Tramadol SSRIs

Tramadol is a central-acting analgesic, effective for mild to moderate acute and chronic pain. It impairs nociception by a unique mechanism that is not completely understood. In animal models, it binds to the /u. opioid receptor and is a weak inhibitor of serotonin and norepinephrine reuptake, actions similar to those ascribed to the SSRIs and TCAs. Seizures have been reported in patients taking tramadol. Abuse potential is low, but does exist. 

Fenfluramine Dextromethorphan Meperidine Methylene dioxymethamphetamine Meta-chlorophenylpiperazine (mCPP) Trazodone (mCPP) Selegiline Nefazodone Trazodone Pethidine Tramadol Mirtazapine TCA medications Venlafaxine SSRI agents... 

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... 

Tramadol has some activity in blocking the re-uptake of 5HT and can also cause 5HT neurotoxicity in combination with SSRIs. 

The simultaneous use of tramadol and SSRIs is probably not uncommon in clinical practice, and it is therefore likely that some patients can take this combination without developing 5HT toxicity. When symptoms of the 5HT syndrome develop it may be that, as in this case, that there is a factor in the individual patient that increases the risk. 

The analgesic drug tramadol can cause 5HT toxicity in association with SSRIs. Venlafaxine is also a potent reuptake inhibitor, and perhaps not surprisingly has been reported to cause features of the 5HT syndrome in a patient taking tramadol (49). 

SSRIs OPIOIDS 1. Possible 1 analgesic effect of oxycodone and tramadol 2. T serotonin effects, including possible cases of serotonin syndrome, when opioids (oxycodone, pethidine, pentazocine, tramadol) are co-administered with SSRIs (fluoxetine and sertraline) 3. SSRIs may t codeine, fentanyl, methadone, pethidine and tramadol levels 1. Uncertain. Paroxetine inhibits CYP2D6, which is required to produce the active form of tramadol. 2. Uncertain 3. SSRIs inhibit CYP2D6-mediated metabolism of these opioids 1. Consider using an alternative opioid 2. Look for signs of T serotonin activity, particularly on initiating therapy 3. Watch for excessive narcotization... 

Can cause a fatal serotonin syndrome when combined with drugs that block serotonin reuptake (e.g., SSRIs, SNRIs, sibutramine, tramadol, etc.), so do not use with a serotonin reuptake inhibitor or for up to 5 weeks after stopping the serotonin reuptake inhibitor... 

P450 enzyme inhibition by SSRIs may also augment effects of alcohol, tramadol, methadone, terfenadine (danger of cardiac arrhythmia), -caine anaesthetics and theophylline. 

Tramadol Five reports describe the development of the serotonin syndrome in patients on fluoxetine, paroxetine, or sertraline when tramadol was added. Another patient developed hallucinations with tramadol and paroxetine. Other reports suggest that the SSRI/tramadol combination is therapeutically valuable and normally safe. Also, carefully monitor concomitant use with fluvoxamine. 

This demonstrates that there are sound practical and theoretical reasons for patients on MAOIs to avoid tramadol. Note that the serotonin syndrome has also occurred with tramadol and SSRIs , (p.l222). 

A small study in healthy subjects found no problems when moclobemide was given 24 hours after clomipramine. However, the serotonin syndrome occurred in 3 patients when clomipramine was replaced by mo-clobemide without a washout period or with only a 24-hour washout period, " and in another patient when moclobemide was replaced by clomipramine after only 12 hours. A fatal case of the serotonin syndrome occurred in a patient taking clomipramine and amitriptyline, with symptoms manifesting within 30 minutes of a 300-mg dose of moclobemide. Two other patients developed fatal serotonin syndrome after taking moderate overdoses of moclobemide and clomipramine. The serotonin syndrome has been reported in at least 8 other cases of moclobemide and clomipramine overdose, one of which also involved tramadol (see also MAOIs + Opioids Tramadol, p.ll41), another fluoxetine (see also MAOIs or RIMAs + SSRIs, p.l 142), and yet another buspirone (see also MAOIs or RIMAs + Buspirone, p.l 133). Conversely, a case of an overdose of moclobemide and clomipramine resulted in no adverse effects except sinus tachycardia. ... 

Symptoms of the serotonin syndrome have been reported with opioids including hydromorphone, oxycodone, pentazocine, pethidine and tramadol and possibly morphine when given with various SSRIs. Seizures have been seen when dextropropoxy-phene was given with an SSRL... 

The serotonin syndrome has occurred in a number of patients taking SSRIs with tramadol. See SSRIs + Opioids Tramadol , p.l222. 

The incidence of serotonin syndrome-like reactions with opioids and SSRIs is fairly rare (although see tramadol , (p.l222)) however, the possibility of the serotonin syndrome , (p.9), should be considered in patients experiencing altered mental status, autonomic dysfunction and neuromuscular adverse effects while receiving these drugs. 

The CSM in the UK has publicised 27 reports of convulsions and one of worsening epilepsy with tramadol, a reporting rate of 1 in 7000 patients. Some of the patients were given doses well in excess of those recommended, and some were taking SSRIs (5 patients) or tricyclic antidepressants , (p.l87), both of which are known to reduce the convulsive threshold. Similarly, of 124 seizure cases associated with tramadol reported to the FDA in the US, 20 included the concurrent use of SSRIs. ... 

The Australian Adverse Drug Reaction Advisory Committee has stated that tramadol may cause the serotonin syndrome, particularly when it is used at high doses or in combination with other drugs increasing serotonin le vel s of 20 reported cases of the serotonin syndrome associated with tramadol, 16 were taking potentially interacting medicines including SSRIs. Cases of the serotonin syndrome with specific SSRIs are discussed below. 

Tramadol may cause seizures and SSRIs can reduce the seizure threshold, thus if both are taken together the risk is increased. The serotonin syndrome , (p.9), seems to develop unpredictably in some patients given two or more serotonergic drugs (in this case, tramadol and SSRIs). 

Because of the possible increased risk of seizures, tramadol should be used with caution in patients taking drugs such as the SSRIs, which can lower the seizure threshold. The concurrent use of tramadol and SSRIs may also lead to an increase in serotonin-associated effects, which can include the serotonin syndrome. However, the relatively few reported cases of the serotonin syndrome or other reactions due to an interaction between an SSRI and tramadol need to be set in the wider context of apparently uneventful and advantageous use in other patients,although some workers have suggested that the incidence of serotonin syndrome may be underreported. There would seem to be little reason for totally avoiding the concur-... 

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