Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia.

OBJECTIVE: This randomized double-blind multicenter trial evaluated the effects of olanzapine vs. clozapine on subjective well-being, quality of life (QOL) and clinical outcome. METHOD: The primary objective was to demonstrate non-inferiority of olanzapine, mean dosage 16.2 +/- 4.8 (5-25 mg/day) vs. clozapine, mean dosage 209 +/- 91 (100-400 mg/day) regarding improvement on the 'Subjective Well-Being under Neuroleptic Treatment' (SWN) Scale after 26 treatment weeks in 114 patients with schizophrenia. Secondary outcome parameters included: Munich QOL Dimension List (MLDL), Positive and Negative Symptom Scale (PANSS), Clinical Global Impression (CGI). RESULTS: SWN scores improved significantly in both groups, olanzapine was non-inferior to clozapine (group difference 3.2 points in favor of olanzapine; 95% CI: 4.2;10.5). MLDL-satisfaction, PANSS and CGI-S improved similarly, olanzapine yielded a higher CGI Therapeutic Index. Individual SWN and PANSS changes correlated only moderately (r = -0.45). CONCLUSION: Olanzapine was non-inferior to clozapine. The lack of a marked correlation between PANSS and SWN improvements indicates that patients and psychiatrists perceive treatment differently.

Unusual manifestation of hepatic encephalopathy in two Irish wolfhound siblings.

In hepatic encephalopathy the brain lesions are usually characterised by polymicrocavitation, preferentially in the white matter, and the occurrence of Alzheimer type II cells. This paper describes an unusual manifestation of hepatic encephalopathy in two Irish wolfhound siblings in which the white matter was not involved predominantly. Both puppies had developed progressive neurological disturbances and signs of blindness. Histologically, there were widespread spongiform changes in the neuropil and fibre bundles interspersed within the grey matter, and there were some neuronal vacuoles. In both animals, the regions of the brain mainly affected were the nucleus caudatus, amygdala, cerebellar nuclei, mesencephalon, thalamus, hypothalamus and medulla oblongata. An astrogliosis characterised by Alzheimer type II-like cells was also observed. Electron microscopy revealed a splitting of the myelin sheath. No infectious agents such as rabies virus, canine distemper virus or prion proteins were detected. The main findings in the portal regions of the liver consisted of a dilatation of the lymphatic vessels and increased numbers of small arteries, indicating that a portosystemic shunt was the probable cause of the spongiform brain lesions.

[Does acupuncture influence the cardiac autonomic nervous system in patients with minor depression or anxiety disorders?]. / Beeinflusst Akupunktur die autonom kardiale Regulation bei Patienten mit leichten depressiven Episoden oder Angststörungen? Eine randomisierte, plazebokontrollierte Verlaufsstudie.

We undertook this study to evaluate the effects of needle acupuncture on cardiac autonomic nervous system (ANS) function in patients with minor depression or anxiety disorder. Patients (n = 36) were randomly distributed into a verum acupuncture (VA) group (needles were applied at classical acupuncture points, e. g. He7, Pe6, Du20, Bl62, Ex6) or a placebo (PL) group (needles were applied only epidermal at non-acupuncture points). Both groups underwent standardized measurements of the 5-minute resting heart rate variability (HRV), which were performed before the first and after the 9th acupuncture session of an acupuncture series, and also three times (before the start and 5, respectively, 15 minutes after needle application) during the third acupuncture session. Demographic data between the VA and PL group did not differ. Before the start of acupuncture there were also no significant differences in HRV data between these groups. Compared to PL the VA group showed a significant decrease of the mean resting heart rate both, 5 and 15 minutes after needle application, combined with a trend towards an increase of the high frequency (HF; 0.15 - 0.4 Hz) and a decrease of the low frequency (LF; 0.04 - 0.15 Hz) spectral power. The latter effects resulted in an overall significant decrease of the mean LF/HF ratio in VA compared to PL treated patients. This pattern of findings suggests that in patients with minor depression or anxiety only verum acupuncture 1.) leads to a relative increase of cardiovagal modulation of heart rate and 2.) facilitates the physiological regulatory ANS function in response to alterations of external or internal environment. Clinical implications of these findings are discussed.

