Current Psychiatry

CASE: Mute and unresponsive

Mrs. K, a 42-year-old Haitian who is 31 weeks pregnant, presents with a 4-week history of progressive mutism and psychomotor retardation. At inpatient admission, she is awake and alert but does not speak and resists the treatment team’s attempts to engage her. Mrs. K’s eyes are open, but she has a vacant stare and avoids eye contact. Her affect is flat and nonreactive and she appears internally preoccupied. Mrs. K exhibits motoric immobility, displays a rigid posture, and resists attempts to get her to move. Features of catatonic excitement, echo phenomena, posturing, stereotypies, and mannerisms are absent during the initial evaluation.

Mrs. K’s husband reports that they had been on vacation for 6 days before he brought her for psychiatric evaluation. He denies any recent evidence of psychosis or mood disturbance, stating that his wife was excited when she learned of the pregnancy, and attended all prenatal appointments. He reports that when this episode began, Mrs. K stopped talking to her 3-year-old daughter, did not respond to her name, and did not pay attention to those around her.

According to her husband, a similar episode occurred 2 years earlier, during which Mrs. K was selectively mute for approximately 1 month. She did not eat for 5 days and neglected the care of her daughter. There were 2 additional brief periods of prominent psychomotor retardation for which she was hospitalized in Haiti. According to the patient’s aunt, Mrs. K complained that her husband had cast a “voodoo spell” on her because he wanted sole custody of their daughter. Her husband recounted an episode, when they lived in Haiti, during which his wife became paranoid, left the house, and wandered the streets for 2 days.

The medical history is significant for a cervical polyp that was removed 2 years ago. Mrs. K has no history of substance abuse. She was born and raised in Haiti where she studied medicine. Her family reports that Mrs. K’s husband is “controlling,” which causes her distress.

The authors' observations

Catatonia is a neuropsychiatric syndrome that can occur in schizophrenia, mood disorders, mental retardation, neurologic disease, metabolic conditions, and drug intoxication.¹ Catatonia can present in several ways, from catatonic stupor to extreme purposeless agitation; more than 60 catatonic signs and symptoms have been described.¹ According to DSM-5² catatonia is characterized by 3 or more of the following symptoms:

•  stupor 

•  catalepsy

•  waxy flexibility

•  mutism

•  negativism

•  posturing

•  mannerism

•  stereotypy

•  agitation, not influenced by external stimuli

•  grimacing

•  echolalia

•  echopraxia.

Mrs. K exhibited stupor, mutism, posturing, and grimacing (Table 1).² We thought that her catatonic features were secondary to schizophrenia because she had paranoid delusions and displayed disorganized behavior while in Haiti. There was no evidence of past or current mood disorder, metabolic condition, neurologic illness, or substance abuse.

Catatonia and pregnancy

There is little available information to guide clinicians who are treating a pregnant woman who has a catatonic syndrome. Espinola-Nadurille and co-workers described a 22-year-old pregnant (21 weeks) woman from rural Mexico who was hospitalized with agitation, disorganized speech, restlessness, and hallucinations after several weeks of alternating agitation and withdrawal with mutism and refusal to eat or drink.³ This patient developed malignant catatonia with creatine phosphokinase elevation and leukocytosis and eventually responded to treatment with lorazepam and electroconvulsive therapy (ECT). She was given a diagnosis of schizophreniform disorder. Treating her catatonic symptoms did not result in any adverse effects on the pregnancy or the fetus.

Exacerbation of schizophrenia during pregnancy can lead to neglect of pregnancy and prenatal care,⁴ imminent harm to the fetus because of malnutrition and dehydration, and risk of preterm delivery and low weight at birth. Prolonged catatonia can cause medical complications such as decubitus ulcers, incontinence, recurrent urinary tract infections, aspiration pneumonia, increased risk of deep venous thrombosis, malnutrition, and ocular complications because of prolonged staring and reduced blinking (Table 2^5-10). For these reasons, it is important to treat this condition early and aggressively to improve pregnancy outcome and infant well-being.

EVALUATION: Flat affect

The mental status examination on admission describes a tall, black, Haitian woman with unkempt hair and fair hygiene. Mrs. K has a prominent abdomen, consistent with a 31-week pregnancy. She exhibits a blank stare without direct eye contact; she is mute, and exhibits flat affect. We cannot evaluate her thought processes and content because Mrs. K is mute, although she does appear internally preoccupied.

Physical examination on admission is unremarkable; vital signs are stable and within normal limits. Laboratory work-up reveals a urinary tract infection, which is treated with ceftriaxone. Mrs. K also has macrocytic anemia (hemoglobin, 11.7 g/dL; hematocrit, 34.7%; mean corpuscular volume, 99.2 μm³). Albumin is low at 2.6 g/dL. Urine drug toxicology screen is negative. Fingerstick glucose reading is 139 mg/dL. Mrs. K is given a presumptive diagnosis of schizophrenia with catatonia.

Mrs. K’s BFCRS¹¹ score is 22 at admission. She is mute, holds postures for longer than a minute, and is resistant to repositioning. She also has extreme hypoactivity and does not interact with others. She has a fixed, blank stare, and exhibits mild grimacing.

The authors' observations

BFCRS defines each catatonic sign, rates its severity, and provides a standardized schema for clinical examination.¹¹ The BFCRS is preferred for routine use because of its validity, reliability, and ease of administration.¹² The treatment team rated Mrs. K at admission, during the course of treatment, and at discharge, showing a substantial improvement at the end of the hospitalization (Figure).

The authors' observations

Benzodiazepines (particularly lorazepam) and ECT are considered the treatment of choice for catatonic symptoms.¹¹ More than 72% of patients with catatonic symptoms remit after a trial of a benzodiazepine.¹ ECT is considered when patients do not respond to a benzodiazepine after 48 to 72 hours.³ Several cases of complete resolution of catatonic symptoms have been linked to ECT (Table 3).^13-18

A recent retrospective review revealed that patients who do not respond to loraze­pam are more likely to come from a rural setting, have a longer duration of illness, exhibit mutism, and exhibit third-person auditory hallucinations and made phenomena (the feeling that some aspect of the individual is under the external control of others).¹⁹ Case reports of treatment of catatonic patients with ECT vs lorazepam are listed in Table 3.^13-18

In pregnancy, ECT can be considered early in the course of illness. A review of the literature on ECT during pregnancy reported at least partial remission in 78% of studies reporting efficacy data.²⁰ Among these 339 patients, there were 25 fetal or neonatal complications—only 11 of these were related to ECT—and 20 maternal complications, of which 18 were related to ECT. The authors of this review concluded that 1) ECT is an effective treatment for severe mental illness during pregnancy and 2) the risks to fetus and mother are low.

A 2007 study identified 1,979 infants whose mothers reported use of benzodiazepines or hypnotic benzodiazepine-receptor agonists during early pregnancy.²¹ An additional 401 infants born to mothers who were prescribed these medications during late pregnancy also were included in this study. Women who took these medications were at an increased risk for preterm birth and low birth weight. The rate of congenital malformations in this study was moderately increased among infants exposed in early pregnancy (adjusted odds ratio = 1.24 [95% confidence interval, 1.00 to 1.55]).

Because catatonic symptoms can appear during the course of schizophrenia, several antipsychotics have been used to treat this condition. The efficacy and safety of antipsychotics for treating catatonia remains largely unknown, however.¹

OUTCOME: Recovery, baby girl

We begin oral haloperidol, 10 mg/d, for Mrs. K, which we then increase to 20 mg/d. Because she shows little response to haloperidol, we suggest a trial of ECT, but her husband refuses to consent. She is started on IM lorazepam, 6 mg/d.

Mrs. K gradually improves and increases her intake of food and liquids. After 10 days of lorazepam treatment, her BFCRS score decreases to 13. Mrs. K begins to speak and her gaze is less fixed. Negativistic behaviors are nearly absent.

Because we are concerned about Mrs. K’s pregnancy, lab tests are repeated. A complete metabolic panel shows an elevated glucose level (122 mg/dL); urinalysis reveals glycosuria (glucose, 1,000 mg/dL), proteinuria (protein, 10 mg/dL), and ketonuria, (ketones, 20 mg/dL). She is transferred to the obstetrics service for evaluation of gestational diabetes.

Psychotropics are continued while Mrs. K is on the obstetrics service; she returns to the inpatient psychiatric unit on an insulin regimen. IM lorazepam is increased to 8 mg/d, and haloperidol is decreased from 20 mg/d, to 10 mg/d, to prevent worsening of catatonia, which can occur when catatonic patients receive a psychotropic.¹¹ Three days later, Mrs. K’s BFCRS score is 12 and she shows only mild rigidity. Mrs. K briefly interacts with staff, particularly when she wants something.

Lorazepam is decreased to 1 mg/d in anticipation of cesarean delivery. Mrs. K becomes more adherent with her medications; often, she takes the oral dose of haloperidol, rather than the IM formulation. On mental status examination she exhibits poor eye contact, rather than a fixed gaze, and her BFCRS score decreases to 7 by day 25.

