Intravenous mirtazapine is safe and effective in the treatment of depressed inpatients.

Mirtazapine is a third-generation antidepressant with a dual mode of action. The oral administration has been shown to be effective and safe in the treatment of depressed patients. In this multicenter naturalistic study, we assessed the safety, tolerability, and therapeutic efficacy of intravenously administered mirtazapine in 80 moderately to severely depressed inpatients during a treatment period of 14 days. We found a significant decrease of the Hamilton Depression Rating Scale total score compared to baseline. Side effects were mild and transient. Our data indicate that intravenous mirtazapine is an effective, safe and well-tolerated treatment for depressed inpatients.

Cost-effectiveness of mirtazapine compared to amitriptyline and fluoxetine in the treatment of moderate and severe depression in austria.

This study estimated the cost-effectiveness of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in Austria, as well as the costs related to the discontinuation of antidepressant treatment from the perspective of the Austrian Sick Funds (Gebietskrankenkassen). The economic analyses were based on a meta-analysis of four randomised clinical trials comparing mirtazapine with amitriptyline, and on a six week comparative trial of mirtazapine and fluoxetine which was extrapolated to six months using assumptions derived from the literature. Decision models of the treatment paths and associated resource use attributable to managing moderate and severe depression in Austria were developed from clinical trial data, information on Austrian clinical practice obtained from interviews with an Austrian Delphi panel (comprising psychiatrists and GPs), and from published literature. The models were used to estimate the expected costs to the Gebietskrankenkassen of managing a patient with moderate or severe depression, and the indirect cost per patient to Austrian society due to lost productivity. The expected cost to the Gebietskrankenkassen of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment was estimated to be ATS 4,088 over five months, of which hospitalisations accounted for nearly 69% of the cost. Using mirtazapine instead of amitriptyline for 28 weeks increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%), and reduces the expected cost to the Gebietskrankenkassen by ATS 1,112 per patient (from ATS 31,411 to ATS 30,299). Patients treated with mirtazapine and amitriptyline for 28 weeks are expected to miss 4.76 and 5.01 weeks of work respectively, due to their depression. Hence, the expected indirect cost to Austrian society over this period was estimated to be ATS 58, 787 and ATS 61,851 per patient respectively. Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for a negligible additional cost to the Gebietskrankenkassen of ATS 408 per patient (from ATS 29,205 to ATS 29,613). Patients treated with mirtazapine and fluoxetine for six months are expected to miss 4.53 weeks of work, due to their depression. Hence, the expected indirect cost to Austrian society due to lost productivity was estimated to be ATS 55,900 per patient with either antidepressant. In conclusion, this study suggests that despite the differences in acquisition costs, mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine, supporting the adoption of this treatment in the management of moderate and severe depression in Austria.

Postural control and lifetime alcohol consumption in alcohol-dependent patients.

OBJECTIVES: The aim of this study was to examine the relationship between alcohol consumption and postural control in alcohol-dependent patients. MATERIAL AND METHODS: Posturographic measurements were performed in 82 abstinent patients and in 54 healthy controls. The findings in the patients were compared with those in the controls as well as with the daily alcohol consumption, the consumption during 6 months before the admission for alcohol withdrawal therapy and the estimated lifetime alcohol consumption. RESULTS: Postural control was impaired in alcohol-dependent patients compared to healthy controls. This impairment was related with the lifetime alcohol consumption, but not with the alcohol consumption per day and prior to admission, respectively. Comparing healthy controls, and alcohol-dependent patients with an estimated lifetime alcohol consumption of < 1000 kg and > or = 1000 kg revealed a significant increase in 6 of 8 sway parameters. Furthermore, the lifetime alcohol consumption increased significantly from patients with normal posturographic and clinical findings to those with abnormalities in both examinations. CONCLUSION: This study suggests that postural imbalance in abstinent alcohol-dependent patients is related to the lifetime alcohol consumption.

Ataxia of stance in different types of alcohol dependence--a posturographic study.

