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PubMed1991

[Semiological and psychological predictive factors of response to antidepressive agents].

Since the discovery of the first antidepressive compounds, very few progress have been made for the efficacy of these drugs. All the antidepressants, even the more recent of them, are efficient only in 60 to 75% of the depressive disorders treated. Many studies have been conducted to define clinical or psychological predictive factors of the response to antidepressants. Emphasis was carry mostly on the clinical characteristics of the depressive disorder and the importance of "endogenous" features for the response to treatment, have been well established. Some works have also emphasized the importance of personality disorders and environmental disturbances for the issues of treatment. More recent works aim to define the characteristics of the best responders to more selective antidepressive compounds. But, it is still very difficult today to define precisely what are the clinical or psychological features which are specifically responsive to antidepressive drugs.

Antidepressive Agents↗
PubMed1989

[Arrhythmogenic effects of antidepressive agents demonstrated by programmed ventricular pacing].

Tricyclic antidepressants and phenothiazines have been blamed for increasing the incidence of sudden death. One of their known mechanisms of action in such cases is to induce torsades de pointes by a so-called "quinidine-like" effect. We report the case of a female patient who was rescued from an episode of cardiac arrest which occurred two months after a myocardial infarction. Right ventricular programmed pacing strongly suggested an arrhythmogenic effect to the antidepressant the patient was receiving. This type of treatment seems to be capable of facilitating the induction of a monomorphous ventricular tachycardia which may degenerate into ventricular fibrillation.

Antidepressive Agents, Tricyclic↗
PubMed1986

[Torsade de pointes caused by tricyclic antidepressive agents. Description of a clinical case].

Tricyclic antidepressant drugs are known to cause often electrocardiographic abnormalities and to induce sometimes cardiac rhythm disturbances. We report a case of a patient on antidepressant therapy (Desipramine Hydrochloride, 50 mg/die, and Dothiepin Hydrochloride, 150 mg/die), without any underlaying heart disease, admitted to our Coronary Care Unit for recurrent syncopal episodes. An ECG on admission showed Sinus Tachycardia with Ectopic Ventricular Beats and recurrent runs of Torsade de Pointes, a distinctive form of Ventricular Tachycardia. Lignocaine i.v. was only transiently effective. Both Isoprenaline and Atropine Sulphate i.v. were uneffective. Ventricular Fibrillation occurred and cardioversion was achieved by a single DC shock. Amiodarone i.v. and electrical overdrive only temporarily suppressed ventricular arrhythmias. Magnesium Sulphate i.v. (bolus + infusion) induced a definitive suppression of Torsades de Pointes. One day later no more arrhythmias were present.

Antidepressive Agents, Tricyclic↗
PubMed1995

[Long-term clinical effects of antidepressive agents].

According to long term studies with antidepressants versus placebo, the therapeutic efficacy is prolonged: a long term treatment in full dosage seems to reduce from almost half the risk of relapse and recurrence till five years, during recurrent major affective disorders. We should therefore be cautious and we should not have a systematic prescription for all types of depressions; antidepressants are efficacious but have side effects and we do not know well their abilities in long term use. During bipolar disorders the prescription of long term antidepressants, even in association with normothymics, does not give benefits and can induce rapid cycles. In dysthymias and depressions with personality disorders, a psychotherapy is indicated, and it is difficult to evaluate the efficacy of a long term antidepressant treatment. Tricyclics antidepressants, MAOI's and SSRI's have classical side effects, and they can also induce: modifications of the symptomatology, of cognitive functions, of sleep, eating and sexual behaviours; modifications of the course of depressive illness, induction of manic switches, and may be sometimes an exacerbation of suicidal ideation ... pharmacogenetic modifications with their action on hepatic metabolism, neuroendocrine alterations and long term effects on monoamines. We have also to take into account the long term treatment consequences on quality of life, on self esteem with the importance of psychodynamic and relationships modifications. The use of a long term antidepressant treatment should be adapted to each individual, being cautious of its potential benefits and risks.

Antidepressive Agents↗
PubMedDate not supplied

[Drug interactions and new antidepressive agents].

