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Julie B Penzner,
Melissa Dudas,
Ema Saito,
Vladimir Olshanskiy,
Umesh H Parikh,
Sandeep Kapoor,
Raja Chekuri,
Dominick Gadaleta,
Jennifer Avedon,
Eva M Sheridan,
Jane Randell,
Anil K Malhotra,
John M Kane,
Christoph U Correll
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ABSTRACT: Second-generation antipsychotics (SGAs) are associated with weight gain, metabolic abnormalities, sedation/sleep disturbance, and prolactin abnormalities, especially in youths. Although stimulants have opposing dopamine receptor and adverse effects, it is unclear whether stimulant co-treatment counteracts the therapeutic or side effects of antipsychotics.
This was a naturalistic cohort study including 153 antipsychotic trials in youths aged 4-19 (mean, 11.3 +/- 3.0) years, started on an SGA for clinically significant aggression or oppositionality associated with oppositional defiant disorder, conduct disorder, disruptive behavior disorder not otherwise specified (NOS), impulse control disorder NOS, intermittent explosive disorder, Tourette's disorder, autistic disorder, and pervasive developmental disorder NOS. Patients underwent fasting assessments of body composition, lipids, glucose, insulin, prolactin, sedation, and general efficacy at baseline, weeks 4, 8, and 12, comparing patients co-prescribed stimulants (n = 71) with those not co-prescribed stimulants (n = 82).
Patients received risperidone (33.3%), aripiprazole (29.4%), quetiapine (18.4%), olanzapine (11.8%), ziprasidone (5.9%), or clozapine (0.7%). With and without adjustment for differences in baseline variables (sex, prior stimulant use, primary Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition [DSM-IV] disorders, co-morbid attention-deficit/hyperactivity disorder [ADHD], present in 46.3% of youths not receiving stimulants, and some body composition parameters), patients on versus off stimulants did not differ on any of the assessed outcomes (all p values > or = 0.1).
In contrast to guidelines, stimulant use did not precede or accompany antipsychotic use during the current episode of aggression/oppositionality in almost half of those youths who had aggressive/oppositional behavior and a DSM-IV diagnosis of ADHD. At the clinically prescribed doses, stimulant co-treatment of SGAs did not seem to significantly reduce antipsychotic effects on body composition, metabolic parameters, prolactin, sedation, and broad efficacy.
Journal of child and adolescent psychopharmacology 10/2009; 19(5):563-73. · 2.59 Impact Factor
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ABSTRACT: To describe and compare the relative merits of different identification strategies for individuals at risk for bipolar disorder (BPD).
Selective review of data that support early identification in BPD, with a particular focus on emerging clinical high-risk strategies.
Early detection of individuals at risk for BPD can utilize genetic, endophenotypic and clinical methods. Most published work focuses on genetic familial endophenotypic risk markers for BPD. However, despite encouraging results, problems with specificity and sensitivity limit the application of these data to early prevention programs. In addition, offspring studies of BPD patients systematically exclude the majority of subjects without a first-degree bipolar relative. On the other hand, emerging work in the clinical-high-risk arena has already produced encouraging results. Although still preliminary, the identification of individuals in subsyndromal or attenuated symptom 'prodromal' stages of BPD seems to be an under-researched area that holds considerable promise deserving increased attention. Required next steps include the development of rating tools for attenuated and subsyndromal manic and depressive symptoms and of prodromal criteria that will allow prodromal symptomatology to be systematically studied in patients with recent-onset bipolar, as well as in prospective population-based phenomenology trials and attenuated symptom-based high-risk studies.
Given the current limitations of each early identification method, combining clinical, endophenotypic and genetic strategies will increase prediction accuracy. Since reliable biological markers for BPD have not been established and since most patients with BPD lack a first-degree relative with this disorder, clinical high-risk approaches have great potential to inform early identification and intervention programs.
Bipolar Disorders 07/2007; 9(4):324-38. · 5.29 Impact Factor
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ABSTRACT: The presence and specificity of a bipolar prodrome remains questioned. We aimed to characterize the prodrome prior to a first psychotic and nonpsychotic mania and to examine the phenotypic proximity to the schizophrenia prodrome.
Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective, information regarding the mania prodrome was collected from youth with a research diagnosis of bipolar I disorder and onset before 19 years of age, and/or their caregivers. Only newly emerging, at least moderately severe, symptoms were analyzed. Prodromal characteristics were compared between patients with and without subsequent psychotic mania and with published bipolar and schizophrenia prodrome data.
In 52 youth (age at first mania: 13.4 +/- 3.3 years), the prodrome onset was predominantly "insidious" (>1 year, 51.9%) or "subacute" (1-12 months, 44.2%), while "acute" presentations (<1 month, 3.8%) were rare. The prodrome duration was similar in patients with (1.7 +/- 1.8 years, n = 34) and without (1.9 +/- 1.5 years, n = 18) subsequent psychotic mania (P = .70). Attenuated positive symptoms emerging late in the prodrome and increased energy/goal-directed activity were significantly more common in patients with later psychotic mania. Mania and schizophrenia prodrome characteristics overlapped considerably. However, subsyndromal unusual ideas were significantly more likely part of the schizophrenia prodrome, while obsessions/compulsions, suicidality, difficulty thinking/communicating clearly, depressed mood, decreased concentration/memory, tiredness/lack of energy, mood lability, and physical agitation were more likely part of the mania prodrome.
A lengthy and symptomatic prodrome makes clinical high-risk research a feasible goal for bipolar disorder. The phenotypic overlap with the schizophrenia prodrome necessitates the concurrent study of both illness prodromes.
Schizophrenia Bulletin 06/2007; 33(3):703-14. · 8.80 Impact Factor
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ABSTRACT: Although second-generation antipsychotics (SGAs) are used increasingly in children and adolescents, data on the effectiveness and safety in pediatric populations are still sparse. Much of the safety information is derived from studies conducted in adults. This derivation is problematic because children and adolescents are exposed to SGAs during a phase of unparalleled physical and psychologic development that can affect pharmacokinetic and pharmacodynamic drug actions, efficacy, and side-effect patterns. This article presents an overview of SGA-related side effects in children and adolescents and strategies to monitor health outcomes effectively in youngsters receiving SGAs.
Child and Adolescent Psychiatric Clinics of North America 02/2006; 15(1):177-206. · 2.60 Impact Factor
