What are the adverse reactions to Trazodone (triazolopyridine antidepressant)?

From the Guidelines

Trazodone can cause several adverse reactions, including daytime sedation, dizziness, priapism, and cardiac effects, which can significantly impact a patient's quality of life and increase the risk of morbidity and mortality. According to a retrospective cohort study published in the Journal of Clinical Sleep Medicine in 2018 1, 60% of patients who continued trazodone experienced some side effect, particularly daytime sedation or dizziness. The study also reported that 14 participants discontinued treatment due to intolerable side effects, including priapism, daytime sedation, more vivid nightmares, dry mouth/sinuses, muscle pain, and severe agitation.

Some of the common adverse reactions to trazodone include:

• Daytime sedation or dizziness
• Priapism (prolonged, painful erection) in men
• Cardiac effects like arrhythmias or QT prolongation
• Psychiatric effects, such as increased anxiety, agitation, or worsening depression with suicidal thoughts
• Serotonin syndrome, a rare but serious reaction when trazodone is combined with other serotonergic medications

A clinical practice guideline published in the Journal of Clinical Sleep Medicine in 2015 1 also highlights the risks associated with trazodone, including orthostatic hypotension, cardiac arrhythmias, and increased risk of falls, particularly in elderly patients. The guideline notes that trazodone is widely used off-label as a hypnotic, despite the lack of evidence-based data to support its efficacy with older adults.

Another study published in the Annals of Internal Medicine in 2007 1 found that trazodone was no more effective than placebo for pain relief in patients with chronic low back pain. The study also reported that antidepressants, including trazodone, were associated with a higher risk of adverse events, such as drowsiness, dry mouth, dizziness, and constipation.

Overall, the use of trazodone should be carefully considered, taking into account the potential risks and benefits, and patients should be closely monitored for adverse reactions.

From the FDA Drug Label

1. Adverse Reactions The following serious adverse reactions are described elsewhere in the labeling: Suicidal Thoughts and Behavior in Children, Adolescents and Young Adults [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)] Serotonin Syndrome [see WARNINGS AND PRECAUTIONS (5.2)] Cardiac Arrythmias [see WARNINGS AND PRECAUTIONS (5. 3)] Orthostatic Hypotension and Syncope [see WARNINGS AND PRECAUTIONS (5.4)] Increased Risk of Bleeding [see WARNINGS AND PRECAUTIONS (5.5)] Priapism [see WARNINGS AND PRECAUTIONS (5.6)] Activation of Mania or Hypomania [see WARNINGS AND PRECAUTIONS (5.7)] Discontinuation Syndrome [see WARNINGS AND PRECAUTIONS (5.8)] Potential for Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS (5. 9)] Angle-Closure Glaucoma [see WARNINGS AND PRECAUTIONS (5.10)] Hyponatremia [see WARNINGS AND PRECAUTIONS (5.11)]
2. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice Diarrhea01%5%1% Nausea/Vomiting10%1%13%10% Musculoskeletal Aches/Pains6%3%5%3% Neurological Incoordination5%02%* Tremors3%1%5%4% Other Eyes Red/Tired/Itching3%000 Head Full-Heavy3%000 Malaise3%000 Nasal/Sinus Congestion3%06%3% Weight Gain1%05%2% Weight Loss*3%6%3%
3. 2 Post marketing Experience The following adverse reactions have been identified during post-approval use of Trazodone Hydrochloride Tablets Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure: Blood and lymphatic system disorders: hemolytic anemia, leukocytosis Cardiac disorders: cardio spasm, congestive heart failure, conduction block, orthostatic hypotension and syncope, palpitations, bradycardia, atrial fibrillation, myocardial infarction, cardiac arrest, arrhythmia, ventricular ectopic activity, including ventricular tachycardia and QT prolongation.

The adverse reactions to trazodone include:

• Serious adverse reactions:
  • Suicidal thoughts and behavior
  • Serotonin syndrome
  • Cardiac arrhythmias
  • Orthostatic hypotension and syncope
  • Increased risk of bleeding
  • Priapism
  • Activation of mania or hypomania
  • Discontinuation syndrome
  • Potential for cognitive and motor impairment
  • Angle-closure glaucoma
  • Hyponatremia
• Common adverse reactions:
  • Diarrhea
  • Nausea/vomiting
  • Musculoskeletal aches/pains
  • Neurological incoordination
  • Tremors
  • Eyes red/tired/itching
  • Head full-heavy
  • Malaise
  • Nasal/sinus congestion
  • Weight gain
  • Weight loss
• Post-marketing experience:
  • Blood and lymphatic system disorders (hemolytic anemia, leukocytosis)
  • Cardiac disorders (cardio spasm, congestive heart failure, conduction block, orthostatic hypotension and syncope, palpitations, bradycardia, atrial fibrillation, myocardial infarction, cardiac arrest, arrhythmia, ventricular ectopic activity, including ventricular tachycardia and QT prolongation) 2

From the Research

Adverse Reactions to Trazodone

There are no research papers provided to directly answer the question about adverse reactions to trazodone. However, the studies provided discuss the adverse reactions of selective serotonin reuptake inhibitors (SSRIs), which may be relevant in a broader context.

Adverse Reactions to SSRIs

• The most common adverse reactions to SSRIs include:
  • Gastrointestinal disturbances (especially nausea) 3, 4
  • Neuropsychiatric reactions (particularly headache and tremor) 3
  • Sedation, insomnia, activation, weight gain, impaired memory, excessive perspiration, paresthesia, and sexual dysfunction 4
• Specific SSRIs may have unique adverse reaction profiles:
  • Fluoxetine: more agitation, weight loss, and dermatological reactions 3
  • Fluvoxamine: higher incidence of gastrointestinal symptoms, malaise, sedation, and tremor 3
  • Paroxetine: higher incidence of sedation, tremor, sweating, sexual dysfunction, and discontinuation reactions 3
• It is essential to note that trazodone is not an SSRI, but rather a serotonin antagonist and reuptake inhibitor (SARI), and its adverse reaction profile may differ from that of SSRIs.

Importance of Further Research

Further research is necessary to determine the adverse reaction profile of trazodone specifically, as the provided studies focus on SSRIs.