Current Psychiatry

Case: 'He's okay on weekends'
Nathan, age 13, is referred by his parents for recent school refusal behavior. He has had difficulty adjusting to middle school and has been marked absent one-third of school days this academic year. These absences come in the form of tardiness, skipped classes, and full-day absences.

Nathan complains of headaches and stomachaches and says he feels upset and nervous while in school. His parents, however, complain that Nathan seems fine on weekends and holidays and seems to be embellishing symptoms to miss school. Nathan’s parents are concerned that their son may have some physical or mental condition that is preventing his school attendance and that might be remediated with medication.

Child-motivated refusal to attend school or remain in class an entire day is not uncommon, affecting 5% to 28% of youths at some time in their lives.^1,2

The behavior may be viewed along a spectrum of absenteeism (Figure), and a child may exhibit all forms of absenteeism at one time or another. In Nathan’s case, for example, he could be anxious during school on Monday, arrive late to school on Tuesday, skip afternoon classes on Wednesday, and fail to attend school completely on Thursday and Friday.

In this article you will learn characteristics of school refusal behavior to watch for and assess, and treatment strategies for youths ages 5 to 17. You will also find advice and techniques to offer parents.

Figure A child might exhibit each behavior on this spectrum at different times

Refusal behavior characteristics

School refusal behavior encompasses all subsets of problematic absenteeism, such as truancy, school phobia, and separation anxiety.³ Children and adolescents of all ages, boys and girls alike, can exhibit school refusal behavior. The most common age of onset is 10 to 13 years. Youths such as Nathan who are entering a school building for the first time—especially elementary and middle school—are at particular risk for school refusal behavior. Little information is available regarding ethnic differences, although school dropout rates for Hispanics are often considerably elevated compared with other ethnic groups.^4,5

School refusal behavior covers a range of symptoms, diagnoses, somatic complaints, and medical conditions (Tables 1-3).^6-12 Longitudinal studies indicate that school refusal behavior, if left unaddressed, can lead to serious short-term problems, such as distress, academic decline, alienation from peers, family conflict, and financial and legal consequences. Common long-term problems include school dropout, delinquent behaviors, economic deprivation, social isolation, marital problems, and difficulty maintaining employment. Approximately 52% of adolescents with school refusal behavior meet criteria for an anxiety, depressive, conduct-personality, or other psychiatric disorder later in life.^13-16

Table 1

Common symptoms that could signal school refusal behavior

Table 2

Primary psychiatric disorders among youths with school refusal behavior

Table 3

Somatic complaints and medical conditions
commonly associated with school refusal behavior

Finding a reason for school refusal

If a child has somatic complaints, you can expect to find that the child is:

• suffering from a true physical malady
• embellishing low-grade physical symptoms from stress or attention-seeking behavior
• reporting physical problems that have no medical basis.

A full medical examination is always recommended to rule out organic problems or to properly treat true medical conditions.

Four functions. If no medical condition is found, explore the reasons a particular child refuses school. A common model of conceptualizing school refusal behavior involves reinforcers:^1,2

• to avoid school-based stimuli that provoke a sense of negative affectivity, or combined anxiety and depression; examples of key stimuli include teachers, peers, bus, cafeteria, classroom, and transitions between classes
• to escape aversive social or evaluative situations such as conversing or otherwise interacting with others or performing before others as in class presentations
• to pursue attention from significant others, such as wanting to stay home or go to work with parents
• to pursue tangible reinforcers outside of school, such as sleeping late, watching television, playing with friends, or engaging in delinquent behavior or substance use.

The first 2 functions are maintained by negative reinforcement or a desire to leave anxiety-provoking stimuli. The latter 2 functions are maintained by positive reinforcement, or a desire to pursue rewards outside of school. Youths may also refuse school for a combination of these reasons.¹⁷ In Nathan’s case, he was initially anxious about school in general (the first function). After his parents allowed him to stay home for a few days, however, he was refusing school to enjoy fun activities such as video games at home (the last function).

Box

Assessment scale. One method for quickly assessing the role of these functions is the School Refusal Assessment Scale-Revised.^18,19 This scale poses 24 questions, the answers to which measure the relative strength of each of the 4 functions. Versions are available for children and parents, who complete their respective scales separately (see Related resources). Item means are calculated across the measures to help determine the primary reason for a child’s school refusal.

In addition to using the assessment scale, you may ask interview questions regarding the form and function of school refusal behavior (Tables 4,5). Take care to assess attendance history and patterns, comorbid conditions, instances of legitimate absenteeism, family disruption, and a child’s social and academic status. Specific questions about function can help narrow the reason for school refusal.

Assess specific school-related stimuli that provoke absenteeism such as social and evaluative situations, whether a child could attend school with a parent (evidence of attention-seeking), and what tangible rewards a child receives for absenteeism throughout the school day. Information about the form and function of school refusal behavior may also be evident during in-office observations of the family. Data from the School Refusal Assessment Scale-Revised, interviews, and observations can then be used to recommend particular treatment options.

Table 4

Questions related to forms of school refusal behavior

Table 5

Questions related to functions of school refusal behavior

Treating youths who refuse school

Treatment success will be better assured if you work closely with school personnel and parents to gather and share information, coordinate a plan for returning a child to school, and address familial issues and the child’s comorbid medical problems that impact attendance.

