Serotonin depressive symptoms

Venlafaxine (Effexor, Effexor XR). Venlafaxine works by blocking the reuptake of both serotonin and norepinephrine. Because of this dual action, some believe that venlafaxine may be more effective than the SSRIs when treating severe depression. Its side effects and toxicity are similar to the SSRIs with abdominal discomfort, sexual dysfunction, and anxiety being commonly reported. At higher doses, it may mildly elevate blood pressure therefore, blood pressure should be checked periodically. When stopping venlafaxine, serotonin discontinuation symptoms may be especially problematic. Therefore, gradually tapering of the dose every 2-4 weeks is recommended. 

The closest things to true antiserotonin medications used by psychiatrists are those used to treat serotonin-induced side effects. In particular, cyproheptadine has an overall serotonin-blocking effect. With repeated use, this medication can theoretically cause depression and anxiety, and there are case reports of recurrence of depressive symptoms following frequent administration of cyproheptadine. 

These data and findings from serotonin depletion studies show that, in patients treated successfully, NA and serotonin systems are involved in maintenance of drug-induced remission. However, the absence of an increased severity in depressive symptoms in drug-free patients with depression suggests that alterations in serotonin and catecholamine release may not be causally involved in the pathophysiology of mood disorders. 

Patients with SAD have been found to be resistant to exacerbation of depressive symptoms following acute tryptophan depletion ( 32), suggesting that dysfunction of central serotonin mechanisms may be less relevant to the pathophysiology of SAD than other forms of major depression. 

Pharmacotherapy. Despite the ambiguity around FM, antidepressants are a reasonable pharmacological candidate for treating FM for the following reasons (a) depression is thought to mediate depressive symptoms (b) as noted above, serotonin may underlie the pathophysiology of FM and (c) tricyclic antidepressants tend to be efficacious in treating pain (39). Data from meta-analytic... 

Several studies have discussed the relationship between serum cholesterol and suicide, violence, anxiety disorders, depressive disorders, and schizophrenia [1-3]. Some of these papers suggested that low or lowering cholesterol levels could cause or worsen depressive symptoms and increase the risks of suicide and violence death. There are many reports that discussed the relationships between the lipid profiles, depression, and suicide from the viewpoints of decreased serotonergic transmission on suicide behavior [4, 5], lower serum cholesterol and serotonin levels [6, 7], serum cholesterol levels and polymorphism in the promoter region of the serotonin transporter gene for depression and suicide [8-10], low serum cholesterol and suicide risk [11, 12], and serotonergic receptor function [13, 14]. These studies supported the hypothesis that reduced cholesterol levels resulted in reduced central serotonin transmission. 

A recent study showed that immunotherapy with IFN-a was follov ed by an increase of depressive symptoms and serum kynurenine concentrations on the one hand, and reduced concentrations of tryptophan and serotonin on the other hand (Bonaccorso et al., 2002). The kynurenine/tryptophan ratio, which reflects the activity of IDO, increased significantly. Changes in depressive symptoms v ere significantly positively correlated vdth kynurenine and negatively correlated with serotonin concentrations (Bonaecorso etal., 2002). This study and others (Capuron et al., 2003) clearly show that the IDO activity is increased by IFN, leading to an increased kynurenine production and a depletion of tryptophan and serotonin. The further metabolism of kynurenine, however, seems to play an additional crucial role for the psychopathological states. 

This data, coupled with numerous positive outcome studies of the effectiveness of antidepressants, has led to the development of the monoamine (or biogenic amine) hypothesis of depression. The theory holds that depressive symptoms are ushered in by a malfunction of either norepinephrine (NE) or serotonin (5-HT) neurons, which play critical roles in the functioning of the limbic system and the adjacent hypothalamus. The basic neuronal malfunction is felt to be identical for either NE or 5-HT neurons, thus what follows (a description of the pathophysiology of NE neurons) can also be seen to occur in individuals in whom 5-HT neurons are affected. For reasons that are not well understood, patients with major depression (with vegetative symptoms) appear to suffer from either NE or 5-HT dysfunction, but probably not both simultaneously (although some exceptions exist). 

For the patient with persistent depressive symptoms, antidepressants are often necessary. However, the possibility of triggering a "switch" into mania must always be considered. Attempts have been made to develop reliable recommendations for the predictive risk of antidepressant-induced mania or hypomania (Kupfer, Carpenter, and Frank 1988, Altshuler et al. 1995). Stoll and colleagues (1994) report less risk with monoamine oxidase inhibitors or bupropion than with tricyclics or serotonin specific antidepressants. Due to lack of controlled studies and heterogeneous data sources, this issue remains controversial and is far from resolved. 

When they occur, depressive symptoms should be treated actively using a combination of cognitive-behavioral therapy and an antidepressant drug. Of the available antidepressants, selective serotonin reuptake inhibitors (SSRIs) have the most favourable combination of efficacy and side-effect profile for the elderly, regardless of the presence of medical co-morbidities. Although the dual agent venlafaxine has been proposed as an alternative agent for older patients who are either non-responders or partial responders to SSRIs, the frail elderly may be particularly vulnerable to its side effects (Hayes 2004). 

One theory is that women with PMS are abnormally sensitive to progesterone secreted following ovulation, and that this reduces levels of pyridoxine. Pyridoxine is a coenzyme in the final step of the biosynthesis of serotonin, a neurotransmitter known to have potent effects on mood, and its deficiency may contribute to the depressive symptoms. 

Psychiatric evaluation of a patient after 6 weeks of treatment with a monoamine oxidase inhibitor (MAOI) shows no improvement. The psychiatrist now writes a prescription for fluoxetine which the patient starts two days after her final dose of the MAOI. Since the MAOIs used as antidepressants continue to exert effects for 2 or more weeks after discontinuance, the most likely result of the administration of fluoxetine now will be to cause (A) A rapid amelioration of her depressive symptoms Electrocardiographic abnormalities Extrapyramidal dysfunction The serotonin syndrome Weight gain... 

As was previously mentioned, a hangover-like syndrome is common the next day after use of MDMA. MDMA withdrawal, which is thought to be caused by serotonin depletion, can last for weeks and includes symptoms of depression, anxiety, restlessness, and insomnia (Allen et al. 1993 McGuite et al. 1994). No specific treatments are currently indicated fot this withdtawal syndrome, although the antidepressant bupropion may be helpful (Solhkhah... 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

ANSWER I think that elearly it is possible that there is no neurotoxieity in humans. I think all of us would like for this to be the ease. And maybe it is the ease. We have talked about this a lot with fenfluramine, and we have done studies with paraehloroamphetamine in whieh we have given it orally to rats at relatively low doses, but still anoreetie doses, over 90 days. We have seen depletion of serotonin, but that was fully reversible depletion. It eame baek when the drug was stopped. I think there may be no neurotoxieity at the oral doses used in humans. I think that would be great if that is the ease. That would explain why there is no depression or other kinds of symptoms. But I don t feel comfortable about relying on the laek of reporting of depression as real evidence that there is no neurotoxieity. We simply need to have better data on that. 

---