By the end of lorazepam treatment, Mrs. K has fully recovered from her catatonic state. She interacts with staff, engages with the treatment team, and is excited to go home. At discharge, she is given a diagnosis of schizophrenia with catatonia, and is taking haloperidol, 5 mg, twice a day. She gives birth to a healthy girl.

The authors' observations

Mrs. K was treated initially with haloperidol for several reasons. Haloperidol is relatively safe during pregnancy (FDA pregnancy category C) as shown by a recent multicenter, prospective, cohort study in which babies exposed in utero to haloperidol showed a congenital malformation (limb defect) rate within the expected baseline risk for the general population.²² Lorazepam is FDA category D for use in pregnancy and can cause preterm delivery,²³ floppy infant syndrome, and withdrawal syndromes.²⁴ We did not use a second-generation antipsychotic (SGA) because it could have made Mrs. K’s hyperglycemia worse. SGAs can induce gestational diabetes and increase the incidence of large-for-gestational-age newborns, compared with first-generation antipsychotics.²⁴ Last, Mrs. K’s family rejected ECT.

Because of Mrs. K’s poor response to haloperidol, the treatment team decided to start IM lorazepam, which eventually was increased to 8 mg/d. The haloperidol dose was reduced by half to avoid worsening of catatonia and reduce the risk of neuroleptic malignant syndrome.^1,25 When clinical response was achieved, lorazepam was tapered and Mrs. K was discharged with only haloperidol.

In the absence of well-designed prospective follow-up studies, information on the potential impact of prenatal exposure to antipsychotics and benzodiazepines on a child’s cognitive development is limited.²⁶ This case adds to the scant literature on the treatment of catatonia during pregnancy and illustrates how the BFCRS can be utilized during serial patient evaluations to monitor clinical improvement.

Bottom Line

Psychosis and catatonia during pregnancy are associated with complications to mother and child. The Bush-Francis Catatonia Rating Scale can be used to identify and track catatonic symptoms. Lorazepam and electroconvulsive therapy have been used safely and with good outcomes in mentally ill pregnant women when used appropriately.

Related Resources

• Fink M. Catatonia: a syndrome appears, disappears, and is rediscovered. Can J Psychiatry. 2009;54(7):437-445.
• Seethalakshmi R, Dhavale S, Suggu K, et al. Catatonic syndrome: importance of detection and treatment with lorazepam. Ann Clin Psychiatry. 2008;20(1):5-8.
• Salam S, Kilzieh N. Lorazepam treatment of psychogenic catatonia: an update. J Clin Psychiatry, 1988;49(suppl):16-21.

Drug Brand Names

Ceftriaxone • Rocephin                 Olanzapine • Zyprexa

Haloperidol • Haldol                     Short-acting Insulin • Novolin, Humulin

Lorazepam • Ativan 

Disclosures

Dr. Runyan receives grant support from Lippincott, Williams, & Wilkins. Drs. Durant, Prudent, and Sotelo report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Mute and unresponsive

Mrs. K, a 42-year-old Haitian who is 31 weeks pregnant, presents with a 4-week history of progressive mutism and psychomotor retardation. At inpatient admission, she is awake and alert but does not speak and resists the treatment team’s attempts to engage her. Mrs. K’s eyes are open, but she has a vacant stare and avoids eye contact. Her affect is flat and nonreactive and she appears internally preoccupied. Mrs. K exhibits motoric immobility, displays a rigid posture, and resists attempts to get her to move. Features of catatonic excitement, echo phenomena, posturing, stereotypies, and mannerisms are absent during the initial evaluation.

Mrs. K’s husband reports that they had been on vacation for 6 days before he brought her for psychiatric evaluation. He denies any recent evidence of psychosis or mood disturbance, stating that his wife was excited when she learned of the pregnancy, and attended all prenatal appointments. He reports that when this episode began, Mrs. K stopped talking to her 3-year-old daughter, did not respond to her name, and did not pay attention to those around her.

According to her husband, a similar episode occurred 2 years earlier, during which Mrs. K was selectively mute for approximately 1 month. She did not eat for 5 days and neglected the care of her daughter. There were 2 additional brief periods of prominent psychomotor retardation for which she was hospitalized in Haiti. According to the patient’s aunt, Mrs. K complained that her husband had cast a “voodoo spell” on her because he wanted sole custody of their daughter. Her husband recounted an episode, when they lived in Haiti, during which his wife became paranoid, left the house, and wandered the streets for 2 days.

The medical history is significant for a cervical polyp that was removed 2 years ago. Mrs. K has no history of substance abuse. She was born and raised in Haiti where she studied medicine. Her family reports that Mrs. K’s husband is “controlling,” which causes her distress.

The authors' observations

Catatonia is a neuropsychiatric syndrome that can occur in schizophrenia, mood disorders, mental retardation, neurologic disease, metabolic conditions, and drug intoxication.¹ Catatonia can present in several ways, from catatonic stupor to extreme purposeless agitation; more than 60 catatonic signs and symptoms have been described.¹ According to DSM-5² catatonia is characterized by 3 or more of the following symptoms:

•  stupor 

•  catalepsy

•  waxy flexibility

•  mutism

•  negativism

•  posturing

•  mannerism

•  stereotypy

•  agitation, not influenced by external stimuli

•  grimacing

•  echolalia

•  echopraxia.

Mrs. K exhibited stupor, mutism, posturing, and grimacing (Table 1).² We thought that her catatonic features were secondary to schizophrenia because she had paranoid delusions and displayed disorganized behavior while in Haiti. There was no evidence of past or current mood disorder, metabolic condition, neurologic illness, or substance abuse.

Catatonia and pregnancy

There is little available information to guide clinicians who are treating a pregnant woman who has a catatonic syndrome. Espinola-Nadurille and co-workers described a 22-year-old pregnant (21 weeks) woman from rural Mexico who was hospitalized with agitation, disorganized speech, restlessness, and hallucinations after several weeks of alternating agitation and withdrawal with mutism and refusal to eat or drink.³ This patient developed malignant catatonia with creatine phosphokinase elevation and leukocytosis and eventually responded to treatment with lorazepam and electroconvulsive therapy (ECT). She was given a diagnosis of schizophreniform disorder. Treating her catatonic symptoms did not result in any adverse effects on the pregnancy or the fetus.

Exacerbation of schizophrenia during pregnancy can lead to neglect of pregnancy and prenatal care,⁴ imminent harm to the fetus because of malnutrition and dehydration, and risk of preterm delivery and low weight at birth. Prolonged catatonia can cause medical complications such as decubitus ulcers, incontinence, recurrent urinary tract infections, aspiration pneumonia, increased risk of deep venous thrombosis, malnutrition, and ocular complications because of prolonged staring and reduced blinking (Table 2^5-10). For these reasons, it is important to treat this condition early and aggressively to improve pregnancy outcome and infant well-being.

EVALUATION: Flat affect

The mental status examination on admission describes a tall, black, Haitian woman with unkempt hair and fair hygiene. Mrs. K has a prominent abdomen, consistent with a 31-week pregnancy. She exhibits a blank stare without direct eye contact; she is mute, and exhibits flat affect. We cannot evaluate her thought processes and content because Mrs. K is mute, although she does appear internally preoccupied.

Physical examination on admission is unremarkable; vital signs are stable and within normal limits. Laboratory work-up reveals a urinary tract infection, which is treated with ceftriaxone. Mrs. K also has macrocytic anemia (hemoglobin, 11.7 g/dL; hematocrit, 34.7%; mean corpuscular volume, 99.2 μm³). Albumin is low at 2.6 g/dL. Urine drug toxicology screen is negative. Fingerstick glucose reading is 139 mg/dL. Mrs. K is given a presumptive diagnosis of schizophrenia with catatonia.

Mrs. K’s BFCRS¹¹ score is 22 at admission. She is mute, holds postures for longer than a minute, and is resistant to repositioning. She also has extreme hypoactivity and does not interact with others. She has a fixed, blank stare, and exhibits mild grimacing.

The authors' observations

BFCRS defines each catatonic sign, rates its severity, and provides a standardized schema for clinical examination.¹¹ The BFCRS is preferred for routine use because of its validity, reliability, and ease of administration.¹² The treatment team rated Mrs. K at admission, during the course of treatment, and at discharge, showing a substantial improvement at the end of the hospitalization (Figure).

