Prophylaxis Of Affective Disorders Research Articles

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly ( P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.

Non-pharmacological prophylaxis of affective disorders: A current view with clinical observations in case series of depressed patients

Non-pharmacological prophylaxis of affective disorders: A current view with clinical observations in case series of depressed patients

The mechanism of lithium action: state of the art, ten years later

1. Lithium is an effective drug for both treatment and prophylaxis of bipolar disorder. However, the mechanism of lithium action is still unknown. 2. The inositol depletion hypothesis is supported by biochemical and behavioral data in rats, but primate inositol levels are higher than in rodents and may obviate the effects of depletion. 3. Inhibition of 5HT autoreceptors by lithium is supported by biochemical and behavioral data in rats but would seem more related to lithium's antidepressant than to its antimatic or prophylactic effects. 4. Lithium induces increases in levels of the anti-apoptotic factor Bcl-2. This effect could be most relevant for treatment of neurodegenerative disorders. 5. Lithium inhibits glycogen synthase kinase-3, which is involved in a wide range of signal transduction pathways. However, this lithium effect occurs at high concentrations and may be more relevant for its toxic effect. 6. Lithium in low concentrations induced accumulation of PAP, which affects several cellular processes including RNA processing. However, PAP phosphatase is present more in peripheral tissues than in brain. This lithium effect could explain some of its peripheral side effects. 7. Chronic lithium administration upregulates glutamate reuptake and thus decreases glutamate availability in synapse. Glutamate is an excitatory neurotransmitter and its reduction could exert an antimanic effect. 8. Biochemical and clinical experiments are necessary to determine the key mechanism of lithium efficacy in treatment and prophylaxis of affective disorders.

Carbamazepine inhibits the potentiation by adenosine analogues of agonist induced inositolphosphate formation in hippocampal astrocyte cultures

Carbamazepine (CBZ) resembles lithium in its beneficial effects in therapy and prophylaxis of affective disorders. Since lithium is presumed to act via an attenuation of the inositolphosphate/Ca(2+)-second messenger system, it is of particular interest whether or not CBZ might also have inhibitory effects on this type of signal transduction. CBZ is an antagonist of adenosine A1-receptor subtypes. We show here that activation of adenosine A1-receptors potentiates the phenylephrine induced formation of inositolphosphates in hippocampal astrocytes and that this potentiating effect is inhibited by CBZ at a therapeutically relevant concentration. These results indicate that CBZ can by antagonism of adenosine A1-receptors inhibit the inositolphosphate/Ca(2+)-signalling in neural pathways regulated by adenosine.

The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders

The prophylactic efficacy of carbamazepine slow release (CBZ) at ke different blood levels and lithium carbonate slow release (LI) was compared in a retrospective/prospective, randomized, 2-year open trial. 84 patients with a DSM-III-R diagnosis of recurrent affective disorder who had no prophylactic medication in the 2 years preceding the trial (no LI nonresponders), were randomly allocated to three treatment groups: CBZ low (15–25 μol/1), CBZ high (28–40 μmol/1) and LI (0.6–0.8 μmol/1). Fifty-eight patients completed the full observation period of 2 years, 26 patients dropped out. There were no statistically significant differences in the efficacy of the prophylactic treatment for bipolar patients. For the unipolar patients, the group with a low CBZ serum level showed no reduction in the duration of episodes. The two other treatment groups seem to be equal in attenuation of a unipolar course of an affective disorder.

