Pharmaceuticals

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224 KiB

Open AccessReview

Role of 5-HT₃ Receptors in the Antidepressant Response

by Cécile Bétry, Adeline Etiévant, Chris Oosterhof, Bjarke Ebert, Connie Sanchez and Nasser Haddjeri

Pharmaceuticals 2011, 4(4), 603-629; https://doi.org/10.3390/ph4040603 - 7 Apr 2011

Cited by 62 | Viewed by 15141

Abstract

Serotonin (5-HT)₃ receptors are the only ligand-gated ion channel of the 5-HT receptors family. They are present both in the peripheral and central nervous system and are localized in several areas involved in mood regulation (e.g., hippocampus or prefrontal cortex). Moreover, they [...] Read more.

Serotonin (5-HT)₃ receptors are the only ligand-gated ion channel of the 5-HT receptors family. They are present both in the peripheral and central nervous system and are localized in several areas involved in mood regulation (e.g., hippocampus or prefrontal cortex). Moreover, they are involved in regulation of neurotransmitter systems implicated in the pathophysiology of major depression (e.g., dopamine or GABA). Clinical and preclinical studies have suggested that 5-HT₃ receptors may be a relevant target in the treatment of affective disorders. 5-HT₃ receptor agonists seem to counteract the effects of antidepressants in non-clinical models, whereas 5-HT₃ receptor antagonists, such as ondansetron, present antidepressant-like activities. In addition, several antidepressants, such as mirtazapine, also target 5-HT₃ receptors. In this review, we will report major advances in the research of 5-HT₃ receptor’s roles in neuropsychiatric disorders, with special emphasis on mood and anxiety disorders. Full article

(This article belongs to the Special Issue Antidepressants)

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423 KiB

Open AccessReview

Monoaminergic Antidepressants in the Relief of Pain: Potential Therapeutic Utility of Triple Reuptake Inhibitors (TRIs)

by Guillaume Hache, François Coudore, Alain M. Gardier and Bruno P. Guiard

Pharmaceuticals 2011, 4(2), 285-342; https://doi.org/10.3390/ph4020285 - 26 Jan 2011

Cited by 30 | Viewed by 17735

Abstract

Over 75% of depressed patients suffer from painful symptoms predicting a greater severity and a less favorable outcome of depression. Imaging, anatomical and functional studies have demonstrated the existence of common brain structures, neuronal pathways and neurotransmitters in depression and pain. In particular, [...] Read more.

Over 75% of depressed patients suffer from painful symptoms predicting a greater severity and a less favorable outcome of depression. Imaging, anatomical and functional studies have demonstrated the existence of common brain structures, neuronal pathways and neurotransmitters in depression and pain. In particular, the ascending serotonergic and noradrenergic pathways originating from the raphe nuclei and the locus coeruleus; respectively, send projections to the limbic system. Such pathways control many of the psychological functions that are disturbed in depression and in the perception of pain. On the other hand, the descending pathways, from monoaminergic nuclei to the spinal cord, are specifically implicated in the inhibition of nociception providing rationale for the use of serotonin (5-HT) and/or norepinephrine (NE) reuptake inhibitors (SSRIs, NRIs, SNRIs), in the relief of pain. Compelling evidence suggests that dopamine (DA) is also involved in the pathophysiology and treatment of depression. Indeed, recent insights have demonstrated a central role for DA in analgesia through an action at both the spinal and suprasinal levels including brain regions such as the periaqueductal grey (PAG), the thalamus, the basal ganglia and the limbic system. In this context, dopaminergic antidepressants (i.e., containing dopaminergic activity), such as bupropion, nomifensine and more recently triple reuptake inhibitors (TRIs), might represent new promising therapeutic tools in the treatment of painful symptoms with depression. Nevertheless, whether the addition of the dopaminergic component produces more robust effects than single- or dual-acting agents, has yet to be demonstrated. This article reviews the main pathways regulating pain transmission in relation with the monoaminergic systems. It then focuses on the current knowledge regarding the in vivo pharmacological properties and mechanism of action of monoaminergic antidepressants including SSRIs, NRIs, SNRIs and TRIs. Finally, a synthesis of the preclinical studies supporting the efficacy of these antidepressants in analgesia is also addressed in order to highlight the relative contribution of 5-HT, NE and DA to nociception. Full article

(This article belongs to the Special Issue Antidepressants)

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74 KiB

Open AccessReview

Pharmacogenetics of SSRIs and Sexual Dysfunction

by Liana Osis and Jeffrey R. Bishop

Pharmaceuticals 2010, 3(12), 3614-3628; https://doi.org/10.3390/ph3123614 - 15 Dec 2010

Cited by 16 | Viewed by 9895

Abstract

Sexual dysfunction (SD) is a common and disconcerting side effect of selective serotonin reuptake inhibitors (SSRIs) that often influences a patient’s desire to continue long-term antidepressant treatment. Studies specifically assessing changes in sexual well-being over time illustrate that the incidence of sexual side [...] Read more.

