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PubMed1977

[Double-blind comparison of the effects of a new tricyclic antidepressant (Lofepramine) and a tetracyclic antidepressant (maprotiline)].

Two random groups of depressed out-patients were treated with either Maprotiline or the new antidepressant Lofepramine. The depressive state was assessed by using the Hamilton Depression Scale (HAM-D) before and after 1, 3 and 6 weeks of treatment. Both drugs produced remarkable improvement globally in total HAM-D score as well as in the symptom clusters. The differences in both groups are not significant, but compiling the results of adverse reactions and the therapeutic effect, the treatment outcome in the Lofepramine group was slightly superior.

Adolescent↗

PubMed2026

Antidepressant use among American adults in a 50-state survey.

BACKGROUND: Antidepressants are among the most prescribed medications in the USA, yet challenges in access to mental health treatment persist. OBJECTIVE: To assess current and lifetime antidepressant and psychotherapy use among American adults, and examine attitudes towards potential federal restrictions on antidepressant prescribing. METHODS: We conducted a cross-sectional survey study using data from a national non-probability internet-based panel weighted to approximate national demographics (age, gender, race and ethnicity, education, US census region, and urbanicity) based on 2020 US Census data. Data were collected between 10 April and 27 May 2025 from 30 810 adults residing in the USA. The primary outcomes were self-reported current and past antidepressant and psychotherapy use, and support for or opposition to potential federal restrictions on antidepressant prescribing. Logistic regression models estimated demographic and treatment-related features associated with these outcomes. FINDINGS: Among 30 115 respondents with complete antidepressant data, 16.6% reported current antidepressant use, and of 30 098 respondents with psychotherapy data, 10.4% reported current psychotherapy. Use of both treatments was significantly greater among White respondents compared with all other racial groups. When asked about potential federal restrictions on doctors prescribing antidepressants, 16.4% of respondents supported and 48.0% opposed such regulation, with lesser opposition among those of male gender (OR 0.69, 95% CI 0.65 to 0.73), and greater opposition among those with lifetime antidepressant treatment (OR 2.37, 95% CI 2.21 to 2.54). CONCLUSIONS: Antidepressant and psychotherapy use remains unevenly distributed across demographic groups. A significant proportion of adults in every US state oppose efforts to restrict access to antidepressant prescribing, reflecting broad public support for maintaining access to treatment. CLINICAL IMPLICATIONS: Findings from this study suggest that restrictive policies on antidepressant prescribing are unlikely to align with public sentiment and may risk exacerbating existing inequities in care.

Humans↗

PubMed1979

[Classification of the antidepressants (author's transl)].

The antidepressants can be classified chemically. The standard division is between the tricyclic antidepressants and the chemically heterogeneous MAOIs. Many other compounds can be included among the antidepressants, e.g. the bicyclics and possibly also the beta-stimulants, the alpha-blockers and ions such as rubidium. As regards the mechanisms of action, we have the antidepressants which act selectively upon serotonin and those which act more particularly upon noradrenaline. This notion must be extended. Dopamine may be involved in certain depressive syndromes and also other systems may have a role, such as electrolyte systems, cell permeability and the multiple influences which have a bearing upon the monoamines. Finally, the effect upon receptors and their nature are discussed. A third type of classification refers to the therapeutic spectrum of the drug. We have the sedative antidepressants, active in agitated depression and the stimulant antidepressants which are active in retarded depression. However, the two categories of antidepressants have the same global antidepressant action.

Antidepressive Agents↗

PubMed1979

Specific tricyclic antidepressant binding sites in rat brain.

The discovery of high-affinity binding sites for psychoactive drugs such as benzodiazepines, opiates and neuroleptics has opened up new approaches to the study of these drugs and their mechanisms of action. Although most tricyclic antidepressants inhibit neuronal uptake of noradrenaline and serotonin, their mechanism of action remains unclear. Changes in the sensitivity of the beta-receptor after chronic tricyclic antidepressant treatment suggest that they modulate noradrenergic neurotransmission. Tricyclic antidepressants also act directly on cholinergic, histaminergic, alpha-adrenergic and serotonergic receptors. It is not clear, however, which, if any, of these effects are related to the primary antidepressant effect or whether they are simply responsible for some of the side effects. We have thus investigated the possibility that specific binding sites for tricyclic antidepressants exist in the central nervous system. So far, binding studies using 3H-labelled tricyclic antidepressant drugs have only detected binding to histaminergic H2 and cholinergic muscarinic receptors and low-affinity binding. We demonstrate here a population of specific high-affinity binding sites for 3H-imipramine on brain membranes which may be responsible for the antidepressant effects of these drugs.

