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PubMed1987

3-[(2-ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity.

The 3-[(2-ethoxyphenoxy)methyl]piperidine derivatives 3-5 were synthesized and screened as potential antidepressant agents by the reserpine interaction test in mice and the evaluation of reuptake inhibition of biogenic amines in pig brain synaptosomal fractions. In addition, their anticonvulsant activity, tested by pentyleneetrazole antagonism, and approximate acute toxicity were evaluated. In vivo and in vitro tests showed that compounds 3 and 5 possess a biological activity comparable to that of the antidepressant drug viloxazine.

Animals↗
PubMed1994

Recognizing and treating depression.

The increasing number of antidepressant agents available presents the problem of selecting the right one for a given patient. The choice is guided by the benefits and risks of these drugs within the context of the recommended treatment strategy.

Antidepressive Agents↗
PubMed1993

Antidepressant-induced rapid cycling: six case reports.

We report six cases of rapid mood cycling induced by antidepressant treatment. The key to effective treatment involved the recognition of the pattern of apparent remission, relapse, antidepressant and/or stimulant adjustment, remission, relapse, etc. Hypomanic episodes were frequently mild and could be mistaken for remission. The destabilizing effects of antidepressant drugs were not corrected by the addition of mood stabilizers, necessitating the withdrawal of the antidepressant agent. All but one case responded to such withdrawal. Two cases required the addition of high-dose L-thyroxine for stabilization. Implications for an effective treatment protocol are discussed.

Adult↗
PubMed2006

Antidepressants for patients with tinnitus.

BACKGROUND: Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. It has been compared with chronic pain, and may be associated with depression or depressive symptoms which can affect quality of life and the ability to work. Antidepressant drugs have been used to treat tinnitus in patients with and without depressive symptoms. OBJECTIVES: To assess the effectiveness of antidepressants in the treatment of tinnitus and to ascertain whether any benefit was due to a direct tinnitus effect or a secondary effect due to treatment of concomitant depressive states. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) The Cochrane Library Issue 1, 2006); MEDLINE (January 1951 to 2006); EMBASE (1974 to 2006), CINAHL (to 2006), PSYCINFO (to 2006), LILACS (to 2006), and Cambridge Scientific Abstracts. The date of the most recent search was March 2006. SELECTION CRITERIA: Randomised controlled clinical studies of antidepressant drugs versus placebo in patients with tinnitus. DATA COLLECTION AND ANALYSIS: The studies retrieved were critically appraised and data extracted independently by two authors. Where necessary study authors were contacted for further information. MAIN RESULTS: Five trials involving 525 patients were included. Four of these trials looked at the effect of tricyclic antidepressants on tinnitus, investigating 405 patients. One trial investigated the effect of a selective serotonin reuptake inhibitor (SSRI) in a group of 120 patients. No trials involving other antidepressant agents met the inclusion criteria. Only the trial using the SSRI drug met the highest quality standard. None of the other included trials met the highest quality standard, due to use of inadequate outcome measures, large drop out rates or failure to separate the effects on tinnitus from the effects on symptoms of anxiety and depression. All the trials assessing tricyclic antidepressants suggested that there was a slight improvement in tinnitus but these effects may have been attributable to methodological bias. The trial that investigated the SSRI drug found no overall improvement in any of the validated outcome measures that were used in the study although there was possible benefit for a subgroup that received higher doses of the drug. This observation merits further investigation. Reports of side effects including sedation, sexual dysfunction and dry mouth were common. AUTHORS' CONCLUSIONS: There is insufficient evidence to say that antidepressant drug therapy improves tinnitus.

Antidepressive Agents↗
PubMed2001

Selection of antidepressant drugs in general practice.

