New Criteria Aid in Neuroleptic Malignant Syndrome Diagnosis

BOSTON – Clinical application of the first consensus-based criteria for neuroleptic malignant syndrome should expedite the diagnosis of the life-threatening complication of antipsychotic drug treatment by replacing current "ad hoc approaches," Dr. Ronald J. Gurrera said at the American Psychiatric Association Institute on Psychiatric Services.

Additionally, the new criteria, developed using the Delphi technique by a 17-member international expert panel of psychiatrists, neurologists, anesthesiologists, and emergency medicine specialists convened by the Neuroleptic Malignant Syndrome Information Service, will facilitate clinical research, which has been hampered by the lack of universally accepted criteria, said Dr. Gurrera, a geriatric psychiatrist affiliated with the VA Boston Healthcare System.

The expert panel reached consensus on the following diagnostic criteria for neuroleptic malignant syndrome (NMS), derived through five iterations of group sampling with controlled feedback:

• Exposure to a dopamine agonist, or dopamine-agonist withdrawal, within the past 72 hours.

• Hyperthermia.

• Rigidity.

• Mental status alteration.

• Elevated creatine phosphokinase.

• Sympathetic nervous system lability, defined as the presence of two or more of these features: elevated blood pressure, blood pressure fluctuation, diaphoresis, or urinary incontinence.

• Tachycardia and tachypnea.

• Negative work-up for infectious, toxic, metabolic, and neurologic causes.

Although NMS is rare – prevalence estimates range from 0.02% to 2.44% among patients taking neuroleptic drugs – it is a significant source of morbidity and mortality in these patients, Dr. Gurrera said, noting that mortality is estimated to be as high as 12%. Morbidity from NMS includes rhabdomyolysis, pneumonia, renal failure, seizures, arrhythmias, disseminated intravascular coagulation (DIC), and respiratory failure. Mortality usually results from respiratory failure, cardiovascular collapse, myoglobinuric renal failure, arrhythmias, or DIC, he said in a poster presentation.

Although the condition is thought to occur more frequently with the use of high-potency conventional antipsychotics, NMS is a potential adverse effect of any antipsychotic agent, including the newer atypical antipsychotics, Dr. Gurrera said, noting that there is no evidence to suggest an association with any particular neuroleptic agent over another.

Despite the availability of DSM-IV-TR research criteria for NMS, which require that both severe muscle rigidity and elevated temperature be present after recent administration of an antipsychotic as well as two associated signs, symptoms, or laboratory findings that are not better accounted for by a substance-induced, neurologic, or general medical condition, it can be difficult to distinguish the symptoms of NMS from some of the other, more common side effects of antipsychotic medications, such as dystonias, parkinsonism, and akathisia, and from other conditions that present with the same symptoms, Dr. Gurrera said. Given the potential severity of the disorder, however, antipsychotic medication should be discontinued in any patient with symptoms of NMS, "even before the diagnosis is definitive," he said.

The rate of mortality associated with NMS has decreased in recent years, from an estimated high of 30%, most likely reflecting an increased awareness of the condition and more conservative antipsychotic prescribing practices, as well as the use of atypical antipsychotics, Dr. Gurrera said. The increased recognition of the disorder can lead to earlier diagnosis and treatment, reducing the number of lethal cases of NMS, he said, stressing the need for clinicians to be aware of the early signs and clinical features of the condition.

Dr. Gurrera reported having no relevant conflicts of interest.

BOSTON – Clinical application of the first consensus-based criteria for neuroleptic malignant syndrome should expedite the diagnosis of the life-threatening complication of antipsychotic drug treatment by replacing current "ad hoc approaches," Dr. Ronald J. Gurrera said at the American Psychiatric Association Institute on Psychiatric Services.

Additionally, the new criteria, developed using the Delphi technique by a 17-member international expert panel of psychiatrists, neurologists, anesthesiologists, and emergency medicine specialists convened by the Neuroleptic Malignant Syndrome Information Service, will facilitate clinical research, which has been hampered by the lack of universally accepted criteria, said Dr. Gurrera, a geriatric psychiatrist affiliated with the VA Boston Healthcare System.

The expert panel reached consensus on the following diagnostic criteria for neuroleptic malignant syndrome (NMS), derived through five iterations of group sampling with controlled feedback:

• Exposure to a dopamine agonist, or dopamine-agonist withdrawal, within the past 72 hours.

• Hyperthermia.

• Rigidity.

• Mental status alteration.

• Elevated creatine phosphokinase.

• Sympathetic nervous system lability, defined as the presence of two or more of these features: elevated blood pressure, blood pressure fluctuation, diaphoresis, or urinary incontinence.

• Tachycardia and tachypnea.

• Negative work-up for infectious, toxic, metabolic, and neurologic causes.

