Case Reports
Mitchell et al (2017)8 described a case report of a 66-year-old male who presented to the emergency room with altered mental status, insomnia, and agitated aggressive behavior initiating 2 weeks prior. His past medical history included severe, recurrent major depressive disorder with psychotic features. The patient was administered RISPERDAL CONSTA 25 mg every 2 weeks for the past 4 years and received his last dose 6 days prior to admission. Other medications included duloxetine 60 mg daily. On the second day of admission, the patient was started on aripiprazole 10 mg twice daily without the primary physician being aware of the current RISPERDAL CONSTA treatment. On day 8, due to worsening depression with hallucinations, a different psychiatrist ordered his next scheduled dose of RISPERDAL CONSTA 25 mg. On day 12, a third psychiatrist discontinued the aripiprazole and prescribed RISPERDAL CONSTA 37.5 mg and oral risperidone 2 mg twice daily, unaware of the previous injection. Over the next few days the patient experienced fluctuating tachycardia, muscle rigidity, diaphoresis, increases in psychomotor activity, cognitive function decline with psychotic and primitive behavior, cold/clammy skin, nausea, vomiting and diarrhea. On day 10 the patient experienced hypotension and acute kidney injury, fluctuating elevated temperatures and labile blood pressure. On day 17 his CK level ranged from 373 U/L to 783 U/L and would then return to baseline. On day 19 the consult team discovered the inappropriate RISPERDAL CONSTA dose earlier in his admission and suspected that his symptoms may be due to NMS. The oral risperidone was decreased, and the patient slowly improved with supportive care.
Yamashita et al (2013)9 reported a case of a 50-year-old man with a history of chronic schizophrenia, hospitalized several times due to nonadherence with oral APs including haloperidol. The patient received risperidone 3 mg/day for 7 days prior to initiating RISPERDAL CONSTA 25 mg. Two weeks later, the RISPERDAL CONSTA dose was increased to 37.5 mg. Oral risperidone was discontinued 5 weeks after RISPERDAL CONSTA initiation. Concomitant medications included levomepromazine 30 mg/day, trazodone 50 mg/day and flunitrazepam 2 mg/day. The patient received a total of 4 doses of RISPERDAL CONSTA prior to being discharged to a home-visit nursing service. Ten days after discharge, the patient experienced dysphagia which limited his oral intake. The previous oral risperidone regimen was re-initiated to promote medication adherence. Fourteen weeks after his first RISPERDAL CONSTA injection, the patient was rehospitalized presenting with tremors, rigidity, dysphagia, tachycardia, diaphoresis, urinary incontinence and delirium. Laboratory data revealed leukocytosis and increased creatine phosphokinase (CPK) 1089 IU/L. NMS was suspected. Oral risperidone was discontinued, and intravenous hydration started. Fever, marked rigidity, and an increased CPK (1387) continued through day 4. Oral biperiden 2 mg was administered on day 3 with no improvement. Parenteral dantrolene 40 mg/day was initiated on day 4 resulting in marked improvement day 5. Creatine phosphokinase decreased to 826 IU/L and fell to within normal range by day 8. On day 16, the dantrolene was discontinued and by day 17, NMS was no longer apparent. After a 7-week hospital stay, olanzapine 5 mg was started and gradually increased to 10 mg. The patient did not experience any further occurrence of NMS in the 11 months post-discharge.
Bharadwaj et al (2010)3 described a case report of a 38-year old female who presented to the emergency room with dysphagia, difficulty talking, and drooling. Her past medical history included dependence to heroin and amphetamine, paranoid schizophrenia, and a severe head injury occurring 15 months prior the hospital visit. For 1 year prior to admission, the patient was on RISPERDAL CONSTA 37.5 mg every 2 weeks, risperidone 3 mg nightly, and lithium carbonate 250 mg twice daily. Since the patient experienced extrapyramidal symptoms, the medications were discontinued, and the patient was subsequently treated with benztropine. In addition, the patient was prescribed olanzapine 10 mg at night and paroxetine 20 mg in the morning. Over the next month, she developed frequent and profuse sweating, slowed movements, unsteady gait, falls, dysphagia, occasional low-grade fever and severe sialorrhea. Throughout her hospitalization, she also demonstrated lead-pipe muscle rigidity in all four extremities, severe nausea, tachycardia, coarse hand tremors, tongue fasciculations, and unstable blood pressure. Abnormal laboratory findings included slightly elevated liver function tests and a serum creatine kinase level of 40 U/L. The patient was diagnosed with NMS based on DSM IV criteria. All medications except for benztropine 4 mg daily were discontinued. Within 8 days, her symptoms resolved. Two days before discharge, she developed paranoid thinking, at which point olanzapine 5 mg was initiated. During follow-up, the patient did not exhibit any reemerging physical or psychiatric symptoms. The authors note that the patient did not have symptoms of severe NMS, but the symptoms could have been due to serotonin syndrome due to the presence of nausea. The authors concluded the need for exercising caution in using a selective serotonin reuptake inhibitor with atypical AP combinations, especially in patients with preexisting brain injury.
