תוצאת חיפוש

Animal Models of Psychiatric Diseases: Possibilities, Limitations, Examplesand Demonstration of Use

Haim Einat, RH Belmaker

Beer Sheva Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel

Animal models of psychopathology serve as a central tool for psychopharmacologists in their attempts to develop new, more efficient medications for psychiatric disorders, and in the efforts to explore the mechanisms of conventional and novel drugs. The development of efficient models for psychiatric diseases is complicated since the mechanisms of the disorders are not clear, major parts of the diagnosis depend on verbal communication with the patient and many of the symptoms are expressed mainly through the subjective experiences of the afflicted individual.

Inspite of these difficulties, effective models were developed for most psychiatric diseases. The development of such models is based on their validation in three different dimensions: face validity - behavioral similarities between the model and the disorder; construct validity - similarities between the mechanisms related to the model and a mechanistic theory of the disease; predictive validity - that the model response to the conventional medications that are effective in the disease and will not respond to drugs that are not effective in the disease.

The present paper presents three known models of depression; each induced in a different way and therefore represents a group of models:

*     Reserpine-induced hypoactivity - represents the group of pharmacologically induced models.

*     Forced swim test - represents the group of behaviorally induced models.

*     Flinders Sensitive Line - represents the group of genetically induced models.

The use of these models in an attempt to examine the range of action of a new potential antidepressant and its mechanisms of action is demonstrated with a recent set of experiments with inositol.

Treatment of Hypertension with Losartan

R. Zimlichman

Dept. of Medicine and Hypertension, Wolfson Medical Center, Holon

The efficacy, safety and side-effects of treatment with losartan (Ocsaar) was studied for the first time in Israel in a large group of patients with mild to moderate hypertension in several community clinics. The 421 patients (51% men) aged 30-86 years (mean 58.6) received 50 mg of losartan daily, increased when necessary to 100 mg, and/or a second antihypertensive drug was given. After 4 weeks blood pressure was normalized in 344 and after 12 weeks in 363. Side-effects were minimal and treatment was effective in all age groups.

When are Menopausal Symptoms Psychiatric?

Helen Shoenfeld

Talbia Mental Health Center, Jerusalem

Nervousness, sleep disorders, mood instability and sexual dysfunction are frequent symptoms during menopause. It is commonly believed that they are due to the characteristic menopausal hormonal changes. However, they also commonly occur in psychiatric disorders unrelated to the menopause. The literature deals with the characteristic psychological aspects and studies have examined the ways in which menopausal phenomena are related to the hormonal background and its effect on the brain.

The clinical menopausal picture may be complicated by secondary psychiatric disease. Also, menopausal symptoms and symptoms of previous psychiatric disease may coexist. In addition, menopause may precipitate psychiatric disorders in women predisposed to them.

Accumulated personal myths and expectations related to the menopause are likely to affect the way in which a woman copes with it. Important factors in this connection include education, culture and certain life events. In all such cases precise evaluation of the etiology, with its intermingled gynecological and psychiatric factors is required. Such women should be treated by both a gynecologist and a psychiatrist.

We present 5 cases, 4 of which were sent to the menopause clinic and were then referred for psychiatric evaluation and treatment. The other case presented at a psychiatric clinic due to a first acute psychostate. Laboratory tests showed typical changes of menopause.
 

Multicenter Community-Based Trial of Amlodipine in Hypertension

C. Yosefy, J.R. Viskoper, Y. Leshem, Y. Rav-Hon, G.I. Rosenberg, E. Yaskil

(Representing the 39 Investigators of Project AML-IL-95-001, WHO Collaborative Center for Prevention of CV Diseases) Ben-Gurion University of the Negev, Beer Sheba; Barzilai Medical Center, Ashkelon; Hypertension Clinic, Kupat Holim Afula; Statistics Consulting Unit, Haifa University; and Promedico Ltd., Petah Tikva

The safety and efficacy of Amlodipine (AML) for mild to moderate hypertension was evaluated in a "real life" setting. This open non-comparative trial included 123 men and 143 women (age 30-91 years, mean 59.4). All had sitting diastolic blood pressure (DBP) between 95 and 115 mmHg, confirmed in most by 2 baseline measurements, 2 weeks apart.

Eligible patients were given AML 5 mg daily as add-on or monotherapy and were evaluated 4 weeks later. If DBP was then >90 mmHg, the daily dose was raised to 10 mg; those with <90 mmHg remained on 5 mg. AML was continued for 8 weeks. Other BP-lowering drugs were unchanged.

Of the original 266 patients 22 (8.2%) withdrew due to adverse events (AE), and others were protocol violators, lost to follow-up or withdrew, leaving 211 available for efficacy analysis. In this major group BP was reduced from 165±15/101±4 to 139±11/83±5 after 12 weeks of AML (p<0.05). The reduction was greater in those under 70 years, from 173±12/100±5 to 142±12/80±4 (p<0.05). In those with BMI>30 kg/m², BP decreased from 165±15/101±5 to 140±12/83±5 (p<0.05).

Mean change in heart rate was -1.5 bpm (p<0.05). Mean final AML dose was 5.5 mg/day. The most common AML-related AE requiring cessation of the drug was pedal edema in 2.6% of the 266 patients; in 3.7% it persisted during therapy. Other AE occurring in >1% were dizziness in 1.8%, headache 1.5%, flushing 1.1% and fatigue 1.1%.

We conclude that AML is an effective and well-tolerated antihypertensive suitable for most hypertensive patients.