Although NMS is rare – prevalence estimates range from 0.02% to 2.44% among patients taking neuroleptic drugs – it is a significant source of morbidity and mortality in these patients, Dr. Gurrera said, noting that mortality is estimated to be as high as 12%. Morbidity from NMS includes rhabdomyolysis, pneumonia, renal failure, seizures, arrhythmias, disseminated intravascular coagulation (DIC), and respiratory failure. Mortality usually results from respiratory failure, cardiovascular collapse, myoglobinuric renal failure, arrhythmias, or DIC, he said in a poster presentation.

Although the condition is thought to occur more frequently with the use of high-potency conventional antipsychotics, NMS is a potential adverse effect of any antipsychotic agent, including the newer atypical antipsychotics, Dr. Gurrera said, noting that there is no evidence to suggest an association with any particular neuroleptic agent over another.

Despite the availability of DSM-IV-TR research criteria for NMS, which require that both severe muscle rigidity and elevated temperature be present after recent administration of an antipsychotic as well as two associated signs, symptoms, or laboratory findings that are not better accounted for by a substance-induced, neurologic, or general medical condition, it can be difficult to distinguish the symptoms of NMS from some of the other, more common side effects of antipsychotic medications, such as dystonias, parkinsonism, and akathisia, and from other conditions that present with the same symptoms, Dr. Gurrera said. Given the potential severity of the disorder, however, antipsychotic medication should be discontinued in any patient with symptoms of NMS, "even before the diagnosis is definitive," he said.

The rate of mortality associated with NMS has decreased in recent years, from an estimated high of 30%, most likely reflecting an increased awareness of the condition and more conservative antipsychotic prescribing practices, as well as the use of atypical antipsychotics, Dr. Gurrera said. The increased recognition of the disorder can lead to earlier diagnosis and treatment, reducing the number of lethal cases of NMS, he said, stressing the need for clinicians to be aware of the early signs and clinical features of the condition.

Dr. Gurrera reported having no relevant conflicts of interest.

BOSTON – Clinical application of the first consensus-based criteria for neuroleptic malignant syndrome should expedite the diagnosis of the life-threatening complication of antipsychotic drug treatment by replacing current "ad hoc approaches," Dr. Ronald J. Gurrera said at the American Psychiatric Association Institute on Psychiatric Services.

Additionally, the new criteria, developed using the Delphi technique by a 17-member international expert panel of psychiatrists, neurologists, anesthesiologists, and emergency medicine specialists convened by the Neuroleptic Malignant Syndrome Information Service, will facilitate clinical research, which has been hampered by the lack of universally accepted criteria, said Dr. Gurrera, a geriatric psychiatrist affiliated with the VA Boston Healthcare System.

The expert panel reached consensus on the following diagnostic criteria for neuroleptic malignant syndrome (NMS), derived through five iterations of group sampling with controlled feedback:

• Exposure to a dopamine agonist, or dopamine-agonist withdrawal, within the past 72 hours.

• Hyperthermia.

• Rigidity.

• Mental status alteration.

• Elevated creatine phosphokinase.

• Sympathetic nervous system lability, defined as the presence of two or more of these features: elevated blood pressure, blood pressure fluctuation, diaphoresis, or urinary incontinence.

• Tachycardia and tachypnea.

• Negative work-up for infectious, toxic, metabolic, and neurologic causes.

Although NMS is rare – prevalence estimates range from 0.02% to 2.44% among patients taking neuroleptic drugs – it is a significant source of morbidity and mortality in these patients, Dr. Gurrera said, noting that mortality is estimated to be as high as 12%. Morbidity from NMS includes rhabdomyolysis, pneumonia, renal failure, seizures, arrhythmias, disseminated intravascular coagulation (DIC), and respiratory failure. Mortality usually results from respiratory failure, cardiovascular collapse, myoglobinuric renal failure, arrhythmias, or DIC, he said in a poster presentation.

Although the condition is thought to occur more frequently with the use of high-potency conventional antipsychotics, NMS is a potential adverse effect of any antipsychotic agent, including the newer atypical antipsychotics, Dr. Gurrera said, noting that there is no evidence to suggest an association with any particular neuroleptic agent over another.

Despite the availability of DSM-IV-TR research criteria for NMS, which require that both severe muscle rigidity and elevated temperature be present after recent administration of an antipsychotic as well as two associated signs, symptoms, or laboratory findings that are not better accounted for by a substance-induced, neurologic, or general medical condition, it can be difficult to distinguish the symptoms of NMS from some of the other, more common side effects of antipsychotic medications, such as dystonias, parkinsonism, and akathisia, and from other conditions that present with the same symptoms, Dr. Gurrera said. Given the potential severity of the disorder, however, antipsychotic medication should be discontinued in any patient with symptoms of NMS, "even before the diagnosis is definitive," he said.

The rate of mortality associated with NMS has decreased in recent years, from an estimated high of 30%, most likely reflecting an increased awareness of the condition and more conservative antipsychotic prescribing practices, as well as the use of atypical antipsychotics, Dr. Gurrera said. The increased recognition of the disorder can lead to earlier diagnosis and treatment, reducing the number of lethal cases of NMS, he said, stressing the need for clinicians to be aware of the early signs and clinical features of the condition.

Dr. Gurrera reported having no relevant conflicts of interest.