The authors' observations

Benzodiazepines (particularly lorazepam) and ECT are considered the treatment of choice for catatonic symptoms.¹¹ More than 72% of patients with catatonic symptoms remit after a trial of a benzodiazepine.¹ ECT is considered when patients do not respond to a benzodiazepine after 48 to 72 hours.³ Several cases of complete resolution of catatonic symptoms have been linked to ECT (Table 3).^13-18

A recent retrospective review revealed that patients who do not respond to loraze­pam are more likely to come from a rural setting, have a longer duration of illness, exhibit mutism, and exhibit third-person auditory hallucinations and made phenomena (the feeling that some aspect of the individual is under the external control of others).¹⁹ Case reports of treatment of catatonic patients with ECT vs lorazepam are listed in Table 3.^13-18

In pregnancy, ECT can be considered early in the course of illness. A review of the literature on ECT during pregnancy reported at least partial remission in 78% of studies reporting efficacy data.²⁰ Among these 339 patients, there were 25 fetal or neonatal complications—only 11 of these were related to ECT—and 20 maternal complications, of which 18 were related to ECT. The authors of this review concluded that 1) ECT is an effective treatment for severe mental illness during pregnancy and 2) the risks to fetus and mother are low.

A 2007 study identified 1,979 infants whose mothers reported use of benzodiazepines or hypnotic benzodiazepine-receptor agonists during early pregnancy.²¹ An additional 401 infants born to mothers who were prescribed these medications during late pregnancy also were included in this study. Women who took these medications were at an increased risk for preterm birth and low birth weight. The rate of congenital malformations in this study was moderately increased among infants exposed in early pregnancy (adjusted odds ratio = 1.24 [95% confidence interval, 1.00 to 1.55]).

Because catatonic symptoms can appear during the course of schizophrenia, several antipsychotics have been used to treat this condition. The efficacy and safety of antipsychotics for treating catatonia remains largely unknown, however.¹

OUTCOME: Recovery, baby girl

We begin oral haloperidol, 10 mg/d, for Mrs. K, which we then increase to 20 mg/d. Because she shows little response to haloperidol, we suggest a trial of ECT, but her husband refuses to consent. She is started on IM lorazepam, 6 mg/d.

Mrs. K gradually improves and increases her intake of food and liquids. After 10 days of lorazepam treatment, her BFCRS score decreases to 13. Mrs. K begins to speak and her gaze is less fixed. Negativistic behaviors are nearly absent.

Because we are concerned about Mrs. K’s pregnancy, lab tests are repeated. A complete metabolic panel shows an elevated glucose level (122 mg/dL); urinalysis reveals glycosuria (glucose, 1,000 mg/dL), proteinuria (protein, 10 mg/dL), and ketonuria, (ketones, 20 mg/dL). She is transferred to the obstetrics service for evaluation of gestational diabetes.

Psychotropics are continued while Mrs. K is on the obstetrics service; she returns to the inpatient psychiatric unit on an insulin regimen. IM lorazepam is increased to 8 mg/d, and haloperidol is decreased from 20 mg/d, to 10 mg/d, to prevent worsening of catatonia, which can occur when catatonic patients receive a psychotropic.¹¹ Three days later, Mrs. K’s BFCRS score is 12 and she shows only mild rigidity. Mrs. K briefly interacts with staff, particularly when she wants something.

Lorazepam is decreased to 1 mg/d in anticipation of cesarean delivery. Mrs. K becomes more adherent with her medications; often, she takes the oral dose of haloperidol, rather than the IM formulation. On mental status examination she exhibits poor eye contact, rather than a fixed gaze, and her BFCRS score decreases to 7 by day 25.

By the end of lorazepam treatment, Mrs. K has fully recovered from her catatonic state. She interacts with staff, engages with the treatment team, and is excited to go home. At discharge, she is given a diagnosis of schizophrenia with catatonia, and is taking haloperidol, 5 mg, twice a day. She gives birth to a healthy girl.

The authors' observations

Mrs. K was treated initially with haloperidol for several reasons. Haloperidol is relatively safe during pregnancy (FDA pregnancy category C) as shown by a recent multicenter, prospective, cohort study in which babies exposed in utero to haloperidol showed a congenital malformation (limb defect) rate within the expected baseline risk for the general population.²² Lorazepam is FDA category D for use in pregnancy and can cause preterm delivery,²³ floppy infant syndrome, and withdrawal syndromes.²⁴ We did not use a second-generation antipsychotic (SGA) because it could have made Mrs. K’s hyperglycemia worse. SGAs can induce gestational diabetes and increase the incidence of large-for-gestational-age newborns, compared with first-generation antipsychotics.²⁴ Last, Mrs. K’s family rejected ECT.

Because of Mrs. K’s poor response to haloperidol, the treatment team decided to start IM lorazepam, which eventually was increased to 8 mg/d. The haloperidol dose was reduced by half to avoid worsening of catatonia and reduce the risk of neuroleptic malignant syndrome.^1,25 When clinical response was achieved, lorazepam was tapered and Mrs. K was discharged with only haloperidol.

In the absence of well-designed prospective follow-up studies, information on the potential impact of prenatal exposure to antipsychotics and benzodiazepines on a child’s cognitive development is limited.²⁶ This case adds to the scant literature on the treatment of catatonia during pregnancy and illustrates how the BFCRS can be utilized during serial patient evaluations to monitor clinical improvement.

Bottom Line

Psychosis and catatonia during pregnancy are associated with complications to mother and child. The Bush-Francis Catatonia Rating Scale can be used to identify and track catatonic symptoms. Lorazepam and electroconvulsive therapy have been used safely and with good outcomes in mentally ill pregnant women when used appropriately.

Related Resources

• Fink M. Catatonia: a syndrome appears, disappears, and is rediscovered. Can J Psychiatry. 2009;54(7):437-445.
• Seethalakshmi R, Dhavale S, Suggu K, et al. Catatonic syndrome: importance of detection and treatment with lorazepam. Ann Clin Psychiatry. 2008;20(1):5-8.
• Salam S, Kilzieh N. Lorazepam treatment of psychogenic catatonia: an update. J Clin Psychiatry, 1988;49(suppl):16-21.

Drug Brand Names

Ceftriaxone • Rocephin                 Olanzapine • Zyprexa

Haloperidol • Haldol                     Short-acting Insulin • Novolin, Humulin

Lorazepam • Ativan 

Disclosures

Dr. Runyan receives grant support from Lippincott, Williams, & Wilkins. Drs. Durant, Prudent, and Sotelo report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Mute and unresponsive

Mrs. K, a 42-year-old Haitian who is 31 weeks pregnant, presents with a 4-week history of progressive mutism and psychomotor retardation. At inpatient admission, she is awake and alert but does not speak and resists the treatment team’s attempts to engage her. Mrs. K’s eyes are open, but she has a vacant stare and avoids eye contact. Her affect is flat and nonreactive and she appears internally preoccupied. Mrs. K exhibits motoric immobility, displays a rigid posture, and resists attempts to get her to move. Features of catatonic excitement, echo phenomena, posturing, stereotypies, and mannerisms are absent during the initial evaluation.

Mrs. K’s husband reports that they had been on vacation for 6 days before he brought her for psychiatric evaluation. He denies any recent evidence of psychosis or mood disturbance, stating that his wife was excited when she learned of the pregnancy, and attended all prenatal appointments. He reports that when this episode began, Mrs. K stopped talking to her 3-year-old daughter, did not respond to her name, and did not pay attention to those around her.

According to her husband, a similar episode occurred 2 years earlier, during which Mrs. K was selectively mute for approximately 1 month. She did not eat for 5 days and neglected the care of her daughter. There were 2 additional brief periods of prominent psychomotor retardation for which she was hospitalized in Haiti. According to the patient’s aunt, Mrs. K complained that her husband had cast a “voodoo spell” on her because he wanted sole custody of their daughter. Her husband recounted an episode, when they lived in Haiti, during which his wife became paranoid, left the house, and wandered the streets for 2 days.

The medical history is significant for a cervical polyp that was removed 2 years ago. Mrs. K has no history of substance abuse. She was born and raised in Haiti where she studied medicine. Her family reports that Mrs. K’s husband is “controlling,” which causes her distress.

The authors' observations

Catatonia is a neuropsychiatric syndrome that can occur in schizophrenia, mood disorders, mental retardation, neurologic disease, metabolic conditions, and drug intoxication.¹ Catatonia can present in several ways, from catatonic stupor to extreme purposeless agitation; more than 60 catatonic signs and symptoms have been described.¹ According to DSM-5² catatonia is characterized by 3 or more of the following symptoms:

•  stupor 

•  catalepsy

•  waxy flexibility

•  mutism

•  negativism

•  posturing

•  mannerism

•  stereotypy

•  agitation, not influenced by external stimuli

•  grimacing

•  echolalia

•  echopraxia.

Mrs. K exhibited stupor, mutism, posturing, and grimacing (Table 1).² We thought that her catatonic features were secondary to schizophrenia because she had paranoid delusions and displayed disorganized behavior while in Haiti. There was no evidence of past or current mood disorder, metabolic condition, neurologic illness, or substance abuse.

