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PubMed1995

Notes on the use of fluvoxamine as treatment of depression in HIV-1-infected subjects.

Fluvoxamine belongs to the class of selective serotonin reuptake inhibitors (SSRIs) which have recently gained large popularity as antidepressant agents essentially because they lack the most troublesome adverse effects of older antidepressants (i.e. tricyclic antidepressants) such as anticholinergic effects and cardiotoxicity. Recent studies in the literature suggest that HIV-1 infected subjects are affected by depressive episodes with a relatively high frequency, often requiring an antidepressant treatment. Due to its favorable adverse effects profile, we used fluvoxamine as first line treatment for sixteen depressed HIV-1 infected subjects. They were administered the drug at a daily dosage of 100 mg in the evening. Fluvoxamine provided a good clinical efficacy for six of these patients, whereas the other ten had to discontinue the drug because of the presence of severe adverse effects such as acute total insomnia, gastro-intestinal disturbances together with anorexia, aggressive and impulsive behavior and excessive sedation. The observed fluvoxamine side-effects are not typical or specific for this particular patient group since they are also described in seronegative subjects taking fluvoxamine; however, our findings seem to indicate that they become more frequent and more severe when the drug is administered to HIV-1 infected patients.

Adult↗

PubMed1997

[Customary antidepressive treatment in Hungary: moclobemid therapy in everyday practice].

Treatment data with moclobemide have been obtained from clinical practices of 91 Hungarian psychiatrists. Three hundred and twenty seven patients were included in the multicenter postmarketing surveillance study and observed during an 8 week treatment period. The mean age of the patients was 50 years, 71% were woman and 33% were outpatients. Sixty-five percent had preexisting depression. Previous antidepressant treatment for this episode had been received by 45%, with the most common reasons for change to moclobemide being inadequate response. Moclobemide was indicated in patients with mainly moderate to severe major depression and dysthymia. The frequency of comorbidity was 44%. The dosage of moclobemide was usually started at 300 or 450 mg/day and increased to 600 mg/day only in some patients. Three divided daily dosages were administered in 53% of the patients. Nine percent discontinued the treatment before the end of the observation period. 87% had no reported adverse events. The most common adverse events were sedation (3.7%), agitation (3%) and insomnia (3%). Concommitant medication from all major drug groups were taken by 250 (76.6%) patients, with no adverse interactions. The current therapeutic habits of the Hungarian psychiatrists in treatment of depression were also revealed. The findings in the normal clinical psychiatric practice suggest that moclobemide is a safe drug with excellent tolerability in the treatment of various subgroups of depressive disorders and especially useful in patients with coexisting physical illness. Moclobemide is a favourable alternative to the modern effective antidepressant agents in the Hungarian clinical practice.

Antidepressive Agents↗

PubMed1987

Cardiovascular toxicity of antidepressant medications.

This article reviews the cardiovascular effects of the standard tricyclic antidepressant agents and the cardiovascular effects of the newer antidepressant drugs. The cardiovascular effects of the standard tricyclic agents are orthostatic hypotension, conduction delay, and a potent antiarrhythmic effect. Patients with congestive heart failure receiving cardiac medications are at greatly increased risk for orthostatic hypotension, while patients with preexisting conduction delay are at risk for heart block. Of the newer antidepressant drugs, mianserin, nomifensine, and bupropion initially appeared to be most promising in terms of cardiovascular effects, but subsequently proved to have other serious liabilities; these agents require further testing. Trazodone has emerged as the antidepressant drug with the least risk of death in overdose, and as a useful alternative to the standard tricyclic antidepressant drugs in patients with preexisting conduction disease. However, trazodone therapy has been associated with some adverse effects, and, therefore, from the data presented in this paper, it can be concluded that no drug currently available is without some cardiovascular risk.

Antidepressive Agents↗

PubMed1975

Reinforcement schedules and extrapolations to humans from animals in behavioral pharmacology.

Behavior controlled by various schedules of reinforcement is useful for characterizing drugs as well as for analyzing the mechanisms of action of their effects on behavior. Conditioned avoidance techniques have been useful for studying neuroleptics and for predicting their clinical antipsychotic acitivity; the possible involvement of dopaminergic mechanisms in the effect of neurolpetics on avoidance behavior is discussed. Tricyclic antidepressant agents have been studied in assays involving interactions with other agents, such as cocaine, amphetamine and tetrabenazine. One type of operant behavior, Sidman avoidance, has been used as particularly sensitive assay for such drug interactions. Another schedule, in which "observing" responses in pigeons are measured. seems to provide a method for studying antidepressants without involving drug interaction phenomena. For tricyclic compounds, facilitation of observing responses and weak potency of conditioned avoidance inhibition constitute a pharmacological profile that seems to have some predictive value for clinical imipramine-like antidepressant activity. "Conflict (punishment) schedules have been useful for predicting antianxiety activity in man. Although the degree of anticonflict effect observed is consistent with Dew's rate dependency hypothesis, this principle does not fully account for the observed drug effects. In the conflict model, the actions of benzodiazepines differ in drug-naive versus drug-experienced animals. Experiments with parachlorophenylalnine have not yet provided clear support for the postulated role of serotonin in related phenomena.

