Antidepressants serotonergic drugs

Serotonergic drugs - antidepressants maprotUine, monoamine oxidase inhibitors, drug combinations with specific serotonin reuptake inhibitors causing the serotonin syndrome - lithium, LSD, MDMA... 

Following the first report of this syndrome, many other cases have been described involving tryptophan and MAOIs ,(p. 1151), the tricyclic antidepressants and MAOIs , (p.ll49), and, more recently, the SSRIs , (p.ll42) but other serotonergic drugs have also been involved and the list continues to grow. 

The case reports detailed above suggest that some patients may develop a pharmacodynamic interaction. Concurrent use of lithium and olanzapine need not be avoided but be aware that there is some risk of developing adverse reactions to the combination. The presence of other serotonergic drugs (e.g. antidepressants such as SSRIs) or dopamine antagonists (e.g. antipsychotics such as haloperidol) is likely to increase the risk of an interaction. 

Although the evidence is limited, it appears that nefazodone can cause a marked rise in ciclosporin levels, with an increase in adverse effects. Alternative antidepressants should probably be used, or concurrent therapy very well monitored. Similar caution would seem prudent with fluvoxamine, and possibly fluoxetine. Citalopram, and sertraline do not appear to alter ciclosporin levels and may therefore be suitable alternatives. Serotonin syndrome is a rare adverse effect, usually associated with the use of more than one serotonergic drug (see The serotonin syndrome , (p.9)). 

The manufacturer advises caution if duloxetine is used with SSRIs (see below), tricyclic antidepressants , (p.l240), St John s wort , (p.l224), venlafaxine, or tryptophan, because the concurrent use of more than one serotonergic drug has rarely resulted in the serotonin syndrome , (p.9). > ... 

Bupropion may increase venlafaxine plasma levels. Antimus-carinic adverse effects can develop in patients taking fluoxetine and venlafaxine. Venlafaxine combined with other serotonergic antidepressants may increase the risk of bleeding and/or the serotonin syndrome. The serotonin syndrome has also been reported in patients taking venlafaxine with mirtazapine or trazodone some of these patients were also taking other serotonergic drugs. 

Information appears to be limited to these reports, three of which are by the same author. The incidence is not known but if venlafaxine and any tricyclic antidepressant are given concurrently, be alert for any evidence of increased antimusearinie adverse effects. Although there appears to be only one report, the possibility of an increased risk of seizures with concurrent use should be borne in mind. It may be necessary to withdraw one or other of the two drugs. The reports of the serotonin syndrome highlight the need for caution when one or more serotonergic drugs are given either concurrently or within a short period of each other. 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

However, experience proves that depression can be reversed by drugs that augment serotonergic and noradrenergic transmission (and reinstated by a deficit in the synthesis of these monoamines). These, then seem to be crucial targets that ultimately determine mood. This would explain why, despite numerous neurochemical options for the causes of depression, all antidepressants developed so far (and even those discovered by chance) target these neuronal systems. Whatever the cause of depression, therefore, its relief seems to rest on appropriate secretion of these monoamines. This would be entirely... 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

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