Sumatriptan SSRIs

Uses Obesity Action Blocks uptake of norepinephrine, serotonin, dopamine Dose 10 mg/d PO, may to 5 mg after 4 wk Caution [C, -] w/ SSRIs, Li, dextromethorphan, opioids Contra MAOI w/in 14 d, uncontrolled HTN, arrhythmias Disp Caps SE HA, insomnia, xerostomia, constipation, rhinitis, tach, HTN Interactions T Risk of serotonin synd W/ dextromethorphan, ergots, fentanyl, Li, meperidine, MAOIs, naratriptan, pentazocine, rizatriptan, sumatriptan, SSRIs, tryptophan, zolmitriptan, St. John s wort effects W/ cimetidine, erythromycin, ketoconazole T CNS depression W/ EtOH EMS Use fentanyl w/ caution, may T risk of serotonin synd concurrent EtOH use can T CNS depression OD May cause tach, HTN, diaphoresis, HA, fever, agitation, muscle tremors, and Szs symptomatic and supportive... 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

Serotonin syndrome SSRIs, second generation antidepressants, MAOIs, linezolid, tramadol, meperidine, fentanyl, ondansetron, sumatriptan, MDMA, LSD, St. John s wort, ginseng Hypertension, hyperreflexia, tremor, clonus, hyperthermia, hyperactive bowel sounds, diarrhea, mydriasis, agitation, coma onset within hours Sedation (benzodiazepines), paralysis, intubation and ventilation consider 5-HT2 block with cyproheptadine or chlorpromazine... 

Drugs used in the treatment of acute migraine, such as sumatriptan and rizatriptan, are 5-HTiB/iD-receptor agonists and could theoretically interact pharmacodynami-cally with SSRIs to cause serotonin toxicity. Triptans are metabolized mainly by monoamine oxidase, which makes pharmacokinetic interactions with SSRIs unlikely. Although case series have suggested that sumatriptan can be safely combined with SSRIs (SEDA-22, 14), there are occasional reports of toxicity. 

Caution has been advocated when SSRIs such as fluoxetine are combined with the triptans that are used to treat acute episodes of migraine (SEDA-24,16). There are case reports of symptoms suggestive of serotonin toxicity when fluoxetine has been combined with sumatriptan, perhaps because the SSRI can potentiate the 5-HT1B/iD agonist effects of the triptan (SEDA-22,14). 

Treatment of 12 healthy volunteers with paroxetine (20 mg/day for 14 days) did not alter the pharmacokinetics or pharmacodynamic effects of an acute dose of rizatriptan (10 mg orally) (29). These data are reassuring, but (as with sumatriptan) it is possible that sporadic cases of 5-HT neurotoxicity could still occur when rizatriptan is combined with an SSRI. 

Feverfew 1. Antimigraine drugs, e.g. sumatriptan t risk of episodes of tachycardia and hypertension (may be dangerous) The parthenolide constituent of feverfew has been shown to inhibit the release of serotonin and prostaglandins. Sumatriptan is an SSRI Avoid concomitant use... 

The serotonin syndrome is a rare but dangerous complication of SSRIs and features restlessness, tremor, shivering and myoclonus possibly leading on to convulsions, coma and death. Risk is increased by co-administration with drugs that enhance serotonin transmission, especially MAOIs, the antimigraine drug sumatriptan and St. John s Wort. 

Because sibutramine inhibits serotonin uptake, and because the serious serotonin syndrome has been seen when serotonergic drugs were taken with SSRIs, the manufacturers say that sibutramine should not be taken with any serotonergic drugs. They name dextromethorphan, dihydroergot-amine, fentanyl, pentazocine, pethidine (meperidine), SSRIs, sumatriptan, and tryptophan. Possible cases have been reported for sibutramine and SSMs , (below).The US manufacturers also include lithium in their list. Note that this list is not exhaustive (see MAOIs under (d) above) and a case of the serotonin syndrome has been seen when venla-faxine was given with sibutramine. ... 

The SSRIs normally appear not to interact with the triptans, but there are a few rare cases of dyskinesias when sumatriptan was given with an SSRl, and there is some evidence to surest that the serotonin syndrome may occasionally develop. Venlafaxine and duloxetine are predicted to interact similarly. Fluvoxamine modestly inhibits the metabolism of frovatriptan, and may inhibit the metabolism of zolmitriptan. 

A study in 11 healthy subjects found that paroxetine 20 mg daily for 16 days had no effect on the response to a 6-mg dose of subcutaneous sumatriptan, as measured by prolactin levels. The sumatriptan levels remained unaltered, its cardiovascular effects were unchanged and no clinically significant adverse effects occurred. Other studies report that the concurrent use of sumatriptan and SSRIs (fluoxetine 20 to 60 mg daily, fluvoxamine 200 mg daily, paroxetine 20 to 50 mg daily, sertraline 50 to 100 mg daily) was successful and uneventful. No adverse effects have been noted in 148 other patients. However, a case report describes a 65-year-old woman who had been taking paroxetine 20 mg [daily] for a number of years, who developed confusion, strange behaviour, sinus tachycardia, hypertension and hyperthermia shortly after starting sumatriptan. The serotonin syndrome was diagnosed, and she recovered completely on withdrawal of the two drugs. ... 

Additionally, in Canada, post-marketing surveillance of the voluntary reports reeeived by the manufacturers of fluoxetine, identified 2 cases that showed good evidence, and another 4 cases that showed some, but not strong evidence, of reactions consistent with the serotonin syndrome in patients also taking sumatriptan. Other cases describe a decrease in the efficacy of sumatriptan with fluoxetine, dyskinesias and dystonias with sumatriptan and paroxetine, and twenty possible cases of the serotonin syndrome with sumatriptan and SSRIs. ... 

The manufacturers of sumatriptan also say that they have rare post-marketing reports of weakness, hyperreflexia and incoordination following the use of sumatriptan and SSRIs. ... 

Macor also exploited the Mori-Ban indole synthesis to synthesize several anti-migraine analogues of sumatriptan and homo-tiyptamines as potent and selective serotonin reuptake inhibitors (SSRIs). Noticeably, the presence of the second bromine (the bromine passenger ) on the substrate was not significantly deleterious to the reaction although a small amount of the 7-bromoindole might be sacrificed at the end of the reaction to consume the active palladium catalyst. The approach to 7-bromoindole could provide a general method to access 7-bromoindoles (a rare class of indole derivatives), which then could be further manipulated for the synthesis of more complex 7-substituted indoles. 

---