Journal of Clinical Psychiatry

4/10/00 New Treatment Approaches: Role of Norepinephrine in Depression
Source: Journal of Clinical Psychiatry, 2000; 61, (Suppl.1), 5
Abstract: The data reviewed in this article suggest that both noradrenergetic and serotonergic systems are involved in antidepressant action, but specific impairment that underlies depression is unclear and is likely to vary among patients.These findings suggest that the cause of depression is more complex than just alteration in the levels of 5-HT and/or NE. For some patients, depression may be more directly caused by dysfunction in brain areas or neuronal systems modulated by monoamine systems. The authors propose that antidepressant drugs may enhance neurotransmission in normal noradrenergic or serotonergic neurons and, through a time - dependet but as yet undiscovered process, restore function to barain areas modulated by monoamine neurons. Future research should focus on understanding of the adaptive changes that follow enhancement of synaptic levels of monoamines in neuronal circuits of the frontal cortex, amygdala, and hippocampus.
4/10/00 New Treatment Approaches: Clinical Issues in Long-Term Treatment with Antidepressants
Source: Journal of Clinical Psychiatry, 2000; 61, (Suppl.2), 20
Abstract: Most patients with major depression require some form of long-term antidepressant treatment. Optimizing efficacy and minimizing side effects are essential during the acute and long-term treatment for depression. Compliance with antidepressant treatment is under discussion.
4/10/00 New Approaches to the Treatment of Refractory Depression
Source: Journal of Clinical Psychiatry, 2000; 61, (Suppl.1), 26
Abstract: Augmentation and switching strategies for refractory depression treatment are under discussion. Advantages, disadvantages, and level of support for a number of new treatment strategies is reviewed.
1/27/00 Scientific Expert Meeting: Antidepressants in Clinical Practice
Source: Journal of Clinical Psychiatry, 1999; 60, (Suppl.17)
Abstract: This Supplement is devoted to the introductuon of novel antidepressant mirtazapine. Its antidepresssant effect appears to be related to dual enhancement of central noradrenergic and serotonergic neurotransmission by blockade of adrenoceptors, and 5-HT2 and 5-HT3 receptors. This results in a better tolerability, and sleep improvement. Mirtazapine is safe, and effective during long-term use and does not give sexual side effects. Antidepressants such as mitrazapine and nefazodone, which possess 5-HT2 blocking properties are useful treatment option for depressed people with insomnia.
1/26/00 New Developments in the Treatment of Depression
Source: Journal of Clinical Psychiatry, 1999; 60, (Suppl.14), 10-15
Abstract: New studies clearly suggest that the latest generation of antidepressants offer a more rapid response to treatment, an improved response rate, and superior long-term efficacy than conventional therapy. Dual acting drugs, such as venalafaxine, mirtazapine, and pindolol are under consideration.
1/26/00 Long -Term Nature of Depression
Source: Journal of Clinical Psychiatry, 1999; 60, (Suppl.14), 3-9
Abstract: This Article focuses on the 4"arms" of preventative treatment of depression: psychoeducatiobn, pharmacology, adherence, and psychotherapy. Full-dose pharmacotherapy as a maintenance antidepressant therapy is recommended. Longer term models of CBT and IPT provide nonpharmacologic alternatives.
7/19/99 Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder.
Source: Journal of Clinical Psychiatry, 1999; 60, (6), 400-406
Abstract: The long-term efficacy and tolerability of the antidepressant reboxetine, a unique selective NRI, were assessed in an international study. Reboxetine treatment over 1 year is more effective than placebo in the prevention of relapse in patients with recurrent depression. The low relapse rates at the end of the second 6 months of treatment further suggest that reboxetine effectively prevents recurrence of depressive symptoms following episode resolution. Reboxetine is well tolerated in long-term treatment of depression, a finding that bodes well for long-term patient compliance.
Goal of antidepressant therapy
Source: Journal of Clinical Psychiatry 1999; 60, (suppl. 6), 3-24
Controlled clinical trial results and other lines of evidence have established that a variety of antidepressant treatments are capable of producing excellent efficacy outcomes, the actual long-term outcomes observed in clinical practice are rather disappointing. A life time prevalence of approximately 17% has been reported, and the likelihood of recurrence is more than 50%. Depression is now seen as a chronic medical disorder. The future of antidepressant treatment should focus on drugs that will induce and maintain long-term recovery. A growing body of clinical data with venlafaxine demonstrates a consistently higher remission rate of 35% to 45% or greater, particularly with higher doses, in comparative studies with TCAs or SSRIs (20% to 30%). It is recommended for long-term preventative therapy for patients with histuries of highly recurrent depressive episodes.
Depression and its subtypes
Source: Journal of Clinical Psychiatry 1998; 59, (suppl. 18), 3-38

