Greta Koinig

Hypothalamic-pituitary-gonadal axis in depressed premenopausal women: Elevated blood testosterone concentrations compared to normal controls

To assess the function of the hypothalamic-pituitary-gonadal (HPG) axis in major depression, a multihormonal study was carried out in 20 depressed premenopausal women. Serum concentrations of LH, FSH, estradiol, progesterone, testosterone, and GnRH-stimulated LH and FSH were measured before initiation of treatment (on the first day after menstruation) and during clomipramine treatment (same time one menstrual cycle later). Significantly higher blood concentrations of testosterone were found in untreated patients compared to normal controls. Furthermore, there was a significant negative correlation between Hamilton depression scores and estradiol concentrations of patients. The efficacy of clomipramine treatment was not related to hormonal parameters.

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.

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.

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.

The Blunted TSH Response to TRH — What Does It Tell Us? Biological Monitoring During Psychopharmacological Treatment

The past two decades have witnessed an intensive search for a biological substrate in “functional” psychiatric disorders. Psychoneuroendocrinology has offered a fertile field for such investigations, as the perturbations in hormone levels may reflect certain important CNS processes (Langer et al. 1985). Of the several endocrine systems studied, the pituitary-thyroid subsystem has produced certain significant observations which point to applications in clinical practice. Interest in the pituitary-thyroid subsystem seems to have its origins in the reported association between thyroid dysfunction and psychiatric conditions (for review see Loosen and Prange 1984). An impetus to research into the thyroid subsystem applicable to psychiatric disorders was given by the observation that one of the hormones — thyrotropin-releasing hormone (TRH), which regulates the thyroid subsystem — is secreted by hypothalamus (Prange et al. 1987).

Neuroendocrine Factors in Antidepressant Drug Therapy

The reliable prediction of recovery and relapse and the identification of the therapeutic mechanisms of action of drugs given in the treatment of depressed patients remain unresolved issues in psychiatry and clinical psychopharmacology. Psychoneuroendocrine techniques have been used with some success in the attempt to improve the accuracy of prediction of treatment outcome.1 Among such techniques the application of the thyrotropin-releasing hormone (TRH) test, i.e., the response of thyrotropin (thyroid-stimulating hormone; TSH) to TRH, has proved of most practical utility.2

“Isoflurane Narcotherapy” in Depression: Methodological Issues

Preliminary observations of our study on the therapeutic effects of deep anesthesia with insoflurane in psychiatric patients have been reported elsewhere1. After awakening from the first anesthesia, antidepressant effects were observed in 9 of the 11 patients, who had been classified as depressives (by Research Diagnostic Criteria, RDC) refractory to conventional antidepressant drug therapy. The therapeutic effect diminished gradually over several days unless another session of “isoflurane narcotherapy” (ISONAR) was given. That study was uncontrolled; currently, a double-blind controlled study comparing the efficacy of electroconvulsive treatment (ECT) with ISONAR is in preparation. A synopsis of methodological and theoretical considerations is presented here as a consequence of many observations and discussions in this explorative state of affairs. If a potentially new mode of treatment such as ISONAR is to be given an optimal chance for proof of efficacy, it is important that the appropriate clinical indication and administration procedure be established (the two most important factors in pharmacological therapy).

Neuroendokrine Studien zur therapeutischen Wirkung von Antidepressiva und Neuroleptika — Das Konzept der entaktivierenden Wirkung

Seit der Entdeckung der Neuroleptika (Chlorpromazin; Delay et al. [4]) und Antidepressiva (Imipramin; Kuhn [9]) werden diese Pharmaka weltweit — wenn auch nicht immer erfolgreich — in der psychiatrischen Therapie angewendet. Viele Analogpraparate der „Originale“ sind seither synthetisch hergestellt worden, z. T. mit vergleichbarem psychopharmakologischem Profil. Obwohl heute die allgemeine Wirksamkeit dieser Medikamente erwiesen ist, bleibt ungeklart, warum trotz adaquater Indikation und Therapie einige Patienten therapieresistent sind.