Animals↗

PubMed2026

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p < 0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62 min, 95% CI 0.18-7.06; p < 0.05) and reduced mean power output (mean difference - 19.97 W, 95% CI - 36.87 to - 3.06; p < 0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans↗

PubMedDate not supplied

[Neurochemical mechanisms of the action of tricyclic antidepressants of the imipramine group].

The main role in determination of the pharmacologic effects of the imipramine groups antidepressants is given to their influence on neurotransmitters metabolism in synapses, the activity of enzymic systems regulating the transport of ions, as well as on the system of cyclic AMP metabolism. Interaction of tricyclic antidepressants with membrane and, as the result, distrubance in reuptake of transmitters (epinephrine and 5-hydroxytryptamine) in neurons is supposed to be one of the mechanisms of synaptic transmission regulation. The possible role in inhibition of biological amines deamination, in particular of phenylethylamine, in antidepressive effect of tricyclic antidepressants is discussed. It is supposed that the thymoanaleptic effects of the imipramine group antidepressants are due to activation of central serotoninergic processes, and their psychoanaleptic effect due to activation of the adrenergic system. Inhibition of the Na+, K+-ATPase activity quilizing effect of tricyclic antidepressants.

Adenosine Triphosphatases↗

PubMed1979

Monitoring of antidepressant drug plasma levels: the next ten years.

Future studies of the relationship between plasma level and drug response in depressed patients ought to take the following facts into consideration: 1. Selective drug analytical methods must be used and subjected to quality control. Methods for the major urinary metabolite(s) of the parent drug should also be developed. 2. Each drug has individual pharmacokinetic and pharmacodynamic properties--it is unlikely that one drug will be effective in all patients even under optimal kinetic conditions. 3. The pharmacologic and biochemical effects of hitherto investigated tricyclic antidepressants correlate significantly to the concentrations of parent drug and/or its active metabolite in plasma. 4. It is more likely that a significant correlation will be found between the total tricyclic antidepressant level in plasma and the therapeutic outcome in a patient sample if the range of plasma levels is large--in this case the relatively small interindividual differences in plasma protein binding play a minor role. 5. Concomitant somatic disease may change the kinetics of antidepressant drugs. 6. The clinical methods used for selecting and rating study patients with depressive disorders must be standardized. 7. Novel rapidly acting drugs are desirable because the slow onset of action of tricyclic antidepressant seriously hamper their clinical evaluation. 8. A strong correlation between plasma concentration of an antidepressant drug and clinical outcome is strong evidence that the clinical effect is due to the drug rather than nonpharmacological factors.

Antidepressive Agents↗

PubMed1979

The effect of repeated administration of antidepressant drugs on the responsiveness of rats to catecholamine agonists.

The antidepressant drugs, imipramine (10 mg/kg s.c.), amitriptyline (10 mg/kg s.c.), mianserin (2 mg/kg i.p.), danitracen (3 mg/kg i.p.) or the vehicle were administered to rats twice a day for 4 or 10 days. Clonidine (0.5 mg/kg s.c.) induced in rats chronically treated with the compounds studied an increase in locomotor activity but, at the same time, did not affect or decreased this activity in rats chronically treated with the vehicle or a single dose of an antidepressant. This refers, in particular, to imipramine, amitriptyline and danitracen which have a similar effect. This effect, an increase in motility, was most pronounced and common for all the three drugs (after a 4- and 10-day treatment) when clonidine was administered 72 hours after the last dose of an antidepressant. Only in a few cases the amphetamine-induced hypermotility was enhanced by a chronic administration of antidepressants (a 4-day amitriptyline treatment, 72 hours after the last injection; a 4-day mianserin or danitracen treatment, 48 hours after the last injection). The results obtained seem to suggest that a chronic administration of the antidepressant drugs may cause a change in the sensitivity of the central noradrenaline receptors.

Amitriptyline↗

PubMed1978

Behavioural despair in rats: a new model sensitive to antidepressant treatments.

Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity. Anxiolytic compounds did not affect immobility whereas major tranquilisers enhanced it. Immobility was also reduced by electroconvulsive shock, REM sleep deprivation and "enrichment" of the environment. It was concluded that immobility reflects a state of lowered mood in the rat which is selectively sensitive to antidepressant treatments. Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests.

