Interaction
ALL OPIOIDS: As a CNS depressant, escitalopram has the potential to enhance the adverse or toxic effects of other CNS depressants such as opioids.
DEXTROMETHORPHAN: a) One case study reports a 20-year-old man who developed serotonin syndrome after ingesting dextromethorphan overdoses, while receiving escitalopram.
b) One case study reports that a 6-year-old patient developed serotonin syndrome after ingesting dextromethorphan overdoses while receiving a related drug, sertraline.
FENTANYL/OXYCODONE: a) A case report describes a 59 year old woman who was taking escitalopram and oxycodone and received fentanyl 250 mcg and morphine during surgery. The patient developed symptoms of serotonin syndrome the following morning.
b) A case report describes a 66 year old male who was taking oxycodone 120 mg daily and fentanyl 200 mcg intranasally up to QID. Escitalopram 5 mg/day was initiated and he developed serotonin syndrome. The majority of his symptoms resolved in 2 days but he continued to suffer from blurred vision.
HYDROCODONE: A 90 year old woman was taking hydrocodone and her citalopram 10 mg daily was changed to escitalopram 10 mg daily. She developed hallucinations, and hydrocodone was discontinued due to improved pain. The hallucinations resolved. She had previously taken paroxetine with the same dose of hydrocodone with no hallucinations or signs of serotonin-syndrome.
HYDROMORPHONE: An 81 year old woman who took related drug fluoxetine 20 mg daily and other medications for several years developed abnormal movements, confusion, incoherent speech, sweating, redness, tremor, hyperreflexia and muscle spasm 2 days after starting hydromorphone 12 mg daily. Fluoxetine was stopped and the symptoms resolved.
LOPERAMIDE: QTc prolongation has been observed with escitalopram. Concomitant use with high-dose loperamide (>100 mg/day) may result in an arrhythmia with the potential to develop Torsades de Pointes.
MEPERIDINE: Taking meperidine and escitalopram together increases the risk of serotonin syndrome.
MORPHINE: A patient, who had been taking related drug paroxetine prior to surgery, was given morphine and ondansetron during the surgery. She experienced post-operative delirium (agitation, confusion, uncontrolled limb movements, abnormal ocular function, hypertension, pyrexia, brisk reflexes, ankle clonus, elevated creatinine phosphokinase (CPK)) during the following 2 days.
METHADONE: QTc interval prolongation has been observed with escitalopram, thus concomitant use with methadone may result in an arrhythmia with the potential to develop Torsades de Pointes.
OXYCODONE: Symptoms of serotonin syndrome occurred in a patient taking escitalopram and extended release oxycodone after the oxycodone dose was increased.
TRAMADOL: a) A placebo-controlled crossover study was preformed where 15 healthy volunteers were given escitalopram 20 mg daily and tramadol 150 mg. The median AUC of (+)-O-desmethyltramadol (tramadol metabolite) was decreased by 29% in those taking escitalopram. The analgesic effect was assessed by the cold pressor test; it was unaffected.
b) An increase in seizure risk was noted by the manufacturer of tramadol when used with SSRIs.
c) There are multiple case reports of patients experiencing serotonin syndrome due to a combination of tramadol and related drug citalopram.
d) A 58 year old male patient was taking escitalopram 20 mg daily as well as quetiapine 300 mg daily, oxazepam 60 mg daily, alprazolam 2 mg daily, and zolpidem 12.5 mg daily. He was also treated with baclofen for 5 months for alcohol dependence. He was also on various other medications for non-psychiatric conditions (diabetes, cardiovascular disease, benign prostatic hyperplasia and urinary incontinence). Tramadol 50 mg BID was prescribed, although the patient may have taken more than prescribed. One month later the patient was arrested and diagnosed with a manic episode. He also had a positive urinary screen for tetrahydrocannabinol. Tramadol was discontinued on admission and escitalopram was discontinued 1 week later, but the patient wasn't able to be discharged for 3 months due to his symptoms, despite treatment with quetiapine, oxazepam, and lithium.