Medications have proven useful in alleviating severe cases of anxiety and depression, and cognitive management techniques can be applied to the child, the parents, and the family together.

Anxiolytics or antidepressants. Pharmacotherapy research for school refusal behavior is in its infancy. Some investigators have found, however, that a tricyclic antidepressant (TCA) such as imipramine, 3 mg/kg/d, may be useful in some cases^20,21—generally for youths ages 10 to 17 years with better attendance records and fewer symptoms of social avoidance and separation anxiety.²² Researchers speculate that TCAs, which are not always effective in children, may influence symptoms such as anhedonia or sleep problems that contribute to school refusal behavior.

With respect to substantial child anxiety and depression without school refusal behavior, researchers have focused on selective serotonin reuptake inhibitors (SSRIs). In particular, fluoxetine, 10 to 20 mg/d, fluvoxamine, 50 to 250 mg/d, sertraline, 85 to 160 mg/d, and paroxetine, 10 to 50 mg/d, have been useful for youths with symptoms of general and social anxiety and depression.^23,24

Youths often do not respond to these medications as well as adults do, however, because of the fluid and amorphous nature of anxious and depressive symptomatology in children and adolescents. Careful monitoring is required when treating youth with SSRIs, which have been associated with an increased risk of suicidal behavior.

Psychological techniques. Sophisticated clinical controlled studies have addressed the treatment of diverse youths with school refusal behavior.^25-28 Options for this population may be arranged according to function or the primary reinforcers maintaining absenteeism:

• child-based techniques to manage anxiety in a school setting
• parent-based techniques to manage contingencies for school attendance and nonattendance
• family-based techniques to manage incentives and disincentives for school attendance and nonattendance.

Child-based anxiety management techniques include relaxation training, breathing retraining, cognitive therapy (generally for youths ages 9 to 17), and exposure-based practices to gradually reintroduce a child to school. These techniques have been strongly supported by randomized controlled trials specific to school refusal behavior² and are useful for treating general anxiety and depression as well.

Parent-based contingency management techniques include establishing morning and evening routines, modifying parental commands toward brevity and clarity, providing attention-based consequences for school nonattendance (such as early bedtime, limited time with a parent at night), reducing excessive child questioning or reassurance-seeking behavior, and engaging in forced school attendance under strict conditions. Parent-based techniques have received strong support in the literature in general²⁹ but have been applied less frequently than child-based techniques to youths with school refusal behavior.

Family-based techniques include developing written contracts to increase incentives for school attendance and decrease incentives for nonattendance, escorting a child to school and classes, and teaching youths to refuse offers from peers to miss school.³⁰ As with parent-based techniques, family-based techniques have received strong support in the literature in general, but have been applied less frequently than child-based techniques to youths with school refusal behavior.

Gradual reintroduction to school

A preferred approach to resolve school refusal behavior usually involves gradual reintegration to school and classes. This may include initial attendance at lunchtime, 1 or 2 favorite classes, or in an alternative classroom setting such as a guidance counselor’s office or school library. Gradual reintegration into regular classrooms may then proceed.

If possible, a child should remain in school during the day and not be sent home unless intense medical symptoms are present.³⁰ A recommended list of intense symptoms includes:

• frequent vomiting
• bleeding
• temperature >100° F
• severe diarrhea
• lice
• acute flu-like symptoms
• extreme medical conditions such as intense pain.

Case continued: a full-time student.

A structured diagnostic interview and other behavioral assessment measures show that Nathan meets criteria for generalized anxiety disorder. He worries excessively about his social and academic performance at school and displays several somatic complaints related to anxiety. His treatment thus involves a two-pronged approach:

• sertraline, 50 mg/d, which has been found to significantly reduce symptoms of generalized anxiety disorder in youths ages 5 to 17.
• child-based anxiety management techniques and family therapy to increase incentives for school attendance and limit fun activities during a school day spent at home.

His therapist and family physician collaborate with school personnel to gradually reintroduce Nathan to a full-time academic schedule.

Related resources

• Copies of the child and parent versions of the School Refusal Assessment Scale-Revised are available at www.jfponline.com/Pages.asp?AID=4322&UID=.
• King NJ, Bernstein GA. School refusal in children and adolescents: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 2001;40:197-205.
• Kearney CA. School refusal behavior in youth: a functional approach to assessment and treatment. Washington, DC: American Psychological Association; 2001.
• Kearney CA, Albano AM. When children refuse school: a cognitive-behavioral therapy approach. Parent workbook/therapist’s guide. New York: Oxford University Press; 2000.

Drug brand names

• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Paroxetine • Paxil
• Sertraline • Zoloft

Acknowledgment

Adapted and reprinted with permission from The Journal of Family Practice, August 2006, p 685-92.

Case: 'He's okay on weekends'
Nathan, age 13, is referred by his parents for recent school refusal behavior. He has had difficulty adjusting to middle school and has been marked absent one-third of school days this academic year. These absences come in the form of tardiness, skipped classes, and full-day absences.

