Serotonin syndrome after taking CASE REPORT citalopram BHW Cheng MBBS, MRCP (UK), WWY Mok MBBS, FHKCP (Medicine)
Department of Medicine, Queen Mary Hospital, Pok Fu Lam, Hong Kong
Correspondence to: Dr Benjamin Cheng, Department of Medicine, Queen Mary Hospital, Pok Fu Lam, Hong Kong. E-mail: [email protected]
admission gave a reading of 6.1. When her postural
blood pressure was checked, the systolic reading
Serotonin syndrome is a potentially life-threatening showed 7 to 10 mm Hg drop, so the nifedipine was condition associated with increased serotonergic replaced with amlodipine 2.5 mg daily. activity in the central nervous system. It has been observed in all age groups including newborns She had been diagnosed with anxiety-depression and the elderly.1 It is characterised by a triad of in September 2002 and was given flupentixol (a mental status changes, autonomic hyperactivity typical antipsychotic) 0.5 mg daily, malitracen (a and neuromuscular abnormalities. It is seen with tricyclic antidepressant) 10 mg daily, benzhexol (an therapeutic medication use, inadvertent interactions anti-muscarinic) 2 mg twice a day and lorazepam (a between drugs, as well as intentional self-poisoning.1
benzodiazepine) 2 mg nocte. She developed extra-pyramidal side-effects, including tremors and limb
Citalopram is an antidepressant targeting the rigidity, which contributed to her increased risk of serotonin pathway (a selective serotonin reuptake falling. inhibitor). Indications for citalopram use include treatment of depression, anxiety neurosis, panic After consultation with our psychiatry team, her disorder and obsessive-compulsive disorder. It is psychiatric medications were ceased and switched to well tolerated, with mild side-effects including a dry citalopram 10 mg daily and diazepam 1 mg nocte. mouth, gastrointestinal disturbance and dizziness. It However, she developed a high fever, registering is rarely associated with serotonin syndrome.
a temperature of 40ºC on the second day after starting citalopram. She became very drowsy and
confused. Her blood pressure increased to 180/100 mm Hg, and electrocardiography showed sinus
In November 2008, an 81-year-old Chinese woman tachycardia with a heart rate reaching 130/min. A presented to Queen Mary Hospital after a fall. She neurological examination found no neck stiffness, had hypertension, type-II diabetes and anxiety focal neurological deficits or spontaneous clonus. neurosis managed with regular medical and Nonetheless, she demonstrated limb rigidity and her psychiatric follow-up. She reported experiencing deep tendon reflexes were brisk bilaterally. dizziness, poor postural balance and gait instability, but no loss of consciousness, before her fall. This was The citalopram was stopped immediately and she her second fall in recent years.
was given intravenous fluids. A full septic workup (including blood, urine and sputum cultures) was
Prior to admission, she was taking lisinopril 10 performed, all of which grew nothing. Blood tests mg daily, nifedipine (slow-release) 20 mg twice a day revealed a raised white cell count of 11.7 x109/L for her hypertension, and gliclazide 120 mg twice a (normal range, 4.4-10.1 x109/L), a raised creatine day for her diabetes. Her vital signs were stable on phosphokinase level of 486 U/L (normal range, 40-admission, with a blood pressure of 130/75 mm Hg, 161 U/L), and a mildly raised lactate dehydrogenase a pulse rate of 85/min. Haemostix performed on level of 53 U/L (normal range, 15-37 U/L). Computed
Asian Journal of Gerontology & Geriatrics Vol 4 No 2 December 2009
Serotonin syndrome after taking citalopram
Distinguishing features of serotonin syndrome and neuroleptic malignant syndrome
Hyperactivity including tremors, clonus, hyperreflexia
Hypoactivity including rigidity and bradyreflexia
tomography of her brain revealed age-related most accurate—Hunter toxicity criteria—has 84% atrophic changes only.
sensitivity and 97% specificity,5 when compared with the gold standard diagnosis by a toxicologist. To
The diagnosis of serotonin syndrome related to fulfil the Hunter criteria, a patient must have taken a the newly introduced citalopram was confirmed. serotonergic agent plus show one of the following: The intravenous fluid supplement was maintained, (1) spontaneous clonus, (2) inducible clonus plus her vital signs were closely monitored, and she was agitation or diaphoresis, (3) ocular clonus plus sedated with diazepam 2 mg daily. Her temperature agitation or diaphoresis, (4) tremor and hyperreflexia, returned to normal within 24 hours of stopping the (5) hypertonia and a temperature above 38ºC plus citalopram. She made an uneventful recovery and ocular clonus or inducible clonus. was discharged home after a short rehabilitation exercise course in a convalescent unit.
