| OBJECTIVE: To report on the possible development of serotonin syndrome in a patient receiving clomipramine after clozapine was withdrawn from the treatment regimen. CASE REPORT: A 44-year-old white man with a 23-year history of undifferentiated schizophrenia and obsessive-compulsive behavior had been treated with clozapine and clomipramine for several years. He tolerated both agents together well, with the exception of experiencing chronic constipation. clomipramine was tapered and reduced to 50 mg over a period of 10 days. A worsening of ritualistic behavior was noted, and the clomipramine dosage was increased to 150 mg/d over 14 days. Simultaneously with the clomipramine dosage increase, clozapine was tapered and stopped ever a period of 19 days. The day after clozapine was stopped, while he was still receiving clomipramine 150 mg/d, he began behaving oddly, started sweating profusely, shivering, and became tremulous, agitated, and confused. He was diagnosed with possible serotonin syndrome; his symptoms resolved after clomipramine was stopped but before clozapine was restarted eight days later. DISCUSSION: There are similarities in symptoms between serotonin syndrome and clozapine withdrawal. This article discusses the reasons why this case may represent serotonin syndrome rather than clozapine withdrawal and the possible pharmacologic mechanisms involved. CONCLUSIONS: Clinicians should be aware that removing a serotonin-2a (S-HT2a) antagonist 1mm a treatment regimen including an agent that increases serotonin in the synaptic cleft may worsen clozapine withdrawal or potentially result in serious adverse drug reactions, such as serotonin syndrome. ( info) |
12/67. Adverse reactions to St John's Wort. OBJECTIVE: To report 2 cases of adverse reactions to St John's wort, a popular herbal treatment for depression. METHOD: We present 2 case histories and review the existing literature regarding St John's wort. RESULTS: St John's wort may cause serotonin syndrome in sensitive patients. In addition, St John's wort may be associated with hair loss. CONCLUSIONS: For clinical reasons, it is important to recognize and report adverse reactions to herbal remedies and to document that these treatments have side effects commensurate with their potent action on brain neurochemistry. ( info) |
| We present a case involving a fatality due to the combined ingestion of two different types of antidepressants. A 41-year-old Caucasian male, with a history of depression and suicide attempts, was found deceased at home. Multiple containers of medication, the MAO-inhibitor moclobemide (Aurorix), the SSRI citalopram (Cipramil), and the benzodiazepine lormetazepam (Noctamid) as active substance, as well as a bottle of whiskey were present at the scene. The autopsy findings were unremarkable, but systematic toxicological analysis (EMIT, radioimmunoassay, high-performance liquid chromatography-diode-array detection [HPLC-DAD], gas chromatography-nitrogen-phosphorus detection, and gas chromatography-mass spectrometry) revealed the following: ethanol (0.23 g/L blood, 0.67 g/L urine), lormetazepam (1.65 microg/mL urine), cotinine (0.63 microg/mL blood, 5.08 microg/mL urine), caffeine (1.20 microg/mL urine), moclobemide (and metabolites), and citalopram (and metabolite). There upon, we developed a new liquid chromatographic separation with optimized DAD, preceded by an automated solid-phase extraction, for the quantitation of the previously mentioned antidepressive drugs. The results obtained for blood and urine, respectively, were as follows: Ro 12-5637 (moclobemide N'-oxide) not detected and 424 microg/mL; Ro 12-8095 (3-keto-moclobemide) 2.26 microg/mL and 49.7 microg/mL; moclobemide 5.62 microg/mL and 204 microg/mL; desmethylcitalopram 0.42 microg/mL and 1.22 microg/mL; and citalopram 4.47 microg/mL and 19.7 microg/mL. The cause of death was attributed to the synergistic toxicity of moclobemide and citalopram, both antidepressants, which, by intentional or accidental combined ingestion, can produce a potentially lethal hyperserotoninergic state. Based on the history of the case and pharmacology of the drugs involved, the forensic pathologists ruled that the cause of death was multiple drug intoxication, resulting in a fatal "serotonin syndrome," and that the manner of death was suicide. ( info) |
