Tramadol seizures with

The death of a 36-year-old patient with a history of alcohol dependence who was taking tramadol, venlafaxine, trazodone, and quetiapine has highlighted the increased risk of seizures with concomitant use of tramadol and selective serotonin re-uptake inhibitors (125). 

C. Seizures are not common after opioid overdose but occur occasionally with certain compounds (eg, dextromethorphan, meperidine, propoxyphene, and tramadol). Seizures may occur in patients with renal compromise who receive... 

Emamhadi M, Sanaei-Zadeh H, Nikniya M, Zamani N, Dart RC. Electrocardiographic manifestations of tramadol toxicity with special reference to their ability for prediction of seizures. Am J Emerg Med October 2012 30(8) 1481-5. 

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

Dizziness, vertigo, nausea, vomiting, constipation, and lethargy are all relatively common adverse events. These effects are more pronounced for several days after initiation and following upward dose titration. Seizures have been reported rarely the risk is dose-related and appears to increase with concomitant use of antidepressants, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. Tramadol should be avoided in patients receiving monoamine oxidase (MAO) inhibitors because tramadol inhibits the uptake of norepinephrine and serotonin. 

Seizures Seizures may be aggravated or may occur in individuals with or without a history of convulsive disorders if dosage is substantially increased above recommended levels because of tolerance. Observe patients with known seizure disorders closely for hydromorphone-, meperidine-, morphine-, or tramadol-induced seizure activity. 

Side-effects Typical side-effects of tramadol are nausea, sweating and dizziness. In rare cases seizures after high i.v. doses are reported, mostly in combination with other proconvulsant componds or in patients with reduced seizure theshold (Gardner et al., 2000). Tramadol shows a reduced level of opioid side-effects, especially respiratory depression and constipation are less frequent and severe than with standard opioids such as morphine. Tramadol has a very limited abuse potential and is not subject to narcotic control (Cossmann et al., 1997). 

Tramadol, phenothiazine antipsychotics and the majority of antidepressants, as well as a number of other drugs, can lower the seiznre threshold and are associated with an increased risk of convnlsions [6]. Again, these drugs may accumulate in patients with liver impairment such as cirrhosis or acute liver failure, and care must be taken if choosing to use them. This is especially important in alcoholics, who have an increased risk of seizures from acute alcohol withdrawal [7]. Examples of drugs that can lower the seizure threshold and should be used with caution/avoided are ... 

In patients with alcoholic liver disease who are prone to alcoholic seizures, it is best to avoid pethidine and tramadol because of their epileptogenic potential. 

TCAs OPIOIDS 1. Risk of t respiratory depression and sedation 2. t levels of morphine 3. Case reports of seizures when tramadol was co-administered with TCAs 4. TCAs may t codeine, fentanyl, pethidine and tramadol levels 1. Additive effect 2. Uncertain likely t bioavailability of morphine 3. Unknown 4. TCAs inhibit CYP2D6-mediated metabolism of these opioids 1. Warn patients of this effect. Titrate doses carefully 2. Warn patients of this effect. Titrate doses carefully 3. Consider an alternative opioid 4. Watch for excessive narcotization... 

Tramadol increases fhe risk of seizures in patients taking TCAs Use of TCAs with anticholinergic drugs... 

Tramadol increases the risk of seizures in patients taking TCAs Use of TCAs/tetracyclics with anticholinergic drugs may result in paralytic ileus or hyperthermia Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors may increase TCA/tetracyclic concentrations... 

A 29-year-old woman took tramadol 50 mg 6-hourly for pain associated with the carpal tunnel syndrome. She slowly increased the dose of tramadol and obtained it from several physicians and different hospitals, so that after 3 years she was taking 30 tramadol 50 mg tablets daily. She had two generalized seizures and stopped taking tramadol 1 day later she developed severe opioid withdrawal symptoms, including diarrhea, headache, insomnia, and blurred vision. She was detoxified with tapering doses of tramadol and discharged after 6 days. 

Although associated with less respiratory depression than morphine at recommended doses, tramadol has a side-effect profile that in some ways is similar to that of the previously mentioned opioid analgesics (e.g., dizziness, euphoria, hallucinations, cognitive dysfunction, and constipation). Tramadol alone may enhance the risk of seizures. In addition, concomitant use with serotonin reuptake... 

In general, the concurrent use of most opioids and tricyclics is uneventful, although lethargy, sedation, and respiratory depression have been reported. Tramadol should be used with caution with tricyclic antidepressants because of the possible risk of seizures and the serotonin syndrome. Dextroproposyphene may cause moderate rises in the serum levels of amitriptyline and nortriptyUne, and methadone may moderately raise desipramine levels. The bioavailability and the degree of analgesia of oral morphine is increased by clomipramine, desipramine and possibly amitriptyline. 

Similarly, seizures and the serotonin syndrome have been reported in a woman who took mirtazapine with tramadol, but this may have been due to over-use of the tramadol rather than an interaction. Lethargy, confusion, hypotension, bronchospasm and hypoxia has also been seen following the use of tramadol and mirtazapine, which resolved within hours of both drugs being stopped. ... 

Kahn LH, Alderfer RJ, Graham DJ. Seizures reported with tramadol. JAMA (1997) 278, 1661. 

Two cases of the serotonin syndrome have been reported when tramadol was given with venlafaxine one patient was also receiving mirtazapine. Fatal seizures occurred in an alcoholic man receiving tramadol, venlafaxine, quetiapine and trazodone. 

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... 

Tramadol should be used with caution with SSRIs because of the increased risk of seizures. Several reports describe the development of the serotonin syndrome in patients taking SSRIs with tramadol. Another patient developed hallucinations with tramadol and paroxetine. 

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. ... 

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-... 

One of the main issues related to tramadol is the fact that it blocks serotonin reuptake and may cause serotonin syndrome in susceptible patients. Serotonin syndrome is characterized by neurological and cardiovascular stimulation, and can lead to seizures and death. Risks of developing serotonin syndrome are increased in patients treated with selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. 

Seizures have been reported in patients receiving tramadol. The risk of seizure is increased with doses of tramadol above the recommended range. Concomitant use of tramadol increases the seizure risk in patients taking tricyclic antidepressants, selective serotonin reuptake inhibitors, or other opioids. Tramadol may enhance the seizure risk in patients taking MAO inhibitors, neuroleptics, or other drugs that reduce the seizure threshold. Risk of convulsions may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). 

Relative history of seizure disorder, bipolar disorder (may induce mania), urinary retention, narrow-angle glaucoma, delirium, hyperthyroidism, bradycardia (or drugs that cause bradycardia), or electrolyte disturbance (esp. K+ or Mg ). Use caution in conjunction with other antidepressants (including MAOIs and SSRIs), other anticholinergic medications, drugs that increase plasma levels (phenothiazines, haloperidol, cimetidine), or drugs that lower seizure threshold (esp. tramadol). Use caution in elderly, children/adolescents. 

NERVOUS SYSTEM No association between initial EKG, sex or initial presenting vital signs with propensity to experience seizure after intentional tramadol overdose [73 -]. Patients who did experience seizures after tramadol use did not tend to have recurrent seizures and did not need to be placed on long-term antiepileptics [74 ]. It was foxmd that seizures occur in about 7/100 (7%) of patients with tramadol toxicity [74 ]. Seizures from tramadol have also been reported in children [75 ]. 

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