Procarbazine and antidepressants: a retrospective review of the risk of serotonin toxicity

Psychooncology. 2014 Jan;23(1):108-13. doi: 10.1002/pon.3378. Epub 2013 Aug 29.


Background: Procarbazine is an anticancer agent that also inhibits monoamine oxidase, an enzyme responsible for the metabolism of various catecholamines, including serotonin.

Methods: A retrospective chart review of lymphoma patients who were treated with both procarbazine and an antidepressant, as well as procarbazine alone, was performed to determine if signs and symptoms of serotonin toxicity were present.

Results: A total of 65 patients received procarbazine between 2004 and 2010 and were eligible to be included in the study. Twenty-six of these patients received an antidepressant in combination with procarbazine, with selective serotonin reuptake inhibitors being the most common type of antidepressant. No patients in the study were diagnosed with serotonin toxicity, nor did any meet Hunter's diagnostic criteria for serotonin toxicity. Diarrhea, tremor, and shivering were the symptoms from Sternbach's criteria that were further analyzed, with diarrhea occurring 8.54% of the time, tremor occurring 5.53% of the time, and shivering occurring 2.51% of the time in patients who received an antidepressant with their procarbazine. Despite these symptoms, the diagnosis of serotonin toxicity according to Sternbach's criteria was determined to be unlikely.

Conclusions: In this small sample of patients treated with procarbazine plus an antidepressant (most typically SSRIs), there were no reports of serotonin toxicity, nor did any patients demonstrate symptoms consistent with serotonin toxicity. The authors urge clinicians to ensure depression is adequately managed in cancer patients who are undergoing procarbazine therapy, starting with typical first-line antidepressant agents.

Keywords: antidepressant; cancer; depression; oncology; procarbazine; serotonin toxicity.

MeSH terms

  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Drug Interactions
  • Female
  • Humans
  • Lymphoma / drug therapy
  • Male
  • Middle Aged
  • Procarbazine / adverse effects*
  • Procarbazine / therapeutic use
  • Retrospective Studies
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin / toxicity*


  • Antidepressive Agents
  • Antineoplastic Agents
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Procarbazine