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Venlafaxine- and Trazodone-Induced Serotonin Syndrome

2001; American Psychiatric Association; Volume: 158; Issue: 12 Linguagem: Inglês

10.1176/appi.ajp.158.12.2088

1535-7228

Robert E. McCue, Michel Joseph,

Schizophrenia research and treatment

Back to table of contents Previous article Next article Letter to the EditorFull AccessVenlafaxine- and Trazodone-Induced Serotonin SyndromeROBERT E. McCUE, M.D., and MICHEL JOSEPH, M.D., ROBERT E. McCUE, M.D., and MICHEL JOSEPH, M.D., Brooklyn, N.Y.Published Online:1 Dec 2001https://doi.org/10.1176/appi.ajp.158.12.2088AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Serotonin syndrome results from excessive serotonin stimulation and is characterized by confusion, restlessness, myoclonus, hyperreflexia, diaphoresis, and tremor (1). The original descriptions focused on the interaction between monoamine oxidase inhibitors and serotonergic agents. Serotonin syndrome has subsequently been reported to occur with drug combinations involving selective serotonin reuptake inhibitors (SSRIs) and other serotonergic agents (2, 3). In this case, a patient taking venlafaxine and trazodone developed signs of serotonin syndrome.Mr. A was a 50-year old man with a past history of recurrent depression who was hospitalized for a several-week history of depression characterized by depressed mood, anhedonia, hopelessness, insomnia, and suicidal ideation. He had no psychosis or cognitive impairment. He had a history of opioid dependence since age 19, but his addiction was being treated with methadone. His past medical history was remarkable for his being seropositive for HIV for 10 years (without treatment) and seropositive for hepatitis C for 36 months. The results of laboratory tests at admission were remarkable for mildly elevated hepatic enzyme levels. Two months before admission, Mr. A's CD4 lymphocyte level was 436 cells/μl.Mr. A began taking extended-release venlafaxine; his dose was increased over 7 days to 225 mg/day. He also received 100 mg of trazodone at bedtime for insomnia, 100 mg t.i.d. of docusate sodium for constipation, and 120 mg/day of methadone. Eighteen days after hospitalization, Mr. A developed disorientation, restlessness, myoclonic jerking, gross tremulousness, and diaphoresis. He was afebrile; his other vital signs were unremarkable. Concurrent results of laboratory tests were not significantly different from those at admission, except for a decreased CO2 level of 19.1 mmol/liter, an increase in aspartate aminotransferase level to 95 U/liter, and an increase in creatine kinase level to 2277 U/liter. The latter was subsequent to several intramuscular injections given to manage agitation. A computerized tomography scan of his head revealed moderate cerebral atrophy but no acute pathology. After 36 hours, during which Mr. A's condition deteriorated, all medications were discontinued. He was given intravenous hydration. Within 24 hours his clinical status improved dramatically. He began taking methadone and docusate sodium again; he was given mirtazapine for depression. The remainder of his hospitalization was uneventful.We believe that this was a case of serotonin syndrome that was precipitated by the combination of venlafaxine and trazodone, both of which inhibit the reuptake of serotonin. The clinical features of this episode and their rapid resolution when medication was discontinued support this. Methadone may have been a contributing factor to serotonin syndrome because it increases serotonin synthesis in laboratory animals (4). However, the patient had taken SSRIs in the past while also taking methadone, without ill effects. While venlafaxine and trazodone can be used together in most cases, our patient's chronic medical problems may have made him more vulnerable to effects of the drugs used in combination. Use of this combination requires caution in this population. An agent without serotonergic effects should be considered if a hypnotic is required in addition to treatment with venlafaxine.References1. Sternbach H: The serotonin syndrome. Am J Psychiatry 1991; 148:705-713Link, Google Scholar2. Muly EC, McDonald W, Steffens D, Book S: Serotonin syndrome produced by a combination of fluoxetine and lithium (letter). Am J Psychiatry 1993; 150:1565Link, Google Scholar3. Reeves RR, Bullen JA: Serotonin syndrome produced by paroxetine and low-dose trazodone (letter). Psychosomatics 1995; 36:159-160Crossref, Medline, Google Scholar4. Bowers MB, Kleber HD: Methadone increases mouse brain 5-hydroxyindoleacetic acid (letter). Nature 1971; 229:134-135Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByPsychopharmacological properties and therapeutic profile of the antidepressant venlafaxine10 August 2022 | Psychopharmacology, Vol. 239, No. 9Drug-Induced Hyperthermia ReviewCureus, Vol. 196Forensic Science International, Vol. 251, Vol. 120Psychosomatics, Vol. 55, No. 3Psychiatric Quarterly, Vol. 84, No. 4CNS Drugs, Vol. 26, No. 1Forensic Science, Medicine, and Pathology, Vol. 7, No. 2Forensic Science International, Vol. 198, No. 1-3Use of trazodone as an adjunctive agent in the treatment of canine anxiety disorders: 56 cases (1995–2007)Journal of the American Veterinary Medical Association, Vol. 233, No. 12Adverse Drug Reaction Bulletin, Vol. &NA;, No. 243Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 30, No. 6Psychiatry and Clinical Neurosciences, Vol. 60, No. 1Monoaminergic‐based Pharmacotherapy for Depression29 January 2008Expert Opinion on Drug Safety, Vol. 4, No. 5Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects1 July 2016 | Journal of Psychopharmacology, Vol. 18, No. 4Chest, Vol. 125, No. 5Serotonin Syndrome Induced by Low-Dose Venlafaxine4 December 2016 | Annals of Pharmacotherapy, Vol. 37, No. 2Pharmacoepidemiology and Drug Safety, Vol. 11, No. 4Journal of Head Trauma Rehabilitation, Vol. 17, No. 4Adverse Drug Reaction Bulletin, Vol. &NA;, No. 217Reactions Weekly, Vol. &NA;, No. 894 Volume 158Issue 12 December 2001Pages 2088-2089 Metrics History Published online 1 December 2001 Published in print 1 December 2001