OTHER OPIOIDS: The serotonergic effects of SSRIs may be enhanced by concomitant use with serotonergic opioids.
Mechanism
ALL OPIOIDS: b) The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.
DEXTROMETHORPHAN: Serotonin syndrome is a dose-related response to the use of serotonergic drugs, often in combination. Genetic polymorphism in CYP2D6 function leads to differences in the ability to metabolize dextromethorphan which may explain the differences in clinical experiences reported by those who abuse dextromethorphan for its dissociative effects.
FENTANYL: a,b) Additive serotonergic effects could contribute to an increased risk of serotonin syndrome.
LOPERAMIDE: Both escitalopram and high dose loperamide can cause QTc interval prolongation. When used together, these effects may be additive.
MEPERIDINE: Additive serotonergic effects could contribute to an increased risk of serotonin syndrome.
METHADONE: Additive QTc prolongation.
TRAMADOL: a) The analgesic effect of tramadol is thought to be mediated mainly by the (+)-O-desmethyltramadol metabolite.
b) Tramadol can cause seizures, and SSRIs can lower the seizure threshold.
c) Additive serotonergic effects could contribute to an increased risk of serotonin syndrome.
d) The parent compound is an inhibitor of serotonin and norepinephrine reuptake (structural analog of venlafaxine).
OTHER OPIOIDS: Additive serotonergic effects.
Significance
ALL OPIOIDS: It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.
DEXTROMETHORPHAN: If therapeutic doses of dextromethorphan and an SSRI are enough to elicit serotonin syndrome, then the combination of these drugs should be avoided. One case study suggests that supra-therapeutic doses of dextromethorphan are a risk factor for the development of serotonin syndrome.
FENTANYL, MEPERIDINE, TRAMADOL: Fentanyl, meperidine, and tramadol may not be the best choice for analgesic therapy in patients currently maintained on escitalopram due to increased risk of serotonin syndrome. If these combinations cannot be avoided patients should be monitored for signs of serotonin syndrome.
LOPERAMIDE:Due to increased risk of QTc interval prolongation, it is recommended to avoid concomitant use of high-dose loperamide (>100 mg/day) and escitalopram.
METHADONE: Due to increased risk of QTc interval prolongation, caution is recommended with concomitant use of methadone and escitalopram.
TRAMADOL: a) The change in metabolism of tramadol does not appear to affect analgesic efficacy.
b) Caution with concomitant use of tramadol and SSRIs is recommended in patients who already have increased risks of seizures.
d) As the exact dose taken is unknown, tramadol abuse is possible. The significance of this case report is unclear, but the mechanism of action of tramadol makes it possible for it to induce mania.
OTHER OPIOIDS: While there is the potential for increased risk of serotonin syndrome with the concomitant use of SSRIs and opioids, it appears to be relatively rare. Little evidence exists to suggests a contraindication to concomitant use; however, it is recommended to monitor for serotonin syndrome-like symptoms if used in patients with altered mental status, autonomic dysfunction, or those experiencing neuromuscular adverse effects.
Serious Risk for Harm
ALL OPIOIDS: Escitalopram can cause sleepiness, dizziness and confusion. Opioid use can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.
Serious Risk for Harm
LOPERAMIDE: Use of both escitalopram and very high doses of loperamide (more than 100 mg in one day) can cause abnormal heart rhythm. Mixing these two medications could make the chance of having a deadly abnormal heart beat more likely, so this cocktail should be avoided.
METHADONE: Methadone and escitalopram can both affect heart rhythm. When methadone is combined with escitalopram, it could lead to a severe abnormal heart rhythm that is very dangerous and can even cause death.
Serious Risk for Harm
DEXTROMETHORPHAN: When high doses of dextromethorphan are combined with escitalopram, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.
FENTANYL: When combined with escitalopram, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.
HYDROMORPHONE: When combined with escitalopram, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.
MEPERIDINE: When combined with escitalopram, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.
MORPHINE: When combined with escitalopram, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.
TRAMADOL: When combined with escitalopram, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.
If you have epilepsy, taking tramadol with escitalopram could make you have seizures more often.