Clozapine Treatment in Very Early Onset Schizophrenia

Mozes, Tamar; Toren, Paz; Chernauzan, Nadejda; Mester, Roberto; Yoran-Hegesh, Roni; Blumensohn, Rachel; Weizman, Abraham

doi:10.1097/00004583-199401000-00010

Cited by 70 publications

(28 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Weight gain and metabolic changes have been described in this population [4,5]. However, the weight gain in the present study is greater than that seen in more chronic pediatric patients [9,29,37,38] that may have already gained weight due to antipsychotic treatment prior to study entry. Therefore, first episode psychosis patients may be a population at greater risk for this side effect, regardless of the age.…”

Section: Discussioncontrasting

confidence: 59%

Olanzapine compared to quetiapine in adolescents with a first psychotic episode

Arango

Robles

Parellada

et al. 2009

Eur Child Adolesc Psychiatry

View full text Add to dashboard Cite

Objective: To compare the efficacy, safety, and tolerability of olanzapine and quetiapine in adolescents with first episode psychosis. Method: Fifty adolescents (age 16 ± 1.25) with a first episode of psychosis were randomized to quetiapine or olanzapine in a 6-month open label study. Efficacy and side effect scales, as well as vital signs and laboratory data were recorded at baseline, 7, 15, 30, 90, and 180 days (end of study). Results: Out of the total sample included in the study, 32 patients completed the trial (quetiapine n = 16, olanzapine n = 16). Patients in both treatment groups had a significant reduction in all clinical scales with the exception of the negative scale of the Positive and Negative Symptom Scale (PANSS) for olanzapine and the general psychopathology scale of the PANSS for quetiapine. The only difference between treatment arms on the clinical scales was observed on the patients' strength and difficulties questionnaire (SDQ) scale, with greater improvement for olanzapine. Patients on olanzapine gained 15.5 kg and patients on quetiapine gained 5.5 kg. Conclusion: Olanzapine and quetiapine reduced psychotic symptoms in this adolescent sample. Patients on olanzapine gained significantly more weight. Side effects with both drugs seemed to be more prevalent than those reported in adult studies

show abstract

Section: Discussioncontrasting

confidence: 59%

Olanzapine compared to quetiapine in adolescents with a first psychotic episode

Arango

Robles

Parellada

et al. 2009

Eur Child Adolesc Psychiatry

View full text Add to dashboard Cite

show abstract

“…For these patients, a trial of the atypical neuroleptic clozapine can be considered, if strict guidelines for clinical management of clozapine are followed (Remschmidt et al, 1994a,b). Several uncontrolled studies have provided evidence that clozapine might be effective in children and adolescents with treatment-refractory schizophrenia (Birmaher et al, 1992;Blanz and Schmidt, 1993;Frazier et al, 1994;Gordon et al, 1994;Mozes et al, 1994;Piscitelli et al, 1994;Remschmidt et al, 1994;Siefen and Remschmidt, 1986;Towbin et al, 1994). Nonetheless, about 30% of adolescents with treatment-resistant schizophrenia do not respond to clozapine in open-label treatments (Remschmidt et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Blood biogenic amines during clozapine treatment of early-onset schizophrenia