Nathan complains of headaches and stomachaches and says he feels upset and nervous while in school. His parents, however, complain that Nathan seems fine on weekends and holidays and seems to be embellishing symptoms to miss school. Nathan’s parents are concerned that their son may have some physical or mental condition that is preventing his school attendance and that might be remediated with medication.

Child-motivated refusal to attend school or remain in class an entire day is not uncommon, affecting 5% to 28% of youths at some time in their lives.^1,2

The behavior may be viewed along a spectrum of absenteeism (Figure), and a child may exhibit all forms of absenteeism at one time or another. In Nathan’s case, for example, he could be anxious during school on Monday, arrive late to school on Tuesday, skip afternoon classes on Wednesday, and fail to attend school completely on Thursday and Friday.

In this article you will learn characteristics of school refusal behavior to watch for and assess, and treatment strategies for youths ages 5 to 17. You will also find advice and techniques to offer parents.

Figure A child might exhibit each behavior on this spectrum at different times

Refusal behavior characteristics

School refusal behavior encompasses all subsets of problematic absenteeism, such as truancy, school phobia, and separation anxiety.³ Children and adolescents of all ages, boys and girls alike, can exhibit school refusal behavior. The most common age of onset is 10 to 13 years. Youths such as Nathan who are entering a school building for the first time—especially elementary and middle school—are at particular risk for school refusal behavior. Little information is available regarding ethnic differences, although school dropout rates for Hispanics are often considerably elevated compared with other ethnic groups.^4,5

School refusal behavior covers a range of symptoms, diagnoses, somatic complaints, and medical conditions (Tables 1-3).^6-12 Longitudinal studies indicate that school refusal behavior, if left unaddressed, can lead to serious short-term problems, such as distress, academic decline, alienation from peers, family conflict, and financial and legal consequences. Common long-term problems include school dropout, delinquent behaviors, economic deprivation, social isolation, marital problems, and difficulty maintaining employment. Approximately 52% of adolescents with school refusal behavior meet criteria for an anxiety, depressive, conduct-personality, or other psychiatric disorder later in life.^13-16

Table 1

Common symptoms that could signal school refusal behavior

Table 2

Primary psychiatric disorders among youths with school refusal behavior

Table 3

Somatic complaints and medical conditions
commonly associated with school refusal behavior

Finding a reason for school refusal

If a child has somatic complaints, you can expect to find that the child is:

• suffering from a true physical malady
• embellishing low-grade physical symptoms from stress or attention-seeking behavior
• reporting physical problems that have no medical basis.

A full medical examination is always recommended to rule out organic problems or to properly treat true medical conditions.

Four functions. If no medical condition is found, explore the reasons a particular child refuses school. A common model of conceptualizing school refusal behavior involves reinforcers:^1,2

• to avoid school-based stimuli that provoke a sense of negative affectivity, or combined anxiety and depression; examples of key stimuli include teachers, peers, bus, cafeteria, classroom, and transitions between classes
• to escape aversive social or evaluative situations such as conversing or otherwise interacting with others or performing before others as in class presentations
• to pursue attention from significant others, such as wanting to stay home or go to work with parents
• to pursue tangible reinforcers outside of school, such as sleeping late, watching television, playing with friends, or engaging in delinquent behavior or substance use.

The first 2 functions are maintained by negative reinforcement or a desire to leave anxiety-provoking stimuli. The latter 2 functions are maintained by positive reinforcement, or a desire to pursue rewards outside of school. Youths may also refuse school for a combination of these reasons.¹⁷ In Nathan’s case, he was initially anxious about school in general (the first function). After his parents allowed him to stay home for a few days, however, he was refusing school to enjoy fun activities such as video games at home (the last function).

Box

Assessment scale. One method for quickly assessing the role of these functions is the School Refusal Assessment Scale-Revised.^18,19 This scale poses 24 questions, the answers to which measure the relative strength of each of the 4 functions. Versions are available for children and parents, who complete their respective scales separately (see Related resources). Item means are calculated across the measures to help determine the primary reason for a child’s school refusal.

In addition to using the assessment scale, you may ask interview questions regarding the form and function of school refusal behavior (Tables 4,5). Take care to assess attendance history and patterns, comorbid conditions, instances of legitimate absenteeism, family disruption, and a child’s social and academic status. Specific questions about function can help narrow the reason for school refusal.

Assess specific school-related stimuli that provoke absenteeism such as social and evaluative situations, whether a child could attend school with a parent (evidence of attention-seeking), and what tangible rewards a child receives for absenteeism throughout the school day. Information about the form and function of school refusal behavior may also be evident during in-office observations of the family. Data from the School Refusal Assessment Scale-Revised, interviews, and observations can then be used to recommend particular treatment options.

Table 4

Questions related to forms of school refusal behavior

Table 5

Questions related to functions of school refusal behavior

Treating youths who refuse school

Treatment success will be better assured if you work closely with school personnel and parents to gather and share information, coordinate a plan for returning a child to school, and address familial issues and the child’s comorbid medical problems that impact attendance.

Medications have proven useful in alleviating severe cases of anxiety and depression, and cognitive management techniques can be applied to the child, the parents, and the family together.