Sexual dysfunction (SD) is a common and disconcerting side effect of selective serotonin reuptake inhibitors (SSRIs) that often influences a patient’s desire to continue long-term antidepressant treatment. Studies specifically assessing changes in sexual well-being over time illustrate that the incidence of sexual side effects from SSRIs ranges from 20% to 70%, depending on the characteristics of the study sample assessed. Developing strategies to predict who may be at the highest risk for adverse changes in their sexual well-being is an important step in improving the quality of life and treatment of patients who require antidepressant therapy. Pharmacogenetic studies of SSRI-associated SD have identified associations between serotonin and glutamate system genes with aspects of SD. The results of studies investigating genetic variations in drug metabolism enzymes and their relationships to antidepressant-associated adverse effects have been mixed. Continued efforts to characterize the relationships between genetic markers and antidepressant outcomes, and to translate this knowledge to patient care, have the potential to significantly improve the empiric selection of antidepressant agents and to minimize the risk for intolerable side effects. Full article

(This article belongs to the Special Issue Antidepressants)

161 KiB

Open AccessReview

Atypical Antipsychotics and Other Therapeutic Options for Treatment of Resistant Major Depressive Disorder

by Rubo J. Seo, Holly MacPherson and Allan H. Young

Pharmaceuticals 2010, 3(12), 3522-3542; https://doi.org/10.3390/ph3123522 - 3 Dec 2010

Cited by 6 | Viewed by 8696

Abstract

Antidepressant therapies, such as selective serotonin reuptake inhibitors (SSRIs), are current first-line treatments for Major Depressive Disorder. However, over 50% of treated patients show an inadequate response to initial antidepressant therapy. If the therapeutic outcomes from two antidepressant therapies are suboptimal, potentially resulting [...] Read more.

Antidepressant therapies, such as selective serotonin reuptake inhibitors (SSRIs), are current first-line treatments for Major Depressive Disorder. However, over 50% of treated patients show an inadequate response to initial antidepressant therapy. If the therapeutic outcomes from two antidepressant therapies are suboptimal, potentially resulting in Treatment Resistant Depression, subsequent strategies include switching to another antidepressant or augmenting treatment by combining with other agents. When combined with SSRIs, atypical antipsychotics have supplementary action on dopaminergic and noradrenergic systems. Studies on combined treatment with atypical antipsychotics have shown significantly increased remission rates, shortened response times, and favorable side effects. Augmentation of antidepressants with atypical antipsychotics is now an acceptable treatment strategy which leads to increased remission rates and better outcomes for patients. Full article

(This article belongs to the Special Issue Antidepressants)

116 KiB

Open AccessReview

Beneficial Effects of Tianeptine on Hippocampus-Dependent Long-Term Memory and Stress-Induced Alterations of Brain Structure and Function

by Phillip R. Zoladz, Carmen Muñoz and David M. Diamond

Pharmaceuticals 2010, 3(10), 3143-3166; https://doi.org/10.3390/ph3103143 - 11 Oct 2010

Cited by 10 | Viewed by 15858

Abstract

Tianeptine is a well-described antidepressant which has been shown to prevent stress from producing deleterious effects on brain structure and function. Preclinical studies have shown that tianeptine blocks stress-induced alterations of neuronal morphology and synaptic plasticity. Moreover, tianeptine prevents stress from impairing learning [...] Read more.

Tianeptine is a well-described antidepressant which has been shown to prevent stress from producing deleterious effects on brain structure and function. Preclinical studies have shown that tianeptine blocks stress-induced alterations of neuronal morphology and synaptic plasticity. Moreover, tianeptine prevents stress from impairing learning and memory, and, importantly, demonstrates memory-enhancing properties in the absence of stress. Recent research has indicated that tianeptine works by normalizing glutamatergic neurotransmission, a mechanism of action that may underlie its effectiveness as an antidepressant. These findings emphasize the value in focusing on the mechanisms of action of tianeptine, and specifically, the glutamatergic system, in the development of novel pharmacotherapeutic strategies in the treatment of depression. Full article

(This article belongs to the Special Issue Antidepressants)

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106 KiB

Open AccessReview

Antidepressants and Suicide Risk: A Comprehensive Overview

by Maurizio Pompili, Gianluca Serafini, Marco Innamorati, Elisa Ambrosi, Gloria Giordano, Paolo Girardi, Roberto Tatarelli and David Lester

Pharmaceuticals 2010, 3(9), 2861-2883; https://doi.org/10.3390/ph3092861 - 30 Aug 2010

Cited by 35 | Viewed by 14591

Abstract

The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year), with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly [...] Read more.

