A 12-week single-blind trial of quetiapine for the treatment of mood symptoms in adolescents at high risk for developing bipolar I disorder. J Clin Psychiatry

Division of Bipolar Disorders Research, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0559, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 05/2007; 68(5):789-95.
Source: PubMed


To investigate the effectiveness and tolerability of quetiapine for the treatment of adolescents at high risk for developing bipolar I disorder.
Twenty adolescents (aged 12-18 years) with mood symptoms that did not meet DSM-IV-TR criteria for bipolar I disorder and who had at least one first-degree relative with bipolar I disorder were recruited from August 2003 to June 2005 to participate in a single-blind, 12-week prospective study of quetiapine. Subjects were diagnosed using the Washington University in St. Louis Kiddie Schedule of Affective Disorders and Schizophrenia and were symptomatic, defined by a Young Mania Rating Scale (YMRS) score > or = 12 or a Childhood Depression Rating Scale-Revised Version (CDRS-R) score > or = 28 at baseline. The primary effectiveness measure was an endpoint Clinical Global Impressions-Improvement scale (CGI-I) score < or = 2 ("much" or "very much" improved). Secondary efficacy measures included change from baseline to endpoint in YMRS and CDRS-R scores.
Mood disorder diagnoses in the adolescents consisted of bipolar disorder not otherwise specified (N = 11), dysthymia (N = 3), bipolar II disorder (N = 3), cyclothymia (N = 2), and major depressive disorder (N = 1). The majority of patients (N = 12, 60%) were non-responders to previous trials of psychotropic agents. Fifteen subjects (75%) completed all study visits. Eighty-seven percent of patients were responders (CGI-I < or = 2) to quetiapine at week 12 (mean +/- SD endpoint dose = 460 +/- 88 mg/day). YMRS scores decreased from 18.1 +/- 5.5 at baseline to 8.7 +/- 7.9 at endpoint (p < .0001), and CDRS-R scores decreased from 38.2 +/- 9.8 to 27.7 +/- 9.3, (p = .0003). The most frequently reported adverse events were somnolence, headache, musculoskeletal pain, and dyspepsia. No subjects discontinued study participation due to adverse events.
Although these findings are limited by the small sample size and open-label treatment, the results suggest that quetiapine may be an effective treatment for mood symptoms in adolescents with a familial risk for developing bipolar I disorder.

