Tricyclic Antidepressants Should Be Avoided in Suicidal Patients
Tricyclic antidepressants (TCAs) should not be prescribed to patients with a history of suicide due to their highly lethal potential in overdose. 1
Why TCAs Are Dangerous
TCAs have a fatal toxicity index 5 to 8 times higher than newer antidepressants and are the most common cause of death from prescription drug overdose. 2, 3 The American Academy of Child and Adolescent Psychiatry explicitly states that "tricyclics should not be prescribed, because of their greater lethal potential" in suicidal patients. 1
Specific High-Risk TCAs
Within the TCA class, certain agents are particularly lethal:
- Amoxapine has the highest hazard index (292 per 1000 ingestions), making it the most dangerous antidepressant in overdose 4
- Maprotiline (hazard index 211) and desipramine (hazard index 187) are also extremely toxic 4
- Dosulepin and doxepin are 2.6-2.7 times more toxic than amitriptyline, which itself is highly lethal 5
Mechanism of Lethality
TCAs cause death through:
- Lethal cardiac arrhythmias including QRS prolongation beyond 100 milliseconds 1, 3
- Rapid clinical deterioration where patients may appear stable initially but "quickly deteriorate and die before your eyes" 6
- Extreme toxicity in children even at very small doses 6
Safer Alternatives: SSRIs
SSRIs are the preferred antidepressant class for patients with suicide risk because they have dramatically lower lethal potential in overdose. 1, 7
SSRI Safety Profile
- SSRIs have a hazard index of 0.5 (95% CI 0.4-0.7) compared to TCAs at 13.8 (95% CI 13.0-14.7) 5
- All SSRIs had low hazard indices in comparative toxicity studies 4
- The American Academy of Child and Adolescent Psychiatry notes that "in contrast to the highly lethal potential of tricyclic antidepressants when taken in overdoses, SSRIs have low lethal potential" 1
Important SSRI Caveat
Within the SSRI class, citalopram has higher case fatality (1.1) than other SSRIs (0.3), though still far safer than TCAs. 5 Consider fluoxetine, sertraline, or paroxetine as first-line options for maximum safety in overdose.
Other Antidepressants to Avoid
Beyond TCAs, several other agents carry elevated overdose risk:
- MAO inhibitors fall in the more severe half of antidepressants by hazard index 4
- Venlafaxine (SNRI) has a case fatality rate ratio of 2.5, intermediate between TCAs and SSRIs 5
- Bupropion is in the more severe half of antidepressants for overdose toxicity 4
Critical Monitoring Requirements
When SSRIs are prescribed to suicidal patients:
- Monitor for akathisia, which has been associated with SSRI-induced suicidal ideation, particularly with fluoxetine 1, 7
- Systematically inquire about suicidal ideation before and after treatment initiation, especially during the first few weeks 1, 7
- Ensure third-party medication monitoring by family members who can regulate dosage and report mood changes 1, 7
- Watch for behavioral activation/agitation in the first month, which may require dose reduction 1
Additional Medications to Avoid
Benzodiazepines and phenobarbital should also be avoided in suicidal patients as they may reduce self-control and have disinhibiting effects that can precipitate suicide attempts. 1, 7 Phenobarbital additionally has high lethal potential in overdose. 1