| The serotonin syndrome results when serotonergic activity increases to abnormally high levels. It occurs with selective serotonin reuptake inhibitors (SSRIs), opioids, and other serotonergic agents when the serotonin system has been modulated by another serotonergic agent or compromised by illness. Although the symptoms are quite variable, the syndrome is characterized by a triad of altered mental status, neuromuscular abnormalities, and autonomic dysfunction. The authors report the probable occurrence of the serotonin syndrome with serotonin receptor subtype 3 (5-HT(3)) antagonist therapy when used to control nausea associated with chemotherapy in two seriously ill children. The first case involves combined use with mirtazapine and the second with fentanyl. These agents may pose a potential risk when used in such combination in seriously ill patients. ( info) |
15/67. serotonin syndrome in HIV-infected individuals receiving antiretroviral therapy and fluoxetine. OBJECTIVE: To describe HIV-infected individuals taking antidepressants who developed the serotonin syndrome due to drug--drug or drug--food interactions. DESIGN AND SETTING: Case studies carried out at the HIV Outpatient Clinic, Atlanta veterans Affairs Medical Center. PARTICIPANTS AND INTERVENTIONS: HIV-positive patients who were receiving antiretroviral and antidepressant therapies and presented with symptoms consistent with the serotonin syndrome. Their antidepressants were discontinued or the doses reduced in order to resolve the symptoms. RESULTS: Five cases of serotonin syndrome developed after patients who were taking antidepressants ingested P450 inhibitors. CONCLUSIONS: Serotonin syndrome should be suspected in patients on serotonergic medications who present with mental status change, autonomic dysfunction, and neuromuscular abnormalities. Suspicion should be heightened in those who are ingesting substances known to inhibit P450 enzymes, such as protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and grapefruit juice. ( info) |
| OBJECTIVE: To report a psychiatric patient who developed serotonin syndrome after a medication overdose and whose marked mydriasis was quickly reversed by administration of cyproheptadine. This phenomenon was confirmed when other cases of serotonin syndrome were studied. METHOD: In the index patient as well as in three subsequent cases of serotonin syndrome, pupil diameter, muscle tone, mental status, and vital signs were monitored before and after a test dose of cyproheptadine as medications were discontinued and antiserotonergic therapy begun. RESULTS: In each patient, cyproheptadine produced rapid reversal of mydriasis within one hour of the initial dose. Other signs of serotonin syndrome remitted more slowly. As the signs and symptoms of serotonin syndrome remitted and pupils returned to normal size and reactiveness, cyproheptadine therapy seemed to produce mydriasis after each dose. Cessation of therapy after this point did not result in recurrence of symptoms. One patient developed serotonin syndrome twice. Two patients developed serotonin syndrome during treatment with medications that are partial serotonin antagonists (mirtazapine and nefazodone). CONCLUSIONS: Rapid reversal of mydriasis in serotonin syndrome by cyproheptadine may serve as a specific suppressive test for the condition, and possibly may add to our understanding of the syndrome. Treatment with cyproheptadine is not thought to abbreviate the illness, but provides symptomatic relief while symptoms persist. ( info) |
| OBJECTIVE: To document a case of serotonin syndrome associated with the combined use of fluvoxamine and mirtazapine, and to discuss the pharmacodynamic and pharmacokinetic interactions that were the likely causes of this potentially serious adverse drug reaction (ADR). CASE SUMMARY: A 26-year-old white woman with a 12-year history of anorexia nervosa was being treated with fluvoxamine. After mirtazapine was added to her therapy, she developed tremors,restlessness, twitching, flushing, diaphoresis, and nausea,symptoms that are consistent with serotonin syndrome. DISCUSSION: The possible causes of this ADR are discussed, including the effects of fluvoxamine and mirtazapine alone, the possible pharmacodynamic and pharmacokinetic interactions of these two drugs, and the patients underlying anorexia nervosa. CONCLUSIONS: An increasing number of drugs that affect serotonin are available and are indicated for various disorders. Since there is a significant likelihood of these agents being prescribed concomitantly, clinicians must be aware of possible interactions that could lead to serotonin syndrome. ( info) |
