The Tridimensional Personality Questionnaire as a predictor of relapse in detoxified alcohol dependents. The European Fluvoxamine in Alcoholism Study Group.

Personality traits have been found as strong predictors for treatment response in different psychiatric disorders. We administered the Tridimensional Personality Questionnaire, which measures the three personality dimensions: novelty seeking, harm avoidance (HA), and reward dependence, as introduced by Cloninger in a multicenter study (11 centers in the United Kingdom, Eire, Switzerland, and Austria) with detoxified alcohol-dependent patients (n = 521). The objective of this study was to evaluate a possible predictive value of these three dimensions on relapse over 1 -year follow up. A logistic regression analysis showed that novelty seeking is a strong predictor for relapse in detoxified male alcoholics (p = 0.0007; p values adjusted for treatment), but not in females. In both sexes, HA and reward dependence were of no predictive value. However, we found a trend for significance of HA for predicting "early" relapse (4 weeks) in females (p = 0.074). Our results show that Tridimensional Personality Questionnaire personality traits have direct clinical applications for prediction of relapse in detoxified alcohol dependents and indicate the necessity of additional therapeutic treatment in risk groups.

Biperiden and haloperidol plasma levels and extrapyramidal side effects in schizophrenic patients.

Anticholinergic drugs such as biperiden are used for the treatment of extrapyramidal side effects (EPS) induced by neuroleptics such as haloperidol. The effects of biperiden and haloperidol plasma levels on EPS were studied in 29 chronically ill schizophrenics. The results show relationships between biperiden dose and biperiden plasma levels (BPL), and between BPL and haloperidol plasma levels (HPL). Neither BPL nor HPL seem to influence EPS.

The tridimensional personality model: influencing variables in a sample of detoxified alcohol dependents. European Fluvoxamine in Alcoholism Study Group.

C.R. Cloninger proposed a biosocial model for personality, linking personality traits to patterns of responses to various external stimuli, including alcohol. The Tridimensional Personality Questionnaire (TPQ) was administered in a multicenter study to detoxified alcohol-dependent patients (N = 521). The objectives of the study were to evaluate (1) the expression of the three personality dimensions, novelty-seeking (NS), harm avoidance (HA), and reward dependence (RD), of the TPQ in this sample, and (2) the influence of different variables on these personality dimensions. The following variables were selected for a multiple and a stepwise regression analysis: sex, family history for major psychiatric disorders, marital status, occupation, age at study enrollment, age of onset of alcoholism, serum cholesterol level, intake of neuroleptics or benzodiazepines for detoxification, and severity of depression and anxiety. In comparison to Austrian normative data, both sexes of detoxified alcohol addicts scored higher in HA. The variables examined explain 23% of the variance of NS and 35% of HA. Only one variable, namely age of onset, is significantly influencing NS (19% explained variance). HA is significantly influenced by three variables: anxiety state, anxiety trait, and sex (32% explained variance). RD is not influenced by any of the variables examined.

Isoflurane narcotherapy in depressive patients refractory to conventional antidepressant drug treatment. A double-blind comparison with electroconvulsive treatment.

This is the first report on a controlled study comparing the therapeutic and non-therapeutic (side) effects of electroconvulsive treatment (ECT) and isoflurane narcotherapy (ISONAR; deep anesthesias with the inhalation of anesthetic isoflurane) in drug-refractory, severely depressed women, who had been randomly allocated either to ECT (n = 10) or ISONAR (n = 10). Patients from each group were subjected to a total of six treatment sessions (two sessions per week) and maintained on a fixed antidepressant drug dose. The antidepressant efficacy of either treatment was evaluated for each treatment session (in search of a 'rapid antidepressant effect') and at weekly intervals. Cognitive functions or signs of an organic brain syndrome were evaluated by means of psychological tests and extensive EEG analyses. Rapid antidepressant effects of the first treatment session were only significant in patients on ISONAR; in the subsequent treatment sessions, ECT also induced rapid antidepressant effects. Antidepressant effects during the treatment period were comparable, and patients on ISONAR improved further during follow-up, whereas patients on ECT tended to relapse. ISONAR-treated patients improved in most psychometric variables, whereas patients on ECT deteriorated. Finally, the EEG patterns of the ISONAR-treated patients remained normal or augmented (dominant alpha power), whereas patients on ECT developed an increase in abnormalities in EEG patterns and theta/delta power. This indicates an organic brain syndrome in patients on ECT.