Depression is a common psychiatric illness and since majority of patients suffering from depression are first seen and treated by general practitioners, it is important for them to identify and treat depressive illness more effectively. Fortunately, depression is a treatable condition. Identifying the optimal antidepressant agent requires careful consideration of the patient's age, health status, and history of response to antidepressants. Other considerations include adverse effect profile, cost of drug therapy and convenient dosage schedule. Selective serotonin reuptake inhibitors are well tolerated and are considered by many to be the agents of choice in primary care treatment of depression because of their favourable adverse effect profile. Heterocyclic antidepressants are preferred in elderly patients and patients with medical problems. Tricyclic antidepressants can also be of great help specially to younger group of patients and patients who have failed to respond to other antidepressants.

Antidepressive Agents↗
PubMed1987

Recent studies on selective serotonergic antidepressants: trazodone, fluoxetine, and fluvoxamine.

In recent years, the role of serotonin in the pathophysiology of depressive disorders has been intensively studied. These studies have been complemented by the development of newer antidepressant agents that exert specific effects on serotonin systems. This paper reviews the pharmacology of these newer compounds and contrasts it with those of the standard tricyclic antidepressants. The current status of various serotonergic agents is discussed. Results are reviewed from recent double-blind studies comparing three compounds (trazodone, fluoxetine, and fluvoxamine) to a standard tricyclic antidepressant. Relative efficacy, dropout rates, optimal dosages, and side effects are emphasized. Data from studies on trazodone and fluoxetine suggest that lower dosages may prove as effective (if not more effective) than very high dosages. Implications of these data are discussed. Side effects of fluoxetine and fluvoxamine include primarily nausea, weight loss, insomnia, and anxiety. Possible application of specific serotonin reuptake blockers in the treatment of obsessive-compulsive disorder and in the reduction of alcohol consumption is also reviewed.

Animals↗
PubMed2001

New 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants.

A series of new 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives were synthesized in an attempt to find a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. Title compounds were evaluated for in vitro activity on 5-HT1A receptor and 5-HT transporter. They show high nanomolar affinity for both activities, and in particular, compounds 1-(5-chlorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (7) and 1-(5-fluorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (8) show values (nM) of K(i)=30 and 2.3 for 5-HT1A receptors and K(i)=30 and 12 for serotonin transporters, respectively. In GTPgammaS binding assays, compound 8 revealed antagonist properties to 5-HT1A receptors. Such a pharmacological profile could lead to potent antidepressant agents with new dual mechanism of action.

Animals↗
PubMed2003

[Premature orgasm in the male].

To date, we have no uniform definition of ejaculatio praecox. In a qualitative approach, premature ejaculation is ascribed to a failure to control excitement. As causes, organic disorders and erectile dysfunction must be excluded. The majority of cases, however, are due to psychological or partnership problems. The history-taking should aim, in particular, to uncover possible anxiety in conjunction with premature orgasm, and also to establish the reactions of the partner. As therapy, medication (local anesthetics, antidepressive agents, PDE-5 inhibitors) and sexual-therapeutic measures are available. Since few sufferers take the initiative in seeking treatment, particular importance attaches to providing the public with information about the therapeutic options for treating this common disorder.

Anesthetics, Local↗
PubMed2003

Sildenafil citrate for the management of antidepressant-associated erectile dysfunction.

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated erectile dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil citrate, a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability of sildenafil in the treatment of antidepressant-associated erectile dysfunction have been confirmed in double-blind, placebo-controlled trials.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

[Use of antidepressant drugs in schizophrenic patients with depression].