The aim of this study was to assess the prevalence of ataxia of stance in different types of alcohol-dependent patients. Posturographic measurements were performed in 82 abstinent alcohol-dependent patients and 54 healthy controls in order to analyse postural control. According to Lesch and co-workers, alcohol dependence was classified as total abstinence (Type I), drinking without loss of control (Type II), fluctuating course (Type III), and persistent severe drinking (Type IV). The mechanisms of alcohol dependence in these subtypes can be summarized as follows: Type I patients drink alcohol to counteract symptoms of alcohol withdrawal; Type II patients use alcohol as an agent for solving conflicts; Type III patients drink alcohol to 'treat' an affective disorder; and Type IV patients have a history of pre-alcoholic neurological and/or psychiatric disorders. The neurological examination showed pathological findings in 39%, whereas posturographic measurements uncovered impaired postural control in 61% (chi2 = 8.8, P = 0.003). Comparing the different study groups revealed that ataxia of stance was most common in alcohol-dependent patients classified as Type IV (tau = 0.24, P = 0.005). In conclusion, posturographic measurements are superior to the clinical examination in detecting postural imbalance in alcohol-dependent patients. The prevalence of postural imbalance is highest in patients classified by Lesch as Type IV. Consequently, this type of alcohol dependence -- characterized by pre-alcoholic neurological and/or psychiatric disorders, bears the highest risk of developing ataxia of stance.

"Wineglass" confabulations among brain-damaged alcoholics on the Wechsler Memory Scale-Revised visual reproduction subtest.

Confabulation is a clinically well-documented accompaniment of selective types of memory impairment, especially in brain-damaged alcoholics. This study reports specific occurrences of visual confabulation consisting of spontaneous alterations of Card D of the Visual Reproduction subtest of the Wechsler Memory Scale-Revised. The resemblance of a wineglass was fashioned by a 90-degree rotation into a "bowl and stem", observed in six of 30 brain-damaged alcoholics. There were no such instances in 132 other patients, including alcoholic controls, those with Parkinson's Disease, temporal lobe epileptics (pre- or post-surgery), and those with neurotoxic exposure. When asked, the subjects who identified the figure as a wineglass or similar drinking instrument reported that they had drawn it as originally shown to them. "Wineglass" confabulators had shorter periods of abstinence, longer drinking histories and lower intellectual functioning than their brain-damaged peers or an alcoholic control group. These findings lend support for the association of alcohol-related confabulation with visual, as well as previously-documented verbal material among brain-damaged alcoholics.

Comparison of acamprosate and placebo in long-term treatment of alcohol dependence.

BACKGROUND: About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence. METHODS: In this multicentre, double-blind, placebo-controlled study, we recruited 455 patients, aged 18-65 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1998 mg daily for bodyweight > 60 kg; 1332 mg daily for < or = kg) or placebo for 360 days. Patients were assessed on the day treatment started and on days 30, 90, 180, 270, and 360 by interview, self-report, questionnaire, and laboratory screening. Patients were classified as abstinent, relapsing, or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. FINDINGS: Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication. The acamprosate (n = 224) and placebo (n = 224) groups were well matched in terms of baseline demographic and alcohol-related variables. 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase: of those withdrawn, 104 (52 in each group) relapsed, 69 (33 vs 36, respectively) were lost to follow-up, 63 (31 vs 32) refused to continue treatment, 16 (15 vs 11) had concurrent illness, three (two vs one) died, ten (six vs four) had adverse side-effects, one (acamprosate treated) received the wrong medication, and three (placebo treated) were non-compliant. The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p < 0.001, Mantel-Cox). At the end of treatment, 41 (18.3%) acamprosate-treated and 16 (7.1%) placebo-treated patients had been continuously abstinent (p = 0.007). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (138.8 [SD 137.5] vs 103.8 [119.0] days; p = 0.012). 148 patients (79 acamprosate, 69 placebo) completed 27 months follow-up: 27 (11.9%) acamprosate-treated and 11 (4.9%) placebo-treated patients remained continuously abstinent, and the mean cumulative abstinence duration was 230.8 days (259.1) and 183.0 days (235.2), respectively. Apart from occasional diarrhoea, there was no difference in side-effects between groups. INTERPRETATION: Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients.

Severe global amnesia presenting as Wernicke-Korsakoff syndrome but resulting from atypical lesions.