Anxiolytics or antidepressants. Pharmacotherapy research for school refusal behavior is in its infancy. Some investigators have found, however, that a tricyclic antidepressant (TCA) such as imipramine, 3 mg/kg/d, may be useful in some cases^20,21—generally for youths ages 10 to 17 years with better attendance records and fewer symptoms of social avoidance and separation anxiety.²² Researchers speculate that TCAs, which are not always effective in children, may influence symptoms such as anhedonia or sleep problems that contribute to school refusal behavior.

With respect to substantial child anxiety and depression without school refusal behavior, researchers have focused on selective serotonin reuptake inhibitors (SSRIs). In particular, fluoxetine, 10 to 20 mg/d, fluvoxamine, 50 to 250 mg/d, sertraline, 85 to 160 mg/d, and paroxetine, 10 to 50 mg/d, have been useful for youths with symptoms of general and social anxiety and depression.^23,24

Youths often do not respond to these medications as well as adults do, however, because of the fluid and amorphous nature of anxious and depressive symptomatology in children and adolescents. Careful monitoring is required when treating youth with SSRIs, which have been associated with an increased risk of suicidal behavior.

Psychological techniques. Sophisticated clinical controlled studies have addressed the treatment of diverse youths with school refusal behavior.^25-28 Options for this population may be arranged according to function or the primary reinforcers maintaining absenteeism:

• child-based techniques to manage anxiety in a school setting
• parent-based techniques to manage contingencies for school attendance and nonattendance
• family-based techniques to manage incentives and disincentives for school attendance and nonattendance.

Child-based anxiety management techniques include relaxation training, breathing retraining, cognitive therapy (generally for youths ages 9 to 17), and exposure-based practices to gradually reintroduce a child to school. These techniques have been strongly supported by randomized controlled trials specific to school refusal behavior² and are useful for treating general anxiety and depression as well.

Parent-based contingency management techniques include establishing morning and evening routines, modifying parental commands toward brevity and clarity, providing attention-based consequences for school nonattendance (such as early bedtime, limited time with a parent at night), reducing excessive child questioning or reassurance-seeking behavior, and engaging in forced school attendance under strict conditions. Parent-based techniques have received strong support in the literature in general²⁹ but have been applied less frequently than child-based techniques to youths with school refusal behavior.

Family-based techniques include developing written contracts to increase incentives for school attendance and decrease incentives for nonattendance, escorting a child to school and classes, and teaching youths to refuse offers from peers to miss school.³⁰ As with parent-based techniques, family-based techniques have received strong support in the literature in general, but have been applied less frequently than child-based techniques to youths with school refusal behavior.

Gradual reintroduction to school

A preferred approach to resolve school refusal behavior usually involves gradual reintegration to school and classes. This may include initial attendance at lunchtime, 1 or 2 favorite classes, or in an alternative classroom setting such as a guidance counselor’s office or school library. Gradual reintegration into regular classrooms may then proceed.

If possible, a child should remain in school during the day and not be sent home unless intense medical symptoms are present.³⁰ A recommended list of intense symptoms includes:

• frequent vomiting
• bleeding
• temperature >100° F
• severe diarrhea
• lice
• acute flu-like symptoms
• extreme medical conditions such as intense pain.

Case continued: a full-time student.

A structured diagnostic interview and other behavioral assessment measures show that Nathan meets criteria for generalized anxiety disorder. He worries excessively about his social and academic performance at school and displays several somatic complaints related to anxiety. His treatment thus involves a two-pronged approach:

• sertraline, 50 mg/d, which has been found to significantly reduce symptoms of generalized anxiety disorder in youths ages 5 to 17.
• child-based anxiety management techniques and family therapy to increase incentives for school attendance and limit fun activities during a school day spent at home.

His therapist and family physician collaborate with school personnel to gradually reintroduce Nathan to a full-time academic schedule.

Related resources

• Copies of the child and parent versions of the School Refusal Assessment Scale-Revised are available at www.jfponline.com/Pages.asp?AID=4322&UID=.
• King NJ, Bernstein GA. School refusal in children and adolescents: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 2001;40:197-205.
• Kearney CA. School refusal behavior in youth: a functional approach to assessment and treatment. Washington, DC: American Psychological Association; 2001.
• Kearney CA, Albano AM. When children refuse school: a cognitive-behavioral therapy approach. Parent workbook/therapist’s guide. New York: Oxford University Press; 2000.

Drug brand names

• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Paroxetine • Paxil
• Sertraline • Zoloft

Acknowledgment

Adapted and reprinted with permission from The Journal of Family Practice, August 2006, p 685-92.

Case: 'He's okay on weekends'
Nathan, age 13, is referred by his parents for recent school refusal behavior. He has had difficulty adjusting to middle school and has been marked absent one-third of school days this academic year. These absences come in the form of tardiness, skipped classes, and full-day absences.

Nathan complains of headaches and stomachaches and says he feels upset and nervous while in school. His parents, however, complain that Nathan seems fine on weekends and holidays and seems to be embellishing symptoms to miss school. Nathan’s parents are concerned that their son may have some physical or mental condition that is preventing his school attendance and that might be remediated with medication.

Child-motivated refusal to attend school or remain in class an entire day is not uncommon, affecting 5% to 28% of youths at some time in their lives.^1,2

The behavior may be viewed along a spectrum of absenteeism (Figure), and a child may exhibit all forms of absenteeism at one time or another. In Nathan’s case, for example, he could be anxious during school on Monday, arrive late to school on Tuesday, skip afternoon classes on Wednesday, and fail to attend school completely on Thursday and Friday.