INTRODUCTION: Depression is common in people with schizophrenia and is associated with substantial morbidity explaining also the considerable attention and recognition of this entity as suggested by the inclusion of the post-psychotic depression in DSM IV and ICD 10. The prevalence of this disorder varies according to the type of approach used (range between 7% to 75%). Prescription of antidepressants plus antipsychotic treatment is frequent in clinical practice (11 to 43%). BACKGROUND: Pharmacokinetic and metabolic interactions have been identified. The cytochrome P450 has been identified as being implicated in the metabolism of most psychotropics, mainly through the CYP1A2, CYP2C19, CYP2D6, CYP3A4 isoenzymes. Tricyclic antidepressants are likely to increase chlorpromazine plasma levels. Similarly, antipsychotics such as perphenazine, chlorpromazine or haloperidol can increase antidepressant plasma levels, through the inhibition of CYP 450 isoenzymes (CYP2D6). Most of the Specific Serotonin Recapture Inhibitors (SSRIs) are likely to inhibit one or several CYP450 isoenzymes. The inhibition is moderate to marked for CYP1A2 (fluvoxamine and fluoxetine), CYP2C19 (fluoxetine, fluvoxamine and sertraline), CYP2D6 (paroxetine, fluoxetine and sertraline), and CYP3A4 (fluvoxamine, fluoxetine and sertraline). In the US, one-fourth of psychiatrists report the use of depression-rating scales in schizophrenic patients. Non specific scales (Hamilton Depression Rating Scale or Beck Depression Inventory) are the most commonly used in spite of the fact that these scales do not allow the distinction of depressive from negative symptoms in schizophrenic patients. LITERATURE FINDINGS: Due to these limitations, more specific assessment tools for depressive symptoms in schizophrenia are required. Two specific scales for assessing depressive symptoms in schizophrenic patients have been constructed and validated. The Calgary Depression Scale (CDS) is a nine item scale, each item scored from 0 to 3. This scale was derived from the HDRS and the Present State Examination. Factor analysis showed that the CDS is unidimensional, has high internal consistency, and significant strong correlation with scores on the HDRS, Beck and BPRS depression scales. The CDS has been validated in different languages (Brazilian, Danish, French...). It has been shown that there is no overlap between negative or extrapyramidal and depressive symptoms assessed by the PDS in schizophrenic patients. The Psychotic Depression Scale (PDS) is a 32 item scale derived from the HDRS, PANSS, CPRS and AMDP, each item being rated from 0 to 7. A principal component analysis of the PDS items using a Varimax rotation disclosed 8 orthogonal components that account for 71% of the variance. These components involved the following dimensions : depressive mood, inhibition, vegetative signs, paranoid signs, strangeness of thought, inverse vegetative signs, guilt feelings and cognitive signs. The analysis revealed that the 'depressive mood' factor of the PDS was correlated with the 'depressive' factor and was slightly correlated with the cognitive factor of the PANSS. This first factor was not correlated with either the "negative" factor of the PANSS, or the Positive or Excitement factor of the PANSS. Hence, this PDS, factor distinguished depressive signs from negative symptoms. Due to their metrologic properties, specific scales should be preferred. However, only one open trial (of an antipsychotic) and two double blind controlled trials (one comparison of 2 antipsychotics and one comparison of an cholinesterase inhibitor versus placebo) have been published using the CDS. Likewise, only one double blind controlled trial using the PDS (comparison of 2 antipsychotics) has been published. No study of the effect of antidepressants in depressed schizophrenic patients has been published, using either the CDS or the PDS assessment criteria. DISCUSSION: These specific scales are rarely used in clinical practice. Only about 1% of the US psychiatrists reported the use of the Calgary Depression Scale. Several open clinical trials have assessed the efficacy of antidepressant agents added to antipsychotic in patients with schizophrenia. They have produced inconsistent results but have suffered from methodological limits (short duration of the studies, non homogeneous inclusion criteria, heterogeneous assessment methods...). Due to the lack of a reference drug, double blind placebo-controlled trial are necessary. A recent meta-analysis has been performed on results of trials that have investigated the clinical efficacy of antidepressant medication (either tricyclics, SSRIs or others) in the treatment of depression in schizophrenic patients. In a subset of 5 trials (209 patients), the proportion improved in the antidepressant group was 26% (95% CI 10 to 42) higher than in the placebo group. The estimated number needed to treat was 4. In a subgroup of 6 studies (267 patients), the standardized mean difference on the HDRS score was -0.27 (95% CI - 0.7 to -0.2). There was no evidence that antidepressant treatment induced a deterioration of psychotic symptoms in these trials. CONCLUSION: The results provide weak evidence for the efficacy of antidepressants in patients with schizophrenia and depression. Today, the only SSRI tested in the treatment of depression in schizophrenic patients is sertraline. One study led to positive results. Since the meta-analysis, one additional study has been performed comparing sertraline to placebo. No difference between the 2 treatment groups was demonstrated but the power of the trial was rather low. Further research is required to determine the best approach towards treating depression in patients with schizophrenia, with clinical trials performed for longer periods, using appropriate assessment criteria such as depressive symptoms and quality of life.