Catatonia and pregnancy

There is little available information to guide clinicians who are treating a pregnant woman who has a catatonic syndrome. Espinola-Nadurille and co-workers described a 22-year-old pregnant (21 weeks) woman from rural Mexico who was hospitalized with agitation, disorganized speech, restlessness, and hallucinations after several weeks of alternating agitation and withdrawal with mutism and refusal to eat or drink.³ This patient developed malignant catatonia with creatine phosphokinase elevation and leukocytosis and eventually responded to treatment with lorazepam and electroconvulsive therapy (ECT). She was given a diagnosis of schizophreniform disorder. Treating her catatonic symptoms did not result in any adverse effects on the pregnancy or the fetus.

Exacerbation of schizophrenia during pregnancy can lead to neglect of pregnancy and prenatal care,⁴ imminent harm to the fetus because of malnutrition and dehydration, and risk of preterm delivery and low weight at birth. Prolonged catatonia can cause medical complications such as decubitus ulcers, incontinence, recurrent urinary tract infections, aspiration pneumonia, increased risk of deep venous thrombosis, malnutrition, and ocular complications because of prolonged staring and reduced blinking (Table 2^5-10). For these reasons, it is important to treat this condition early and aggressively to improve pregnancy outcome and infant well-being.

EVALUATION: Flat affect

The mental status examination on admission describes a tall, black, Haitian woman with unkempt hair and fair hygiene. Mrs. K has a prominent abdomen, consistent with a 31-week pregnancy. She exhibits a blank stare without direct eye contact; she is mute, and exhibits flat affect. We cannot evaluate her thought processes and content because Mrs. K is mute, although she does appear internally preoccupied.

Physical examination on admission is unremarkable; vital signs are stable and within normal limits. Laboratory work-up reveals a urinary tract infection, which is treated with ceftriaxone. Mrs. K also has macrocytic anemia (hemoglobin, 11.7 g/dL; hematocrit, 34.7%; mean corpuscular volume, 99.2 μm³). Albumin is low at 2.6 g/dL. Urine drug toxicology screen is negative. Fingerstick glucose reading is 139 mg/dL. Mrs. K is given a presumptive diagnosis of schizophrenia with catatonia.

Mrs. K’s BFCRS¹¹ score is 22 at admission. She is mute, holds postures for longer than a minute, and is resistant to repositioning. She also has extreme hypoactivity and does not interact with others. She has a fixed, blank stare, and exhibits mild grimacing.

The authors' observations

BFCRS defines each catatonic sign, rates its severity, and provides a standardized schema for clinical examination.¹¹ The BFCRS is preferred for routine use because of its validity, reliability, and ease of administration.¹² The treatment team rated Mrs. K at admission, during the course of treatment, and at discharge, showing a substantial improvement at the end of the hospitalization (Figure).

The authors' observations

Benzodiazepines (particularly lorazepam) and ECT are considered the treatment of choice for catatonic symptoms.¹¹ More than 72% of patients with catatonic symptoms remit after a trial of a benzodiazepine.¹ ECT is considered when patients do not respond to a benzodiazepine after 48 to 72 hours.³ Several cases of complete resolution of catatonic symptoms have been linked to ECT (Table 3).^13-18

A recent retrospective review revealed that patients who do not respond to loraze­pam are more likely to come from a rural setting, have a longer duration of illness, exhibit mutism, and exhibit third-person auditory hallucinations and made phenomena (the feeling that some aspect of the individual is under the external control of others).¹⁹ Case reports of treatment of catatonic patients with ECT vs lorazepam are listed in Table 3.^13-18

In pregnancy, ECT can be considered early in the course of illness. A review of the literature on ECT during pregnancy reported at least partial remission in 78% of studies reporting efficacy data.²⁰ Among these 339 patients, there were 25 fetal or neonatal complications—only 11 of these were related to ECT—and 20 maternal complications, of which 18 were related to ECT. The authors of this review concluded that 1) ECT is an effective treatment for severe mental illness during pregnancy and 2) the risks to fetus and mother are low.

A 2007 study identified 1,979 infants whose mothers reported use of benzodiazepines or hypnotic benzodiazepine-receptor agonists during early pregnancy.²¹ An additional 401 infants born to mothers who were prescribed these medications during late pregnancy also were included in this study. Women who took these medications were at an increased risk for preterm birth and low birth weight. The rate of congenital malformations in this study was moderately increased among infants exposed in early pregnancy (adjusted odds ratio = 1.24 [95% confidence interval, 1.00 to 1.55]).

Because catatonic symptoms can appear during the course of schizophrenia, several antipsychotics have been used to treat this condition. The efficacy and safety of antipsychotics for treating catatonia remains largely unknown, however.¹

OUTCOME: Recovery, baby girl

We begin oral haloperidol, 10 mg/d, for Mrs. K, which we then increase to 20 mg/d. Because she shows little response to haloperidol, we suggest a trial of ECT, but her husband refuses to consent. She is started on IM lorazepam, 6 mg/d.

Mrs. K gradually improves and increases her intake of food and liquids. After 10 days of lorazepam treatment, her BFCRS score decreases to 13. Mrs. K begins to speak and her gaze is less fixed. Negativistic behaviors are nearly absent.

Because we are concerned about Mrs. K’s pregnancy, lab tests are repeated. A complete metabolic panel shows an elevated glucose level (122 mg/dL); urinalysis reveals glycosuria (glucose, 1,000 mg/dL), proteinuria (protein, 10 mg/dL), and ketonuria, (ketones, 20 mg/dL). She is transferred to the obstetrics service for evaluation of gestational diabetes.

Psychotropics are continued while Mrs. K is on the obstetrics service; she returns to the inpatient psychiatric unit on an insulin regimen. IM lorazepam is increased to 8 mg/d, and haloperidol is decreased from 20 mg/d, to 10 mg/d, to prevent worsening of catatonia, which can occur when catatonic patients receive a psychotropic.¹¹ Three days later, Mrs. K’s BFCRS score is 12 and she shows only mild rigidity. Mrs. K briefly interacts with staff, particularly when she wants something.

Lorazepam is decreased to 1 mg/d in anticipation of cesarean delivery. Mrs. K becomes more adherent with her medications; often, she takes the oral dose of haloperidol, rather than the IM formulation. On mental status examination she exhibits poor eye contact, rather than a fixed gaze, and her BFCRS score decreases to 7 by day 25.

By the end of lorazepam treatment, Mrs. K has fully recovered from her catatonic state. She interacts with staff, engages with the treatment team, and is excited to go home. At discharge, she is given a diagnosis of schizophrenia with catatonia, and is taking haloperidol, 5 mg, twice a day. She gives birth to a healthy girl.

The authors' observations

Mrs. K was treated initially with haloperidol for several reasons. Haloperidol is relatively safe during pregnancy (FDA pregnancy category C) as shown by a recent multicenter, prospective, cohort study in which babies exposed in utero to haloperidol showed a congenital malformation (limb defect) rate within the expected baseline risk for the general population.²² Lorazepam is FDA category D for use in pregnancy and can cause preterm delivery,²³ floppy infant syndrome, and withdrawal syndromes.²⁴ We did not use a second-generation antipsychotic (SGA) because it could have made Mrs. K’s hyperglycemia worse. SGAs can induce gestational diabetes and increase the incidence of large-for-gestational-age newborns, compared with first-generation antipsychotics.²⁴ Last, Mrs. K’s family rejected ECT.

Because of Mrs. K’s poor response to haloperidol, the treatment team decided to start IM lorazepam, which eventually was increased to 8 mg/d. The haloperidol dose was reduced by half to avoid worsening of catatonia and reduce the risk of neuroleptic malignant syndrome.^1,25 When clinical response was achieved, lorazepam was tapered and Mrs. K was discharged with only haloperidol.

In the absence of well-designed prospective follow-up studies, information on the potential impact of prenatal exposure to antipsychotics and benzodiazepines on a child’s cognitive development is limited.²⁶ This case adds to the scant literature on the treatment of catatonia during pregnancy and illustrates how the BFCRS can be utilized during serial patient evaluations to monitor clinical improvement.

Bottom Line

Psychosis and catatonia during pregnancy are associated with complications to mother and child. The Bush-Francis Catatonia Rating Scale can be used to identify and track catatonic symptoms. Lorazepam and electroconvulsive therapy have been used safely and with good outcomes in mentally ill pregnant women when used appropriately.

Related Resources

• Fink M. Catatonia: a syndrome appears, disappears, and is rediscovered. Can J Psychiatry. 2009;54(7):437-445.
• Seethalakshmi R, Dhavale S, Suggu K, et al. Catatonic syndrome: importance of detection and treatment with lorazepam. Ann Clin Psychiatry. 2008;20(1):5-8.
• Salam S, Kilzieh N. Lorazepam treatment of psychogenic catatonia: an update. J Clin Psychiatry, 1988;49(suppl):16-21.

