Issues for Surgery
Risk of withdrawal symptoms if omitted (see Further Information).
Possible loss of symptom control if omitted.
Risk of serotonin syndrome if continued (see Interaction(s) with Common Anaesthetic Agents and Interaction(s) with other Common Medicines used in the Perioperative Period).
Risk of bleeding if continued (see Further Information).
Risk of QT-interval prolongation if venlafaxine continued (see Interaction(s) with other Common Medicines used in the Perioperative Period).
Advice in the Perioperative period
Elective and Emergency Surgery
Continue – check sodium levels pre-operatively (see Further Information).
For patients taking duloxetine who may decide to quit smoking during the perioperative period see Further Information.
Monitor electrolytes, particularly sodium, if risk factors for hyponatraemia (see Further Information).
If a long Nil by Mouth (NBM) period is anticipated, or if there are concerns with enteral absorption, advice on alternative preparations / routes should be sought from a Psychiatrist.
Interaction(s) with Common Anaesthetic Agents
Central Nervous System (CNS) Excitation (Serotonin Syndrome)
Some opioids act as weak serotonin reuptake inhibitors (SRIs) and can precipitate serotonin syndrome in conjunction with other serotonergic medication. Symptoms of serotonin syndrome have been reported in patients taking venlafaxine with tramadol or methadone; however, symptoms of serotonin syndrome may occur if SNRIs are given concomitantly with any of the following1, 2:
Patients should be monitored closely and the possibility of serotonin toxicity considered if patients experience altered mental state, autonomic dysfunction or neuromuscular adverse effects with concomitant treatment1, 2.
The manufacturers of duloxetine and venlafaxine advise caution with concomitant administration of other centrally acting medications (e.g. benzodiazepines, opioids or sedating antihistamines3, 4, 5).
QT-Interval Prolongation (see also Interaction(s) with other Common Medicines used in the Perioperative Period)
Anaesthetic agents that may be used in the perioperative period that are known to, or predicted to, prolong the QT-interval include1, 2: -
*monitor ECG if concurrent use unavoidable; if risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia) use greater caution
**monitor ECG with concurrent use if risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia).
Interaction(s) with other Common Medicines used in the Perioperative Period
CNS Excitation (Serotonin Syndrome)
Methylthioninium Chloride (Methylene Blue)
Monitor patients for symptoms of serotonin syndrome such as fever, tremors, diarrhoea, and agitation. Concurrent treatment should be stopped if serotonin syndrome occurs1.
CNS Depression (see Interaction(s) with Common Anaesthetic Agents)
Venlafaxine, but not duloxetine, is known to cause QT-interval prolongation1, 2, 3, 4, 5. Co-administration of venlafaxine with other medicines known to prolong the QT-interval must be based on a careful assessment of the potential risks and benefits for each patient since the risk of torsade de pointes may increase 2.
Medicines that may be used in the perioperative period that are known to prolong or predicted to prolong the QT-interval include1, 2: -
*monitor ECG with concurrent use if risk factors for QT-interval prolongation also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia)
Increased Risk of Bleeding (see also Further Information)
Concomitant use of SNRIs with other medications that can increase the risk of bleeding e.g. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) or Low Molecular Weight Heparins (LMWHs) may have an additive effect1. 3, 4. 5. If the combination of SNRI and NSAID cannot be avoided, gastroprotection with a H2-receptor antagonist or proton pump inhibitor should be considered for the duration of concomitant use, particularly in elderly patients (who seem at greater risk of SNRI-associated bleeding) or patients with a history of gastrointestinal bleeding)2.
Increased Risk of Hyponatraemia (see also Further Information)
Concomitant use of SNRIs with NSAIDS may increase the risk of hyponatraemia1.
Abruptly stopping or interrupting treatment with SNRIs is not recommended; venlafaxine is associated with a higher risk of withdrawal effects compared with other antidepressants1. Common withdrawal symptoms include nausea, vomiting, headache, anxiety, dizziness, paraesthesia, sleep disturbances, tremor and sweating1, 3, 4, 5. Generally symptoms are mild or moderate and last a few weeks; however, in some cases withdrawal symptoms can be severe and prolonged. Withdrawal reactions usually occur within a few days of stopping an SNRI. The risk of withdrawal is increased if SNRIs are stopped suddenly after regular administration for more than 8 weeks4, 5.
Serotonin released from platelets potentiates platelet aggregation. SNRIs can block platelets reuptake of serotonin from the bloodstream leading to serotonin depletion, impairment of haemostatic function and an increased risk of bleeding. There are reports of bleeding abnormalities (gastrointestinal bleeding, ecchymoses, epistaxis, haematomas and purpura) in patients receiving SNRIs3, 4, 5. This risk is further increased with concomitant use of other medications known to affect platelet function (see Interaction(s) with other Common Medicines used in the Perioperative Period). Venlafaxine may have similar effects on surgical and post-operative bleeding as SSRIs, but duloxetine may not affect bleeding risk7 (see Selective Serotonin Reuptake Inhibitors monograph).
Hyponatraemia, likely due to inappropriate secretion of antidiuretic hormone has been associated with SNRIs3, 4, 5. Caution is required in patients at increased risk of hyponatraemia, such as elderly, or volume depleted/dehydrated patients or patients treated with diuretics or NSAIDs3, 4, 5.
Quitting smoking pre-operatively improves surgical outcomes through reducing risk of post-operative complications8. Tobacco is known to induce CYP1A2 resulting in reduced duloxetine plasma concentrations in smokers2, 4, 5. If a patient taking duloxetine decides to quit smoking during the perioperative period, they should be advised to report any increase in side effects to the prescriber as dosage adjustments may be necessary.