Amitriptyline, Clomipramine, Dosulepin, Doxepin, Imipramine, Lofepramine, Nortriptyline, Trimipramine
Issues for Surgery
For depression - risk of withdrawal symptoms if omitted (see Further Information).
Lower doses (used for neuropathic pain, abdominal pain, migraine prophylaxis) - risk of loss of symptom control if omitted.
Risk of hypotension and cardiac arrhythmias if continued (see Interaction(s) with Common Anaesthetic Agents).
Potentiated effects of vasopressors if continued (see Interaction(s) with Common Anaesthetic Agents).
For clomipramine: risk of QT-interval prolongation if continued (see Interaction(s) with Common Anaesthetic Agents and Interaction(s) with other Common Medicines used in the Perioperative Period).
Advice in the Perioperative period
Elective and Emergency Surgery
Due to increased risk of arrhythmias and interactions with vasopressor drugs inform anaesthetist on the day of surgery if patient is taking a TCA 1, 2, 3, 4, 5, 6, 7, 8 (see Interaction(s) with Common Anaesthetic Agents).
Patients Prescribed High Dose TCAs for Depression
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
TCAs may increase risk of cardiac arrhythmias and hypotension during general anaesthesia1, 2, 3, 4, 5, 6, 7, 8, 9. There have been case reports of prolonged cardiac arrhythmias with concomitant use of nortriptyline with halothane and imipramine with halothane and pancuronium; however, it is thought to be a class effect9.
TCAs are expected to prolong the duration of barbiturate anaesthesia; however, as the dose should be titrated to response this should be managed by standard anaesthetic practice9.
Whilst the manufacturers of some TCAs recommend concomitant administration of sympathomimetic agents is avoided4, 6, 7, 8, this is not thought to be necessary provided much reduced doses are used and titrated carefully against clinical response9.
Central Nervous System (CNS) depression
Concomitant use of TCAs with anaesthetic agents, benzodiazepines or opioids may have an additive effect on CNS depression3, 5, 6.
CNS Excitation (Serotonin Syndrome)
Clomipramine and imipramine are predicted to have serotonergic effects9; amitriptyline has also been associated with serotonin syndrome11, 12. Some opioids act as weak serotonin reuptake inhibitors (SRIs) and can precipitate serotonin syndrome in conjunction with other serotonergic medication. Symptoms of serotonin syndrome may occur if TCAs with serotonergic activity are given concomitantly with1, 9, 12: -
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.
QT-Interval Prolongation (see also under 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, 9: -
*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)
** 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
Interaction(s) with other Common Medicines used in the Perioperative Period
CNS Depression (see Interaction(s) with Common Anaesthetic Agents above)
TCAs may cause QT-interval prolongation1, 2, 3, 5, 6, 8. This is most notable with clomipramine; the risk with other TCAs is largely in overdose9. Co-administration 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.
Medicines that may be used in the perioperative period that are known to prolong the QT-interval include9: -
*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 Hyponatraemia (see also Further Information)
Concomitant use of SSRIs with NSAIDS may increase the risk of hyponatraemia1.
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.
Increased Risk of Bleeding (see also Further Information)
Concomitant use of clomipramine with other medications that can increase the risk of bleeding e.g. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) may have an additive effect3.
Abruptly stopping or interrupting treatment with TCAs is not recommended. The risk of withdrawal is increased if TCAs are stopped suddenly after regular administration for more than 8 weeks1. Withdrawal effects may occur within 5 days of stopping treatment, they are usually mild and self-limiting, but in some cases may be severe1. Withdrawal symptoms include malaise, chills, headache, increased perspiration, anxiety, agitation, sleep disturbance, hypomania, mania and cardiac arrhythmias10.
Hyponatraemia, possibly because of inappropriate secretion of antidiuretic hormone has been associated with antidepressants. Whilst this is not common with TCAs caution is required in patients at increased risk of hyponatraemia, such as elderly, or volume depleted / dehydrated patients or patients treated with diuretics6, 12.
Clomipramine has significant serotonergic activity and therefore may increase the risk of bleeding3 (see Selective Serotonin Reuptake Inhibitors monograph).