serotonin syndrome is a rare but potentially fatal side effect of antidepressants that results from the effects of drug activity on both central and peripheral serotonergic receptors . a 78-year - old japanese female with a 2-year history of major depressive disorder was treated with escitalopram ( 10 mg / d ) , risperidone ( 1 mg / d ) , and nitrazepam ( 5 mg / d ) . one month after beginning this drug regimen , she was transferred to the emergency department and immediately hospitalized due to suspicion of a urinary tract infection and dehydration . five days later , the patient s physical condition had recovered ; therefore , the same dose of escitalopram ( 10 mg / d ) was readministered . the patient subsequently developed convulsions accompanied by impaired consciousness , high fever , and myoclonus of both upper extremities . based on these clinical signs and symptoms , we suspected serotonin syndrome ; therefore , escitalopram was discontinued , and a fluid infusion was initiated . this case suggests that the careless readministration of selective serotonin reuptake inhibitors ( ssris ) is harmful to at - risk patients , like those in poor physical condition and the elderly . serotonin syndrome is a rare but potentially fatal side effect of antidepressants that results from the effects of drug activity on both central and peripheral serotonergic receptors . this syndrome consists of a combination of mental status changes , neuromuscular hyperactivity , and autonomic hyperactivity.1 serotonin syndrome is also associated with increased serotonergic activity in the central nervous system . selective serotonin reuptake inhibitors ( ssris ) may be the most commonly implicated group of medications associated with serotonin syndrome.1 ssris are the most common antidepressant drugs used in the treatment of major depressive and anxiety disorders . ssris are better tolerated than tricyclic antidepressants ( tcas ) by older patients because ssris exhibit superior side effect profiles , including fewer anticholinergic side effects.2,3 a network meta - analysis suggested that escitalopram is superior to other antidepressants with respect to both efficacy and tolerability.4 we present a case of serotonin syndrome induced by the readministration of escitalopram after a short - term interruption in an elderly woman with depression . the ethics committee of hirosaki university , school of medicine does not require approvals for a case report . the patient was a 78-year - old japanese female with a 2-year history of major depressive disorder , a right putamen infarction 3 years prior to the serotonin syndrome event described in this report and hypertension , an overactive bladder , and depression . she was treated with 10 mg / d of escitalopram , 30 mg / d of mirtazapine , and 5 mg / d of nitrazepam for more than 6 months . at 1 month before the occurrence of serotonin syndrome , mirtazapine was discontinued and replaced with 1 mg / d of risperidone because the patient had exhibited aggressive behavior toward her husband and had also experienced hallucinations and paranoid delusions . following this change in her treatment regimen , the patient s psychiatric symptoms improved ; however , she developed bradykinesia . approximately 1 month later , she was transferred to the emergency department of tsugaru general hospital due to somnolence , fever , and bradykinesia . a urinalysis was significant for hematuria , a 3 + test for protein , a 2 + test for leukocyte esterase , and a specific gravity of at least 1.030 . the patient s serum creatinine level , blood urea nitrogen level , white cell count , and c - reactive protein ( crp ) level were 0.72 mg / dl , 15.4 mg / dl , 7,620 and 0.16 g / ml , respectively . the patient was negative for influenza antigens a and b. she was immediately hospital - ized in the internal medicine ward of the same hospital due to suspicion of a urinary tract infection and dehydration . because her physicians believed that her bradykinesia may have been caused by her medications , all psychotropic drugs were discontinued . she was treated with intravenous fluid replacement and levofloxacin ( 500 mg / d ) . her general condition gradually improved ; however , her low - grade fever ( from 37.0c to 38.0c ) persisted . at 5 days following the discontinuation of her psychotropic drugs , treatment with 10 mg / d of escitalopram on the evening of the first day following escitalopram readministration , the patient developed insomnia and confusion and was restrained to ensure her safety . on the morning of the second day following escitalopram readministration , she experienced a convulsive seizure , and her oxygen saturation decreased . even after the convulsions were suppressed via