Posted by SLS on November 13, 2000, at 11:30:01
In reply to Zyprexa and brain shrinkage., posted by steve on November 12, 2000, at 16:23:38
Hi folks.
I don't think this decreased volume thing should be of concern. Even if Zyprexa does reduce the volume of parts of the brain, the specific structures studied in these two investigations are not related to cognition or mood. There doesn't seem to be any concern to be found in the medical literature regarding such a change, either theoretically or in real life observations. Other structures of the brain (with the possible exception of the thalamus) are not affected at all.
I thought I should offer my interpretations of the two abstracts cited. I included three abstracts at the end of this post that help support the conclusion that too great a volume of the areas studied is undesirable. In addition, clozapine does not act to change the volume of these structures unless they have been previously enlarged by the prior usage of the older typical neuroleptic antipsychotics, in which case they are reduced. Both clozapine and Zyprexa are representative drugs of the newer atypical neuroleptics as compared to the older typical neuroleptics like Haldol. The word "atypical" was originally chosen to describe the greatly reduced potential for these drugs to produce EPS side effects and tardive-dyskinesia. Tardive dyskinesia is an irreversible (mostly) motor-control disorder that involves involuntary movements of the face, head, tongue and neck.
* Schizophrenia itself is sometimes associated with an enlargment of striatal volume. Perhaps part of the long-term therapeutic effects of clozapine and Zyprexa involve the reduction of the volume of these structures to nominal values.
* Since tardive-dyskinesia is associated with an increase in volume of striatum and a supersensitivity of the neurons there, perhaps the usage clozapine and Zyprexa can arrest or reverse the manifestation of this "irreversible" neuroleptic-induced condition.
- atypical = clozaril = Clozaril
- typical = haloperidol = Haldol
- caudate nucleus, putamen, globus pallidus, basal ganglia = striatum
- MRI = magnetic resonance imagingOld Typical Neuroleptics
- Haldol (haloperidol)
- Loxitane (loxapine)
- Mellaril (thioridazine)
- Navane (thiothixene)
- Prolixin (fluphenazine)
- Stelazine (trifluoperazine)
- Thorazine (chlorpromazine)
- Tranxene (clorazepate)
- Trilafon (perphenazine)
New Atypical Neuroleptics- Clozaril (clozapine)
- Risperdal (risperidone)
- Seroquel (quetiapine)
- Zeldox (ziprasidone)
- Zyprexa (olanzapine)ABSTRACT #1: Experiment using rats.
Actas Esp Psiquiatr 1999 Sep-Oct;27(5):341-6[Clozapine: neuropsychological and neuroimaging studies].
Perez-Gomez M, Junque C
* My interpretation:1. Visual memory:
- clozapine decreases2. Verbal memory:
- Haldol decreases3. Controlled verbal fluency:
- clozapine improves4. Visuoconstructive functions:
- clozapine improves
5. Volume of caudate nuclei of basal ganglia. This structure is responsible for controlling the voluntary movements produced by higher brain functions (motor cortex) and establishing postures. Excessive activity in this area is thought to be responsible for tardive-dyskinesia and is more active in boys who have ADD.TOO MUCH caudate nucleus is BAD
- Haldol increases
- clozapine decreasesABSTRACT #2: Experiment using rats.
: Life Sci 1999;64(18):1595-602 Related Articles, Books, LinkOut
Effects of chronic treatment with typical and atypical antipsychotic drugs on the rat striatum.Lee H, Tarazi FI, Chakos M, Wu H, Redmond M, Alvir JM, Kinon BJ, Bilder R, Creese I, Lieberman JA
* My interpretation:1. Volume of caudate nuclei of basal ganglia. This structure is responsible for controlling the voluntary movements produced by higher brain function (motor cortex) and establishing postures. Excessive activity in this area are thought to be responsible for tardive-dyskinesia and is more active in boys who have ADD. In other words, too much caudate nucleus is no good
TOO MUCH caudate nucleus is BAD
- Haldol increases
- clozapine decreases
- clozapine REVERSES the increase produced by Haldol
Just my 2½ cents.- Scott
---------------------------------------------------------------
SUPPORTIVE ABSTRACTS USING HUMAN SUBJECTS
I highlighted the important text by using upper case letters.
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56: Am J Psychiatry 1999 Aug;156(8):1200-4
Change in basal ganglia volume over 2 years in patients with schizophrenia: typical versus atypical neuroleptics.
