Serotonin syndrome

The combination of serotonergic drugs, such as SSRIs, with MAOIs can result in a potentially fatal hypermetabolic reaction, often 

The combination of MAOIs with meperidine, and perhaps with other phenylpiperidine analgesics, also has been implicated in fatal reactions attributed to the serotonin syndrome. Aspirin, nonsteroidal anti-inflammatory drugs, and acetaminophen should be used for mild to moderate pain. Of the narcotic agents, codeine and morphine are safe in combination with MAOIs, although doses may need to be lower than usual. 

The MAOIs cause significant hypotension, which is often the dose-limiting side effect of these drugs. Expansion of intravascular volume through administration of salt tablets or fludrocortisone may be an effective treatment. 

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MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

Gillman, PK (1999) The serotonin syndrome and its treatment. J. Psychopharmacol. 13 100-109. Heal, DJ, Cheetham, SC, Prow, MR, Martin, KF and Buckett, WR (1998) A comparison of the effects on central 5-HT function of sibutramine hydrochloride and other weight-modifying drugs. Brit. J. Pharmacol. 125 301-308. 

MAOIs Pharmacodynamic—serotonin syndrome Serotonergic antidepressants... 

Synergy of therapeutic pharmacological effects St. John s Wort will induce serotonin syndrome when co-administered with SSRIs. 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

The risk of potentially serious side effects should be enough to preclude the prescription of antidepressants for their placebo benefit, but this is not the only hazard associated with these medications. On 19 July 2006 the FDA issued a public-health advisory warning that, when taken in conjunction with other drugs that can affect serotonin levels, antidepressants can induce a life-threatening disorder called the serotonin syndrome .5 The serotonin syndrome is caused by an excess of serotonin in a person s body. 

FDA, Combined Use of 5-Hydroxytryptamine Receptor Agonists (Triptans), Selective Serotonin Reuptake Inhibitors (SSRIs) or Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) May Result in Life-Threatening Serotonin Syndrome , FDA Public Health Advisory (2006) http //www.fda.gov/Cder/Drug/advisory/ S SRI S S200607.htm... 

Prator, Bettina C., Serotonin Syndrome , Journal of Neuroscience Nursing 38, no. 2 (2006) 102-05... 

Parrott, A.C., Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity, Pharmacol. Biochem. Behav. 71(4), 837-844, 2002. 

Spanos, L.J. and Yamamoto, B.K., Acute and subchronic effects of methylenedioxymethamphetamine [(+/-)MDMA] on locomotion and serotonin syndrome behavior in the rat, Pharmacol. Biochem. Behav. 32(4), 835-840, 1989. 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

The answer is a. (Hardman, p 444) This patient has the serotonin syndrome Serotonin is already present in increased amounts in synapses because of blockade of its reuptake by the SSRls. The amount of serotonin that is present is further increased when breakdown by MAO is inhibited. The serotonin syndrome can be life threatening. 

The combination of an SSRI with another 5-HT augmenting agent can lead to the serotonin syndrome, which is characterized by symptoms such as clonus, hyperthermia, and mental status changes. 

Increased or decreased antidepressant response increased toxicity Decreased antihypertensive efficacy Decreased antihypertensive efficacy Increased hypoglycemic effects Possible additive lowering of seizure threshold Decreased antihypertensive efficacy tachycardia CNS stimulation Increased therapeutic and possibly toxic effects of both drugs hypertensive crisis delirium seizures hyperpyrexia serotonin syndrome Increased hypoglycemic effects... 

Venlafaxine MAOIs Potential for hypertensive crisis, serotonin syndrome, delirium... 

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