Drug Brand Names

Ceftriaxone • Rocephin                 Olanzapine • Zyprexa

Haloperidol • Haldol                     Short-acting Insulin • Novolin, Humulin

Lorazepam • Ativan 

Disclosures

Dr. Runyan receives grant support from Lippincott, Williams, & Wilkins. Drs. Durant, Prudent, and Sotelo report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Delirium is a common condition in hospitalized older patients. Often, a report of a “change in mental status” is the reason geriatric patients are sent to the emergency room for evaluation, although delirium also can develop after admission.

Delirium is a marker of underlying medical illness that needs careful workup and treatment. The condition can be iatrogenic, resulting from prescribed medication or a surgical procedure; most often, it is the consequence of multiple factors. Delirium can be expensive, because it increases hospital length of stay and overall costs—particularly if the patient is discharged to a nursing facility, not to home. Patients with delirium are at higher risk of death.

Delirium often goes unrecognized by physicians and nursing staff, and is not documented in medical records. Educating the medical staff on the identification and management of delirium is a key role for consulting psychiatrists.

CASE: Confused and agitated

Ms. T, a 93-year-old resident of an assisted living facility with a history of three
cerebral vascular accidents, atrial fibrillation, hypertension, multiple deep venous thromboses, blindness in her right eye, and deafness in her right ear without a hearing aid, is brought to the hospital after a syncopal episode lasting 10 minutes that was followed by slurred speech, confusion, and transient hypotension. Her dentist recently started her on azithromycin.

In the emergency room, Ms. T’s elevated blood pressure is managed with hydralazine and diltiazem. A CT scan of the head rules out hemorrhagic stroke. Complete blood count and tests of electrolytes, vitamin B12, and thyroid-stimulating hormone are within normal limits; urinalysis is negative for urinary tract infection.

Ms. T is noted to be in and out of sleep, with some confusion. She is maintained without oral food or fluids because of concerns about her ability to swallow. After 5 or 6 hours in the ER, Ms. T is transferred to a medical unit, where she becomes agitated and paranoid, with the delusion that her daughter is an impostor. She yells, is combative, and refuses medication.

Her confusion and behaviors become worse at night: She pulls out her IV line and telemetry leads. Blood pressure remains elevated, for which she receives additional doses of hydralazine.

For behavioral management, the medical team orders a one-time IM dose of haloperidol and starts her on risperidone, 0.5 mg every 4 hours as needed, which Ms. T refuses to take. She is incontinent and has foul-smelling urine.

Ms. T’s family is shocked at her condition; nursing staff is frustrated. With her worsening paranoia, delusions, and combative behaviors towards the nursing staff, psychiatry is consulted.

How to recognize and diagnose

The Box lists DSM-5 criteria for delirium.¹ The key feature is a disturbance in attention—what was referred to in DSM-IV-TR as “disturbance in consciousness.” That finding contrasts with what is seen in dementia, with its hallmark memory impairment and chronic deterioration.

In a hospital setting, the question is often asked: Does this patient have dementia or delirium? In many cases, the answer is both, because preexisting cognitive impairment is an important risk factor for delirium.

In addition to the standard clinical interview, several screening instruments or delirium rating scales have been developed. The most commonly used (Table 1) is the Confusion Assessment Method developed by Inouye and colleagues.²

Subtypes of delirium have been described, largely based on motor activity. Patients can present as hyperactive, hypoactive, mixed, or neither.³ Psychiatrists are more likely to be consulted regarding patients with hyperactive delirium, because they are the ones who scream, pull out their IV line, hallucinate, and are delusional, insisting they “have to go home”—such as the patient described in the case above.

Patients with hypoactive delirium often, on the other hand, are difficult to recognize; they present with lethargy, drowsiness, apathy, and confusion. They become withdrawn and answer slowly⁴; often, psychiatry is consulted to assess them for depression.

Delirium can be difficult to diagnose in patients with underlying dementia, who are not able to provide information. In such cases, obtaining collateral information from a family member or primary caretaker is crucial. Knowing the patient’s baseline helps to determine whether there has been an acute change in mental status.

CASE CONTINUED: Acute mental status changes

Ms. T’s daughter reports that her mother has not been in this condition before. At baseline, Ms. T has had memory problems but no paranoia, delusions, or agitated behaviors. Her daughter also reports that Ms. T has visual and hearing impairments and is not wearing her hearing aid.

The acute change in mental status and the perceptual disturbances indicate that Ms. T has delirium, not dementia.

Who is likely to develop delirium?

Risk factors for delirium (Table 2) include preexisting cognitive impairment, older age, vision and hearing impairment, use of psychoactive drugs, severe illness, azotemia and dehydration, a metabolic abnormality, and infection. Male sex also seems to be a risk factor, perhaps because men are more likely to abuse alcohol before admission.

Many patients become delirious after starting a new medication. An experienced geriatrician teaches that the main causes of delirium are “drugs, drugs, drugs, infections, and everything else” (Kenneth Rockwood, MD, personal communication, 2012). At admission, urinary tract infection and pneumonia are common causes of delirium, especially in geriatric patients.

What is the clinical course?

The clinical course varies widely. Delirium often is the reason that a patient is brought to the hospital, presenting with the condition at admission or early in hospitalization. The highest incidence among surgical patients appears to be on the third postoperative day—in some cases because of alcohol or drug withdrawal.

As noted in the DSM-5 criteria, delirium often comes on acutely, over hours or days. Symptoms can persist for weeks after initial onset of episodes of delirium.⁵ Symptoms fluctuate over the course of the day; at times, they can be missed if a provider sees the patient only while she (he) is clearer and doesn’t review nursing notes from other shifts.

How does delirium affect outcome?

Delirium has been shown to be associated with prolonged hospital stay (21 days, compared with 11 days in the absence of delirium), functional decline during hospitalization, and increased admission to long-term care (36% compared with 13%).⁶ In a study by O’Keefe and Lavan,⁶ delirious patients were more likely to sustain falls and to develop urinary incontinence, pressure sores, and other complications during hospitalization.

Older patients with delirium superimposed on dementia had a more than twofold increased risk of mortality compared with patients with dementia alone or with neither dementia nor delirium.⁷ Rockwood found that an episode of delirium was associated with a much higher rate of subsequent dementia.⁸

Think of an acute medical illness as a “stress test” for the brain, such that, if the patient develops delirium, it suggests an underlying brain disease that was not evident before the acute episode. After hip fracture, for example, delirium was independently associated with poor functional recovery at 1 month⁹ and at 2 years.¹⁰

Older patients admitted to a skilled nursing facility with delirium are more likely to experience one or more complications (73% compared with 41%).¹¹ In the study by Marcantonio and colleagues, patients with delirium were more than twice as likely to be hospitalized again within 30 days (30% and 13%), and less than half as likely to be discharged to the community (30% and 73%). Table 3 summarizes the impact of delirium on outcomes.

Appropriate management steps

Identifying and treating underlying medical illness is the definitive treatment for delirium; in a geriatric patient with multiple medical comorbidities the pathogenesis often is multifactorial or a definitive precipitant cannot always be identified.¹²

Managing a patient with delirium includes both non-pharmacotherapeutic interventions, which should be considered first-line, and pharmacotherapeutic interventions. Non-pharmacotherapeutic interventions include, but are not limited to:

•  support and close observation by nursing staff

•  placing a clock or calendar in the room

•  frequent reorientation and reminders

•  placing familiar possessions in the room

•  putting the patient in an isolated room with a window

•  regulating the sleep-wake cycle.⁴

Pharmacotherapeutic intervention in delirium should be used for behavioral symptoms, but only for the minimum duration necessary⁴ and preferably oral or IV. No drugs are FDA-approved for delirium, which means that use of any agent is off-label.¹³

Antipsychotics are the mainstay of pharmacotherapy for delirium in most settings. The use of antipsychotics relates to the dopamine excess-acetylcholine deficiency hypothesis of delirium pathophysiology.¹² Haloperidol remains the first-line agent because it is available in multiple dosages and can be given by various routes. IV haloperidol appears to carry less risk of extrapyramidal symptoms than oral haloperidol does but, as with all antipsychotics, its use warrants monitoring for QTc prolongation.¹²

Studies have not shown that atypical antipsychotics are superior to typical antipsychotics for delirium. Multiple studies have shown that atypicals are as efficacious as haloperidol.

Benzodiazepines are the treatment of choice for delirium caused by alcohol withdrawal. A Cochrane review found no evidence that benzodiazepines were helpful in treating delirium unrelated to alcohol withdrawal.¹⁴ In some studies, benzodiazepines were associated with an increased risk of delirium, especially in patients in the intensive care unit.¹⁵

More recently, cholinesterase inhibitors have been used to treat delirium. The reasoning behind their use is the hypothesis of a central cholinergic deficiency in delirium.¹² Regrettably, there have been few well-conducted studies of these agents in delirium, and a Cochrane review found no significant benefit for cholinesterase inhibitors.¹⁶ With the same hypothesis in mind, anticholinergic medications in patients with delirium should be avoided because these agents could exacerbate delirium by further decreasing the acetylcholine level.