Antidepressive Agents↗
PubMed1989

GABA-mediated modification of despair behavior in mice.

Gamma-aminobutyric acid (GABA) and GABA agonists exhibited biphasic response on forced swimming-induced despair behavior in mice; smaller doses, GABA (100 mg/kg), muscimol (0.05 and 0.1 mg/kg), baclofen (0.5 and 1 mg/kg), sodium valproate (100 mg/kg), piracetam (25 mg/kg), and fengabine (10 and 20 mg/kg) decreasing forced swimming-induced immobility period, while higher doses enhancing the immobility period. GABA, muscimol, and baclofen also reversed reserpine-induced prolongation of the forced swimming-induced immobility. When GABA was administered with antidepressant agents, it potentiated the effect of some classical antidepressants. Bicuculline and picrotoxin, the GABAergic antagonists, by themselves enhanced the forced swimming-induced immobility period, but they had no significant effect on reserpine-induced prolongation of the immobility period. When animals were chronically exposed to forced swimming, there was a gradual increase of the immobility period which was reduced on treatment with GABAergic agents. It is suggested that GABA has a modulatory role in reversing forced swimming-induced despair and also in potentiating the effect of antidepressants.

Animals↗
PubMed1988

Paroxetine, a selective 5-hydroxytryptamine uptake inhibitor with antidepressant properties, lacks amphetamine-like stimulus properties in an operant drug discrimination bioassay in rodents.

To evaluate whether the novel antidepressant paroxetine has any possible amphetamine-like actions, rats were trained to discriminate (+)-amphetamine sulphate in a standard two lever operant drug discrimination (DD) procedure using a fixed ratio 10 schedule of food reinforcement with a quantal, lever selection, index of the amphetamine stimulus. The 'training' dose of amphetamine was 1 mg kg-1, i.p. Rats trained with this dose of amphetamine (n = 15) learned the drug discrimination rapidly over 30 training sessions and discriminative performance in these animals was subsequently maintained at a high level of accuracy (90% correct) over a prolonged time. In tests in these trained animals, amphetamine itself and the antidepressant agents nomifensine and tranylcypromine all produced clear, unequivocal dose-related generalization to amphetamine with ED50s of 0.2, 0.5 and 1.6 mg kg-1 respectively (as determined by probit analyses). In tests with paroxetine hydrochloride it was established that, over the dose range 0.3 to 10 mg kg-1, no evidence was seen of generalization to the amphetamine stimulus. These data confirm earlier studies which suggested that some antidepressants may possess abuse potential because of their ability to induce amphetamine-like internal states. In contrast, paroxetine is devoid of such properties.

Animals↗
PubMed1993

An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment-resistant depression.

Flesinoxan, a full 5-HT1A receptor agonist, was administered (4-8 mg) to treatment-resistant depressed patients in an open study. Safety and tolerance of the substance appeared satisfactory. Headache, dizziness and nausea were the most frequently reported side effects. The observations suggested that flesinoxan is an antidepressant agent and that it may be of particular value in some difficult, treatment-resistant depressions. Based on these observations, a double-blind, placebo-controlled evaluation of flesinoxan's efficacy appears warranted.