[Acupuncture in patients with minor depressive episodes and generalized anxiety. Results of an experimental study]. / Akupunktur bei leichten bis mittelschweren depressiven Episoden und Angststörungen. Ergebnisse einer experimentellen Untersuchung.

In a placebo-controlled, randomized, modified double-blind study we investigated the effects of body needle acupuncture (n = 10) in 43 patients with minor depression (ICD 10 F32.0, F32.1) and 13 patients with generalized anxiety disorders (ICD10 F41.1). The severity of the disease was assessed by the Clinical Global Impression Scale (CGI). Treatment response was defined as a significant improvement in CGI. An intent-to-treat analysis was performed to compare treatment responses between verum- and placebo acupuncture. After completing an total of 10 acupuncture sessions the verum acupuncture group (n = 28) showed a significantly larger clinical improvement compared to the placebo group (Mann-Whitney test, p < 0.05). There were significantly more responders in the verum-compared to the placebo group (60.7% vs. 21.4%; chi-square test, p < 0.01). In contrast, no differences in the response rates were evident just after 5 acupuncture sessions. A multivariate analysis with the independent factor acupuncture (verum vs. placebo) and the results of the results of the additional rating scales (total score of HAMA, HAMD, Bf-S, BL) as dependent variables (ANOVA, 1:54 D.F.) revealed a clear trend towards lower HAMA scores in the verum group after completing 10 acupunctures (F3.29, p = 0.075). This corresponds well to the high response rate of 85.7% in patients with generalized anxiety disorders, in whom verum acupuncture was applied. Our results indicate that needle acupuncture (Du.20, Ex.6, He.7, Pe.6, Bl.62) leads to a significant clinical improvement as well as to a remarkable reduction in anxiety symptoms in patients with minor depression or with generalized anxiety disorders. The total sum of acupuncture sessions and the specific location of acupuncture needle insertions might be important factors for bringing about therapeutic success.

Competition to co-operation in national health services: evidence of social and cultural effects as management issues.

AIMS: This review examines how the management of health and health services is affected by the context of historical, social and scientific developments. BACKGROUND: The paper was prepared for the author's inaugural lecture as Professor of Health Services Research at Canterbury Christ Church University College. METHODS: The review had the benefit of being conducted during a 3-year NHS research and development study of decision-making in the nursing profession. A systematic literature review was conducted, yielding bibliographical data for analysis of health service issues. CONCLUSION: There is a case for including management decisions on appropriate research measures in the health service. Another finding of this analysis is that the management of common needs-based budgets, for example through co-operative purchasing, is a way forward to reconfigure services and reallocate funds, in a context of anomalies and inequalities in health care.

Screening for concomitant alcohol abuse in schizophrenia: clinical significance of the Munich Alcoholism Test and laboratory tests.

For the early and correct diagnosis of the comorbidity of schizophrenia and alcoholism, a valid laboratory marker would be most helpful in clinical practice. Seventy schizophrenics admitted to a general psychiatric unit of an urban hospital located in a large industrial area in Germany prospectively underwent a detailed addiction history, the Munich Alcoholism Test (MALT) and determinations of serum gamma-glutamyltransferase (gammaGT) and carbohydrate-deficient transferrin (CDT). Cutoff levels for laboratory tests represented the 95th percentile of data obtained from 100 matched healthy controls. Using the MALT, we found evidence of concomitant alcohol consumption in 42.8% of the study patients. The sensitivities of gammaGT and CDT for detecting alcohol abuse (confirmed using DSM III-R criteria) were 70.6 and 58.8%, respectively. Our data suggest that the MALT can be used as a reliable screening test for alcohol use in schizophrenia. In neuroleptic-treated schizophrenics with pathological gammaGT, but low MALT scores, the corresponding CDT may serve as a highly specific marker to verify a concomitant alcohol abuse.

Cardiovascular autonomic reactivity in schizophrenics under neuroleptic treatment: A potential predictor of short-term outcome?