In this article you will learn characteristics of school refusal behavior to watch for and assess, and treatment strategies for youths ages 5 to 17. You will also find advice and techniques to offer parents.

Figure A child might exhibit each behavior on this spectrum at different times

Refusal behavior characteristics

School refusal behavior encompasses all subsets of problematic absenteeism, such as truancy, school phobia, and separation anxiety.³ Children and adolescents of all ages, boys and girls alike, can exhibit school refusal behavior. The most common age of onset is 10 to 13 years. Youths such as Nathan who are entering a school building for the first time—especially elementary and middle school—are at particular risk for school refusal behavior. Little information is available regarding ethnic differences, although school dropout rates for Hispanics are often considerably elevated compared with other ethnic groups.^4,5

School refusal behavior covers a range of symptoms, diagnoses, somatic complaints, and medical conditions (Tables 1-3).^6-12 Longitudinal studies indicate that school refusal behavior, if left unaddressed, can lead to serious short-term problems, such as distress, academic decline, alienation from peers, family conflict, and financial and legal consequences. Common long-term problems include school dropout, delinquent behaviors, economic deprivation, social isolation, marital problems, and difficulty maintaining employment. Approximately 52% of adolescents with school refusal behavior meet criteria for an anxiety, depressive, conduct-personality, or other psychiatric disorder later in life.^13-16

Table 1

Common symptoms that could signal school refusal behavior

Table 2

Primary psychiatric disorders among youths with school refusal behavior

Table 3

Somatic complaints and medical conditions
commonly associated with school refusal behavior

Finding a reason for school refusal

If a child has somatic complaints, you can expect to find that the child is:

• suffering from a true physical malady
• embellishing low-grade physical symptoms from stress or attention-seeking behavior
• reporting physical problems that have no medical basis.

A full medical examination is always recommended to rule out organic problems or to properly treat true medical conditions.

Four functions. If no medical condition is found, explore the reasons a particular child refuses school. A common model of conceptualizing school refusal behavior involves reinforcers:^1,2

• to avoid school-based stimuli that provoke a sense of negative affectivity, or combined anxiety and depression; examples of key stimuli include teachers, peers, bus, cafeteria, classroom, and transitions between classes
• to escape aversive social or evaluative situations such as conversing or otherwise interacting with others or performing before others as in class presentations
• to pursue attention from significant others, such as wanting to stay home or go to work with parents
• to pursue tangible reinforcers outside of school, such as sleeping late, watching television, playing with friends, or engaging in delinquent behavior or substance use.

The first 2 functions are maintained by negative reinforcement or a desire to leave anxiety-provoking stimuli. The latter 2 functions are maintained by positive reinforcement, or a desire to pursue rewards outside of school. Youths may also refuse school for a combination of these reasons.¹⁷ In Nathan’s case, he was initially anxious about school in general (the first function). After his parents allowed him to stay home for a few days, however, he was refusing school to enjoy fun activities such as video games at home (the last function).

Box

Assessment scale. One method for quickly assessing the role of these functions is the School Refusal Assessment Scale-Revised.^18,19 This scale poses 24 questions, the answers to which measure the relative strength of each of the 4 functions. Versions are available for children and parents, who complete their respective scales separately (see Related resources). Item means are calculated across the measures to help determine the primary reason for a child’s school refusal.

In addition to using the assessment scale, you may ask interview questions regarding the form and function of school refusal behavior (Tables 4,5). Take care to assess attendance history and patterns, comorbid conditions, instances of legitimate absenteeism, family disruption, and a child’s social and academic status. Specific questions about function can help narrow the reason for school refusal.

Assess specific school-related stimuli that provoke absenteeism such as social and evaluative situations, whether a child could attend school with a parent (evidence of attention-seeking), and what tangible rewards a child receives for absenteeism throughout the school day. Information about the form and function of school refusal behavior may also be evident during in-office observations of the family. Data from the School Refusal Assessment Scale-Revised, interviews, and observations can then be used to recommend particular treatment options.

Table 4

Questions related to forms of school refusal behavior

Table 5

Questions related to functions of school refusal behavior

Treating youths who refuse school

Treatment success will be better assured if you work closely with school personnel and parents to gather and share information, coordinate a plan for returning a child to school, and address familial issues and the child’s comorbid medical problems that impact attendance.

Medications have proven useful in alleviating severe cases of anxiety and depression, and cognitive management techniques can be applied to the child, the parents, and the family together.

Anxiolytics or antidepressants. Pharmacotherapy research for school refusal behavior is in its infancy. Some investigators have found, however, that a tricyclic antidepressant (TCA) such as imipramine, 3 mg/kg/d, may be useful in some cases^20,21—generally for youths ages 10 to 17 years with better attendance records and fewer symptoms of social avoidance and separation anxiety.²² Researchers speculate that TCAs, which are not always effective in children, may influence symptoms such as anhedonia or sleep problems that contribute to school refusal behavior.