The mechanism of action of new antidepressants is characterized by a specific inhibition of the serotonin reuptake at synaptic level. In France, fluoxetine, fluvoxamine, and more recently paroxetine are extensively used. Based on a review of the literature, the authors report the interactions of these new antidepressants with psychotropic and other drugs, that are frequently associated with them. All studies report the frequent occurrence of interaction when the new serotonergic antidepressants are associated with tricyclic ones. The increase of tricyclic drug plasma levels is often high with side effects as a consequence. If the pharmacodynamic aspects of these interactions are not well known, the pharmacokinetics are easier to understand, due to the power of these new antidepressants to inhibit cytochrome P450.

Antidepressive Agents↗
PubMed1993

[Antidepressive agents and memory].

It is important that antidepressants, now increasingly used in ambulatory treatment of many patients, should not be detrimental to cognition and memory. It is difficult to assess these effects. One must make a distinction between the direct effects of antidepressants on cognition, related to their intrinsic properties, and indirect effects secondary to mood improvement. The tests used in studies essentially focus on psychomotricity and do not accurately evaluate the effects on cognition itself. Indeed, there are different kinds of memory which would require specific investigations. It has nevertheless been demonstrated that acute administration of sedative antidepressants with a marked anticholinergic component are detrimental to the memory processes. However, following prolonged administration, tolerance may develop within 1 to 3 weeks. Some antidepressants, however, especially serotonergics, do not cause any disturbances of memory. In depressed subjects, it seems that, overall, long-term antidepressant treatment improves cognitive functions. This effect is due to the combination of drug tolerance and of the indirect effects secondary to mood improvement. Elderly subjects appear to be more sensitive to the detrimental effects on memory and they develop drug tolerance more slowly. Lastly, two studies have reported that serotonin re-uptake inhibitors might have beneficial effects on memory disorders secondary to acute or chronic alcohol abuse.

Adult↗
PubMed1993

Some biochemical properties of the new potential antidepressant agent N-methyl-N-propargyl-2-(1-methyl-5-methoxyindolyl)methylamine.

The biochemical properties of the new methyl indole derivative IM-24 (N-methyl-N-propargyl-2(1-methyl-5-methoxyindolyl)methylamine HCl) have been investigated. The activity on both forms of monoamine oxidase MAO was tested in several nervous and non nervous tissues ex vivo after chronic administration. IM-24 is mainly an inhibitor of the activity of MAO A without any effect on intestinal MAO B at the doses studied. IM-24 was compared with tricyclic antidepressants in tests for serotonin (5HT), noradrenaline (NA) and dopamine (DA) uptake inhibition in vitro. IM-24 is mainly an inhibitor of the 5HT uptake mechanism but is less active than paroxetine and chlorimipramine which are very potent 5HT-uptake inhibitors. Radioligand binding techniques in rat brain ex vivo showed that IM-24 after chronic administration (21 days) produces no change in the number or the affinity of the alpha 2-adrenoceptors. IM-24 reduces by 70% the number of 5HT2 receptors but does not modify the affinity for the ligand. IM-24 is thus an interesting compound which combines monoamine oxidase inhibition with inhibition of 5HT uptake. Both these actions will lead to an increase of the availability of serotonin at the synaptic site.

Animals↗
PubMed1975

Tricyclic antidepressant agents. I. Comparison of the inhibition of the uptake of 3-H-noradrenaline and 14-C-5-hydroxytryptamine in slices and crude synaptosome preparations of the midbrain-hypothalamus region of the rat brain.