Schulz¹,

Fleischhaker²,

Clement³

et al. 1997

J. Neural Transmission

View full text Add to dashboard Cite

The aims of this investigation were to evaluate long-term and short-term effects of clozapine-treatment on plasma biogenic amines and psychopathology measures in adolescents with schizophrenia (DSM-III-R criteria). The long-term study was conducted in a study sample of 40 young patients (age 14-22 years) following a mean of 3.4 years of neuroleptic treatment. During the study, 20 patients received clozapine, and the other 20 patients were treated with standard neuroleptic medications. At the beginning of the open clinical trials, the patients had already been receiving clozapine treatment for 24 +/- 15 months. Assessment of the biochemical and psychopathological measures was performed on six occasions at consecutive 6-week intervals during maintenance treatment with clozapine or conventional neuroleptics. Blood levels of serotonin, 3-methoxy-4-hydroxy-phenylglycol (MHPG), norepinephrine, and epinephrine were significantly higher in clozapine-treated patients than in conventionally treated patients. During long-term treatment, higher serotonin levels were associated with significantly fewer negative symptoms of schizophrenia, whereas higher MHPG levels were correlated with less depression. The short-term effects of clozapine were assessed in a second and independent study sample. After failing on conventional neuroleptics in clinical trials lasting a mean of 1.6 years, 15 inpatients (aged 11-20 years) received clozapine. Weekly ratings of psychopathological symptoms using standard rating scales were performed in parallel to blood samplings for measurements of biogenic amines and serum levels of clozapine. These measures were obtained for 6 weeks during conventional neuroleptic treatment and for 6 weeks during the open-label clozapine trial. Serum levels of serotonin and plasma norepinephrine levels were significantly higher during treatment with clozapine than during pretreatment with typical neuroleptics. A comparison of plasma epinephrine levels in responders (n = 7) and nonresponders (n = 8) to clozapine revealed that response to clozapine can be predicted by epinephrine levels prior to initiation of treatment with clozapine (responders ranging from 32.2 to 90.3 pg/ml; nonresponders ranging from 92.5 to 473.5 pg/ml). Additionally, subjects who responded to clozapine showed increased mean plasma concentrations of MHPG and epinephrine during treatment with this drug in comparison to the levels measured during pretreatment with typical neuroleptic medication. Nonresponders to clozapine failed to show this increase. Finally, in responders to clozapine a negative linear relationship between negative symptoms of schizophrenia and the concentrations of plasma norepinephrine and serum serotonin were observed. In conclusion, our results demonstrate that plasma epinephrine levels prior to initiation of clozapine therapy predict response to this atypical neuroleptic. Our findings derived from short-term and maintenance treatment with clozapine suggest involvement of norepinephrine, epinephrine and serotonin in the therape...

show abstract

“…Several uncontrolled studies have provided evidence that clozapine might be an effective therapy for children and adolescents with schizophrenia (Birmaher et al 1992, Frazier et al 1994, Jacobsen et al 1994, Levkovitch et al 1994, Mozes et al 1994, Remschmidt et al 1992, Schulz et al 1994, Siefen and Remschmidt 1986. Nonetheless, about 30% of adolescents with schizophrenia do not respond to clozapine in open-label treatments (Remschmidt 1992).…”

Section: Introductionmentioning

confidence: 99%

Correlated Changes in Symptoms and Neurotransmitter Indices during Maintenance Treatment with Clozapine or Conventional Neuroleptics in Adolescents and Young Adults with Schizophrenia

Schulz

Fleischhaker²,

Remschmidt³

1996

Journal of Child and Adolescent Psychopharmacology

View full text Add to dashboard Cite

A study of 40 young patients (age 14-22 years) with DSM-III-R schizophrenia (without substance abuse) was conducted following a mean of 3.4 years of neuroleptic treatment. After failing on conventional agents in clinical trials lasting a mean of 2 years, 20 patients were prospectively maintained on open-label clozapine (mean 324 mg daily), and another 20 patients continued on typical neuroleptics (mean 465 mg chlorpromazine-equivalents daily). Patients were then sampled for biochemical measures and assessed for psychopathology (Brief Psychiatric Rating Scale, Scales for the Assessment of Positive/ Negative Symptoms) on six occasions at consecutive 6-week intervals-during maintenance treatment on clozapine or conventional neuroleptics. There were 22-fold interindividual differences in clozapine levels and also high intraindividual differences over time. Maintenance dosage was linearly related to plasma levels of clozapine and its metabolites. Prolactin levels were elevated with typical neuroleptics but not clozapine. Blood levels of serotonin, methoxyhydroxyphenylglycol (MHPG), norepinephrine, and epinephrine (but not dopamine) were significantly higher in clozapine-treated patients than in conventionally treated patients. Higher serotonin levels were associated with significantly fewer negative symptoms, whereas higher MHPG levels were correlated with less depression. These findings suggest involvement of norepinephrine and serotonin in the pathophysiology of schizophrenia (with depression associated with lower MHPG levels and negative symptoms associated with lower serotonin levels) and in the therapeutic actions of clozapine. Speculatively, a treatment strategy of targeting specific neurotransmitter systems might be based on the presence of specific symptoms in adolescents and young adults with schizophrenia.

show abstract

Clozapine Treatment in Very Early Onset Schizophrenia

Cited by 70 publications

References 12 publications

Olanzapine compared to quetiapine in adolescents with a first psychotic episode

Olanzapine compared to quetiapine in adolescents with a first psychotic episode

Blood biogenic amines during clozapine treatment of early-onset schizophrenia

Correlated Changes in Symptoms and Neurotransmitter Indices during Maintenance Treatment with Clozapine or Conventional Neuroleptics in Adolescents and Young Adults with Schizophrenia

Contact Info

Product

Resources

About