With respect to substantial child anxiety and depression without school refusal behavior, researchers have focused on selective serotonin reuptake inhibitors (SSRIs). In particular, fluoxetine, 10 to 20 mg/d, fluvoxamine, 50 to 250 mg/d, sertraline, 85 to 160 mg/d, and paroxetine, 10 to 50 mg/d, have been useful for youths with symptoms of general and social anxiety and depression.^23,24

Youths often do not respond to these medications as well as adults do, however, because of the fluid and amorphous nature of anxious and depressive symptomatology in children and adolescents. Careful monitoring is required when treating youth with SSRIs, which have been associated with an increased risk of suicidal behavior.

Psychological techniques. Sophisticated clinical controlled studies have addressed the treatment of diverse youths with school refusal behavior.^25-28 Options for this population may be arranged according to function or the primary reinforcers maintaining absenteeism:

• child-based techniques to manage anxiety in a school setting
• parent-based techniques to manage contingencies for school attendance and nonattendance
• family-based techniques to manage incentives and disincentives for school attendance and nonattendance.

Child-based anxiety management techniques include relaxation training, breathing retraining, cognitive therapy (generally for youths ages 9 to 17), and exposure-based practices to gradually reintroduce a child to school. These techniques have been strongly supported by randomized controlled trials specific to school refusal behavior² and are useful for treating general anxiety and depression as well.

Parent-based contingency management techniques include establishing morning and evening routines, modifying parental commands toward brevity and clarity, providing attention-based consequences for school nonattendance (such as early bedtime, limited time with a parent at night), reducing excessive child questioning or reassurance-seeking behavior, and engaging in forced school attendance under strict conditions. Parent-based techniques have received strong support in the literature in general²⁹ but have been applied less frequently than child-based techniques to youths with school refusal behavior.

Family-based techniques include developing written contracts to increase incentives for school attendance and decrease incentives for nonattendance, escorting a child to school and classes, and teaching youths to refuse offers from peers to miss school.³⁰ As with parent-based techniques, family-based techniques have received strong support in the literature in general, but have been applied less frequently than child-based techniques to youths with school refusal behavior.

Gradual reintroduction to school

A preferred approach to resolve school refusal behavior usually involves gradual reintegration to school and classes. This may include initial attendance at lunchtime, 1 or 2 favorite classes, or in an alternative classroom setting such as a guidance counselor’s office or school library. Gradual reintegration into regular classrooms may then proceed.

If possible, a child should remain in school during the day and not be sent home unless intense medical symptoms are present.³⁰ A recommended list of intense symptoms includes:

• frequent vomiting
• bleeding
• temperature >100° F
• severe diarrhea
• lice
• acute flu-like symptoms
• extreme medical conditions such as intense pain.

Case continued: a full-time student.

A structured diagnostic interview and other behavioral assessment measures show that Nathan meets criteria for generalized anxiety disorder. He worries excessively about his social and academic performance at school and displays several somatic complaints related to anxiety. His treatment thus involves a two-pronged approach:

• sertraline, 50 mg/d, which has been found to significantly reduce symptoms of generalized anxiety disorder in youths ages 5 to 17.
• child-based anxiety management techniques and family therapy to increase incentives for school attendance and limit fun activities during a school day spent at home.

His therapist and family physician collaborate with school personnel to gradually reintroduce Nathan to a full-time academic schedule.

Related resources

• Copies of the child and parent versions of the School Refusal Assessment Scale-Revised are available at www.jfponline.com/Pages.asp?AID=4322&UID=.
• King NJ, Bernstein GA. School refusal in children and adolescents: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 2001;40:197-205.
• Kearney CA. School refusal behavior in youth: a functional approach to assessment and treatment. Washington, DC: American Psychological Association; 2001.
• Kearney CA, Albano AM. When children refuse school: a cognitive-behavioral therapy approach. Parent workbook/therapist’s guide. New York: Oxford University Press; 2000.

Drug brand names

• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Paroxetine • Paxil
• Sertraline • Zoloft

Acknowledgment

Adapted and reprinted with permission from The Journal of Family Practice, August 2006, p 685-92.

Controlled clinical trial results can help you make two prescribing decisions:

• Is an antipsychotic the right choice for this patient?
  
• If yes, which agent?
  

Prescribing antipsychotics off-label can be worthwhile when a patient gets better, but even then two worries remain:

• Most uses of antipsychotics for nonpsychotic illness are not evidence-based.
  
• This practice may expose clinicians to liability if the patient gets worse.
  

Consider the use of second-generation antipsychotics (SGAs) to manage acute behaviors in patients with dementia. The FDA ordered a black box warning in 2005 that SGAs may increase mortality risk in older patients. In October, the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer’s Disease (CATIE-AD) reported that SGAs’ side effects offset their benefits when compared with placebo (see Will CATIE-AD change dementia treatment?).¹

What do you do when FDA-approved drugs fail to help your patient with dementia, unipolar depression, anxiety disorders, or other nonpsychotic symptoms, and SGAs may be the next consideration? The answers lie in managing side effects and knowing which antipsychotic uses are supported by data from controlled clinical trials, which we review here.

Box 1

Prescribing considerations

For a variety of reasons (Box 1), SGAs have rapidly assumed a major role in treating nonpsychotic disorders. Thirty-one percent of psychotropics are dispensed off-label,² and Buckley³ reported in a 3-state survey that 70% of SGA prescriptions were written for indications other than schizophrenia.