Animals↗

PubMed2005

Submissive behavior in mice as a test for antidepressant drug activity.

Previously, with the administration of antidepressant drugs, it has been demonstrated that the rat model of clinical depression, known as the reduction of submissive behavior model (RSBM), has considerable validity. The present study is an attempt to extend the model to mice. Several antidepressant drugs as well as a number of non-antidepressant agents were administered to mice that had been identified as submissive in a behavioral testing situation. Imipramine, desipramine, amoxapine and fluoxetine, representing three different classes of antidepressant drugs, were each able to increase competitive behavior in submissive mice and to decrease the dominance level between dominant and submissive mice in the behavioral tests. The stimulant amphetamine also reduced submissive behavior while yohimbine (also a stimulant), and the antianxiety agent diazepam had no such effect. The neuroleptic drug thiothixen had antidepressant-like effect on submissive C57BL/6J mice behavior. We conclude that like the rat model of depression from which it was developed, the mouse model responds to various antidepressants as predicted and thus may serve as a potential model of clinical depression.

Adrenergic alpha-Antagonists↗

PubMed2002

A survey of prescribing practices in the treatment of depression.

BACKGROUND: With the increasing number and type of antidepressants available to clinicians, there is a need to better understand current prescribing practices and to what degree these practices reflect research findings. The purpose of this study was to examine prescribing practices in a sample of psychiatrists attending a psychopharmacology review course and compare these results with empirical evidence. METHOD: 439 of 800 clinicians asked (55%) responded to a 10-item questionnaire that was given prior to beginning the review course. Items covered three major content areas: first-line preferences in the treatment of depression, antidepressant agents most associated with certain side effects, and first-line preferences in the treatment of certain depressive subtypes. RESULTS: 214 (49%) clinicians indicated a belief that one antidepressant type is more efficacious than others. Of these 214 clinicians, 103 (48%) indicated selective serotonin reuptake inhibitors (SSRIs) as being most efficacious, while 53 (25%) indicated venlafaxine as being most efficacious; 378 (93%) clinicians indicated SSRIs as their first-line treatment preference. Mirtazapine (56%) was endorsed as most likely to be associated with weight gain, fluoxetine (57%) with sexual dysfunction, paroxetine (48%) with a discontinuation syndrome, and fluoxetine (52%) with agitation. For the treatment of anxious, atypical, and melancholic depression, SSRIs were the first choice of treatment (58%, 57%, and 57%), and for depression with prominent insomnia, mirtazapine and nefazadone (31% and 27%) were the first choices of treatment. CONCLUSIONS: Despite the lack of evidence of a significant difference in efficacy between older and newer agents, clinicians perceive the newer agents to be more efficacious than the older drugs [tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)] even in the melancholic and anxious depressive subtypes. Similarly, although sexual dysfunction and agitation appear to occur at similar rates with all the SSRIs, fluoxetine was perceived to be most likely to cause these side effects. These findings are significant as they highlight the discrepancy between empirical evidence and clinical practices and suggest that other factors influence clinicians' medication choices in the treatment of depression.

Antidepressive Agents↗

PubMed1988

The pharmacological profile of Org 6906, a potential non-sedative antidepressant that combines monoamine uptake inhibition with alpha 2-adrenolytic activity.