The effects of valproate in brain monoamines of juvenile rats after stress

Mitsikostas Dimos, Anastasia sfikakis, Zetta Papadopoulou-Daifoti and Dionisios Varonos. The Effects of Valproate in Brain Monoamines of Juvenile Rats after Stress. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17(2): 295–310. 1. 1. Clinical data suggest that valproate (VPA) may be useful in prophylaxis of affective disorders, which show disturbances of the serotoninergic system. On the other hand, chronic stress has an adverce effect on affective disorders, those with disturbances of the serotonergic system, especially. 2. 2.In order to study the effects of VPA on brain monoamines and acute stress, 200 mgr VPA /Kgr was administered intraperitoneal (ip) to juvenile male rats; the control group was treated with NaCL 0.9% ip. After 30 min, all animals were evoked on predictable neurogenic or systemic stress (30 min foot shock, or 15 min ether stress, respectively), and 48 hours later, VPA or NaCL were administered ip again; 30 min afterwards, the rats were decapitated. Rats without stress were also sacrificed 30 min after VPA or NaCL administration. 3. 3. Measurements of brain monoamines noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT). and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxy- indoleacetic acid (5-HIAA), were done in Frontal Cortex (FC), Hypothalamus (HY) and Striatum (S), by High Performance Liquid Chromatography (HPLC). 4. 4. Compared with the control stress group the level of 5-HIAA in the FC was significantly increased (P<0.01) in VPA stress rats; in the HY and in S the increase of 5-HIAA was not significant. No remarkable differences were observed in NA, DA, 5-HT and DOPAC concentrations, in any of the brain regions. No changes in brain monoamine levels were found in non stress rats, either. 5. 5. The augmentation of 5-HIAA level after VPA administration and after stress, in correlation with the decrease of 5-HIAA that is observed in depression, support the hypothesis that VPA may be effective in affective disorders by influencing the serotoninergic system.

Calcium-antagonistic effects of carbamazepine in epilepsies and affective psychoses.

Carbamazepine (CBZ) is known to have beneficial effects in the treatment of epilepsies and in the prophylaxis of affective disorders. Since increased transmembrane calcium fluxes and intracellular calcium concentrations play a key role in the generation of epilepsies and possibly also in the development of these psychiatric disorders the effects of CBZ on epileptic discharges (elicited by caffeine, penicillin and low Mg2+) in CA3 neurons of hippocampal slices were compared with those of the organic calcium antagonist verapamil and found to be almost the same.

Carbamazepine in the Prophylaxis of Mood Disorders

Alternatives to lithium are desirable in the prophylaxis of affective disorders, especially in patients who are intolerant of or do not respond to that drug. In the past few years the anticonvulsant carbamazepine has been in the foreground of discussion. Twenty-four patients with affective disorders (17 unipolar depressed, six bipolar, and one unipolar manic) were included in a comparative trial of lithium and carbamazepine; 12 had been pretreated with lithium without a satisfactory effect. All patients received carbamazepine (four received it in combination with lithium) over a mean time span of 20.2 months. Eighty percent of the patients improved with carbamazepine treatment. Side effects were infrequent.

Lithium for the control of aggressive and self-mutilating behaviour.

Lithium has been used for many years in the treatment and prophylaxis of affective disorders. Since 1969, evidence has been accumulating in relation to its effectiveness in the control of aggressive behaviour. This review summarizes the published evidence.

Acute Treatment, Long-term Management, and Prophylaxis of Affective Disorders

Acute Treatment, Long-term Management, and Prophylaxis of Affective Disorders

Lithium long-term treatment--does it act via serotonin?

The mode of action of lithium salts used in the prophylaxis of affective disorders is still unknown. During the last decade, animal data have provided considerable evidence that chronic administration of lithium within a "therapeutic range" induces 5-HT agonistic effects in the brain. Among other possible reasons this may be due to increased synthesis of 5-HT. After presenting the main animal data in this area, some recent findings in lithium-treated patients are reviewed supporting the biochemical and neurophysiological results. Taking into account that, firstly, lithium possesses antiaggressive effects in animals and men, and secondly, that (auto-)aggression seems to be related to a low concentration of 5-HIAA in CSF, and thirdly, that a close relationship exists between depression and aggressive behavior, the proof of 5-HT agonistic effects in humans may enable us to formulate an integrative theory on the mode of action of lithium salts.

The relationship between serum lithium levels and clinical response.

A guiding principle in the use of lithium salts in the treatment of mental illness is to maintain the serum lithium level between 0.8 and 1.2 mmol/L. This article reviews the limited evidence on which such a recommendation is male. The pharmacokinetics of lithium ion and difficulties inherent in serum lithium estimation are briefly examined. Clinical studies which looked specifically for a relationship between lithium dosage and serum concentration are reviewed. Treatment studies of lithium in mania and prophylaxis of affective disorders are assessed for indirect evidence to support a relationship between favorable therapeutic outcome and recommended serum levels.