Using antipsychotics for nonpsychotic symptoms is a longstanding clinical practice. In schizophrenia patients, antipsychotics have been shown to improve psychotic and nonpsychotic symptoms: agitation, violence, negative symptoms, social isolation, depression, suicidality, anxiety, insomnia, poor appetite, compulsions, cognition, smoking, alcohol and drug use, polydipsia, tardive dyskinesia, and tardive dystonia. Some clinicians may view these reports as evidence that antipsychotics might relieve these symptoms in patients with nonpsychotic disorders as well, but the issue is more complicated than that (Box 2).⁴

Caveats. SGAs do offer clinicians unique tools; no other class of psychotropics can claim efficacy in psychotic disorders, bipolar disorder, depression, and other disorders we describe in this review. On the other hand:

• Although some SGAs are approved for bipolar disorder and one was recently approved to treat irritability in autism (Table 1), most SGA uses in nonpsychotic disorders are off-label and supported by few—if any—large, randomized, controlled trials.
  
• Antipsychotics can cause the very symptoms they relieve, including depression, obsessive-compulsive disorder (OCD), anxiety, poorer cognition, agitation, mania, insomnia, and abnormal movements.
  
• Few controlled studies have compared SGAs to usual first-line treatments; most have evaluated SGAs as adjuncts to other psychotropics—such as serotonin reuptake inhibitors (SRIs)—for patients with treatment-resistant disorders.
  
• Published head-to-head studies have rarely compared the efficacy of various SGAs in treating nonpsychotic disorders.
  
• Long-term safety studies of SGAs for nonpsychotic indications have not been done.
  

Table 1

Bipolar and other nonpsychotic indications FDA-approved for SGAs

Prescribing decisions. SGA’s potential adverse effects complicate clinical decision-making. First you must decide whether to use an SGA for your patient with a nonpsychotic disorder.

Box 2

• patient history and clinical characteristics
  
• potential side effects
  
• individual therapeutic response to previous medications.
  

Table 2

SGA uses in nonpsychotic disorders supported by evidence
from published double-blind clinical trials*

Dementia

Most Alzheimer’s patients—75% to 90%—experience behavioral problems during this progressive dementia. Double-blind studies have found risperidone (mean dosage ~1 mg/d) and olanzapine (mean dosage 5 to 10 mg/d) effective in reducing agitation and aggression, even in nonpsychotic patients with Alzheimer’s disease or vascular dementia.^5,6 Quetiapine, ≤100 mg/d, was not more effective than placebo in reducing agitation.⁷ One study comparing IM olanzapine with IM lorazepam and placebo in acute agitation found both active treatments more effective than placebo.⁸

CATIE-AD—sponsored by the National Institute of Mental Health—compared olanzapine, risperidone, and quetiapine with placebo in 421 outpatients with behavioral symptoms such as psychosis, agitation, or aggressiveness.¹ No significant differences were seen in overall effectiveness (measured as discontinuation for any cause⁹), although patients receiving olanzapine (mean dosage 5.5 mg/d) or risperidone (mean dosage 1 mg/d) had lower discontinuation rates for lack of efficacy than those receiving placebo.

Unfortunately, the results of the first phase of CATIE-AD provide no clear guidance on the therapeutic strategy to use in dementia. Its findings do suggest two secondary conclusions, however, about using SGAs for patients with dementia:

• Because quetiapine, mean dosage 56.5 mg/d, was not more effective than placebo on any measures, consider higher dosages when using this agent.
  
• Close attention to preventing and treating SGAs’ side effects is the key to effectively treating agitation and psychosis in dementia.
  

Recommendation. Nonpharmacologic interventions are an important part of treating behavioral problems in patients with dementia.^13,14 Antipsychotics—particularly SGAs—have shown efficacy for psychosis and agitation in these patients and remain the first therapeutic option. The CATIE-AD investigators recommend that clinicians evaluate potential risks and benefits of pharmacotherapy and discuss these with patients and caregivers.¹ Also:

• Consider which SGAs have the lowest risk of causing side effects for an individual patient.
  
• Start with low dosages and increase as needed, based on efficacy and tolerability.
  

Bipolar disorder

Acute mania. Five SGAs—aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone—are FDA-approved for acute mania (Table 1). Large double-blind studies supporting this indication show that SGAs have efficacy in treating mania as monotherapy and in combination with lithium or divalproex.¹⁵ These clinical trials included patients who were not psychotic at baseline.

Antipsychotic dosages in these studies were within the ranges used in schizophrenia treatment studies. Combining an SGA with lithium or divalproex generally yields greater reductions in mania rating scale scores, higher response rates, and higher remission rates than using lithium or divalproex alone. No published study has compared SGAs with each other in mania, but differences in efficacy among these compounds are likely to be small.¹⁶

Bipolar depression. SGAs’ efficacy in bipolar depression has been evaluated in double-blind studies, and quetiapine and the olanzapine/fluoxetine combination are FDA-approved for this indication.