Plasma concentrations of haloperidol and prolactin and clinical outcome in acutely psychotic patients.

This study was aimed at disclosing possible relationships between short term therapeutic outcome and certain ranges in plasma concentrations of haloperidol and of prolactin. Acutely psychotic patients (n = 28) were diagnosed (by RDC) as schizophrenics acute subtype (n = 17), schizoaffectives manic type, acute subtype (n = 8) and manics (n = 3). Parenteral haloperidol was the pharmacological treatment mostly given; the dose was kept constant intraindividually but varied between patients from 5 to 40 mg/d (median 15 mg/d). Data for statistical analyses of possible psychobiological relationships were analyzed at 12 days (median) of haloperidol regimen, that is at a relatively early cut-off in treatment. Keeping the methodological difficulties in mind, certain ranges in plasma concentrations of haloperidol (16-26.9 mg/ml; (Fig. 1) and of prolactin (64-159.9 mg/ml; (Fig. 2) were found to be associated-statistically independently-with a favourable therapeutic outcome. The rate of recovery was best if a patient came to lie with both plasma levels within these therapeutic ranges (Fig. 3). It is concluded that the combination of pharmacological and neuroendocrinological techniques in psychiatric research may be of substantial use for clinical purposes.

[The function of lytic effector cells in schizophrenic patients]. / Funktion lytischer Effektorzellen bei schizophrenen Patienten.

The present study aimed at elucidating lytic effector cell function in 32 schizophrenic patients and comparing the results with data obtained in 27 normal probands. Natural killer cell (NK) activity and antibody dependent cellular cytotoxicity (ADCC) were tested. Schizophrenics did not differ from normal controls in either test system. Within the schizophrenic group, higher NK activity was detected in patients with neuroleptic monotherapy (p less than 0.05). Patients given a combination of neuroleptics, antidepressants and/or lithium did not differ from drug-free patients in either test system. There was no influence of psychopathological variables on lytic effector cell function.

[Placebo-controlled studies with mianserin. Discussion from the viewpoint of a re-evaluated placebo concept]. / Placebokontrollierte Studien mit Mianserin. Erörterung aus der Sicht eines aufgewerteten Placebobegriffes.

In this paper the literature on placebo-controlled studies with Mianserin is being commented in view of the enclosed discourse "Placebo: Beyond pretense and nuisance variable." This paper's purpose is to enrich the understanding of the effect of a drug under everyday therapeutic conditions, an understanding, that derives from the physicians synthesis of personal uncontrolled observations of a drug's profile and the reported "mean-effect" in placebo-controlled studies.

Response of thyrotropin to thyrotropin-releasing hormone as predictor of treatment outcome. Prediction of recovery and relapse in treatment with antidepressants and neuroleptics.

We determined whether the response of thyrotropin (TSH) to thyrotropin-releasing hormone could predict the outcome of treatment with antidepressant and neuroleptic drugs. We studied 114 female patients diagnosed as having major and minor depressive, manic, schizoaffective, and schizophrenic disorders. A blunted TSH response (less than 5 microU/mL [less than 5 mU/L]) at admission was associated with recovery after nine weeks of inpatient treatment using clomipramine hydrochloride for depression and haloperidol for psychosis. A blunted TSH response at discharge was associated with early relapse in depressives receiving clomipramine maintenance therapy. Our findings support the notion that the thyrotropin-releasing hormone test is a "state" marker that may be of use in predicting the outcome of treatment with antidepressant and neuroleptic drugs.

[Long-term administration of antidepressive agents: maintenance therapy and phase prevention]. / Langzeitgabe antidepressiver Medikamente: "Erhaltungstherapie" und "Phasenprophylaxe".

Long-term regimen of psychotropic drugs in depression is particularly indicated in those patients who benefit most from the drugs, namely patients of the "endogenous" or "endogenomorphic" type. Medication over months or even years is indicated for two frequently concurrent reasons: firstly for "maintenance therapy", i.e., medication should be continued after remission of the depressive syndrome because of not yet identifiable "vulnerability" to relapse in many patients and, secondly, for "prophylactic therapy", i.e. medication can be given during apparent psychological health and in the absence of any imminent risk in order to prevent a possible new episode of depression. Long-term regimen of both types of medication is different, though not decisively so. Neither can cure a patient of depression; however, recurrence of the psychopathological syndrome can be successfully prevented. This paper presents a practical and updated discussion of various questions related to long-term regimen with psychotropic drugs used in depression: tricyclic antidepressants, lithium, carbamazepine and others.