The simultaneous uptake of 3-H-l-noradrenaline (NA) and 14-C-5-hydroxytryptamine (5-HT) in slices from the midbrain-hypothalamus region of the rat brain was compared with the corresponding uptake in crude synaptosome preparations of the same brain region. In both preparations the uptake of the two amines was selective at the concentration used (1 times 10- minus 7 M or lower). The KM values for the amines (NA: 2 times 10- minus 7 M in synaptosomes and 5 times 10- minus 7 M in slices; 5-HT: 8 times 10- minus 8 M in synaptosomes and 6 times 10- minus 7 M in slices) and the inhibitory concentrations (IC50) of the antidepressant agents were lower in the synaptosome experiments than in the slices experiments. Moreover the order of the inhibitory activities differed between the two preparations. In the slices experiments the NA uptake was inhibited most markedly by desipramine followed by imipramine greater than chlorimipramine = nortriptyline greater than or equal to amitriptyline greater than or equal to chlordesipramine whereas in the synaptosome experiments the order was desipramine greater than nortriptyline greater than or equal to chlordesipramine greater than or equal to imipramine greater than amitriptyline greater than or equal to chlorimipramine. For the 5-HT uptake in slices the order of activity was: chlorimipramine greater than imipramine greater than or equal to amitriptyline greater than or equal to chlordesipramine = desipramine greater than or equal to nortriptyline whereas in the synaptosome preparations the order was: chlorimipramine greater than imipramine greater than or equal to amitriptyline greater than or equal to chlordesipramine greater than nortriptyline = desipramine. The role of protein binding and diffusion barriers in the causation of the difference in the results obtained with the two preparations is discussed.

Amitriptyline↗
PubMed1991

[Antidepressive agents in the treatment of masked moods].

Quantitatively, the diagnosis and treatment of depressive disorders is mainly a matter for the general practitioner and internist, although masked forms of depression are, of course, associated with specific problems. If careful examination suggests the likelihood of underlying endogenous depression, treatment with anti-depressants is indicated primarily. In this paper, the pharmacological properties of these drugs are briefly reviewed, and basic suggestions for their practical application discussed. Both in the hospital and outpatient setting, therapy-resistant forms of endogenous depression pose a major problem: these patients are often elderly and the clinical presentation may be that of a masked depression. However, special therapeutic strategies may often have a positive effect in such cases.

Antidepressive Agents↗
PubMed1982

Experimental studies on the effects of physostigmine and of isoproterenol on toxicity produced by tricyclic antidepressant agents.

The IV infusion of nortriptyline and amitriptyline (0.5 mg/kg/min) in anesthetized cats produced death within 60 min of continuous infusion. The tricyclic antidepressant agents produced a quinidine-like depression of the myocardium characterized by bradycardia, depression of contractile force, conduction defects, bradyarrhythmias, and hypotension. The simultaneous IV infusion of isoproterenol (0.1 microgram/ kg/min) produced significant protection against death produced by the TCA drugs. The results suggested that the positive chronotropic, inotropic, and dromotropic actions of isoproterenol may all be contributory factors in the protection. Pretreatment with a large dose of physostigmine (0.2 mg/kg) produced a rightward shift of the nortriptyline time-mortality curve. The small degree of protection produced by the anticholinesterase drug may be due to a respiratory stimulant action rather than a cardiac action.

Amitriptyline↗
PubMed1998

[Choice of an antidepressive agent].

UNLABELLED: A WIDE SELECTION: New drugs have recently been added to the list of antidepressor agents which includes more than 20 compounds in 1998. The mechanisms of action are quite different. MECHANISM OF ACTION: Better knowledge of each compound and its mechanism of action on the different monoamines functioning in the brain has not been sufficient to determine a pharmacoclinical classification of depression. Likewise, alone mechanism of action is insufficient for choosing the right drug for a given individual. CLINICAL SIGNS: Therapeutic decisions must also take into account the clinical and functional features expressed by the patient, focusing on the importance of the patient-physician relationship in treating patients with states of depression.

Antidepressive Agents↗
PubMed1990

Stimulus properties of tiflucarbine: a novel antidepressant agent.

Tiflucarbine is a structurally novel antidepressant that binds at central serotonin (5-HT) binding sites. There is also evidence that this agent is both a 5-HT1 and a 5-HT2 agonist. To further characterize the serotonergic actions of this agent, tiflucarbine was evaluated in groups of rats trained to discriminate the 5-HT1A agonist 8-OH DPAT, the 5-HT2 agonist DOM, and the nonselective 5-HT agonist 5-OMe DMT from saline. Tiflucarbine resulted in partial generalization in the DOM-trained and in the 8-OH DPAT-trained animals. Although two-thirds of the animals were disrupted, 10 mg/kg of tiflucarbine resulted in stimulus generlization in the 5-OMe DMT-trained animals. It is concluded that tiflucarbine is most likely a nonselective 5-HT agonist.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