Serotonin syndrome is often misdiagnosed as neuroleptic malignant syndrome (NMS),6 but
history, physical examination findings and the clinical course make it possible to distinguish between the
The diagnosis of serotonin syndrome is made solely 2 (Table). Serotonin syndrome develops during the
on clinical grounds. Therefore, a detailed history and 24 hours after starting or escalating the dosage of thorough physical examination are essential.2 In serotonergic agents, whereas NMS develops over particular, a temporal relationship with starting or a days to weeks.4 Serotonin syndrome is characterised change in the dosage of a serotonergic agent is of the by neuromuscular hyperactivity, which includes utmost importance.
tremor, hyperreflexia and myoclonus, whereas patients with NMS show sluggish responses,
Common clinical features of serotonin syndrome including bradyreflexia and rigidity.4 Moreover, NMS include mental status fluctuation, autonomic requires an average of 9 days to resolve, compared hyperactivity and neuromuscular changes. Patients with less than 24 hours in serotonin syndrome.6 Our may startle easily, become drowsy, agitated and patient had been on flupenthixol for 6 years, making restless.3 Autonomic hyperactivity can manifest as NMS much less likely because NMS usually develops hyperthermia, tachycardia and fluctuations in blood within days to weeks of initiating new antipsychotic pressure.4 Neuromuscular hyperactivity (including drugs. rigidity, hyperreflexia and clonus) is common.4 Special attention should be paid when performing Laboratory tests are usually non-specific, showing a neurological examination. Slow, continuous a leucocytosis, elevated creatine phosphokinase horizontal eye movements (ocular clonus) are levels, elevated liver transaminases and metabolic typically seen in serotonin syndrome.1 Tremors, acidosis in severe cases,4 features seen in both akathisia, deep tendon hyperreflexia, bilateral up-
serotonin syndrome and NMS. It should be noted
going Babinski signs and muscle clonus are also that there is no correlation between serum serotonin often seen. Neuromuscular signs are usually more levels and clinical findings,4 and no specific pronounced in the lower extremities.4
laboratory test able to confirm the diagnosis, making a thorough history and physical examination crucial.
Different sets of diagnostic criteria have been Other differential diagnoses for serotonin syndrome developed to define serotonin syndrome. The include malignant hyperthermia, central nervous
Asian Journal of Gerontology & Geriatrics Vol 4 No 2 December 2009 77
system infection, and delirium tremens seen in supportive care enabled the patient to make a good alcohol and benzodiazepine withdrawal.
recovery. Serotonin syndrome has a broad spectrum of clinical severity, from mild cases of flushing and
Management of serotonin syndrome requires diaphoresis to critical cases requiring intubation and quick recognition and prompt withdrawal of all intensive care. Clinicians should be aware of this serotonergic agents. Supportive care should be potentially life-threatening side-effect, and weigh given, aiming at normalising the vital signs.1 In the benefits and risks when selecting treatment and more severe cases, sedation with benzodiazepines deciding whether to continue the causative agent. and the administration of serotonin antagonists (cyproheptadine) may be required.7 Hyperthermic References
and critically ill patients occasionally require paralysis and endotracheal intubation. Cyproheptadine is a 1. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med histamine-1 receptor antagonist with non-specific
2. Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a
5-HT1A and 5-HT2A antagonistic properties. It has
brief review. CMAJ 2003;168:1439.
been reported to be useful for managing serotonin 3. Ganetsky M, Brush E. Serotonin syndrome—what have we syndrome.7-9 Cyproheptadine may lead to sedation
learned? Clin Ped Emerg Med 2005;6:103.
4. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome.
and produce transient hypotension due to the
Presentation of 2 cases and review of the literature. Medicine
reversal of serotonin-mediated increases in vascular
tone, but these side-effects are usually mild and 5. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM.
The Hunter Serotonin Toxicity Criteria: simple and accurate
diagnostic decision rules for serotonin toxicity. QJM 2003;96:635-42. CONCLUSION
6. Mills KC. Serotonin syndrome. A clinical update. Crit Care Clin
7. Graudins A, Stearman A, Chan B. Treatment of the serotonin
Greater use of anti-depressants targeting the
syndrome with cyproheptadine. J Emerg Med 1998;16:615-9.
serotonin pathway is making side-effects of these 8. Baigel GD. Cyproheptadine and the treatment of an unconscious drugs more common. We describe a case of serotonin
patient with the serotonin syndrome. Eur J Anaesthesiol 2003;20:586-8.
syndrome seen in an elderly woman after she was 9. Gillman PK. The serotonin syndrome and its treatment. J
commenced on citalopram. Prompt recognition and
Asian Journal of Gerontology & Geriatrics Vol 4 No 2 December 2009
La desertificación El vandalismo Un daño que puede evitarse Nivel de aplicación Sector de aprendizaje Orientación, Historia, geografía y Ciencias sociales. Ciencias naturales (NB3, NB4). OBJETIVOS DE APRENDIZAJE Identificar los distintos tipos de actos vandálicos, y sus consecuencias para la comunidad. Proteger el entorno natural y promover sus recursos como contexto de
Coping with WORDNET Sense Proliferation Alessandro Artale, Anna Goy*, Bernardo Magnini, Emanuele Pianta & Carlo Strapparava IRST, Istituto per la Ricerca Scientifica e Tecnologica [artale | magnini | pianta | [email protected]] *Dipartimento di Informatica - University of Torino, Italy Abstract 1. Adding Subject Field Labels WORDNET makes a great number of fine-grained