Animals↗

PubMed1979

Interaction of antidepressants with clonidine on rat brain total 3-methoxy-4-hydroxyphenylglycol.

The effects of some antidepressants on brain total 3-methoxy-4-hydroxyphenylglycol (MHPG) were studied in the rat. Desipramine decreased and mianserine increased the brain total MHPG concentration while the other antidepressants had no effect. They were also the only antidepressants that attenuated the lowering action of clonidine on brain total MHPG, but possibly through different mechanisms. Two tertiary amine tricyclic antidepressants, amitriptyline and imipramine, appeared to enhance the lowering action of clonidine on brain total MHPG. The results suggest that antidepressants are heterogeneous in their action on brain noradrenergic mechanisms in the rat.

Animals↗

PubMedDate not supplied

The pharmacology of mianserin (Org. GB 94) Leviron, a really different antidepressant.

The new tetracyclic antidepressant mianserin was clinically shown to be better than placebo and to have less side-effects than the tricyclic antidepressants. It has neither anticholinergic activity nor is it effective in the classical tests of antidepressant activity based on amine re-uptake inhibition. Mianserin shows clear antidepressant activity in tests with muricide rats, in bulbectomised rats and in the acquired immobility test with rats or mice. Mianserin shows effects indicative of anxiolytic activity in several tests, including those using punishment or conflict paradigms. Mianserin is less toxic on the cardiovascular system than the tricyclic antidepressants and on chronic administration to rats and mice does not produce dependence or abstinence.

Aggression↗

PubMed1979

Cyclic AMP in the rat cerebral cortex after stimulation of the locus coeruleus: decrease by antidepressant drugs.

The study concerned the effect of repeated treatment with antidepressant drugs on the elevation of cyclic AMP levels in the rat cerebral cortex following electrical stimulation of the locus coeruleus. Some of the tricyclic and tetracyclic antidepressant drugs inhibited the cyclic AMP response. Desmethylimipramine was the most potent (effective when given 5 mg/kg/day for 2 weeks). Imipramine and nomifensine (daily dose 10 mg/kg for 2 weeks) produced slight decreases, while iprindol and clomipramine were ineffective. After 6 weeks of treatment (daily 10 mg/kg) iprindol, clomipramine and mianserin were without effect. The cyclic AMP response was suppressed by higher doses of the latter two drugs (2 weeks, 20 mg/kg/day). These results indicate that tricyclic and tetracyclic antidepressant drugs are able to decrease cerebral noradrenergic neurotransmission of locus coeruleus neurons, as far as this is mediated by cyclic AMP. It is not clear, however, whether such modification is related to the therapeutic action of antidepressant drugs.

Animals↗

PubMed1979

Effect of various antidepressant drugs on the spontaneous firing rate of locus coeruleus and dorsal raphe neurons of the rat.

The spontaneous firing rate of the noradrenergic neurons of the locus coeruleus and of the serotonergic neurons of the dorsal raphe was recorded with extracellular microelectrodes in chloral hydrate-anesthetized rats. A quantitative comparison of the effect of five tricyclic antidepressants, of tranylcypromine and of mianserin on the spontaneous activity of these two types of cells was performed. All drugs tested, except mianserin reduced the frequency of discharge of the noradrenergic neurons. Intravenous perfusion of the drugs allowed the doses required for inhibition of firing to 50% of the baseline rate (ID50) to be determined. Secondary aminated antidepressants (desipramine and nortriptyline) were more potent inhibitors than their tertiary aminated analogues (imipramine, chlorimipramine and amitriptyline). All drugs tested, except desipramine decreased the rate of firing of the serotonergic cells. In this case, the tertiary aminated antidepressants were much more potent than their secondary analogues. Mianserin was only active at very high doses. These results are in good agreement with the relative potencies of the tricyclic antidepressants for blocking the uptake of noradrenaline and serotonin into central and peripheral neurons.

Action Potentials↗

PubMed1979

[The research of new antidepressants: present orientations (author's transl)].