Adult↗
PubMed1987

Psychoactive agents, seizure production, and sudden death in epilepsy.

Major tranquilizers as well as antidepressant agents have been associated with clinical seizures in patients administered these agents. The incidence of such seizures is generally low when these drugs are administered in therapeutic doses. However, administration of large doses of these agents has been associated with many cases of convulsion production. The effects that these drugs have on animal models of epilepsy have been examined. It appears that the phenothiazines act as convulsant agents at lower doses, whereas, at higher doses, they act as anticonvulsant drugs. Antidepressants, on the other hand, appear to exert an anticonvulsant effect at low doses and convulsant effects at high doses. The mechanism by which these agents alter the seizure threshold is not yet known. Clinically, drugs of lower seizure production potential should be substituted for those drugs with greater potential in treating epileptic patients for psychiatric ailments. The problem of sudden death in epileptic patients is one that must be confronted. Sudden death has most frequently been attributed to autonomic dysfunction and cardiac arrhythmia in these patients. The contribution of stress in sudden death production also must be taken into account. In addition, some psychoactive agents have been associated with sudden death as well as cardiac arrhythmia and seizure production. Thus, in light of the possible additivity of the factors involved in the production of sudden death, the administration of a psychoactive agent to an epileptic patient should be approached with caution. Those agents that do not alter cardiac rhythm or seizure threshold should be administered if a psychoactive agent is deemed necessary for the management of psychiatric illness in the epileptic patient.

Death, Sudden↗
PubMed2002

Enhancing the technology of clinical trials and the trials model to evaluate newly developed, targeted antidepressants.

Concern about disappointing results from recent multi-center trials of new antidepressants prompted several ACNP workshops on "improving the technology of clinical trials." The workshops focused on technical problems, such as patient screening, reliability of clinical ratings, and the role of the placebo control. They aimed to determine how to more effectively apply the current clinical trials model for evaluating antidepressant drugs. The problems confronting the field of clinical trials, however, extend beyond technology. They also included conceptual issues concerning changes in the understanding of depressive disorders and of the multiple actions of antidepressant drugs. Such problems have been further complicated by the rapidly changing field of drug development itself, which is continually refining the targeting of new antidepressant agents. Drugs are increasingly being developed to try to change specific behavioral facets more rapidly and may be less likely, therefore, to act initially on "whole" disorders. To address such issues, a symposium was held in Rhodes in 2000 that focused on such conceptual changes with the goal of developing recommendations to revise the clinical evaluation model. Its purpose was to integrate new knowledge on depression and the mechanisms of action of antidepressant drugs toward developing more efficient methods of drug development. Since the evaluation process will eventually require changes in governmental policy, senior staff from the National Institute of Mental Health (NIMH) , Unites States and Food and Drug Administration (FDA), Unites States participated as well as members of academia, industry and clinical practice. Recommendations for altering clinical trial methodology were made in four areas: patient selection, methodology of evaluation, measuring onset of action, and FDA and NIMH perspectives on current practice. This article discusses these four areas and presents the consensus of the panel participants.

Antidepressive Agents↗
PubMed2000

Antidepressant effects of Banxia Houpu decoction, a traditional Chinese medicinal empirical formula.

Banxia Houpu Decoction, having been used for the treatment of depression-related diseases since ancient times, is a traditional Chinese medicinal empirical formula consisting of Pinellia ternata, Poria cocos, Magnolia officinalis, Perilla frutescens and Zingiber officinale. The effects of the total decoction extract and five fractions therefrom, were evaluated in mice by tail suspension and forced swimming tests. The total 90% ethanol extract of the decoction was shown to possess an antidepressant activity that was close to that of Prozac, an antidepressant agent being applied clinically. Furthermore, the active principles were desmonstrated to be mainly in the aqueous (Bx4) and lipophic (Bx5) parts of the decoction extract while the polyphenol fraction (Bx2) exhibited a moderate action.

Animals↗