Plasma lithium levels and therapeutic outcome in the prophylaxis of affective disorders: a retrospective study.

Patients receiving prophylactic lithium therapy for primary affective disorder during a four year period were studied for recurrence of affective illness. Patients who had affective episodes during this period did not differ from those who remained well in age, sex or diagnosis. Those with a favourable outcome had spent significantly less time at serum lithium levels above 0.9 mmol/litre than those who had a recurrence of affective episodes.

Depression and Hormones. An Outline and Some Perspectives

Despite considerable progress in the treatment and prophylaxis of affective disorders, particularly during the past 15 years, depression remains a major world health problem. With some variation, depending on the country and the investigator, the statistics attest to the high frequency of depressive disorders in the population. The lifetime risk that anyone in North America will suffer from a depression of clinical severity has recently been estimated at between 10% and 15% (e.g., Weissmann & Klerman, 1978). Recent World Health Organization reports indicate that at least one hundred million people are suffering from depression of clinical intensity at any time (Sartorius, 1978). Clearly, effective treatments based on comprehensive understanding of the illness are needed for a disorder of this extent. But extensive investigation of the biological and psychosocial dimensions of affective disorders has produced only limited understanding of the nature of depression.

Patient and Physician Attitudes Toward Lithium

IN the three decades since Cade's discovery,1lithium has moved from a position of therapeutic promise to an extensively studied treatment of choice in bipolar, and certain subtypes of unipolar, affective disorders. Marketing firms and pharmaceutical companies estimate that more than 120,000 Americans currently are taking lithium (G. Graham, MD, Smith Kline & French Laboratories, personal communication), figures consistent with Jenner and Eastwood's2estimate that one person in 2,000 in the United Kingdom is now receiving lithium. However, despite the growing number of patients receiving lithium, its well-established usefulness in the treatment and prophylaxis of affective disorders, and the common clinical impression of frequent problems with compliance, it is not known how many patients actually stop taking lithium against medical advice, for what reasons and for how long, at what point in their therapeutic regime or mood cycles, and whether or not there are sex and age

Major Affective Disorder as a Recurrent Illness

The systematic study of the natural course of affective disorders originated with the pioneer work of Kraepelin¹and has continued until recently. However, with the advent of lithium and its widespread use in the prophylaxis of affective disorders, naturalistic data on the course of the illness has become increasingly unavailable. While reviewing the literature on the subject, one is struck by the discrepancies in the reported results and particularly the disparities concerning the proportion of patients with a single episode or those who experience several episodes during the observation period. It is our working assumption that methodological and population differences account for most, if not all, of the reported inconsistencies. For the purpose of this paper, we reviewed ten of the largest and most frequently quoted studies conducted over the past half century, largely in the predrug era, and concerning the natural course of affective illness. After presenting a

Plasma magnesium and calcium in depression.

Recent investigations suggest that there may be an abnormality of calcium and magnesium in depressive illness. Flach (1964) followed the urinary excretion of calcium in depressed patients maintained on a constant intake of calcium before and during recovery. Those patients that recovered showed a significant decrease in the excretion of calcium. Coiraultet al.(1959) reported an increase in ionized calcium and a decrease in total plasma calcium on recovery from depression. Cade (1964) reported considerably raised total plasma magnesium levels in depressed patients both before and after recovery. A connection between affective disorders and calcium metabolism is suggested by the common occurrence of such states in both hypo- and hypercalcaemia (Denco and Kaelbling, 1962; Rookus and Speelman, 1961). The present paper reports an investigation into total and ionized plasma calcium and magnesium in a group of depressed patients both before and after recovery. The effects of lithium carbonate, a compound used in the treatment and prophylaxis of affective disorders (Baastrup and Schou, 1967; Schou, 1963) on plasma concentrations of magnesium and calcium was also investigated.