The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year), with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20–30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation) in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment. Full article

(This article belongs to the Special Issue Antidepressants)

166 KiB

Open AccessReview

The Impact of Residual Symptoms in Major Depression

by Joshua A. Israel

Pharmaceuticals 2010, 3(8), 2426-2440; https://doi.org/10.3390/ph3082426 - 3 Aug 2010

Cited by 57 | Viewed by 16833

Abstract

The current definition of remission from major depressive disorder does not fully take into account all aspects of patient recovery. Residual symptoms of depression are very common in patients who are classified as being in remission. Patients with residual symptoms are at increased [...] Read more.

The current definition of remission from major depressive disorder does not fully take into account all aspects of patient recovery. Residual symptoms of depression are very common in patients who are classified as being in remission. Patients with residual symptoms are at increased risk of functional and interpersonal impairments, and are at high risk for recurrence of depression. This article discusses the incidence of residual symptoms of depression, as well as the risks and consequences of these symptoms, and will review the state of current treatment. Full article

(This article belongs to the Special Issue Antidepressants)

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161 KiB

Open AccessReview

Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for Links to Aetiology and Possible Treatment

by David A. Slattery and Inga D. Neumann

Pharmaceuticals 2010, 3(3), 702-724; https://doi.org/10.3390/ph3030702 - 16 Mar 2010

Cited by 75 | Viewed by 15755

Abstract

Affective disorders represent the most common psychiatric diseases, with substantial co-morbidity existing between major depressive disorders (MDD) and anxiety disorders. The lack of truly novel acting compounds has led to non-monoaminergic based research and hypotheses in recent years. The large number of brain [...] Read more.

Affective disorders represent the most common psychiatric diseases, with substantial co-morbidity existing between major depressive disorders (MDD) and anxiety disorders. The lack of truly novel acting compounds has led to non-monoaminergic based research and hypotheses in recent years. The large number of brain neuropeptides, characterized by discrete synthesis sites and multiple receptors, represent likely research candidates for novel therapeutic targets. The present review summarises the available preclinical and human evidence regarding the neuropeptide, oxytocin, and its implications in the aetiology and treatment of MDD. While the evidence is not conclusive at present additional studies are warranted to determine whether OXT may be of therapeutic benefit in subsets of MDD patients such as those with comorbid anxiety symptoms and low levels of social attachment. Full article

(This article belongs to the Special Issue Antidepressants)

251 KiB

Open AccessReview

Nitric Oxide Synthase Inhibitors as Antidepressants

by Gregers Wegener and Vallo Volke

Pharmaceuticals 2010, 3(1), 273-299; https://doi.org/10.3390/ph3010273 - 20 Jan 2010

Cited by 92 | Viewed by 17722

Abstract

Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested [...] Read more.

Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO) signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters, including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression. Full article

(This article belongs to the Special Issue Antidepressants)

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171 KiB

Open AccessReview

The Timing of Antidepressant Effects: A Comparison of Diverse Pharmacological and Somatic Treatments

by Rodrigo Machado-Vieira, Jacqueline Baumann, Cristina Wheeler-Castillo, David Latov, Ioline D. Henter, Giacomo Salvadore and Carlos A. Zarate, Jr.

Pharmaceuticals 2010, 3(1), 19-41; https://doi.org/10.3390/ph3010019 - 6 Jan 2010

Cited by 173 | Viewed by 20143

Abstract

Currently available antidepressants used to treat major depressive disorder (MDD) unfortunately often take weeks to months to achieve their full effects, commonly resulting in considerable morbidity and increased risk for suicidal behavior. Our lack of understanding of the precise cellular underpinnings of this [...] Read more.

Currently available antidepressants used to treat major depressive disorder (MDD) unfortunately often take weeks to months to achieve their full effects, commonly resulting in considerable morbidity and increased risk for suicidal behavior. Our lack of understanding of the precise cellular underpinnings of this illness and of the mechanism of action of existing effective pharmacological treatments is a large part of the reason that therapies with a more rapid onset of antidepressant action (ROAA) have not been developed. Other issues that need to be addressed include heterogeneous clinical concepts and statistical models to measure rapid antidepressant effects. This review describes the timing of onset of antidepressant effects for various therapies used to treat MDD. While several agents produce earlier improvement of depressive symptoms (defined as occurring within one week), the response rate associated with such agents can be quite variable. These agents include both currently available antidepressants as well as other pharmacological and non-pharmacological interventions. Considerably fewer treatments are associated with ROAA, defined as occurring within several hours or one day. Treatment strategies for MDD whose sustained antidepressant effects manifest within hours or even a few days would have an enormous impact on public health. Full article

(This article belongs to the Special Issue Antidepressants)

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