Celikel (2009)7 presented a case of a 23-year-old female with a history of mental retardation and an affective disorder with psychotic features. The patient presented to an outpatient clinic with severe muscular rigidity, hypertonia of the limbs and trunk, mutism and akinesia. After 12 days of treatment with both orally dissolving risperidone and olanzapine administered twice daily, the patient experienced a high fever, muscular rigidity, loss of energy, psychomotor retardation, decreased sleep, mutism, sores in her mouth, and sweating. Three to 4 days later, she was treated at a different emergency clinic with RISPERDAL CONSTA 50 mg and haloperidol injection 5 mg. The rigidity continued and the patient experienced difficulty in walking, speaking and eating. The patient returned to the outpatient clinic presenting with tachycardia, subfebrile fever, incontinence, increased blood pressure and heart rate. Blood tests revealed elevated (520 U/L) serum CPK and leukocytosis. A diagnosis of NMS was subsequently made and the patient was hospitalized. AP medications had already been discontinued for 10 days prior to hospitalization. Supportive care included bromocriptine, titrated to 12.5 mg/day. CK levels were 470 U/L on day 1 and 701 U/L on day 3. Parenteral dantrolene 40 mg was initiated with some improvement in rigidity. The patient was transferred to an intensive care unit and continued to receive both psychiatric and medical care.
Mall et al (2008)5 described a case report of a 56-year-old African American female who was admitted to the hospital for chronic paranoid schizophrenia and hypertension. Upon admission, the patient was started on haloperidol decanoate 75 mg once monthly and oral olanzapine 30 mg once daily. The patient had no history of NMS or catatonia with these medications. She continued these medications for over 6 months, after which the oral olanzapine was switched to aripiprazole orally disintegrating tablets 30 mg due to limited improvement in negative symptoms. After limited improvement with aripiprazole orally disintegrating tablets, the patient was started on risperidone oral disintegrating tablets 1 mg twice daily. Seven days after starting oral risperidone, the patient was administered RISPERDAL CONSTA 25 mg by intramuscular injection. Haloperidol 5 mg and lorazepam 2 mg were administered intramuscularly twice during treatment with oral risperidone for agitation, with the second dose being administered 3 days before starting RISPERDAL CONSTA. The last dose of haloperidol decanoate was administered 38 days before the initial dose of RISPERDAL CONSTA. The day after receiving her initial dose of RISPERDAL CONSTA, the patient presented with symptoms of catatonia and NMS. Her symptoms included rigidity (trunk bent over with inability to straighten out), impaired consciousness, psychomotor retardation, tremors, tachypnea, tachycardia (95-110 beats per minutes), bradycardia, a low-grade fever (99.3°F), labile blood pressure, was incontinent of urine, and diaphoretic. Based on laboratory measurements, she had elevated CPK (2267 U/L), elevated blood urea nitrogen (26 mg), and elevated serum aspartate and alanine aminotransferase (127 U/L and 88 U/L, respectively). All AP medications were discontinued, and the patient was started on lorazepam 1 mg and benztropine 1 mg three times a day with supportive measures. Approximately 7 days later, the patient was able to sit comfortably, and her liver enzymes and CPK decreased indicating clinical improvement. Lorazepam and benztropine were tapered off as her symptoms improved and she experienced a full recovery except for continuing tachycardia being noted. The authors note that while a temporal relationship was seen, there is uncertainty between the RISPERDAL CONSTA and onset of NMS symptoms given the small initial release (up to 1% of the dose) and chronic exposure to previous AP medications.
Vazquez et al (2007)6 described a case report of a 38-year-old male with paranoid schizophrenia who was admitted to the emergency room complaining of not feeling well and a fever. Before admission, the patient was stable on risperidone 3 mg/day, RISPERDAL CONSTA 100 mg every 15 days, olanzapine 10 mg/day, topiramate 600 mg/day, and lithium carbonate 800 mg/day. He smoked 80 cigarettes/day but quit 2 weeks before his hospital admission. A few hours after admission, the patient became comatose (Glasgow 6) without neurological focalized deficit, hypotonic, and showed signs of sweating, dyspnea, tachypnea, tachycardia, with a 42.3°C body temperature. After transfer to the intensive care unit (ICU), it was determined his condition was due to working in a moderately hot environment (30-32°C) and his probable diagnoses were heat stroke or NMS. The symptoms consistent with NMS included hyperthermia, augmentation of CPK (4026 U/L), tachycardia, tachypnea, and alteration of consciousness. Rigidity was not apparent in the patient. The patient did not respond to heat stroke treatment or electric convulsive therapy. He was eventually discharged from the ICU with axonal polyneuropathy and fluctuating consciousness but had normal vital signs and no signs of psychotic symptoms. About 2 months later, the patient experienced a psychotic episode and was treated with benzodiazepines and olanzapine. After treatment, he presented with pneumonia and died 2 weeks later due to pneumonia complications and polyneuropathy. The authors concluded smoking cessation may have resulted in pharmacokinetic changes to AP plasma levels.