intravenous diazepam , she remained unconscious ( glasgow coma scale : eye1 , verbal1 , and motor1 ) and exhibited a high fever ( with a maximum fever of 41.5c ) and myoclonus of both upper extremities . enhanced tendon reflexes of both lower extremities were also observed . a urine examination , a blood chemistry test , and a ct scan of the chest and abdomen did not demonstrate the presence of any infectious foci . the patient remained negative for influenza antigens a and b. seizure discharges were not observed on an electroencephalographic examination . based on these clinical signs and symptoms , we suspected serotonin syndrome . therefore , escitalopram was discontinued , and a fluid infusion was initiated . all of her symptoms , with the exception of a slight fever , resolved within a few days after the aforementioned studies were obtained . the patient exhibited mental status changes , myoclonus , hyperreflexia , and fever after the readministration of escitalopram . alternative diagnoses were excluded either via history or via laboratory examination , and the observed symptoms met the diagnostic criteria for serotonin syndrome described by sternbach.5 therefore , based on the patient s clinical course , we concluded that serotonin syndrome had developed due to the readministration of escitalopram . although no symptoms of serotonin syndrome had been observed during approximately 2 years of treatment with 10 mg / d of escitalopram , serotonin syndrome developed on the second day following the resumption of treatment with the same dose of escitalopram after a short - term discontinuation . 5-ht receptor activation is a common cause of both serotonin toxicity and serotonin syndrome.6 additionally , blocking 5-ht2a receptors represents a positive response to serotonin syndrome . cyproheptadine , chlorpromazine , and olanzapine , all of which are capable of blocking 5-ht2a receptors , have exhibited excellent efficacy in the setting of serotonin syndrome . a possible mechanism underlying the development of serotonin syndrome is as follows : firstly , upregulated 5-ht receptors may change following the interruption of escitalopram . secondly , the plasma concentration of escitalopram may increase following its readministration because of the deterioration of the patient s condition . although little data exists regarding the prevalence of escitalopram - induced serotonin syndrome , several cases of this syndrome have been described . one such case involved an 88-year - old female who experienced an interaction between 5 mg of escitalopram and 50 mg of miconazole.7 a second case involved a 27-year - old female who experienced an interaction between 10 mg of escitalopram and 5060 mg of cyclobenzaprine.8 finally , a third case involved a 65-year - old female who experienced an interaction between 10 mg of escitalopram and 600 mg of the antibiotic linezolid.9 to the best of our knowledge , no specific clinical characteristics , with the exception of the accidental combination of serotonergic medications , have been associated with a predisposition to serotonin syndrome . in this case , a urinary tract infection and dehydration were observed prior to the development of serotonin syndrome . therefore , the deterioration of a patient s condition may be a risk factor for serotonin syndrome .
backgroundserotonin syndrome is a rare but potentially fatal side effect of antidepressants that results from the effects of drug activity on both central and peripheral serotonergic receptors.casea 78-year - old japanese female with a 2-year history of major depressive disorder was treated with escitalopram ( 10 mg / d ) , risperidone ( 1 mg / d ) , and nitrazepam ( 5 mg / d ) . 
 one month after beginning this drug regimen , she was transferred to the emergency department and immediately hospitalized due to suspicion of a urinary tract infection and dehydration . 
 all psychotropic drugs were discontinued . 
 five days later , the patient s physical condition had recovered ; therefore , the same dose of escitalopram ( 10 mg / d ) was readministered . 
 the patient subsequently developed convulsions accompanied by impaired consciousness , high fever , and myoclonus of both upper extremities . 
 the tendon reflexes of both lower extremities were enhanced . based on these clinical signs and symptoms 
 , we suspected serotonin syndrome ; therefore , escitalopram was discontinued , and a fluid infusion was initiated . 
 the patient recovered from all symptoms within 3 weeks without receiving additional antidepressants.conclusionthis case suggests that the careless readministration of selective serotonin reuptake inhibitors ( ssris ) is harmful to at - risk patients , like those in poor physical condition and the elderly .