What are the most dangerous side effects of Doxepin (tricyclic antidepressant)?

Most Dangerous Side Effects of Doxepin

The most dangerous side effects of doxepin are cardiac dysrhythmias, severe hypotension, seizures, and CNS depression (including coma), which can be life-threatening, particularly in overdose situations. 1

Cardiovascular Effects

• Cardiac toxicity is a major concern with doxepin, manifesting as:

  • QRS prolongation and QT interval changes on ECG 1
  • Tachyarrhythmias and bradyarrhythmias 2
  • Hypotension, particularly orthostatic hypotension 3
  • Increased risk of cardiac events in patients with preexisting cardiac disease 3, 4

• Despite common belief, doxepin has not been proven to be safer for the heart than other tricyclic antidepressants, with studies showing comparable cardiovascular effects 3, 4

Neurological Effects

• Seizures are a significant risk, especially in overdose situations 1
• CNS depression that can progress to coma 1
• Other neurological effects include:
  • Confusion and disorientation 1
  • Extrapyramidal symptoms 1
  • Ataxia and tremor 1
  • Hallucinations 1

Hematological Effects

• Bone marrow depression can occur, manifesting as:
  • Agranulocytosis 1
  • Leukopenia 1
  • Thrombocytopenia 1
  • Purpura 1

Overdose Risk

• Overdose with doxepin can be fatal 1
• Multiple drug ingestion (including alcohol) is common in deliberate overdose cases 1
• Critical manifestations develop rapidly after overdose, requiring immediate hospitalization 1
• Cardiac monitoring is essential in overdose cases, with observation for at least six hours 1

Drug Interactions

• Potentially dangerous interactions with:
  • MAO inhibitors - can cause serious side effects and even death; MAO inhibitors should be discontinued at least two weeks prior to starting doxepin 1
  • Alcohol - increases risk of CNS depression and overdose danger 1
  • Benzodiazepines - risk of excessive sedation 1
  • CYP2D6 inhibitors (including SSRIs) - can increase doxepin plasma concentrations 1

Special Populations at Risk

• Elderly patients are at higher risk for:

  • Confusion and oversedation 1
  • Falls due to orthostatic hypotension 1
  • Cardiac complications due to higher prevalence of underlying cardiac disease 1

• Patients with cardiac disease:

  • Higher risk of conduction abnormalities and arrhythmias 3, 4
  • One study found 16% of patients with preexisting cardiac conditions discontinued doxepin due to cardiovascular side effects 3

Suicide Risk

• Increased risk of suicide, especially during early treatment phase 1
• The drug's toxicity in overdose makes it particularly dangerous for patients with suicidal ideation 1, 5

Management of Toxicity

• For overdose situations:

  • Immediate cardiac monitoring and ECG 1
  • Airway protection 1
  • Gastric decontamination with activated charcoal 1
  • Sodium bicarbonate for QRS prolongation 1
  • Treatment of seizures with benzodiazepines 1
  • Close monitoring for at least 6 hours, with extended monitoring if signs of toxicity occur 1

• For patients on therapeutic doses experiencing side effects:

  • Dose reduction may help manage anticholinergic effects 1
  • Gradual discontinuation to avoid withdrawal symptoms 1

Doxepin should be used with extreme caution in patients with cardiac disease, seizure disorders, or suicidal ideation, and the lowest effective dose should be prescribed 1.