Because delirium is common in the hospitalized population (especially older patients), a number of studies have examined strategies to prevent or reduce its development. Inouye and colleagues conducted a controlled clinical trial, in which they intervened to reduce six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual and hearing impairment, and dehydration in hospitalized geriatric patients. The number and duration of events of delirium were significantly lower in the intervention group.¹⁷

Brummel et al reported that reducing modifiable risk factors in intensive care unit patients—including sedation management, minimizing deliriogenic medications (anticholinergics, antihistamines), minimizing sleep disruption, and encouraging early mobility—could prevent or reduce the incidence of delirium.¹⁵

CASE CONCLUDED: Return to baseline

Ms. T’s medications are minimized or discontinued, including azithromycin, based on case reports in the literature. She is stabilized hemodynamically.

Clinicians educate Ms. T’s family about delirium. To address Ms. T’s aggressive and paranoid behaviors, clinicians request that a family member is present to reassure Ms. T. She is continued on low-dose haloperidol. The family also is asked to bring Ms. T’s hearing aid and eyeglasses.

MRI is performed after Ms. T’s behavior is under control. The scan is negative for a new stroke.

Repeat blood tests the following day show an elevated white blood cell count; urinalysis is positive for a urinary tract infection. Ms. T is started on antibiotics. Subsequent urine culture shows no bacterial growth; the antibiotics are stopped after 3 days.

Ms. T slowly improves. According to her family, she is back at baseline in 3 or 4 days.

This case illustrates the complexity of trying to identify the precise cause of delirium among the many that could be involved. Often, no single cause can be found.¹⁸

Bottom Line
Delirium is a common and potentially life-threatening condition in hospitalized geriatric patients. General hospital psychiatrists should know how to recognize and treat the condition in collaboration with their medical colleagues.

Related Resources

• Treating delirium: a quick reference guide. Arlington, VA: American Psychiatric Association. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1662986.
• Cook IA. Guideline watch: practice guidelines for the treatment of patients with delirium. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1681952.
• Fearing MA, Inouye SK. Delirium. In: Blazer DG, Steffens D, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. 4th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2009:229-241.
• Ghandour A, Saab R, Mehr D. Detecting and treating delirium—key interventions you may be missing. J Fam Pract. 2011;60(12):726-734.
• Leentjens AF, Rundell J, Rummans T, et al. Delirium: an evidence-based medicine (EBM) monograph for psychosomatic medicine practice. J Psychosom Res. 2012;73:149-152.
• Liptzin B, Jacobson SA. Delirium. In: Sadock BJ, Sadock VA, Ruiz P, eds. Comprehensive textbook of psychiatry. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:4066-4073.

Drug Brand Names

Azithromycin • Zithromax                 Hydralazine • Apresoline

Diltiazem • Cardizem                        Risperidone • Risperdal

Haloperidol • Haldo

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.


Featured Audio
Benjamin Liptzin, MD, describes the distinction between dementia and delirium. Dr. Liptzin is Chair of Psychiatry, Baystate Medical Center, Springfield, Massachusetts, and Professor and Deputy Chair, Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.

Delirium is a common condition in hospitalized older patients. Often, a report of a “change in mental status” is the reason geriatric patients are sent to the emergency room for evaluation, although delirium also can develop after admission.

Delirium is a marker of underlying medical illness that needs careful workup and treatment. The condition can be iatrogenic, resulting from prescribed medication or a surgical procedure; most often, it is the consequence of multiple factors. Delirium can be expensive, because it increases hospital length of stay and overall costs—particularly if the patient is discharged to a nursing facility, not to home. Patients with delirium are at higher risk of death.

Delirium often goes unrecognized by physicians and nursing staff, and is not documented in medical records. Educating the medical staff on the identification and management of delirium is a key role for consulting psychiatrists.

CASE: Confused and agitated

Ms. T, a 93-year-old resident of an assisted living facility with a history of three
cerebral vascular accidents, atrial fibrillation, hypertension, multiple deep venous thromboses, blindness in her right eye, and deafness in her right ear without a hearing aid, is brought to the hospital after a syncopal episode lasting 10 minutes that was followed by slurred speech, confusion, and transient hypotension. Her dentist recently started her on azithromycin.

In the emergency room, Ms. T’s elevated blood pressure is managed with hydralazine and diltiazem. A CT scan of the head rules out hemorrhagic stroke. Complete blood count and tests of electrolytes, vitamin B12, and thyroid-stimulating hormone are within normal limits; urinalysis is negative for urinary tract infection.

Ms. T is noted to be in and out of sleep, with some confusion. She is maintained without oral food or fluids because of concerns about her ability to swallow. After 5 or 6 hours in the ER, Ms. T is transferred to a medical unit, where she becomes agitated and paranoid, with the delusion that her daughter is an impostor. She yells, is combative, and refuses medication.

Her confusion and behaviors become worse at night: She pulls out her IV line and telemetry leads. Blood pressure remains elevated, for which she receives additional doses of hydralazine.

For behavioral management, the medical team orders a one-time IM dose of haloperidol and starts her on risperidone, 0.5 mg every 4 hours as needed, which Ms. T refuses to take. She is incontinent and has foul-smelling urine.

Ms. T’s family is shocked at her condition; nursing staff is frustrated. With her worsening paranoia, delusions, and combative behaviors towards the nursing staff, psychiatry is consulted.

How to recognize and diagnose

The Box lists DSM-5 criteria for delirium.¹ The key feature is a disturbance in attention—what was referred to in DSM-IV-TR as “disturbance in consciousness.” That finding contrasts with what is seen in dementia, with its hallmark memory impairment and chronic deterioration.

In a hospital setting, the question is often asked: Does this patient have dementia or delirium? In many cases, the answer is both, because preexisting cognitive impairment is an important risk factor for delirium.

In addition to the standard clinical interview, several screening instruments or delirium rating scales have been developed. The most commonly used (Table 1) is the Confusion Assessment Method developed by Inouye and colleagues.²

Subtypes of delirium have been described, largely based on motor activity. Patients can present as hyperactive, hypoactive, mixed, or neither.³ Psychiatrists are more likely to be consulted regarding patients with hyperactive delirium, because they are the ones who scream, pull out their IV line, hallucinate, and are delusional, insisting they “have to go home”—such as the patient described in the case above.

Patients with hypoactive delirium often, on the other hand, are difficult to recognize; they present with lethargy, drowsiness, apathy, and confusion. They become withdrawn and answer slowly⁴; often, psychiatry is consulted to assess them for depression.

Delirium can be difficult to diagnose in patients with underlying dementia, who are not able to provide information. In such cases, obtaining collateral information from a family member or primary caretaker is crucial. Knowing the patient’s baseline helps to determine whether there has been an acute change in mental status.

CASE CONTINUED: Acute mental status changes

Ms. T’s daughter reports that her mother has not been in this condition before. At baseline, Ms. T has had memory problems but no paranoia, delusions, or agitated behaviors. Her daughter also reports that Ms. T has visual and hearing impairments and is not wearing her hearing aid.

The acute change in mental status and the perceptual disturbances indicate that Ms. T has delirium, not dementia.

Who is likely to develop delirium?

Risk factors for delirium (Table 2) include preexisting cognitive impairment, older age, vision and hearing impairment, use of psychoactive drugs, severe illness, azotemia and dehydration, a metabolic abnormality, and infection. Male sex also seems to be a risk factor, perhaps because men are more likely to abuse alcohol before admission.

Many patients become delirious after starting a new medication. An experienced geriatrician teaches that the main causes of delirium are “drugs, drugs, drugs, infections, and everything else” (Kenneth Rockwood, MD, personal communication, 2012). At admission, urinary tract infection and pneumonia are common causes of delirium, especially in geriatric patients.

What is the clinical course?

The clinical course varies widely. Delirium often is the reason that a patient is brought to the hospital, presenting with the condition at admission or early in hospitalization. The highest incidence among surgical patients appears to be on the third postoperative day—in some cases because of alcohol or drug withdrawal.

As noted in the DSM-5 criteria, delirium often comes on acutely, over hours or days. Symptoms can persist for weeks after initial onset of episodes of delirium.⁵ Symptoms fluctuate over the course of the day; at times, they can be missed if a provider sees the patient only while she (he) is clearer and doesn’t review nursing notes from other shifts.

How does delirium affect outcome?

Delirium has been shown to be associated with prolonged hospital stay (21 days, compared with 11 days in the absence of delirium), functional decline during hospitalization, and increased admission to long-term care (36% compared with 13%).⁶ In a study by O’Keefe and Lavan,⁶ delirious patients were more likely to sustain falls and to develop urinary incontinence, pressure sores, and other complications during hospitalization.