(dl)-(5 alpha,8 alpha,9 alpha)-5,8,9,10-Tetrahydro-5,9- methanobenzocycloocten-8-amine hydrochloride (Org 6906) is a potential new antidepressant agent, with a neurochemical profile quite different from that of the classical tricyclic antidepressant drugs. The compound was found active in behavioural tests which are considered to be predictive for antidepressant activity, such as the muricidal test in the rat and the acquired immobility model. Neurochemical studies showed that Org 6906 was an inhibitor of the reuptake of monoamines both in vitro and ex-vivo without having appreciable anticholinergic, antihistaminergic or alpha 1-adrenolytic activity. The facilitatory effect on monoaminergic neurotransmission was confirmed by the reversal of hypothermia induced by reserpine. The drug Org 6906 appeared to have selective alpha 2-adrenolytic properties. It facilitated potassium-stimulated release of noradrenaline from slices of cortex, displaced [3H]rauwolscine and [3H]dihydroergocryptine from their binding sites but only weakly blocked alpha 1-adrenoceptors. The alpha 2-adrenolytic properties were also apparent in behavioural interaction models. The compound antagonized the sleep-inducing effects of clonidine in chicks and mice and it antagonized the mydriasis induced by clonidine in the rat. Finally, it was shown that the two enantiomers of Org 6906 contributed almost equally to the relevant neurochemical and behavioural properties.

Adrenergic alpha-Antagonists↗

PubMed2006

Creating more effective antidepressants: clues from the clinic.

Antidepressant medications have eased the suffering of millions of people. In addition to treating depression, antidepressant drugs also treat several anxiety disorders. Unfortunately, there are problematic limitations with antidepressant agents, including a delayed therapeutic response and insufficient efficacy. Emerging evidence shows that atypical antipsychotic agents can be used as augmentation therapy in patients with poor responses to antidepressants. Future drugs combining key features of antidepressant and atypical antipsychotic agents could offer new promise for patients suffering from obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder, generalized anxiety disorder and depression.

Animals↗

PubMed2007

[40 years beta-adrenoceptor blockers in psychiatry].

Beta-adrenoceptor blockers belong to the most successful drug classes of medicine. Mainly they are used in internal medicine. 40 years ago beta-adrenoceptor blockers have occasionally been used in psychiatry for the treatment of anxiety disorders. Over the past four decades, the effects of beta-adrenoceptor blockers in the treatment of schizophrenic and manic psychoses, withdrawal syndromes and aggressive behaviour with temper outbursts has been investigated. Beta-adrenoceptor blockers are also used in the treatment of side-effects of psychopharmacological agents like neuroleptic or antidepressant-induced tachycardias, lithium-induced tremor, antipsychotic-induced akathisia or tardive dyskinesia as well. Since the mid-nineties it has been attempted to improve the efficacy of antidepressant agents by means of the 5-HT-(1a)-receptorantagonist pindolol. Presumedly memory consolidation of traumatic events can be enhanced by adrenergic activation. Therefore some open clinical trials investigated the effects of propranolol, a lipid soluble drug, which crosses the blood-brain barrier easily, to reduce the manifestation of PTSD. The present review presents the results of the literature with respect to the indications for beta-blockers in psychiatry. Considering evidence-based-medicine criteria beta-blockers are indicated to treat lithium-induced tremor, antipsychotic-induced akathisia and to reduce aggressive behavior of patients with brain-injuries.

Adrenergic beta-Antagonists↗

PubMed1994

Modulation of baroreceptor activity by ionic and paracrine mechanisms: an overview.

1. The primary mechanism of activation of baroreceptors is mechanical deformation during vascular stretch. In addition, baroreceptor activity is modulated by ionic mechanisms and by neurohumoral and paracrine factors that act directly on the nerve endings. 2. Ionic mechanisms play a major role in causing baroreceptor activity to decline during a sustained increase in arterial pressure (adaptation) and in the suppression of activity that occurs after pressure returns to basal levels (post-excitatory depression). Activation of a 4-aminopyridine-sensitive K+ channel contributes to adaptation, whereas activation of an electrogenic sodium pump is responsible for post-excitatory depression. 3. Factors released from vascular endothelium exert powerful effects on baroreceptor sensitivity. Prostacyclin increases baroreceptor sensitivity and contributes to baroreceptor activation during vascular stretch. Nitric oxide, endothelin and oxygen-derived free radicals suppress baroreceptor activity particularly at high levels of arterial pressure. The sympathetic neurotransmitter norepinephrine modulates baroreceptor activity: a) indirectly through its vasoconstrictor action, b) directly by binding to alpha-adrenergic receptors on the nerve endings, and c)through release of a cyclooxygenase metabolite, possibly prostacyclin, from endothelium. 4. Endothelial dysfunction contributes to baroreceptor impairment in atherosclerosis and in chronic hypertension. Loss of the excitatory influence of prostacyclin and increased formation of free radicals and possibly endothelin contribute to the baroreceptor dysfunction. Platelets aggregating at sites of endothelial damage in the carotid sinus release a stable diffusible factor that impairs baroreceptor sensitivity. 5. Therapeutic interventions may alter baroreceptor sensitivity through paracrine mechanisms. Treatment of hypertension or atherosclerosis may improve baroreceptor sensitivity by restoring endothelial function. Antiplatelet agents may enhance baroreceptor sensitivity. Antidepressant agents may decrease baroreceptor sensitivity by inhibiting prostacyclin and/or stimulating nitric oxide formation, which may contribute to dysregulation of the circulation in patients treated for depression.