Depression Scale for Research in and Identification of Postpartum Depression

Saralee Glasser, Vita Barell

Health Services Research Unit, Ministry of Health, Sheba Medical Center, Tel Hashomer

Postpartum depression (PPD) is a relatively frequent and serious condition, with negative consequences for the mother, her infant, and the family. From research and clinical experience in many countries, it has been found that PPD can be identified early, and women at risk for developing PPD can be identified before delivery in the framework of primary health care service. The Edinburgh Postnatal Depression Scale (EPDS) has been found valid for this purpose, both in the original English version, and in translation to numerous languages. The Hebrew translation of the EPDS is presented, and it is recommended that Israeli researchers use the same translation to facilitate accumulation of knowledge regarding the epidemiology of PPD and intervention strategies in various Israeli population groups, and for comparison with data from other countries.

Comparison between Every-Day and Every-3-Days Fluoxetine in Young, Moderately Depressed Out-Patients

A. Shiber, H. Reuveni, A. Elhayany, I.Z. Ben-Zion

Psychiatric Dept., Psychiatric Division, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba; and Medical Division for Drug Utilization, Kupat Holim Klalit (Sick Fund)

Fluoxetine is now a well-known and often-used specific serotonin reuptake inhibitor (SSRI) and antidepressant. It has a very long active half- life, from 2-16 days. Our hypothesis was that sufficient therapeutic effectiveness would be achieved by prescribing the drug less frequently than once a day.

To establish whether there is a difference between fluoxetine given daily or every 3 days, we assigned 25 outpatients with mild to moderate, acute major depressions (DSM-IV) to receive fluoxetine (20 mg), either each day or every 3 days. The study was open-labelled, using for assessment the HAM-D, GHQ-28 side-effect checklist and clinical judgment questionnaires. Follow-up lasted 6 months.

Results indicated no differences in the clinical outcomes, except for slightly fewer side-effects in the study group. Although the open label design limits drawing definitive conclusions, our preliminary results provide more information, and support our hypothesis that low-dosage fluoxetine is beneficial. However, more comprehensive, double-blind studies are necessary to confirm our preliminary results.

Pulmonary Hypertension and Multi-Valvular Damage Caused by Anorectic Drugs

Serge E. Goldstein, Yair Levy, Yehuda Shoenfeld

Medical Dept. B and Institute for Immunological Disease Research, Chaim Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Marked obesity is an independent risk factor for multisystem morbidity. The use of anorectic drugs is an aggressive strategy for weight reduction. It appears to be an easy way of dealing with the problem, because the patient needn't change his behavior. However, such treatment is not harmless. At the end of the 60's an outbreak of pulmonary hypertension was associated with the drug aminorex, and it was soon withdrawn from the market. 30 years later it became clear that new-generation anorectic drugs (fenfluramine, dexfenfluramine, phentermine), which were being used world-wide, lead to both pulmonary hypertension and valvular damage.

We describe a woman of 70 with both these complications which developed after prolonged anorectic therapy with a fenfluramine-phentermine combination.

Characteristics of Israeli Primary Health Care Physicians who Treat Depression

Jonathan Rabinowitz, Dina Feldman, Revital Gross, Wienka Boerma

Bar Ilan University, Ramat Gan; Israel Ministry of Health; JDC-Brookdale Institute, Jerusalem; and Netherlands Institute of Primary Health Care (NIVEL)

Primary health care physicians have a pivotal role in treating mental health problems. We determined the proportion of primary care physicians in Israel who treat depression and their characteristics. The study was based on a stratified national random sample of primary care physicians (n677, response rate 78%). From these physicians' reports 22% always treat depression, 36.6% usually, 28.6% sometimes, and 12.6% never. Based on a logistic regression model the physicians who always or usually treated depression were distinguished from the other physicians by their treating more medical conditions on their own, seeing themselves as having more first contact for psychosocial problems, having frequent contact with social workers and specializing in family medicine. Primary health care physicians play a major role in treating depression on their own. This raises new questions about how they treat depression themselves, and under what circumstances they treat or refer to a specialist.

Orthostatic Hypotension as a Manifestation of Malignant Lymphoproliferative Disease

H. Semo, A. Adunsky, E. Grossman

Depts. of Geriatric Medicine and of Medicine D, Chaim Sheba Medical Center, Tel Hashomer

An 85-year-old man was admitted with 6-month history of incapacitating orthostatic hypotension. Investigation led to the discovery of sympathetic dysautonomia, sensorimotneuropathy and malignant lymphoproliferative disease. Several attempts to treat the orhypotension or the neoplastic disease failed to improve his condition. Orthostatic hypotension precipitated by sympathetic dysautonomia may be an infrequent effect of early malignant lymphoproliferative disease.

Water Intoxication following Desmopressin Overdose

D. Segal-Kuperschmit, O. Dali-Gotfrid, A. Luder

Pediatric Dept., Rebecca Sieff Hospital, Safed

Water intoxication is a serious condition which may be caused by desmopressin overdose, with reversible or irreversible neurological complications. In the past, desmopressin was used in endocrinological centers for the treatment of anti-diuretic hormone deficiency (central diabetes insipidus). Indications for hormone treatment have since widened, especially as an effective solution for nocturnal enuresis. It is now often prescribed in community clinics, and its use has been encouraged by extensive promotion. We describe a 15-year-old boy with primary nocturnal enuresis who started treatment with desmopressin 1 year prior to admission. He was allowed to use the drug without supervision, and drank excessively. The result was water intoxication which required admission for intensive care because of loss of consciousness and convulsions for 36 hours.