Reliability and validity of the Newcastle Scales in relation to ICD-9-classification

The assessment of endogenous depression by means of the Newcastle Scales (1965, 1971) has been validated by their correlation with biological findings in many previous studies. However, reliability and cross validation studies are lacking for these scales. We found the reliability of the Newcastle Scales to be sufficient or at least moderate in a sample of 70 inpatients with major depression. In order to cross validate both scales, the clinical classification according to ICD-9 and the assessment of the Newcastle Scales have been performed independently in a sample of 112 inpatients with Major Depressive Disorder (RDC). The rate of agreement between clinical diagnosis and classification acc…

Erste Ergebnisse einer Kombinationstherapie mit Moclobemid und kognitiver Verhaltenstherapie bei Panikstörung mit Agoraphobie

In der Studie wird die Wirksamkeit von Moclobemid, kognitiver Verhaltenstherapie und einer Kombination aus beidem bei der Behandlung von Panikstorung mit Agoraphobie untersucht. Die Hypothesen sind, das sowohl Moclobemid als auch kognitive Verhaltenstherapie einer Behandlung mit Placebo uberlegen sind und das eine Kombinationstherapie zu den besten Resultaten fuhrt. Von insgesamt 123 ambulanten Patienten mit der Diagnose Panikstorung mit Agoraphobie erfullen 55 die Studienkriterien und werden randomisiert einer der vier folgenden Therapiebedingungen zugeordnet: 1) Moclobemid und kognitive Verhaltenstherapie, 2) Moclobemid und Clinical Management, 3) Placebo und kognitive Verhaltenstherapie …

Computerized brain tomography measures compared with spontaneous and suppressed plasma cortisol levels in major depression.

We determined brain density and ventricular measurements with computerized tomography (CT) in 33 depressed patients and compared the results with basal plasma cortisol and its suppressibility by dexamethasone. Mean plasma cortisol was positively related to elevated ventricular brain ratio (VBR). No association could be found between dexamethasone suppression test (DST) status and VBR or any other CT parameter. Elevated plasma cortisol levels and increased VBRs were positively correlated with total scores on the Brief Psychiatric Rating Scale, the Global Assessment Scale and the Bech-Rafaelsen Melancholia Scale, but they were not significantly correlated with total score on the Hamilton Anxi…

Seroquel (ICI 204 636), a putative "atypical" antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters.

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0–6; baseline: 42.0±2.3; mea…

Rezeptordarstellung mit der Single Photonen Emissions Computertomographie (SPECT): Stand der Forschung und Perspektiven

123-Jod markierte Liganden ermoglichen die Darstellung und semiquantitative Messung cerebraler Rezeptoren mit der Single Photonen Emissions Computertomographie (SPECT).

Combination treatment with clozapine and paroxetine in schizophrenia: safety and tolerability data from a prospective open clinical trial.

Clozapine is a drug with many side effects, some of them with potentially hazardous outcome (e.g. seizures, agranulocytosis), if not carefully monitored. It has been shown that the metabolism of clozapine may be affected by concomitant treatment with selective serotonin reuptake inhibitors (SSRIs), while there have been reports of improved efficacy on negative symptomatology of clozapine in combination with SSRIs. Therefore, this prospective open clinical trial was performed to investigate the safety and tolerability of the coadministration of clozapine and paroxetine under control of serum concentrations of clozapine and its metabolites and the effect of this combination treatment on psych…

Are ratings of psychomotor retardation correlated with neuropsychological measurements?

The present study investigated the correlation between retardation, assessed by the Bech-Rafaelsen Melancholia Scale (BRMS), and measurements of reaction time and motor performance in 26 elderly depressed patients. Significant correlations were only detected between motor retardation and the number and duration of faults in the line following part of the motor performance test. The total scores of the BRMS and the Hamilton Depression Scale did not correlate significantly with any of the performed measurements.

PROTON MAGNETIC RESONANCE SPECTROSCOPY IN DEMENTIA OF ALZHEIMER TYPE

Reduced N-acetyl aspartate (NAA) and increased myo-inositol (MI) levels have been reported in patients with dementia of Alzheimer type (DAT) in comparison with controls. We wished to assess the validity of these findings and to evaluate possible correlations of metabolite proportions with cognitive dysfunction in DAT. Twelve patients with DAT and 10 healthy age-matched controls were included. The severity of dementia was assessed using different scales including the Mini-Mental State Examination. MRS was performed with a conventional 1.5 Tesla scanner in a single voxel in the centrum semi-ovale (TE = 30 ms or TE = 136 ms; TR = 1500 ms). The evaluation of MRS results was limited by low inter…

