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At least 19 recordsLinked to original sources
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↗
PubMedDate not supplied

The influence of antidepressants on aggressive behavior in stressed rats: the role of dopamine.

The influence of dopamine (DA) receptor blockers (haloperidol, sulpiride) on electric footshock-induced fighting behavior and on the effect of antidepressants (imipramine, clomipramine, nomifensine, mianserine) was investigated in chronically stressed male Wistar rats. Exploratory activity in an open field was measured in the same groups of animals. The effect of chronic stress and antidepressants on DA utilization in the brain was also investigated. It was shown that 48 h after the last session of repeated stress (various unpredictable stressors over 16 days) the number of fighting attacks was significantly reduced. However in stressed rats treated chronically (for 14 days) with antidepressants the intensity of fighting was restored to control value. On the contrary, when the stressed rats, receiving antidepressants chronically, were pretreated with DA receptor blockers: haloperidol (0.5 mg/kg) or sulpiride (50 mg/kg) but also alpha 1-adrenergic receptor blocker - prazosin (3 mg/kg) the effect of antidepressants was abolished. Exploratory activity was not significantly reduced under influence of stress. Neither antidepressants nor sulpiride modified exploratory activity of stressed rats. Haloperidol and prazosin but not sulpiride decreased this activity of normal, stressed and antidepressant-treated rats. It is concluded that prolonged treatment with antidepressants counteracts the decrease in aggression induced by chronic stress and that DA mechanism participate in this effect of antidepressant drugs.

Aggression↗
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↗
PubMed1978

[Inhibition and antidepressive agents].

The author distinguishes inhibition as a symptom from inhibition as a processus in the three following situations: a) Antidepressants and melancholic inhibition: the action on inhibition is studied referring to Kielholz classification of antidepressants. The author points out the risk of suicide by suppressing inhibition. b) Antidepressants and chronical psychoses: the author compares effects of antidepressants and stimulating neuroleptics in these syndroms. He thinks that with the two types of psychotropic drugs, one can obtain a desinhibitory effect. But antidepressants can be better used in paranoid personnalities, loss of ego boundaries, and some schizophrenic-like syndroms, when neuroleptics seem to be more desinhibitory in hebephrenics. The author stresses the depressive core in these psychotic personnalities. c) The antidepressant effect has been studied in neurotic depressions. The author describes essentially cases with reinforcement of inhibition as a negative therapeutic reaction by antidepressants. It deals with neurotic depressions evoluting on narcissic personnality back ground.

Adjustment Disorders↗
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↗
PubMed1975

Interactions of tricyclic antidepressants and barbiturates in barbiturate-tolerant and nontolerant rats.

Pretreatment of rats with tricyclic antidepressants, imipramine, desipramine, amitriptyline and nortriptyline, at two doses (5 and 25 mg/kg) 20 minutes before administration of barbiturate markedly reduced the latent period of the response to barbital and prolonged the sleeping time induced by pentobarbital (PB) and barbital. The effects were dose-dependent. The prolonged sleeping time produced by PB was associated with decreases in the rates of disappearance of PB from the brain and plasma. The effect of tricyclic antidepressants on PB hypnosis in PB-tolerant and nontolerant rats was apparently not related to change in central nervous system (CNS) sensitivity to PB, since at the time of awakening there were no significant differences in the concentrations of unmetabolized PB in either the plasma or brain of tricyclic antidepressant-treated animals as compared to controls. As barbital is not metabolized, potentiation of barbital hypnosis by tricyclic antidepressants must be attributable to a direct effect on CNS rather than on liver microsomal enzymes. Direct evidence was provided by the findings that amitriptyline accelerated the brain uptake of barbital and that amitriptyline-treated animals lost and recovered the righting reflex at brain barbital levels lower than those of controls. Rats made tolerant to the hypnotic effect of barbital also became tolerant, in varying degrees, to the hyposis-prolonging properties of tricyclic antidepressants. It is concluded that tricyclic antidepressants prolong PB sleeping time in PB-tolerant and nontolerant rats by inhibiting its biotransformation in the liver. The action of tricyclic antidepressants to prolong the hypnotic action of barbital in normal rats is related to their direct effects on CNS sensitivity to barbital, but such effects are makedly diminished after animals become tolerant to barbital.

Amitriptyline↗
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&#x2009;<&#x2009;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&#xa0;min, 95% CI 0.18-7.06; p&#x2009;<&#x2009;0.05) and reduced mean power output (mean difference&#x2009;-&#x2009;19.97 W, 95% CI&#x2009;-&#x2009;36.87 to&#x2009;-&#x2009;3.06; p&#x2009;<&#x2009;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↗
PubMed1975

Tricyclic antidepressant overdose: clinical presentation and plasma levels.

Fifteen patients were studied at 8- to 12-hr intervals during the first 24 hr after overdosing with tricyclic antidepressants, and subsequently followed daily for up to 144 hr. The severity of the overdose was determined by measuring the plasma tricyclic antidepressant level using gas chromatography-mass fragmentography. No correlation was found between total, tertiary, or desmethyl tricyclic antidepressant plasma levels and maximum heart rate, lowest blood pressure, degree of unconsciousness, or EKG changes involving the P-R interval or ST-T wave changes. There was a weak correlation between drug plasma level and maximum pupil size (r = 0.46; p less than 0.05) and a strong correlation between the duration of the QRS complex and tricyclic antidepressant plasma levels (r = 0.75; p less than 0.01). All patients with a total tricyclic antidepressant plasma level greater than or equal to 1,000 ng/ml had a QRS interval greater than or equal to 100 msec. As the total plasma tricyclic level fell, the duration of the QRS interval returned to normal. Thus, the duration of the QRS complex on the electrocardiogram appears to be the most reliable clinical sign for evaluating the seriousness of tricyclic antidepressant overdosage.

