A patient with depression would like to switch her current medicine, an MAOI to an SSRI.
What is the most appropriate way to do this?
Correct Answer A:
Serotonin syndrome is a condition characterized by dangerously high levels of serotonin in your body. It occurs when you take certain combinations of prescription medications that affect serotonin levels.
Signs and symptoms of serotonin syndrome range from restlessness and rapid heartbeat to muscle rigidity and seizures. These go away quickly with treatment, which may include discontinuing use of the medications causing the symptoms along with taking other drugs such as muscle relaxants and serotonin-production blocking agents. If not treated quickly, serotonin syndrome can become life-threatening.
Serotonin syndrome generally occurs when you take multiple drugs that affect serotonin levels in your body. In particular, taking a selective serotonin reuptake inhibitor (SSRI) along with triptans, a class of migraine medications, may cause the condition, potentially raising serotonin to dangerous levels.
However, serotonin syndrome can also occur when you start a single new drug that affects serotonin levels or when you take an increased dose of such a drug that you've previously used.
Therefore it is recommended that when changing from an MAOI to an SSRI, a two week gap should be allowed before starting the SSRI.
A 32-year-old female with a history of depression presents with restlessness, nausea and unstable vital signs. She was recently switched from citalopram to phenelzine. On examination her blood pressure is 140/90 mmHg and she is tachycardic and tachypneic. Her neurological examination is normal aside from hyperreflexia and myoclonus.
What is the most likely diagnosis?
Correct Answer B:
The most common severe adverse effect associated with SSRIs is the development of serotonin syndrome. This syndrome was first described in patients treated with MAOIs who were given other drugs that enhance serotonergic activity. However, ingestion of an MAOI is not required for this syndrome to develop, and its development is unpredictable.
Drug interactions resulting in serotonin syndrome can occur while switching serotonergic pharmacologic agents when an insufficient time lag occurs before initiating the alternative therapy. Residual pharmacologic effect, receptor downregulation or upregulation, and the presence of active metabolites may be causative in these circumstances.
Symptoms of serotonin syndrome include altered mental status, agitation, myoclonus, hyperreflexia, diaphoresis, tremor, diarrhea, incoordination, muscle rigidity, and hyperthermia. The clinical manifestations of serotonin syndrome are diverse, and minor manifestations are common after initiation of SSRI and atypical antidepressant therapy.
Differential Diagnosis of the Serotonin Syndrome from the Neuroleptic Malignant Syndrome: In addition to the associated medications, the time courses of the two syndromes are substantially different. Signs and symptoms of the serotonin syndrome develop within minutes to hours after exposure to the offending agents, whereas NMS typically develops days to weeks after daily exposure to the drug in question. In addition, after symptoms develop and offending drugs are discontinued, NMS can last for as long as 2 weeks, whereas the serotonin syndrome usually resolves quickly, coinciding with the offending drug's pharmacokinetic metabolism. A review of the literature indicates that patients presenting with serotonin syndrome were more likely to exhibit agitation, hyperactivity, clonus and myoclonus, ocular oscillations, shivering, tremors, and hyperreflexia, whereas patients presenting with NMS were more likely to exhibit bradykinesia and lead pipe rigidity.
Which one of the following is contraindicated in a patient taking an SSRI?
Correct Answer D:
Combining serotonergic medications such as SSRIs and MAO inhibitors can lead to the serotonin syndrome, a potentially fatal metabolic reaction. When switching from an SSRI to an MAO inhibitor, a washout period of five half lives of the SSRI is recommended.
A 34-year-old female presents to the emergency department with a severe migraine headache unresponsive to tramadol (Ultram) and sumatriptan (Imitrex) at home. She takes fluoxetine (Prozac) for depression. Soon after being given an injection of meperidine (Demerol), she develops agitation, diaphoresis, tremor, diarrhea, fever and incoordination.
The most likely cause of the patient’s symptoms is:
Correct Answer A: Physicians who prescribe SSRIs such as fluoxetine should be aware of potential drug interactions. Several of the SSRIs may increase the effects of warfarin and raise tricyclic antidepressant levels. Combination of an SSRI with a drug that increases serotonin concentrations may induce the potentially life-threatening serotonin syndrome, with mental status changes, agitation, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, incoordination, and fever.
These drugs include monoamine oxidase inhibitors, tramadol, sibutramine, meperidine, sumatriptan, lithium, St. John’s wort, ginkgo biloba, and atypical antipsychotic agents.
A 22 year old male presents to the emergency department after taking an overdose of fluoxetine (Prozac). His symptoms include fever, tremor, diarrhea, shivering, and sweats. On examination the patient has a temperature of 38.3˚C (100.9˚F) is diaphoretic, and is hyperreflexic with Inducible clonus.
Which one of the following is recommended for treatment of this syndrome?
Correct Answer E:
There are many serotonergic agents that can cause serotonin syndrome, including SSRIs. The severity of the symptoms varies, and therapy should be adjusted accordingly. Mild cases, with hyperreflexia and tremor but no fever, can usually be managed with supportive care, discontinuation of the precipitating drugs, and benzodiazepines. Moderately ill patients should have all cardiorespiratory and thermal abnormalities aggressively corrected, and may benefit from a 5 HT2A antagonist such as cyproheptadine. Hyperthermic patients (temperature >41.1˚C) are severely ill and should receive all of these treatments, as well as immediate sedation, neuromuscular paralysis, and orotracheal intubation.
>Propranolol, a non-selective beta blocker with a long duration of action, may cause hypotension and shock in patients with autonomic instability. Furthermore, propranolol can eliminate tachycardia, which can be used to determine the duration and effectiveness of therapy.
>Bromocriptine and Dantrolene are not useful therapies; case reports citing their use probably involved a misdiagnosis of another condition as the serotonin syndrome. Bromocriptine has actually been implicated in the development of the serotonin syndrome, as has valproate.
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