From the Guidelines
Tricyclic antidepressants (TCAs) are indicated for the treatment of neuropathic pain, particularly when other treatments have been ineffective, as well as for certain cases of depression, anxiety disorders, and insomnia. The use of TCAs for neuropathic pain is supported by studies such as 1, which recommends secondary-amine TCAs (nortriptyline, desipramine) as first-line treatments for neuropathic pain. Some key points to consider when prescribing TCAs include:
- Starting with low doses (e.g., 25-50 mg/day) and gradually increasing to an effective dose, which can range from 75-300 mg/day depending on the specific medication and patient response.
- Using caution in patients with heart conditions, glaucoma, or urinary retention, and contraindicating in patients who have recently used MAO inhibitors.
- Monitoring patients closely, especially during the initial weeks of treatment, due to potential side effects like dry mouth, constipation, and drowsiness.
- Being aware of the potential for cardiac toxicity, and limiting dosages to less than 100 mg/d when possible, as well as obtaining a screening electrocardiogram for patients older than 40 years, as recommended by the NeuPSIG guidelines 1. TCAs work by increasing the levels of neurotransmitters (serotonin and norepinephrine) in the brain, which helps regulate mood and pain perception. Their effectiveness in treating depression and certain pain conditions is well-established, though they are often not first-line treatments due to their side effect profile and potential for toxicity in overdose, as noted in studies such as 1 and 1. In particular, the most recent study 1 found that TCAs were associated with global symptom relief and abdominal pain relief in patients with irritable bowel syndrome, although the quality of evidence was rated as low due to indirectness, risk of bias, and imprecision. Overall, TCAs can be a useful treatment option for certain patients, but their use should be carefully considered and monitored.
From the FDA Drug Label
The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD.
Indications for Tricyclic Antidepressants (TCAs):
- Major Depressive Disorder (MDD): TCAs, such as imipramine and nortriptyline, are indicated for the treatment of MDD.
- Other psychiatric disorders: TCAs may be used to treat other psychiatric disorders, including obsessive-compulsive disorder (OCD).
Key considerations:
- Patients should be monitored for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of treatment.
- Screening for bipolar disorder should be performed before initiating treatment with a TCA.
- TCAs are not approved for use in treating bipolar depression. 2 3
From the Research
Indications for Tricyclic Antidepressants (TCAs)
Tricyclic antidepressants (TCAs) are indicated for various conditions, including:
- Depression, particularly severe depression 4, 5
- Neuropathic pain 6
- Headache and migraine 6
- Gastrointestinal syndromes 6
- Fibromyalgia 6
- Pelvic pain 6
- Insomnia 6
- Psychiatric conditions other than depression 6
Specific Conditions
TCAs may be more efficacious for:
- Severe depression, including melancholic or endogenous depression 4, 5
- Treatment-resistant depression, where other antidepressants have failed
Considerations
When prescribing TCAs, considerations include:
- Potential for serious adverse events, such as increased risk of suicidal thoughts and behaviors 7
- Risk of overdose, which can be lethal 4, 5
- Importance of therapeutic drug monitoring and pharmacogenetics to optimize treatment efficacy and tolerability 8
- Need for comprehensive clinical care and precautions to minimize risk of suicide in patients with suicidal tendencies 4