4-Aminopyridine↗

PubMed1990

Mood disorders. Is your primary care patient depressed?

Treatment of patients with mood disorder can be one of the most rewarding experiences in medicine. Optimal treatment is contingent on accurate diagnosis according to current criteria and terminology. Major depression needs further categorization in reference to atypical or psychotic features, seasonal aspects, melancholia, mania, or dysthymia. Most patients with major depression need pharmacotherapy, often in combination with psychotherapy. A number of therapeutic regimens using various antidepressant agents are available.

Adolescent↗

PubMed1984

[Therapy with antidepressive and tranquilizing agents].

Since the introduction of imipramine in 1957 in the therapy of depression numerous effective antidepressant substances have been developed, which differ from one another in the biochemical as well as clinical profile of action. A psychopathological diagnosis is a prerequisite for application, whereby the differentiation of the endogenous from the non-endogenous depression, or the inhibited from the agitated depression is an important factor. 65% to 70% of endogenously depressive patients respond well to an antidepressant medication. However, the antidepressant effect still seems to be strongly linked to undesirable (mainly anticholinergic) side effects. The main portion of tranquilizers prescribed at present comprises of benzodiazepines, which are given for the manifold types of anxiety and inner restlessness. Their widely spread application has recently become object of criticism: dependency and changes in the personality have been described. Benzodiazepines should therefore only be prescribed under certain conditions, where their very good anxiolytic effect can be applied without damage to the patient.

Anti-Anxiety Agents↗

PubMed1989

The addition of lithium to carbamazepine. Antidepressant efficacy in treatment-resistant depression.

The addition of lithium carbonate to various antidepressant agents, including heterocyclics and monoamine oxidase inhibitors, has been reported to rapidly effect an antidepressant response in otherwise treatment-unresponsive depressed patients. Fifteen depressed patients diagnosed by DSM-III criteria who had not responded to double-blind treatment with carbamazepine were treated with the blind addition of lithium to carbamazepine. Eight patients (53%) responded with a moderate to marked improvement. The time to onset of substantial clinical improvement was rapid; ie, the mean (+/- SD) was 4.1 +/- 2.4 days for lithium potentiation compared with 9.7 +/- 4.1 days in a separate group of depressed patients responding to lithium alone. Side effects during carbamazepine-lithium combination therapy were minimal. The mechanisms by which lithium appears to rapidly potentiate the effects of carbamazepine in treatment-resistant depression are discussed.

Adult↗

PubMed2001

Administration of antidepressants. Single versus split dosing: a meta-analysis.

OBJECTIVE: To evaluate the literature comparing antidepressant effects of multiple daily dosing versus single daily dosing of antidepressants. METHOD: Studies comparing efficacy of single versus multiple daily dosing of antidepressants were reviewed. Data from the clinical trials meeting our inclusion criteria was subgrouped according to the half-life of the antidepressant drug studied. Meta-analyses were carried out to compare antidepressant efficacy of single versus multiple daily dosing overall and separately for the short, intermediate, and long half life antidepressant agent subgroups. RESULTS: The review process identified 22 studies comparing the therapeutic effect of antidepressants according to their dosing schedules. Although most studies used antidepressant medications with short half-lives, none found a significant difference in therapeutic efficacy. Furthermore, the improvement rates in depression scores in between the two groups were almost identical (SDD versus MDD). CONCLUSION: This meta-analytic approach found no advantage for multiple daily dosing and suggests that sustained therapeutic serum levels are not necessary for achievement of therapeutic activity. Antidepressant benefit may simply require a limited duration of exposure above the threshold serum level. Administration of antidepressants in single daily doses appears sufficient to perturb the physiological pathways associated with depression sufficiently to achieve an adaptive therapeutic response. Moreover, a single daily dosing regimen offers the potential advantages of simplicity, increased compliance, and reduced adverse effects, which in turn would increase the overall success rate in treatment of depression.

Antidepressive Agents↗

PubMed2005

Combined antidepressants: clinical experience.