Adolescent↗
PubMed1979

Reevaluation of the indoleamine hypothesis of depression. Evidence for a reduction of functional activity of central 5-HT systems by antidepressant drugs.

The effects of antidepressant drugs on central 5-HT receptor activity were studied in rats and mice. Antidepressant drugs were evaluated for their ability to displace 3H-5-HT and 3H-d-LSD from membrane binding sites in the dorsal neocortex of rats in vitro and for their ability to block 5-HTP and d-LSD induced behavioral effects in mice. The degree of blockade of head-twitches in mice produced by the antidepressants was highly correlated with their affinity for 3H-d-LSD binding sites. A number of antidepressant drugs such as amitriptyline, nortriptyline, mianserine, doxepine, nomifensine and dibenzepine appear to possess marked 5-HT receptor blocking activity at some type of 5-HT receptors in brain. New antidepressant drugs such as zimelidine, which specifically inhibit 5-HT reuptake and do not block 5-HT receptor sites, may after chronic treatment also reduce the functional activity of 5-HT systems by producing adaptive changes in postsynaptic 5-HT mechanisms. Thus, a new indoleamine hypothesis of depression is presented: the therapeutic action of antidepressant drugs may in part be due to a reduced functional acitivity of some central 5-HT systems.

Animals↗
PubMedDate not supplied

[Withdrawal syndrome from antidepressive drugs. Report of 5 cases].

Antidepressant withdrawal symptoms, following abrupt or gradual discontinuation of antidepressants, include general somatic distress (flu-like syndromes, gastro-intestinal disturbances, myalgias, headache, chills, weakness and rhinorrhea), anxiety, agitation, sleep disturbances, movement disorders, cardiac arrhythmias, delirium and manic reactions. Two cases of delirium, an hypomanic reaction and two general distress and movement disorders are reported. Cases 1 and 2 required admission to a general hospital. The etiology of the delirium was difficult to assess as long as the clinicians did not know that patients were taking antidepressants. Case 3 corresponds to the paradoxical activation following antidepressant interruption. Cases 4 and 5 constitutes light withdrawal syndromes. Most of cases are probably unrecognized. These cases reflect the importance in daily practice of the phenomena. It can be concluded from our study that: antidepressants must not be abruptly discontinued when a somatic disease appears. When a patient treated with a psychotropic drug develops delirium, the withdrawal of antidepressant must be suspected and the prescribing physician contacted to know what kind of psychoactive medication was prescribed.

Antidepressive Agents, Tricyclic↗
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

Plasma levels of tricyclic antidepressants and clinical efficacy: review of the literature -- part II.

The authors have critically reviewed the literature regarding the relationship between plasma levels of tricyclic antidepressant and their clinical efficacy. When available, drug-drug interactions, pharmacokinetics, and other factors influencing plasma levels of tricyclic antidepressants are discussed. Although many studies are confounded by significant methodological and statistical problems, it appears to these reviews that the available evidence suggests a curvilinear relationship between nortriptyline plasma levels and antidepressant efficacy in tricyclic responsive endogenously depressed inpatients, with maximal therapeutic efficacy achieved with notriptyline plasma levels between 50-175 ng/ml. The evidence for imipramine supports a linear relationship between plasma levels of imipramine plus desmethylimipramine and clinical response in nondelusional endogenously depressed tricyclic responsive inpatients. For amitriptyline, the picture is less clear. However, with the exception of one well-controlled study, the available evidence suppprts some significant relationship between amitriptyline plus nortriptyline plasma levels and antidepressant efficacy in tricyclic respoonsive endogenously depressed patients, but it is not clear as to whether this is a linear relationship or a curvilinear one. For the other antidepressants: protriptyline, desmethylimipramine, doxepin, clomipramine, maprotiline, and butriptyline, a significant relationship (if any) awaits further elucidation. It is important to point out that these plasma level relationships probably do no generalize to other types of depressions (e.g. neurotic, characterological, delusional, acute situationa, etc.) and clearly do not apply to every endogenous tricyclic responsive patient. /owever, it appears that, in general, a clinician will obtain therapeutic efficacy for endogenously depressed patients if these guidelines are followed. The actual therapeutic levels will depend on the assay's sensitivity and specificity and may vary from center to center, illustrates the importance of each center defining its own therapeutic limits, or conversely all centers adoptina a universal reproducible assay methodology for each compound measured. Despite these limitations, these reviewers feel that routine monitoring of plasma levels of the tricyclic antidepressants is a useful method to maximize therapeutic efficacy and prvent undue side effects, as well as to insure good medication compliance.

Antidepressive Agents, Tricyclic↗
PubMed1977

The efficacy of electroconvulsive therapy and antidepressants in depression.

Electroconvulsive therapy (ECT), antidepressants, and neither treatment were compared by reviewing 609 hospitalizations for depression from 1959 to 1969. The groups receiving ECT had a significantly (p less than 0.001) greater percentage of patient who had marked improvement or a complete response (49%) than either adequate or inadequate antidepressant therapy groups (27%) or the group which received neither ECT nor antidepressants (25%). If antidepressant failures who require ECT are included in the evaluation, the percentage total improvement with ECT (90%) is significantly (p less than 0.001) greater than the adequate (74%) or inadequate (60%) antidepressant groups, or neither treatment (60%). At the end of 7 weeks of hospitalization, 74% of the ECT group had been discharged, significantly more (p less than 0.001) than the adequate antidepressant group, 54%. Delusional depressed patients responded much mor frequently to ECT.

Adjustment Disorders↗
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↗