A female alcoholic presented with Wernicke's encephalopathy subsequent to administration of diazepam and glucose (without thiamine) for treatment of withdrawal seizures. Nystagmus and cerebellar ataxia quickly resolved when administered thiamine, although severe global amnesia consistent with Korsakoff's syndrome persisted. Magnetic resonance imaging (MRI) revealed infarction of the right temporal lobe with hippocampal atrophy, but no lesions of thalamus or atrophy of mammillary bodies. Positron emission tomography (PET) confirmed decreased cerebral metabolic rates for glucose (CMRglu) in the right temporal lobe corresponding to MRI findings, but also significant metabolic asymmetry of dorsal thalamus, i.e. reduced CMRglu in left versus right. This patient is unique in that neuroradiological findings revealed intact mammillary bodies and suggest asymmetrical dysfunctions (structural right temporal and functional left diencephalic) to produce her profound amnesia.

Brain proton magnetic resonance spectroscopy studies in recently abstinent alcoholics.

Chronic alcohol-dependent patients have reduced brain volumes and concomitant neurobehavioral deficits that may recover during abstinence. In 10 chronic alcoholic patients, using localized proton magnetic resonance spectroscopy, we found reliable increases during the first 3-4 weeks of abstinence in the concentrations within the superior cerebellar vermis of choline (Cho)-containing compounds relative to the neuronal marker, N-acetylaspartate (NAA). Lesser changes were observed following 1 month of abstinence, and in one of the patients studied longitudinally over 3 months, a marked reduction in the Cho/NAA ratio was associated with relapse. After detoxification, the Cho/NAA ratio correlated with a composite clinical impression of brain functions. The lowest Cho/NAA was observed in a patient with persisting alcoholic dementia, in striking contrast to reduced relative concentrations of NAA reported in dementia of the Alzheimer's type. Possible molecular explanations for these brain metabolic changes are discussed.

Diagnosis of chronic alcoholism--classificatory problems.

Since Magnus Huss introduced the diagnosis of 'chronic alcoholism' into medical literature in 1849, two unsolved problems concerning classification have remained: (1) Differentiation between problem drinkers and chronic alcoholics fluctuates, whereby the cut point of differentiation between abuse and addiction remains differently defined by different authors. Some authors view alcohol-induced damage as a building-stone of diagnosis of chronic alcoholism whereas other authors define these damages as illnesses developed as a consequence of chronic alcohol intake. This fact is also mirrored in the different definitions of chronic alcoholism by different classification systems, like ICD-9, DMS-III or DMS-III-R. Valid and reliable questionnaires, like the Munich Alcoholism Test or the Problem Drinking Scale did not succeed in solving this problem of definition, either. (2) The fact that chronic alcoholics are sick--in the sense of a biological-medical approach--is undoubted. Our research group was able to prove that chronic alcoholic patients metabolize methanol in a different way from that of healthy persons. The biological, sociological and psychopathological heterogeneity of this illness has been stressed for more than a century. A prospective long-term study carried out over 4-7 years has led to the development of a new typology in chronic alcoholism that is able to differentiate subgroups of chronic alcoholic patients cross-sectionally in a clinical, biochemical and neurophysiological way. Diagnosis according to this typology qualitatively differentiates patients in many spheres other than drinking behavior. These subgroups also require correspondingly modified therapeutic strategies.

Medication and drug abuse in relation to road traffic safety.

Apart from alcohol, various other substances with a psychotropic effect have been discussed recently in relation to their association with road traffic safety. There has been a general lack of hard facts, however, on how much drug use and abuse influence this. In the absence of data on the frequency of such effects, a representative random sample (approx. 8000 persons) of the Austrian population was interviewed and questioned on their drug intake. A smaller sample (2007 persons) was also questioned as to their behaviour regarding road traffic participation. The results showed that those drugs taken most frequently belong to the 'analgesic' group, whilst the frequency in use of substances to which greater importance is attached currently regarding road safety is relatively low (tranquillizers by 4%; strictly 'psychotropic' drugs by 0.3% to 0.6% of the population). These findings are similar to those reported in English-speaking countries. Data analysis showed that socio-cultural factors (age, sex, marital status and profession) influence the frequency and type of drug intake. The definition of drug abuse and addiction used (increase of dosage, inappropriate use, effect changes) proved somewhat unreliable and called into question the criteria used for diagnosis and categorization of persons at risk. In view of the results of previous studies and the importance attached by critics, an unexpected finding of this survey was the minor influence exerted by tranquillizers on road traffic safety. However, the number of cases for individual drug classes was relatively small and there is a need for more broadly based studies of a similar design before reaching firm conclusions.