For serotonin syndrome

Horowitz, B.Z. and Mullins, M.E. (1999) Cyproheptadine for serotonin syndrome in an accidental pediatric sertraline ingestion. Pe-diatr Emerg Care 15 325-327. 

A. Parenteral. Give 0.5-3 mg slow IV not to exceed 1 mg/min (children, 0.01-0.1 mg/kg slow IV over 5 minutes maximum 1 mg/dose) while monitoring heart rate and blood pressure dose may be repeated as needed after 5-10 minutes. The dose required for complete beta receptor blockade is about 0.2 mg/kg. For serotonin syndrome, give 1 mg IV not to exceed 1 mg/min (children 0.1 mg/kg/dose over 10 min maximum 1 mg/dose) every 2-5 minutes until a maximum of 5 mg. May repeat at 6- to 8-hour intervals. 

B. Oral. Oral dosing may be Initiated after the patient is stabilized the dosage range is about 1-5 mg/kg/day in three or four divided doses for both children and adults. For serotonin syndrome, an adult dose of 20 mg every 8 hours has been used. 

The Hunter criteria for serotonin syndrome have an 84% sensitivity and 96% specificity for the diagnosis, and require exposure to a drug known to cause the syndrome and at least one of (a) spontaneous clonus. 

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. 

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

Trazodone, 25 to 100 mg, is often used for insomnia induced by selective serotonin reuptake inhibitors or bupropion. Side effects include serotonin syndrome (when used with other serotonergic drugs), oversedation, a-adrenergic blockade, dizziness, and rarely priapism. 

Serotonin syndrome (sibutramine) The rare, but serious, constellation of symptoms also has been reported with the concomitant use of selective serotonin reuptake inhibitors and agents for migraine therapy (eg, sumatriptan, dihydroergotamine), certain opioids (eg, dextromethorphan, meperidine, pentazocine, fentanyl), lithium, or tryptophan. Because sibutramine inhibits serotonin reuptake, it should not be administered with other serotonergic agents. 

Other etiologies need to be ruled out because many of the symptoms of serotonin syndrome overlap with those of early sepsis or neuroleptic malignant syndrome, conditions associated with significant mortality. It is critical to evaluate for sepsis and to determine that a neuroleptic has not been started or increased prior to the onset of... 

Medications with serotonergic activity may also have other monaminergic or sympathomimetic activity. Combining MAOIs with these medications may result in a complex side effect profile. For example, combining meperidine or dextromethorphan with MAOIs may result in respiratory depression, in addition to symptoms of serotonin excess. Furthermore, interactions between MAOIs and tricyclic antidepressants (TCAs) more commonly result in potentiating shared adverse events such as othostatic hypotension, as opposed to hyperadrenergic crises or the serotonin syndrome. 

A more common approach in difficult to treat cases would be the combination of clomipramine with a SSRI several reports lend support to this practice (Simeon and Thatte, 1990 Figueroa et al., 1998). In this situation, careful attention to the potential pharmacokinetic interactions discussed above are recommended. Sertraline and citalopram are least likely to elevate tricyclic levels due to less potential GYP interactions. By expert consensus, second- (venlafaxine) and third-line (nefazadone and gabapentin) agents may be used when clinical response is inadequate despite a lack of controlled data. Venlafaxine may be substituted for a more typical SSRI while nefazadone or gabapentin may be added to either clomipramine or a SSRI. The combination of venlafaxine with other SSRIs is not generally recommended as it may increase the risk of a serotonin syndrome. The addition of nefazadone to SSRIs presents a lesser risk. 

FIGURE 43.1 Pharmacologic treatment algorithm for full syndrome pediatric PTSD. Based on a snythesis of consensus data and clinical reports in the adult and child literature. The author hers no responsibility for the use of this guideline by third parties. SSRI, selective serotonin reuptake inhibitor NEE, nefaza-done SIB, self injurious behavior VLF, venlafaxine VPA, valproic acid. 

Goodwin FK, Murphy DL, Dunner DL, et al Dthium response in unipolar versus bipolar depression. Am J Psychiatry 129 76-79, 1972 Goodwin GM, DeSouza RJ, Wood AJ, et al TJie enhancement by lithium of the 5-HTlA mediated serotonin syndrome produced by 8-OH-DPAT in the rat evidence for a post-synaptic mechanism. Psychopharmacology 90 488-493, 1986a Goodwin GM, DeSouza RJ, Wood AJ, et al Lithium decreases 5-HTlA and 5-HT2 receptor and alpha-2 adrenoceptor mediated function in mice. Psychopharmacology 90 482-487, 1986b... 

The following side effects apply to the irreversible, nonselective MAOI antidepressants (phenelzine and tranylcypromine). The most common side effects are orthostatic hypotension, headache, insomnia, weight gain, sexual dysfunction, peripheral edema, and afternoon somnolence. Although MAOIs do not have significant affinity for muscarinic receptors, anticholinergic-like side effects are present at the beginning of treatment. Dry mouth is common but not as marked as in TCA therapy. Fortunately, the more serious side effects, such as hypertensive crisis and serotonin syndrome, are not common. 

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. 

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