublished), the Young Mania Rating Scale (YMRS) (9), and the Children’s Global Assessment Scale (CGAS) (10). The DICA-R is a revised version of the DICA (8) that follows DSM-III-R diagnosis criteria. We administered the DICA-R to confirm the diagnosis of mania, to identify past episodes of affective illness, to establish first-episode polarity, and to diagnose lifetime comorbid psychiatric conditions. When we interviewed either parent, we used the parent version in addition to the child–adolescent version. The information obtained from all the sources was reviewed, and 2 experienced child psychiatrists established a consensus diagnosis. The subjects were reassessed by the same investigator at 3 and 6 months, using the DICA-R, YMRS, and CGAS. All subjects received the standard treatment prescribed by the CAP Services, which includes monthly follow-ups and counselling regarding the need for regular medication. The study did not control for this. Recovery from the index episode was defined as the absence of relevant DSM-III-R symptoms or, if present, not more than 2 affective symptoms of mild intensity, with maintenance of the foregoing state for a minimum 8-week interval (1,2). We analyzed the cumulative probability of recovery from the index episode, the level of global functioning, and the predictors of recovery and functioning. The statistical measures selected, based on the sample size, were the Kaplan–Meier survival curve, the log-rank test, and repeated-measures analysis of variance (RMANOVA).
ResultsOut of 817 patients at the CAP Services newly registered during the study period, 26 subjects had mania (3.2%). One dropped out, and 25 subjects completed the study. For 22 (88%) subjects, this was the first-ever psychiatric consultation. Table 1 gives the baseline demographic and clinical characteristics of the sample. All subjects received lithium carbonate for treatment of the index episode, and 21 (84%) continued to receive lithium until the end of the study period. The mean dosage of lithium was 1074 mg daily, and serum level was maintained in the therapeutic range (0.8 to 1.2 mEq/L). Three subjects (12%) did not respond to lithium, and 1 (4%) did not tolerate it. Of the nonresponders, 2 received sodium valproate (mean dosage 1150 mg daily). The subject who did not tolerate lithium received carbamazapine (800 mg daily). In 1 nonresponder, the index episode did not remit during the course of the study. Nonresponse to lithium was defined as < 50% reduction of YMRS scores after at least 4 weeks of lithium treatment at therapeutic levels. Fourteen subjects (56%) needed neuroleptic medication in addition to mood stabilizers. Three (12%) of these patients did not respond to the combination and needed electroconvulsive therapy (ECT). They were given 9 to 11 modified unilateral ECTs on alternate days. All 3 responded to ECT. Clonidine (50 ug daily) was used to treat 1 patient who had comorbid ADHD. All patients continued to receive regular medication until the end of the study period. All subjects had an acute onset (less than 2 weeks) of the index episode. The median duration at the time of presentation was 30 days (mean 32 days, SD 27). The median total duration of the index episode from onset to recovery was 60 days (mean 70 days, SD 44). Twenty-four subjects (96%) recovered from the index episode within the 6-month study period . The subject who did not recover was not considered in our calculation of the time to recovery and total duration of episode. The median time to recovery was 27 days, ranging from 4 to 111 days; mean time to recovery was 32 days (SD 27). Following intake, the cumulative probability of recovery at weeks 2, 4, 6, 8, 16, and 24 was 24%, 56%, 76%, 80%, 88%, and 96%, respectively. We used Kaplan–Meier’s survival curve (log-rank test) to analyze the effects of onset-age, prior episodes of affective illness, first-episode polarity, index-episode polarity, psychotic symptoms, YMRS and CGAS intake scores, comorbidity, and hospitalization on the time to recovery from, and the total duration of, the index episode. None of these covariates predicted time to recovery. However, those with prior episodes of affective illness had significantly longer index episodes (mean 105 days vs 53 days) (log-rank test: P2 = 7.23, df 1; P = 0.0072) The severity of manic symptomatology lessened over the course of the study period, and the level of functioning greatly improved (Table 2).
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