The variabiality of symptoms from patient to patient suggests that, within the larger category of major depression there may be several distinct entities of subtypes. They might respond specifically to different types of treatments. The possibility of matching patient symptom profile with antidepressant mechanism to achieve more rapid response or greater efficacy is discussed. Now this goal is not yet at hand. There is a possibility that agents with multiple mechanisms of action may offer efficacy advantages.
Assessing antidepressant efficacy
Source: Journal of Clinical Psychiatry 1999; 60, (suppl.4).
The purpose of this Supplement is to reexamine the issue of efficacy and completeness of respond to antidepressant treatment. Some subtypes of depression seem to respond preferentially to certain agents. Knowledge of antidepressant mechanism may help clinicians bring about a more thorough and complete response to medication.

Single-receptors antidepressants:
Selective Serotonin Reuptake Inhibitors (SSRI) (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram) combine the effectiveness of their older counterparts with a much-improved side effect profile. They act only at serotonin receptors. They have a wide range of clinical application in the full spectrum of depressive disorders, are well tolerated, with safety in overdose and low seizurogenicity. However, some investigators have suggested that the SSRIs tend to loose efficacy overtime.
It was difficult to develope specific Selective Norepinephrin Reuptake Inhibitors (SNRI) because of cardiovascular sideeffects. Reboxetine appears to be effective and well tolerated.

Multireceptors antidepressants:
They were design to interact with more than one recepror site. Serotonin Norepinerhrin Reuptake Inhibitors (SNRIs) (venlafaxine, mirtazapine, trazodone, nefazodone) act on both serotonin and norepinephrine, but they do not interact with histaminic and cholinergic-adrenergic receptors and thus avoid trublesome advers events such as dry mouth, hypotension, and sedation. Mechanism of action of these antidepressants is different.
Venlafaxine blocks serotonin and norepinephrin receptors.
Trazodone and Nefazodone are reaptake inhibitors.
Mitazapin blocks special serotonin and adrenergic receptors.
Features of all these antidepressants are discussed.

Antidepressants effectivness in severe depression:
Antidepressants respond is affected by type of depression. In severe depression remission rates are relarively low in many of the short term clinical trails of antidepressants, but are likely fo improve with longer trials and aggressive dosing. However, aggresive dosing with the tricyclic antidepressants (TCAs) can be problematic in terms of side effects. Results from studies of the efficacy of the SSRIs in severe depression are conflicting, but, even if they are slightly less efficaious than the TCAs, their favorable side effect profile and fewer consequenses of overdose make them a useful alternative to the TCAs.
Venlafaxine/venlafaxine XR, particularly at high doses, and no anticholinergic effects may offer a greater advantage than either the TCAs or the SSRIs in severely depressed patients. Reboxitine may also have advantages in this group.

Journal of Clinical Psychopharmacology
Involvment of Serotonin and Dopamine in the Mechanism of Action of Novel Antidepressant Drugs
Source: Journal of Clinical Psychopharmacology 1999; 28, (6), 447
In this article, studies reporting the biochemical, behavioral, and clinical effects of tricyclic antidepressants (TCASs), monoamine oxidase ingibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective blockers of presynaptic dopamine (DA) receptors, and antagonists of serotonin-2 (5-hydroxytryptamine-2 [5-HT2]) receptors were reviewed. These antidepressant drugs exert their therapeutic action only after long-term treatment. This effect is ascribed to their ability, after repeated administration, to induce adaptive changes of central monoaminergetic transmission and , in particular, of the 5-HT and DA systsems. It is suggested that drugs acting primarily on the serotonergic system, such as the SSRIs and 5-HT2b/2c receptor antagonists, would exert their antidepressant action by enhancing dopaminergic transmission in the misolimbic system. It is concluded that the use of compounds which disinhibit mesolimbic DA transmission might be useful in the treatment of depression.

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