OBJECTIVE: To review the current literature on the use of combinations of antidepressive agents. METHOD: Literature searches were undertaken and reviewed on the use of combinations of antidepressants. RESULTS: Data sources included surveys, analyses of prescription records, decision algorithms, clinical reports, and studies comparing the monotherapy with combination therapy. More recent surveys recommend combining different selective serotonin reuptake inhibitors (SSRIs), an SSRI plus bupropion or dual action antidepressants plus an SSRI. Decision algorithms recommend an SSRI plus tricyclic antidepressant (TCA) and more recently bupropion plus venlafaxine or mirtazapine. Few controlled clinical trials comparing the combined therapy with monotherapy have been conducted. Beneficial effects have been reported with combinations of TCAs plus mianserin or SSRIs plus mirtazapine. CONCLUSION: Adding or combining antidepressant medications has advantages for the speed of onset and maintaining the existing response. More rigorous clinical trials comparing combination therapy with monotherapy and for the development of rational treatment guidelines are required.

Algorithms↗

PubMed2000

What is to be done? Controversies in the diagnosis and treatment of manic-depressive illness.

BACKGROUND: In recent years, much progress has been made in the diagnosis and treatment of schizophrenia and depression. Bipolar disorder, however, remains frequently misunderstood, leading to inconsistent diagnosis and treatment. Why is the case? What is to be done about it? METHODS: We critically review studies in the nosology of bipolar disorder and the effects of antidepressant agents. RESULTS: Bipolar disorder is underdiagnosed and frequently misdiagnosed as unipolar major depressive disorder. Antidepressants are probably overused and mood stabilisers underused. Reasons for underdiagnosis include patients' impaired insight into mania, failure to involve family members in the diagnostic process, and inadequate understanding by clinicians of manic symptoms. We propose using a mnemonic to aid in diagnosis, obtaining family report, and utilising careful clinical interviewing techniques given the limitations of patients' self-report. We recommend aggressive use of mood stabilisers, and less emphasis on antidepressants. CONCLUSIONS: The state of diagnosis and treatment in bipolar disorder is suboptimal. More diagnostic attention to manic criteria is necessary and the current pattern of use of antidepressant use in bipolar disorder needs to change.

Antidepressive Agents↗

PubMed2003

[Depression after first myocardial infarction. A prospective study on incidence, prognosis, risk factors and treatment].

In these studies patients with first myocardial infarction (MI) were selected for studies focusing on epidemiology, risk factors and treatment of depression post-MI. Two consecutive cohorts of first MI patients were included. The first cohort was selected between May 1994 and May 1997 (n = 206), and the second between May 1997 and October 1999 (n = 206). All patients were screened every 3 months for depression using the SCL-90 and the Zung (cohort 1) or SCL-90, BDI and HADS (cohort 2) until 12 months post-MI. Patients scoring above the cut-off of one of the questionnaires were interviewed using a standardised interview in order to evaluate whether DSM-IV criteria for major depression were met; patients of the second cohort were also interviewed 1 month post-MI, independently of the score of the questionnaires. Of both cohorts data concerning major cardiac events and increased health care consumption were assessed during a 1 to 6 years follow-up period. Patients with major depression were offered treatment in the double-blind placebo-controlled trial with fluoxetine (n = 54). Depression appeared to be a predictor of increased health care consumption, but not of major cardiac events such as cardiac death and recurrent infarction in first myocardial infarction (MI) patients up to 6 years post-MI. This finding is in contrast to findings in the literature indicating that in patient populations with mixed first and recurrent MI, depression is a risk factor for cardiac mortality. In contrast to depression, symptoms of anxiety do predict cardiac mortality and recurrent MI in patients following first MI independently of other risk factors of cardiac mortality. Recognition of risk factors for post-MI depression may help the cardiologist to identify patients at risk for depression. Examples of such risk factors are, according to our studies, complications during admission, such as arrhythmic disorders and recurrent angina pectoris, and prescription of benzodiazepines. Patients at risk can be screened for depression using a 4-item questionnaire, and, if scoring is positive, be referred for psychiatric evaluation. Although the effectivity of antidepressive treatment in MI patients has as yet not been proven, we found that fluoxetine is a cardiac-safe antidepressive agent, but only in mild depression more effective than placebo. The positive effect of antidepressive treatment on cardiac prognosis has as yet not been shown.

Antidepressive Agents, Second-Generation↗

PubMed1971

Rubidium and lithium: opposite effects on amine-mediated excitement.

In mice the activation caused by morphine was antagonized by previous treatment with lithium and was potentiated by previous treatment with rubidium. Other antimanic drugs antagonized the morphine activation as well. The effect of rubidium was similar to that of the antidepressant drugs imipramine and pargyline. Rubidium may merit clinical evaluation as an antidepressant agent in man.

Animals↗