In schizophrenics cardiovascular autonomic reactivity (CAR) can be used as an indicator of autonomic arousal. Using a standardized autonomic test battery (modified according to Ewing and Clarke) we prospectively compared the CAR between 46 actually ill schizophrenics (diagnosis according to DSM-III-R) treated with either haloperidol (n = 26) or clozapine (n = 20) and 30 well-matched healthy volunteers. Multivariate analysis demonstrated a significant effect of neuroleptic medication (haloperidol vs. clozapine) on heart rate and diastolic blood pressure under resting conditions as well as on the heart rate variance (30:15 ratio, deep-breathing, Valsalva) and blood pressure tests (sustained handgrip, Schellong). In addition a positive treatment response (using predefined outcome criteria of the Brief Psychiatric Rating Scale) was independently associated with lower resting heart rates and less impaired 30:15 ratios under neuroleptic medication. Our data indicate that clozapine treatment was associated with a substantial impairment of CAR, which can be explained by the drug's anticholinergic properties in combination with an increase in norepinephrine outflow. The greater heart rate variability in responders might be due to an early neuroleptic-induced decrease of sympathetic activity in the autonomic nervous system, which may precede clinical improvement. Our findings are discussed in relation to neuroleptic-induced changes in plasma catecholamine levels suggested to be useful biological markers in predicting treatment outcome.

Alcoholism, peripheral neuropathy (PNP) and cardiovascular autonomic neuropathy (CAN).

In contrast to diabetic autonomic neuropathy, cardiovascular autonomic neuropathy (CAN) in long-term alcoholics has been studied rarely. Using both standardized bedside tests and computer-assisted analysis of heart rate variability (HRV), we prospectively compared autonomic neurocardial function between 35 strictly selected, detoxified alcoholics (DSM-III-R), and 80 well matched healthy controls. Evidence for a potential CAN was found in 25.7% of all the alcoholics studied and in 41% of those with clinically manifest PNP (n=22). Overall, our results demonstrated a significant association between the presence of a CAN and peripheral neuropathy (PNP) amongst chronic alcoholics (chi-square test P<0.05); there was no evidence of a CAN in any of the alcoholics without a clinically manifest PNP. The CAN was characterized by a dissociated appearance of parasympathetic and sympathetic disorders. Our findings provide reason to suspect that the total lifetime dose of alcohol and the duration of alcohol dependence are the most important factors contributing to the pathogenesis of both PNP and sympathetic dysfunction. As is the case with diabetics, computer-assisted measurements of HRV including spectral analysis appear to be far superior to conventional bedside tests for detecting evidence of cardiovagal dysfunction in long-term alcoholics.

Improved autonomic neurocardial balance in short-term abstinent alcoholics treated with acamprosate.

Standardized investigations on resting heart rate variability (HRV) should provide more information on acamprosate's human pharmacodynamic properties because acamprosate interacts with several neurotransmitter systems which are also involved in maintaining autonomic neurocardiac balance. We performed HRV measurements prospectively in 69 healthy controls and 19 chronic alcoholics to prove the hypotheses that: (1) compared to healthy controls, chronic alcoholics show disturbances in neurocardiac vagal function; and (2) in alcoholics, acamprosate treatment (6-8 days) should further decrease parasympathetic activity if acamprosate interacts with central gamma-aminobutyric acidA receptors in vivo. Cardiovagal dysfunction was initially present in 21% of the alcoholics. After treatment. however, their neurocardiac sympathetic-parasympathetic balance improved significantly.

The tolerability and efficacy of the atypical neuroleptic remoxipride compared with clozapine and haloperidol in acute schizophrenia.

Remoxipride and clozapine are new neuroleptics that are thought to be superior to the substances in use by their efficacy and tolerance. At the University Clinic of Psychiatry in Düsseldorf a double-blind study with 54 patients diagnosed as schizophrenic in accordance with DSM-III was conducted to record the influence of the neuroleptics remoxipride, clozapine and haloperidol on schizophrenic psychosis. The schizophrenic symptoms were rated by the AMDP-system (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie), Brief Psychiatric Rating Scale and the Clinical Global Impression on days 0, 7, 14, 21 and 28 of treatment to evaluate the degree of change in psychopathology. The tolerance of the neuroleptic treatment was checked by the doctor's overall impression and the somatic findings of the AMDP-system. All 3 neuroleptics reduced the schizophrenic symptoms to a similar degree but showed differentiation as to their side effects.