Corson PW, Nopoulos P, Miller DD, Arndt S, Andreasen NC
Department of Psychiatry, University of Iowa College of Medicine, Iowa City 52242, USA. patricia-corson@uiowa.edu
OBJECTIVE: For many years, it has been assumed that medications affect brain chemistry and physiology but not structure. Recent reports suggest that neuroleptic medication changes basal ganglia volume. To explore this possibility, the authors assessed for basal ganglia volume change in individuals who had their basal ganglia structures delineated and measured on magnetic resonance scans at the beginning and end of a 2-year period and who received neuroleptic medication during this time. METHOD: The basal ganglia volumes of 23 male patients with schizophrenia spectrum disorders were measured from manual traces delineating the caudate and lenticular nucleus on magnetic resonance images at admission and 2 years later. Patients' neuroleptic exposure was calculated over the 2 years by using a dose-year formula. RESULTS: During the 2-year period, mean basal ganglia volume of patients receiving predominantly typical neuroleptics increased, while the opposite was observed for patients receiving mostly atypical neuroleptics. Correlation analysis for the entire group showed a positive relationship between the 2-year exposure to typical neuroleptic medication and change in basal ganglia volume and the reverse for exposure to atypical neuroleptics. CONCLUSIONS: IN THIS GROUP, BASAL GANGLIA VOLUME INCREASED FOLLOWING EXPOSURE TO TYPICAL NEUROLEPTICS AND DECREASED FOLLOWING EXPOSURE TO ATYPICAL NEUROLEPTICS.
PMID: 10450260, UI: 99378754
---------------------------------------------------------------41: Eur Arch Psychiatry Clin Neurosci 1999;249 Suppl 4:48-56
Structural neuroimaging in schizophrenia. An integrative view of
neuromorphology.Henn FA, Braus DF
NMR Research, Central Institute of Mental Health, Mannheim, Germany.
henn@as200.zi-mannheim.deThe use of structural magnetic resonance imaging (MRI) in studies of schizophrenia has resulted in a more detailed picture of anatomic areas which may be altered in this syndrome. Thus far, there have been over 130 studies of schizophrenia using MRI and, taken together, they present a clear picture of a group of disorders with altered brain structure. Their major finding is a confirmation of the older pneumoencephalography and computertomography studies showing an enlargement of lateral ventricles and a volume reduction seen in the temporal lobe. When structural studies are carried out in other cortical and subcortical regions, however, the volume reduction is not so uniform, but rather restricted to certain areas in a given patient. IN ADDITION MEDICATION EFFECTS CAN BE SEEN ESPECIALLY IN THE CAUDATE NUCLEUS WHICH TEND TO INCREASE IN VOLUME AFTER LONG-TERM NEUROLEPTIC DRUG USAGE AND AGAIN NORMALIZE UNDER THE ATYPICAL DRUG CLOZAPINE. These data are consistent with a neurodevelopmental model of schizophrenia and with some kind of progressive neurodegenerative process. This review suggests that an integrative model with initial developmental errors may underlie the majority of cases of schizophrenia, but that cases of chronic schizophrenia appear to involve progressive neurodegeneration. In assessing the scatter in available data, it appears that there is no consistent neuropathology across all cases of schizophrenia and preferential areas of dysfunction can be determined. Thus, there seems a collection of subtle neurodevelopmental errors which can lead to various forms of schizophrenia and that at least some types of schizophrenia most probably also involve a neurodegenerative process which could in fact be a consequence of the initial developmental defect.
Publication Types:
Review
Review, tutorialPMID: 10654109, UI: 20119605
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6: Am J Psychiatry 1998 Dec;155(12):1711-7Subcortical MRI volumes in neuroleptic-naive and treated patients with
schizophrenia.Gur RE, Maany V, Mozley PD, Swanson C, Bilker W, Gur RC
Department of Psychiatry, University of Pennsylvania School of Medicine,
Philadelphia, USA.OBJECTIVE: This study examined whether subcortical volumes of the basal ganglia and thalamus in schizophrenic patients are related to neuroleptic exposure and symptom severity. METHOD: Basal ganglia substructures and thalamic volumes were measured with magnetic resonance imaging in 96 patients with schizophrenia (50 men and 46 women) and 128 healthy comparison subjects (60 men and 68 women). Twenty-one of the patients were neuroleptic-naive; of the 75 previously treated patients, 48 had received typical neuroleptics only, and 27 had received typical and atypical neuroleptics. The relation of volume measures to treatment status, exposure to neuroleptics, and symptoms was examined. RESULTS: The neuroleptic-naive patients did not differ from the healthy comparison subjects in subcortical volumes except for lower thalamic volume. In the neuroleptic-naive group, volumes did not correlate with severity of negative symptoms, but higher volumes in both the thalamus and the putamen were associated with more severe positive symptoms. The previously treated group showed higher volumes in the putamen and globus pallidus than the healthy comparison subjects and the neuroleptic-naive patients. IN THE TREATED GROUP, A HIGHER DOSE OF A TYPICAL NEUROLEPTIC WAS ASSOCIATED WITH HIGHER CAUDATE, PUTAMEN, AND THALAMUS VOLUMES, WHEREAS A HIGHER DOSE OF AN ATYPICAL NEUROLEPTIC WAS ASSOCIATED ONLY WITH HIGHER THALAMIC VOLUME. Higher subcortical volumes were mildly associated with greater severity of both negative and positive symptoms. CONCLUSIONS: INCREASED SUBCORTICAL VOLUMES IN TREATED SCHIZOPHRENIC PATIENTS SEEM TO BE MEDICATION-INDUCED HYPERTROPHY. This hypertrophy could reflect structural adaptation to receptor blockade and may moderate the effects of neuroleptic treatment.
poster:SLS
thread:48725
URL: http://www.dr-bob.org/babble/20001102/msgs/48761.html