Brain density in depression: methodological and psychopathological aspects

The relationship between brain density, measured by computerized tomography (CT), and severity of depression was investigated in 44 patients with a major depressive episode according to DSM-III. In order to limit methodological problems, correlations between both the Brief Psychiatric Rating Scale (BPRS) and the Bech-Rafaelsen Melancholia Scale (BRMS) with density values were controlled for age, different ventricle measurements, brain size, and density and size of the skull. The BRMS score correlated inversely with density of the right thalamus, the right head of the caudate, and with parietal grey matter and occipital regions of both hemispheres. Similar, but nonsignificant results, were o…

Stellenwert von Computertomographie und Magnetresonanztomographie in der psychiatrischen Diagnostik

This paper evaluates the role of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of psychiatric disorders according to the "International Classification of Diseases" (ICD-10). Indications for CT/MRI can be derived from ICD-10 for the identification or exclusion of defined cerebral lesions resp. for the etiology in organic disorders. Due to the lack of specific morphological findings, CT/MRI do not contribute to the classification of all other diagnoses. CT/ MRI can only exclude causal organic factors. However, ICD-10 provides only few guidelines for ruling out cerebral pathology (e.g. tumors in bulimic anorexia). Therefore, recommendations for routine CT/MRI-i…

D2-receptor imaging with [123I]IBZM and Single Photon Emission Tomography in psychiatry: a survey of current status

D2-dopamine receptors can be visualized in the human brain in vivo by Single Photon Emission Tomography (SPECT) and the radiolabeled benzamide [123I]IBZM. The present paper reviews the current status of this type of functional brain imaging with respect to basic methodological aspects, data analysis and quantification. The results from published clinical studies in different psychiatric patient populations and normal controls with [123I]IBZM are reviewed. [123I]IBZM-SPECT is a powerful tool for the investigation of D2-dopamine receptor status in psychiatric disorders, different types of drug treatment as well as therapeutic and side effects of pharmacologic agents. However, there still is a…

Latencies of the P300 component of the auditory event-related potential in depression are related to the Bech-Rafaelsen Melancholia Scale but not to the Hamilton Rating Scale for Depression

The relationship between severity of depression and the P300 latency of auditory event-related potential was investigated in 36 patients with a major depressive episode according to DSM-III. Positive correlations were found between of the P300 latency and the total score of the Bech-Rafaelsen Melancholia Scale (BRMS), the 4 retardation items of the BRMS (motor, verbal, intellectual and emotional) and the item for lowered mood. In contrast, latencies were not associated with the scores of the Hamilton Rating Scale for Depression, which considers retardation to a lesser extent than the BRMS.

Randomised placebo-controlled trial of moclobemide, cognitive–behavioural therapy and their combination in panic disorder with agoraphobia

BackgroundIn the treatment of panic disorder with agoraphobia, the efficacy of pharmacological, psychological and combined treatments has been established. Unanswered questions concern the relative efficacy of such treatments.AimsTo demonstrate that moclobemide and cognitive–behavioural therapy (CBT) are effective singly and more effective in combination.MethodFifty-five patients were randomly assigned to an eight-week treatment of: moclobemide plus CBT; moclobemide plus clinical management (‘psychological placebo’); placebo plus CBT; or placebo plus clinical management.ResultsComparisons between treatments revealed strong effects for CBT. Moclobemide with clinical management was not superi…

Haben CT-Untersuchungen einen prädiktiven Wert für den Fünfjahresverlauf bei Patienten mit Depression im Alter für Mortalität, cognitive Einbußen und psychosoziale Faktoren?

Der Zusammenhang zwischen hirnmorphologischen Veranderungen gemessen mit dem Computertomogramm (CT) und psychopathologischen, klinischen und kognitiven Untersuchungen bei depressiven Alterspatienten war 1986 Gegenstand einer Studie. Die jetzt vorliegende Funf-Jahres-Katamnese sollte den pradiktiven Wert computertomographischer Veranderungen bei Depression im Alter darstellen. Von besonderem Interesse war dabei die Uberprufung der von Jacoby et al. (1981) berichteten Ergebnisse bezuglich einer hoheren Zwei-Jahres-Mortalitat bei Patienten mit einer Ventrikelerweiterung. Auserdem sollte untersucht werden, ob eine Hirnatrophie mit der Entwicklung einer Demenz einhergeht bzw. einen ungunstigeren…

Relationships between psychomotor retardation and EEG power spectrum in major depression.