18/67. An unusual presentation of sertraline and trazodone overdose. OBJECTIVE: To report an unusual and life-threatening presentation of an overdose of sertraline and trazodone. CASE SUMMARY: A patient with a history of depression ingested sertraline 6,000 mg and trazodone 1,300 mg in a suicide attempt. Twenty-four hours after antidepressant administration, the patient presented with symptoms of selective serotonin-reuptake inhibitor (SSRI) overdose and serotonin syndrome, and later developed an enlarged tongue consistent with angioedema. A compromised airway resulted and endotracheal intubation was necessary. After intubation, the symptoms subsided and the patient recovered. DISCUSSION: Although SSRIs and trazodone are generally considered to be relatively safe in single-agent overdose, serious delayed reactions can occur, especially if several agents are involved. In this case the patient initially presented with symptoms typical of an SSRI overdose that did not appear to be exceptionally dangerous. Over time, symptoms consistent with angioedema appeared that necessitated intubation. Although previous reports of angioedema have been reported with SSRIs, this is the first report, to our knowledge, of a presentation this severe. CONCLUSIONS: This case demonstrates that overdose with the newer antidepressants can result in unusual and delayed presentations and must be treated with caution. ( info) |
19/67. serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction. OBJECTIVE: To report 2 cases of serotonin syndrome with serious extrapyramidal movement disorders occurring when metoclopramide was coadministered with sertraline or venlafaxine. CASE SUMMARY: A 72-year-old white woman was treated with sertraline for depression for 18 months and was then admitted to the hospital with a fractured tibia. She was administered metoclopramide because of nausea and, within 2 hours, developed agitation, dysarthria, diaphoresis, and a movement disorder. These symptoms recurred following 2 subsequent administrations of metoclopramide. Treatment with diazepam led to resolution of symptoms within 6 hours, and there was no recurrence at 6 weeks' follow-up. A 32-year-old white woman with major depression was treated with venlafaxine for 3 years. She was admitted following a fall and, after being given metoclopramide, developed movement disorder and a period of unresponsiveness. After a second dose of metoclopramide, these symptoms recurred and were associated with confusion, agitation, fever, diaphoresis, tachypnea, tachycardia, and hypertension. She improved with administration of diazepam, but needed repetition of this treatment over the next 16 hours. Symptoms resolved within 2 days, and she continued venlafaxine with no further adverse effects. DISCUSSION: Both cases met Stembach's criteria for serotonin syndrome and had serious extrapyramidal movement disorders. The possible pathophysiologic mechanisms for the adverse reactions include a single-drug effect, a pharmacodynamic interaction, and a pharmacokinetic interaction. We believe that a pharmacodynamic interaction is most likely. CONCLUSIONS: Clinicians should be aware of a risk of serotonin syndrome with serious extrapyramidal reactions in patients receiving sertraline or venlafaxine when metoclopramide is coadministered even in a single, conventional dose. ( info) |
20/67. serotonin syndrome presenting as hypotonic coma and apnea: potentially fatal complications of selective serotonin receptor inhibitor therapy. OBJECTIVE: To describe a patient who developed serotonin syndrome on four separate occasions as a result of monotherapy with two different selective serotonin receptor inhibitors (fluoxetine and cetalopram). DESIGN: Case report. SETTING: Community hospital. patients: Single patient with four episodes of serotonin syndrome. MEASUREMENTS AND MAIN RESULTS: The syndrome was characterized by coma/unresponsiveness (four episodes), dilated pupils (four episodes), salivation (two episodes), dryness of mouth (two episodes), myoclonus like activity of eyelids (four episodes), oculogyric crisis (four episodes), flaccid paralysis of all extremities (four episodes), tremors (two episodes), apnea (two episodes), restlessness (one episode). Recovery occurred within 24 hrs, although muscle pain and weakness persisted for 2 months after stopping fluoxetine. apnea occurred in both episodes associated with fluoxetine therapy. CONCLUSION: apnea and coma may occur in serotonin syndrome. ( info) |