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    • "Several prospective studies have been conducted on the course of illness and long-term prognosis of a manic episode in adolescents, but few exhibit results on the determinants of short-term outcome. To summarize, mixed polarity, low socioeconomic status (SES), young age at onset, previous affective episode , psychosis and female sex were associated, at least in one study, with a poorer outcome (Strober et al., 1995; Geller et al., 2002a; Jairam et al., 2004; Birmaher et al., 2006; DelBello et al., 2007a). However, none reported transition risk to schizophrenia spectrum disorder. "
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    ABSTRACT: Little is known concerning the prognostic significance of manic/mixed episodes in adolescents. In particular, whether the use of psychodynamic-oriented projective psychological testing predicts evolution to schizophrenia at follow-up has not been established. Eighty subjects, aged 12-20years old, consecutively hospitalized for a manic or mixed episode between 1994 and 2003 were recruited. All patients were contacted in 2005-2006 for a follow-up assessment. For the subgroup of adolescents (N=40) who had psychodynamic-oriented psychological testing (Rorschach and TAT), two scores regarding psychosocial risk and schizophrenia risk were computed using the clinical global impression (CGI) assessment based on an overall subjective rating given by a panel of expert psychologists who reviewed all protocols. At follow-up (average 8years), 25 (62.5%) patients, 16 females and nine males, were assessed: 14 still had a diagnosis of bipolar disorder; eight changed to schizo-affective disorder and three to schizophrenia. Inter-rater reliability of both CGI-risk scores (psychosocial risk and schizophrenia risk) showed good clinical consensus with intraclass correlation and Kappa scores ranging from 0.53 to 0.75. Univariate analysis showed that CGI-psychosocial risk score (p=0.017), type of index episode (p=0.049) and CGI-schizophrenia risk score (p=0.09) were associated with transition to schizophrenia spectrum disorder at follow-up. Age, sex, socioeconomic status, duration of stay and the presence of psychotic features at index episode were not associated with the transition. We conclude that the CGI assessment appears to be valid to score risk of poor outcome using psychodynamic-oriented psychological testing and that these scores may predict, in part, the transition to schizophrenia in adolescents with a history of manic/mixed episode.
    Journal of Physiology-Paris 11/2010; 104(5):257-62. DOI:10.1016/j.jphysparis.2010.08.004 · 1.90 Impact Factor
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    • "gh in the course of illness . Fur - ther research also needs to be conducted with atypical antipsychotics in this regard , because , although we did not find that exposure to this class of medication was associated with delayed AAO of mania , a previous study found quetiapine effective acutely in reducing mood symptoms in an at - risk population ( DelBello et al . 2007 ) ."
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    ABSTRACT: Exposure to psychotropic medications before the onset of bipolar disorder (BD) in children may have profound effects on the course of illness. Both antidepressant and stimulant exposure have been proposed to hasten the course of BD development, whereas mood stabilizers have been proposed as protective. We sought to describe psychotropic medication exposure in a cohort of children at risk for BD and retrospectively determine the effect of medication exposure on age at onset (AAO) of BD. Subjects were 106 children and adolescents who had at least 1 parent with BD. Of these, 63 had BD I or BD II and 43 had subsyndromal symptoms of BD. AAO was determined as nearest month of first manic or hypomanic episode. Past psychotropic medication exposure prior to AAO was determined through interview and chart review. Both groups had high rates of exposure to psychotropic medications. Antidepressant or stimulant exposure was not correlated with an earlier AAO of BD. However, mood stabilizer exposure was associated with a later AAO. Children with full or subsyndromal BD are frequently exposed to a variety of psychotropic medications before their first manic episode. Our findings do not support that early stimulant or antidepressant exposure leads to an earlier AAO of BD. However, early mood stabilizer exposure may be associated with delayed AAO. Longitudinal studies are needed to clarify these results.
    Journal of child and adolescent psychopharmacology 02/2010; 20(1):25-32. DOI:10.1089/cap.2009.0036 · 2.93 Impact Factor
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    • "But again results were inconclusive (Delbello et al. 2005). A single-blind trial of quetiapine for the treatment of mood symptoms in adolescent at high risk for developing bipolar I disorder reported good therapeutic response but adolescents recruited did not meet DSM IV criteria for BD (DelBello et al. 2007). There is no published controlled study versus placebo for the other mood stabilizers (carbamazepine , valproate or sodium divalproate), yet a study compared divalproate, with quetiapine adjunction, versus placebo (Delbello et al. 2002). "
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    ABSTRACT: In the absence of recommendations from drug regulatory agencies for most medications to treat severe manic or mixed episode in adolescence, this study aims to (i) describe the pharmacological treatment prescribed in an inpatient setting for acute manic or mixed episodes in adolescents; (ii) determine whether type of episode, duration of stay, improvement, and psychotic features were associated with the nature of the given treatment; (iii) compare the results with evidence-based data. From 1993 to 2003, we received 80 subjects, aged 12 to 20 years, consecutively hospitalized for a manic or mixed episode. Socio-demographic, clinical and treatment data were extracted by reviewing patients' charts. Treatment data were available for 75 subjects. Most patients received a combination treatment including mood stabilizer (82.6%), classical antipsychotic (AP) (86.6%) and atypical AP (24%). Despite prolonged hospitalisation (minimum stay = 17 days), 69 (86.2%) patients were scored very much or much improved at discharge. Secondary therapeutic options occurred in 15 subjects because of poor therapeutic response (N=13), severe adverse effects (N=5) or both. Two patients had electroconvulsive therapy as third therapeutic option. Adolescents with psychotic symptoms were significantly more frequently treated by lithium (Fisher exact test: p=0,0052). No other variable was associated with treatment. This study reported on patterns of medication use that mainly followed treatment recommendations and evidence-based data existing in adults. However, the presence of psychotic features appeared to favour the use of lithium in this French sample.
    Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent 09/2009; 18(3):231-8.
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