A number of promising antidepressant compounds are presently either being developed in the laboratory or are being tested clinically by pharmaceutical firms and universities around the world. New compounds are sought which will provide: 1. fewer side effects, particularly anticholinergic and cardiovascular effects; 2. more rapid onset of action than 7-10 days required of most antidepressants now used; 3. efficacy in a higher percentage of patients than the 65-70 per cent estimated to respond to currently available antidepressant therapies. Compounds now being investigated include: new tricyclics which are unlike those commonly in use; the tetracyclics; the salts of naturally occurring cations such as lithium and rubidium; and various chemically unrelated new compounds. In addition, several drugs currently being tested as anorectics seem promising for future antidepressant drugs research.

Animals↗

PubMed1979

[Mechanisms of action of the antidepressants (author's transl)].

The tricyclic and related antidepressants reduce monoamine uptake at the synapses, block the presynaptic receptors and, after chronic administration, act upon the synthesis of the monoamines and the sensitivity of the post-synaptic receptors. The NA and 5-HT synapses are influenced to different degrees by the antidepressants: for example, desipramine has a preponderance of activity at NA synapses and clomipramine at 5-HT synapses. By combining these findings and by highlighting one or other of these properties, it is possible to come to diametrically opposite conclusions upon the effect of the antidepressants upon monoamine performance (activation or inhibition) and to develop many models of the mechanisms of antidepressant action. The authors describe some of these and stress the model which is at the basis of the studies being carried out at the Department of Psychiatry of the University of Geneva.

Animals↗

PubMed1979

The role of plasma level monitoring of tricyclic antidepressant drugs as an aid to treatment.

Use of the tricyclic antidepressant drugs is the most common pharmacotherapeutic approach to the treatment of depression. It is a common clinical experience to find that a fair proportion of patients fail to show a satisfactory response and that others complain of side-effects. Important factors which influence this situation are the diagnostic criteria used to select patients for drug treatment, the dosage prescribed and individual compliance. Measurement of plasma drug concentrations has been proposed as a more rational way of increasing the efficacy of antidepressant medication and avoiding toxicity. A number of studies have shown a correlation between plasma concentrations of these drugs and clinical effects, but the relationship is far from simple. With amitriptyline and nortriptyline there is good evidence for a 'therapeutic window' within which maximum antidepressant action is obtained. Many patients being treated with these drugs have plasma levels outside recommended therapeutic ranges. Experience in our department has shown that there are a number of clinical situations where routine plasma level monitoring of selected antidepressants is of value: (1) inadequate clinical response; (2) side-effects/toxicity; (3) complicating medical conditions; (4) suspected poor compliance; and (5) long-term therapy. Such measurements are a relatively simple and inexpensive way of maximizing the benefits of drug therapy and a means of tailoring drug dosages to suit individual requirements.

Aged↗

PubMed1976

A possible common mechanism of action of antidepressant treatments: reduction in the sensitivity of the noradrenergic cyclic AMP gererating system in the rat limbic forebrain.

The response of the noNEpinephrine (NE) sensitive cyclic AMP generating system in slices of the rat limbic forebrain after both the acute and chronic administration of the tricyclic antidepressants desipramine (DMI) and iprindole as well as electro-convulsive treatment (ECT) was investigated. Neither the basal level of cyclic AMP nor the hormonal response to NE were altered after administration of a single dose of short term treatment with DMI and iprindole. However, the administration of the antidepressants on a clinically more relevant time basis markedly reduced the sensitivity of the cyclic AMP generating system to NE. This change in sensitivity was not related to the levels of the drugs in brain. The response of cyclic AMP to NE was also reduced by ECT, but the onset of this action was shorter than that observed with the antidepressants. ECT also antagonized the enhanced response of cyclic AMP to NE following destruction of central adrenergic nerve terminals with 6-hydroxydopamine. It thus appears that the therapeutic action of tricyclic antidepressants could be related to postsynaptic adaptive changes in the sensitivity of the noradrenergic adenylate cyclase receptor system rather than to acute presynaptic events.

Animals↗

PubMed1978

Clinical prediction of antidepressant response.

Depression is not a unitary disease and not all cases of depression can be treated alike. Therefore, predictors of antidepressant response to different drugs need to be identified. Premorbid personality, age and sex and family history are useful in prediction. As an example, only females respond to the addition of triiodothyronine to the antidepressant therapy. Endogenous depressions respond favourably to antidepressants, so also do psychotic depressions. On the other hand, delusional depressions do not respond to antidepressants. While atypical depressions are best treated with MAOI, motor retardation improves with imipramine and obsessive symptoms with chlorimipramine. In addition to clinical variables, biochemical and statistical approaches have also yielded significant results in prediction.

Age Factors↗