In 63 depressed patients, the associations between severity of depression, psychomotor retardation, assessed by the Bech-Rafaelsen Melancholia Scale, and EEG spectral analysis were examined. Slow EEG activity (theta 2/alpha 1 bands) was positively and fast activity (alpha 3/beta bands) negatively correlated with the observed retardation. Out of the four retardation subitems (motor, verbal, intellectual and emotional), motor retardation was closest correlated with slow EEG activity.

Benzodiazepinrezeptordarstellung mit JOMAZENIL-SPECT

Die Darstellung der Benzodiazepin-Rezeptordichte (BZD) mit der Single- Photonen-Emissions-Computertomographie (SPECT) wurde durch die Synthese des neuen Radioliganden JOMAZENIL ermoglicht. JOMAZENIL entspricht dem mit Jod-123 markierten Benzodiazepin-Antagonisten Flumazenil und zeichnet sich durch eine hochspezifische Bindung an zentralen BZ-Rezeptoren aus. Verdrangungsexperimente zeigten, das 90–110 Minuten p.i. ca. 80% der Aktivitat der spezifischen Bindung entsprechen [1].

IBZM-SPECT bei Neuroleptikatherapie

Mit IBZM — einem mit Jod-123 markierten Benzamid — ist es erstmalig moglich, die Dopamin-D2-Rezeptoren mit der Single-Photonen-Emissions-Computertomographie (SPECT) darzustellen. Das trotz der fehlenden ab-soluten Quantifizierung mit SPECT diese Methode hilfreich sein kann fur die Messung der D2-Rezeptoren, wurde schon von der Arbeitsgruppe von Brucke [1] dargestellt. Gegenstand unserer eigenen Studien war die Untersuchung der D2-Rezeptorbesetzung (RB) unter Haloperidol, Benperidol und Clozapin im Zusammenhang mit klinischen Daten und Prolaktinspiegeln.

Electrophysiological evidence for an inverse benzodiazepine receptor agonist in panic disorder.

Abstract Inverse agonists of the GABA A receptor clearly decrease the amplitudes of the spontaneous EEG in the P-frequency range. Therefore, we tested the hypothesis that panic patients exhibit a reduction of the EEGs spectral power in the P-frequency band. Ten unmedicated patients with panic disorder and agoraphobia according to DSM-III-R criteria and 10 matched controls were investigated under baseline conditions, after hyperventilation and 30 min after hyperventilation. EEG recordings from the position P z and C z were performed under eyes closed conditions. At baseline conditions the patients suffering from panic disorder depicted a reduced P-power reaching statistically significance fo…

Benzodiazepinrezeptorbindung im [123I]-IOMAZENIL-SPECT in Relation zu Cortisol-Plasmaspiegeln

Mit Iomazenil, dem mit 123Iod markierten Benzodiazepinantagonisten, und der Single Photonen Emissions Tomographie (SPECT) ist die in vivo-Darstellung von Benzodiazepinrezeptoren (BZR) moglich. Wir fanden in fruheren Untersuchungen eine signifikante Verminderung der lomazenil-Bindung bei Panikpatienten im Vergleich zu Patienten mit Depressionen (Schlegel et al. 1994). Zwischen dem GABA/BZR-System und Cortisol sind vielfaltige und komplexe Wirkzusammenhange beschrieben worden (De Souza et al. 1990). Nach Adrenalektomie wurde bei Ratten eine Zunahme der BZR-Dichte beschrieben (Miller et al. 1988, Acuna et al. 1990). Diese Effekte waren nach Corticosteroidgabe reversibel. Wahrend sich der Effek…

Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT

By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminer…

The association between psychopathological aspects and CT measurements in affective disorders.

Occupancy of striatal D 2 -like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic

Rationale: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D2 and D3 dopamine (DA) receptors. Objectives: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [123I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. Methods: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one befo…

Addition of Low-Dose Fluvoxamine to Low-Dose Clozapine Monotherapy in Schizophrenia: Drug Monitoring and Tolerability Data from a Prospective Clinical Trial

Combining fluvoxamine and clozapine may be a strategy to improve therapeutic effects on negative symptoms in schizophrenic patients. Fluvoxamine, however, markedly inhibits the metabolism of clozapine, and hazardous side effects may result. This study prospectively investigated the safety and tolerability of an add-on therapy with fluvoxamine to a clozapine monotherapy in schizophrenic patients. Sixteen schizophrenic patients received 50 mg fluvoxamine as a comedication after having reached steady-state conditions under clozapine monotherapy. Patients were monitored for subjective adverse events, laboratory parameters, EEG and ECG recordings, orthostatic hypotension and their psychopatholog…

Reliability and Validity of the Assessment of Antidepressant Effects

[123I]IBZM SPECT in patients treated with typical and atypical neuroleptics: relationship to drug plasma levels and extrapyramidal side effects

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly di…