Rapid psychotherapeutic effects of anesthesia with isoflurane (ES narcotherapy) in treatment-refractory depressed patients.

Treatment-refractory depressed patients who objected to electroconvulsive therapy (ECT) were given a series of anesthesias with isoflurane (Forane), a modern and established inhalation anesthetic. According to our hypothesis to be tested, the brief period of electrocerebral silence (ES), which can be observed shortly after the grand mal seizure in ECT, may be in itself a crucial biological determinant for the therapeutic effects of ECT. Isoflurane is the only drug known to effect an ES in the EEG in nontoxic concentrations, which does not result in adverse effects on any body organ including the brain; no seizure activity can be observed. Eleven depressed patients received a total of 36 anesthesias with isoflurane (ES narcotherapy). Rapid antidepressant effects were observed in 9 patients (p less than 0.0001). Effects were reproducible and lasted up to several weeks. No adverse effects of anesthesia were noticed.

Release of human neurophysin I during insulin-induced hypoglycemia in depressed patients is abolished after recovery with clomipramine treatment.

Release of human neurophysin I (hNp I) and neurophysin II (hNp II) during insulin-induced hypoglycemia was studied in 10 unipolar depressed women before and after 4-5 weeks of standard antidepressant drug treatment with daily intravenous infusions of clomipramine. Before treatment, a significant increase of hNp I but not of hNp II serum levels in response to hypoglycemia was observed. At retest during clomipramine administration, a marked clinical amelioration occurred in all patients as determined with the Hamilton Rating Scale for Depression; the hNp I response to insulin was abolished, but no effect on hNp II concentration could be demonstrated. No correlation was found between the degree of the depression score decrease and the amplitude of the inhibition of hNp I release or serum levels of clomipramine or its metabolite, desmethylclomipramine. The meaning of this difference in reactivity of the neurohypophyseal system in the course of depressive illness, based on the pharmacological and biochemical profiles of clomipramine action, is discussed.

TSH-response patterns to TRH stimulation may indicate therapeutic mechanisms of antidepressant and neuroleptic drugs.

The study was designed to investigate, by weekly thyrotropin-releasing hormone tests, possible patterns of thyroid-stimulating hormone (TSH) responses which may indicate therapeutic mechanisms of antidepressant and neuroleptic drugs in patients with depressive and paranoid-hallucinatory syndrome during their process of recovery (3-9 weeks). 65 depressed women and 33 paranoid-hallucinatory women have been studied while on antidepressant (clomipramine) or neuroleptic (haloperidol) treatment, respectively. Four patterns of TSH response were observed. Patients with a pattern of a 'disblunting TSH response' (normalization of an abnormal low response) during drug treatment had a significantly higher chance to recover compared to patients with other TSH response patterns. This finding was independent of psychopathological features and drugs used for treatment. A hypothesis of 'malactivation' as a pathogenetic indicator of various psychotic states is being presented.

The TSH-response to TRH: A possible predictor of outcome to antidepressant and neuroleptic treatment.

This study was designed to investigate the possible common patterns of neuroendocrine mechanisms, which may be involved in the therapeutic effects of antidepressant drugs in depressive and of neuroleptic drugs in schizophrenic patients. Sixty-three depressed women (major depressive disorder) and 21 paranoid-hallucinatory women have been studied while on antidepressant (clomipramine) or neuroleptic (haloperidol) treatment, respectively. The neuroendocrine test (TRH-test) was performed at weekly intervals. The change of TSH-response to TRH during treatment, i.e. the treatment associated normalization of a former blunted TSH-response, can tentatively be regarded as a predictor of outcome for depressive and paranoid-hallucinatory patients to their respective drug treatments. Antidepressant and neuroleptic drugs appear to involve the normalization of the TSH-response in their therapeutic effects in that proportion of patients (40%) which showed a blunted TSH-response at admission.

Evidence for an endogenous factor interfering with 3H-diazepam binding to rat brain membranes.

An in vitro "receptor" binding assay has been used to search for an endogenous compound which possibly interacts with benzodiazepine receptors in brain. Such an endogenous 3H-diazepam binding inhibitory factor (DIF) has been found. This compound is unevenly distributed in brain and in various peripheral organs. The partially purified compound appears to have a low molecular weight (below 500) and is not inactivated by proteolytic enzymes.