Older patients with delirium superimposed on dementia had a more than twofold increased risk of mortality compared with patients with dementia alone or with neither dementia nor delirium.⁷ Rockwood found that an episode of delirium was associated with a much higher rate of subsequent dementia.⁸

Think of an acute medical illness as a “stress test” for the brain, such that, if the patient develops delirium, it suggests an underlying brain disease that was not evident before the acute episode. After hip fracture, for example, delirium was independently associated with poor functional recovery at 1 month⁹ and at 2 years.¹⁰

Older patients admitted to a skilled nursing facility with delirium are more likely to experience one or more complications (73% compared with 41%).¹¹ In the study by Marcantonio and colleagues, patients with delirium were more than twice as likely to be hospitalized again within 30 days (30% and 13%), and less than half as likely to be discharged to the community (30% and 73%). Table 3 summarizes the impact of delirium on outcomes.

Appropriate management steps

Identifying and treating underlying medical illness is the definitive treatment for delirium; in a geriatric patient with multiple medical comorbidities the pathogenesis often is multifactorial or a definitive precipitant cannot always be identified.¹²

Managing a patient with delirium includes both non-pharmacotherapeutic interventions, which should be considered first-line, and pharmacotherapeutic interventions. Non-pharmacotherapeutic interventions include, but are not limited to:

•  support and close observation by nursing staff

•  placing a clock or calendar in the room

•  frequent reorientation and reminders

•  placing familiar possessions in the room

•  putting the patient in an isolated room with a window

•  regulating the sleep-wake cycle.⁴

Pharmacotherapeutic intervention in delirium should be used for behavioral symptoms, but only for the minimum duration necessary⁴ and preferably oral or IV. No drugs are FDA-approved for delirium, which means that use of any agent is off-label.¹³

Antipsychotics are the mainstay of pharmacotherapy for delirium in most settings. The use of antipsychotics relates to the dopamine excess-acetylcholine deficiency hypothesis of delirium pathophysiology.¹² Haloperidol remains the first-line agent because it is available in multiple dosages and can be given by various routes. IV haloperidol appears to carry less risk of extrapyramidal symptoms than oral haloperidol does but, as with all antipsychotics, its use warrants monitoring for QTc prolongation.¹²

Studies have not shown that atypical antipsychotics are superior to typical antipsychotics for delirium. Multiple studies have shown that atypicals are as efficacious as haloperidol.

Benzodiazepines are the treatment of choice for delirium caused by alcohol withdrawal. A Cochrane review found no evidence that benzodiazepines were helpful in treating delirium unrelated to alcohol withdrawal.¹⁴ In some studies, benzodiazepines were associated with an increased risk of delirium, especially in patients in the intensive care unit.¹⁵

More recently, cholinesterase inhibitors have been used to treat delirium. The reasoning behind their use is the hypothesis of a central cholinergic deficiency in delirium.¹² Regrettably, there have been few well-conducted studies of these agents in delirium, and a Cochrane review found no significant benefit for cholinesterase inhibitors.¹⁶ With the same hypothesis in mind, anticholinergic medications in patients with delirium should be avoided because these agents could exacerbate delirium by further decreasing the acetylcholine level.

Because delirium is common in the hospitalized population (especially older patients), a number of studies have examined strategies to prevent or reduce its development. Inouye and colleagues conducted a controlled clinical trial, in which they intervened to reduce six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual and hearing impairment, and dehydration in hospitalized geriatric patients. The number and duration of events of delirium were significantly lower in the intervention group.¹⁷

Brummel et al reported that reducing modifiable risk factors in intensive care unit patients—including sedation management, minimizing deliriogenic medications (anticholinergics, antihistamines), minimizing sleep disruption, and encouraging early mobility—could prevent or reduce the incidence of delirium.¹⁵

CASE CONCLUDED: Return to baseline

Ms. T’s medications are minimized or discontinued, including azithromycin, based on case reports in the literature. She is stabilized hemodynamically.

Clinicians educate Ms. T’s family about delirium. To address Ms. T’s aggressive and paranoid behaviors, clinicians request that a family member is present to reassure Ms. T. She is continued on low-dose haloperidol. The family also is asked to bring Ms. T’s hearing aid and eyeglasses.

MRI is performed after Ms. T’s behavior is under control. The scan is negative for a new stroke.

Repeat blood tests the following day show an elevated white blood cell count; urinalysis is positive for a urinary tract infection. Ms. T is started on antibiotics. Subsequent urine culture shows no bacterial growth; the antibiotics are stopped after 3 days.

Ms. T slowly improves. According to her family, she is back at baseline in 3 or 4 days.

This case illustrates the complexity of trying to identify the precise cause of delirium among the many that could be involved. Often, no single cause can be found.¹⁸

Bottom Line
Delirium is a common and potentially life-threatening condition in hospitalized geriatric patients. General hospital psychiatrists should know how to recognize and treat the condition in collaboration with their medical colleagues.

Related Resources

• Treating delirium: a quick reference guide. Arlington, VA: American Psychiatric Association. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1662986.
• Cook IA. Guideline watch: practice guidelines for the treatment of patients with delirium. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1681952.
• Fearing MA, Inouye SK. Delirium. In: Blazer DG, Steffens D, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. 4th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2009:229-241.
• Ghandour A, Saab R, Mehr D. Detecting and treating delirium—key interventions you may be missing. J Fam Pract. 2011;60(12):726-734.
• Leentjens AF, Rundell J, Rummans T, et al. Delirium: an evidence-based medicine (EBM) monograph for psychosomatic medicine practice. J Psychosom Res. 2012;73:149-152.
• Liptzin B, Jacobson SA. Delirium. In: Sadock BJ, Sadock VA, Ruiz P, eds. Comprehensive textbook of psychiatry. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:4066-4073.

Drug Brand Names

Azithromycin • Zithromax                 Hydralazine • Apresoline

Diltiazem • Cardizem                        Risperidone • Risperdal

Haloperidol • Haldo

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.


Featured Audio
Benjamin Liptzin, MD, describes the distinction between dementia and delirium. Dr. Liptzin is Chair of Psychiatry, Baystate Medical Center, Springfield, Massachusetts, and Professor and Deputy Chair, Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.

Delirium is a common condition in hospitalized older patients. Often, a report of a “change in mental status” is the reason geriatric patients are sent to the emergency room for evaluation, although delirium also can develop after admission.

Delirium is a marker of underlying medical illness that needs careful workup and treatment. The condition can be iatrogenic, resulting from prescribed medication or a surgical procedure; most often, it is the consequence of multiple factors. Delirium can be expensive, because it increases hospital length of stay and overall costs—particularly if the patient is discharged to a nursing facility, not to home. Patients with delirium are at higher risk of death.

Delirium often goes unrecognized by physicians and nursing staff, and is not documented in medical records. Educating the medical staff on the identification and management of delirium is a key role for consulting psychiatrists.

CASE: Confused and agitated

Ms. T, a 93-year-old resident of an assisted living facility with a history of three
cerebral vascular accidents, atrial fibrillation, hypertension, multiple deep venous thromboses, blindness in her right eye, and deafness in her right ear without a hearing aid, is brought to the hospital after a syncopal episode lasting 10 minutes that was followed by slurred speech, confusion, and transient hypotension. Her dentist recently started her on azithromycin.

In the emergency room, Ms. T’s elevated blood pressure is managed with hydralazine and diltiazem. A CT scan of the head rules out hemorrhagic stroke. Complete blood count and tests of electrolytes, vitamin B12, and thyroid-stimulating hormone are within normal limits; urinalysis is negative for urinary tract infection.

Ms. T is noted to be in and out of sleep, with some confusion. She is maintained without oral food or fluids because of concerns about her ability to swallow. After 5 or 6 hours in the ER, Ms. T is transferred to a medical unit, where she becomes agitated and paranoid, with the delusion that her daughter is an impostor. She yells, is combative, and refuses medication.

Her confusion and behaviors become worse at night: She pulls out her IV line and telemetry leads. Blood pressure remains elevated, for which she receives additional doses of hydralazine.

For behavioral management, the medical team orders a one-time IM dose of haloperidol and starts her on risperidone, 0.5 mg every 4 hours as needed, which Ms. T refuses to take. She is incontinent and has foul-smelling urine.

Ms. T’s family is shocked at her condition; nursing staff is frustrated. With her worsening paranoia, delusions, and combative behaviors towards the nursing staff, psychiatry is consulted.

How to recognize and diagnose

The Box lists DSM-5 criteria for delirium.¹ The key feature is a disturbance in attention—what was referred to in DSM-IV-TR as “disturbance in consciousness.” That finding contrasts with what is seen in dementia, with its hallmark memory impairment and chronic deterioration.

In a hospital setting, the question is often asked: Does this patient have dementia or delirium? In many cases, the answer is both, because preexisting cognitive impairment is an important risk factor for delirium.

In addition to the standard clinical interview, several screening instruments or delirium rating scales have been developed. The most commonly used (Table 1) is the Confusion Assessment Method developed by Inouye and colleagues.²

Subtypes of delirium have been described, largely based on motor activity. Patients can present as hyperactive, hypoactive, mixed, or neither.³ Psychiatrists are more likely to be consulted regarding patients with hyperactive delirium, because they are the ones who scream, pull out their IV line, hallucinate, and are delusional, insisting they “have to go home”—such as the patient described in the case above.

Patients with hypoactive delirium often, on the other hand, are difficult to recognize; they present with lethargy, drowsiness, apathy, and confusion. They become withdrawn and answer slowly⁴; often, psychiatry is consulted to assess them for depression.

Delirium can be difficult to diagnose in patients with underlying dementia, who are not able to provide information. In such cases, obtaining collateral information from a family member or primary caretaker is crucial. Knowing the patient’s baseline helps to determine whether there has been an acute change in mental status.

CASE CONTINUED: Acute mental status changes

Ms. T’s daughter reports that her mother has not been in this condition before. At baseline, Ms. T has had memory problems but no paranoia, delusions, or agitated behaviors. Her daughter also reports that Ms. T has visual and hearing impairments and is not wearing her hearing aid.

The acute change in mental status and the perceptual disturbances indicate that Ms. T has delirium, not dementia.

Who is likely to develop delirium?

Risk factors for delirium (Table 2) include preexisting cognitive impairment, older age, vision and hearing impairment, use of psychoactive drugs, severe illness, azotemia and dehydration, a metabolic abnormality, and infection. Male sex also seems to be a risk factor, perhaps because men are more likely to abuse alcohol before admission.

Many patients become delirious after starting a new medication. An experienced geriatrician teaches that the main causes of delirium are “drugs, drugs, drugs, infections, and everything else” (Kenneth Rockwood, MD, personal communication, 2012). At admission, urinary tract infection and pneumonia are common causes of delirium, especially in geriatric patients.

What is the clinical course?

The clinical course varies widely. Delirium often is the reason that a patient is brought to the hospital, presenting with the condition at admission or early in hospitalization. The highest incidence among surgical patients appears to be on the third postoperative day—in some cases because of alcohol or drug withdrawal.

As noted in the DSM-5 criteria, delirium often comes on acutely, over hours or days. Symptoms can persist for weeks after initial onset of episodes of delirium.⁵ Symptoms fluctuate over the course of the day; at times, they can be missed if a provider sees the patient only while she (he) is clearer and doesn’t review nursing notes from other shifts.

How does delirium affect outcome?

Delirium has been shown to be associated with prolonged hospital stay (21 days, compared with 11 days in the absence of delirium), functional decline during hospitalization, and increased admission to long-term care (36% compared with 13%).⁶ In a study by O’Keefe and Lavan,⁶ delirious patients were more likely to sustain falls and to develop urinary incontinence, pressure sores, and other complications during hospitalization.

Older patients with delirium superimposed on dementia had a more than twofold increased risk of mortality compared with patients with dementia alone or with neither dementia nor delirium.⁷ Rockwood found that an episode of delirium was associated with a much higher rate of subsequent dementia.⁸

Think of an acute medical illness as a “stress test” for the brain, such that, if the patient develops delirium, it suggests an underlying brain disease that was not evident before the acute episode. After hip fracture, for example, delirium was independently associated with poor functional recovery at 1 month⁹ and at 2 years.¹⁰

Older patients admitted to a skilled nursing facility with delirium are more likely to experience one or more complications (73% compared with 41%).¹¹ In the study by Marcantonio and colleagues, patients with delirium were more than twice as likely to be hospitalized again within 30 days (30% and 13%), and less than half as likely to be discharged to the community (30% and 73%). Table 3 summarizes the impact of delirium on outcomes.

Appropriate management steps

Identifying and treating underlying medical illness is the definitive treatment for delirium; in a geriatric patient with multiple medical comorbidities the pathogenesis often is multifactorial or a definitive precipitant cannot always be identified.¹²

Managing a patient with delirium includes both non-pharmacotherapeutic interventions, which should be considered first-line, and pharmacotherapeutic interventions. Non-pharmacotherapeutic interventions include, but are not limited to:

•  support and close observation by nursing staff

•  placing a clock or calendar in the room

•  frequent reorientation and reminders

•  placing familiar possessions in the room

•  putting the patient in an isolated room with a window

•  regulating the sleep-wake cycle.⁴

Pharmacotherapeutic intervention in delirium should be used for behavioral symptoms, but only for the minimum duration necessary⁴ and preferably oral or IV. No drugs are FDA-approved for delirium, which means that use of any agent is off-label.¹³

Antipsychotics are the mainstay of pharmacotherapy for delirium in most settings. The use of antipsychotics relates to the dopamine excess-acetylcholine deficiency hypothesis of delirium pathophysiology.¹² Haloperidol remains the first-line agent because it is available in multiple dosages and can be given by various routes. IV haloperidol appears to carry less risk of extrapyramidal symptoms than oral haloperidol does but, as with all antipsychotics, its use warrants monitoring for QTc prolongation.¹²

Studies have not shown that atypical antipsychotics are superior to typical antipsychotics for delirium. Multiple studies have shown that atypicals are as efficacious as haloperidol.

Benzodiazepines are the treatment of choice for delirium caused by alcohol withdrawal. A Cochrane review found no evidence that benzodiazepines were helpful in treating delirium unrelated to alcohol withdrawal.¹⁴ In some studies, benzodiazepines were associated with an increased risk of delirium, especially in patients in the intensive care unit.¹⁵

More recently, cholinesterase inhibitors have been used to treat delirium. The reasoning behind their use is the hypothesis of a central cholinergic deficiency in delirium.¹² Regrettably, there have been few well-conducted studies of these agents in delirium, and a Cochrane review found no significant benefit for cholinesterase inhibitors.¹⁶ With the same hypothesis in mind, anticholinergic medications in patients with delirium should be avoided because these agents could exacerbate delirium by further decreasing the acetylcholine level.

Because delirium is common in the hospitalized population (especially older patients), a number of studies have examined strategies to prevent or reduce its development. Inouye and colleagues conducted a controlled clinical trial, in which they intervened to reduce six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual and hearing impairment, and dehydration in hospitalized geriatric patients. The number and duration of events of delirium were significantly lower in the intervention group.¹⁷

Brummel et al reported that reducing modifiable risk factors in intensive care unit patients—including sedation management, minimizing deliriogenic medications (anticholinergics, antihistamines), minimizing sleep disruption, and encouraging early mobility—could prevent or reduce the incidence of delirium.¹⁵

CASE CONCLUDED: Return to baseline

Ms. T’s medications are minimized or discontinued, including azithromycin, based on case reports in the literature. She is stabilized hemodynamically.

Clinicians educate Ms. T’s family about delirium. To address Ms. T’s aggressive and paranoid behaviors, clinicians request that a family member is present to reassure Ms. T. She is continued on low-dose haloperidol. The family also is asked to bring Ms. T’s hearing aid and eyeglasses.

MRI is performed after Ms. T’s behavior is under control. The scan is negative for a new stroke.

Repeat blood tests the following day show an elevated white blood cell count; urinalysis is positive for a urinary tract infection. Ms. T is started on antibiotics. Subsequent urine culture shows no bacterial growth; the antibiotics are stopped after 3 days.

Ms. T slowly improves. According to her family, she is back at baseline in 3 or 4 days.

This case illustrates the complexity of trying to identify the precise cause of delirium among the many that could be involved. Often, no single cause can be found.¹⁸

Bottom Line
Delirium is a common and potentially life-threatening condition in hospitalized geriatric patients. General hospital psychiatrists should know how to recognize and treat the condition in collaboration with their medical colleagues.

Related Resources

• Treating delirium: a quick reference guide. Arlington, VA: American Psychiatric Association. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1662986.
• Cook IA. Guideline watch: practice guidelines for the treatment of patients with delirium. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1681952.
• Fearing MA, Inouye SK. Delirium. In: Blazer DG, Steffens D, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. 4th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2009:229-241.
• Ghandour A, Saab R, Mehr D. Detecting and treating delirium—key interventions you may be missing. J Fam Pract. 2011;60(12):726-734.
• Leentjens AF, Rundell J, Rummans T, et al. Delirium: an evidence-based medicine (EBM) monograph for psychosomatic medicine practice. J Psychosom Res. 2012;73:149-152.
• Liptzin B, Jacobson SA. Delirium. In: Sadock BJ, Sadock VA, Ruiz P, eds. Comprehensive textbook of psychiatry. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:4066-4073.

Drug Brand Names

Azithromycin • Zithromax                 Hydralazine • Apresoline

Diltiazem • Cardizem                        Risperidone • Risperdal

Haloperidol • Haldo

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.


Featured Audio
Benjamin Liptzin, MD, describes the distinction between dementia and delirium. Dr. Liptzin is Chair of Psychiatry, Baystate Medical Center, Springfield, Massachusetts, and Professor and Deputy Chair, Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.