Olanzapine plus fluoxetine was more effective in improving depressive symptoms than olanzapine alone in a double-blind study of 833 adults with depressive symptoms of bipolar I disorder, as measured by Montgomery-Åsburg Depression Rating Scale (MADRS) scores. Olanzapine alone was more effective than placebo. Mean dosages were olanzapine, 7.4 mg/d, and fluoxetine, 39.3 mg/d, in combination therapy and olanzapine, 9.7 mg/d, as monotherapy.

MADRS scores indicated that combination therapy—but not olanzapine alone—improved core depressive symptoms such as sadness, lassitude, inability to feel, and pessimistic thoughts.¹⁷

Quetiapine. A double-blind, placebo-controlled trial (BOLDER I) evaluated quetiapine in 542 outpatients experiencing a major depressive episode associated with bipolar I or II disorder. After 8 weeks, quetiapine at 300 or 600 mg/d was more effective than placebo in reducing depressive symptoms, as measured by MADRS score changes.

Response rates were 58% with quetiapine and 36% with placebo; remission rates were 53% with quetiapine and 28% with placebo. Most symptoms, including core depression items, improved significantly with quetiapine, compared with placebo.¹⁸ Results of a second double-blind study (BOLDER II) have been presented at conferences but have not been fully published.

Risperidone. A smaller double-blind study compared risperidone plus placebo, paroxetine plus placebo, and risperidone plus paroxetine in 30 patients in the depressed phase of bipolar I or II disorder. Patients continued taking mood stabilizers during the study. After 12 weeks, depressive symptoms improved significantly in all three groups, with no significant differences.¹⁹

Maintenance therapy. Olanzapine and aripiprazole are FDA-approved for maintenance therapy in bipolar disorder (Table 1).

Unipolar depression

FGAs have shown efficacy in depression in multiple controlled studies.²⁰ SGAs have been evaluated mostly as add-on therapies in antidepressant-resistant depression.

Olanzapine. Shelton et al²¹ compared olanzapine monotherapy, fluoxetine monotherapy, and combined treatment in 34 nonpsychotic, treatment-resistant depressed subjects. Olanzapine plus fluoxetine was more effective than either agent alone. A subsequent double-blind study, however, showed similar efficacy after 8 weeks among the three treatments and nortriptyline monotherapy. Patients in the double-blind trial appeared to respond more rapidly to combined treatment than to the monotherapies.²²

Risperidone. A multiphase study of the efficacy of risperidone augmentation in treatment-resistant major depression began when 489 outpatients (2% with psychotic symptoms) received open-label citalopram, 20 to 60 mg/d. After 4 to 6 weeks, 386 nonresponders entered the augmentation phase with open-label risperidone, 0.25 to 2 mg/d. After 4 to 6 weeks of combination therapy, 241 (63%) patients whose symptoms resolved entered a double-blind discontinuation phase, in which they were randomly assigned to augmentation with risperidone or placebo, while on citalopram.

Median time to relapse during the double-blind phase was 102 days with risperidone augmentation and 85 days with placebo—not a statistically significant difference. Relapse rates after 24 weeks were 53.3% and 54.6%, respectively.²³ This study showed that the improvement observed after adding risperidone was not sustained over time.

Quetiapine. In a prospective single-blind study, paroxetine augmented with quetiapine, 200 mg/d, was compared to paroxetine alone in major depression with anxiety.²⁴ Combination therapy was more effective in improving anxiety and depression symptoms.

Others. Open-label, add-on studies indicate that aripiprazole and ziprasidone can improve treatment-resistant depression.^25-27

Anxiety disorders

OCD. SGAs also have been investigated as augmentation therapy for patients with OCD resistant to SRIs. A single-blind study of 27 patients found adjunctive quetiapine more effective than placebo in improving OCD symptoms.²⁸ SGAs were more effective than placebo as augmentation therapy to SRIs for treatment-refractory OCD in double-blind, placebo-controlled studies using mean dosages of:

• risperidone, 2.2 mg/d
  
• olanzapine, 11 mg/d
  
• quetiapine, 300 mg/d.^29-31
  

In other trials:

• A small double-blind study of patients with social anxiety disorder found olanzapine monotherapy more effective than placebo.³⁴
  
• Low-dose risperidone (mean dosage 1.1 mg/d) improved core symptoms of generalized anxiety disorder in a 5-week, double-blind, placebo-controlled trial.³⁵
  
• Some authors have reported clinical improvement of panic disorder with olanzapine augmentation.³⁶
  

Developmental disorders

Antipsychotics represent one-third of all filled psychotropic prescriptions for individuals with pervasive developmental disorders (PDD).³⁷ Haloperidol and thioridazine are the only two FDA-approved FGAs for severe behavioral problems in PDD (and for hyperactivity with conduct disorders). Recently, risperidone received FDA approval for the treatment of irritability associated with autistic disorder in children.

Risperidone—the most-studied SGA in the PDD population—has shown efficacy in autism and in PDD not otherwise specified. Risperidone at dosages >3 mg/d improved repetitive behavior and aggression in adult patients.³⁸

In children with autism, risperidone can improve tantrums, aggression, and self-injury. In a study of risperidone’s effect on autism’s core symptoms, the authors reported improvements in repetitive and stereotyped behavior but not in social relatedness or verbal communication.³⁹

Double-blind studies have shown positive effects on aggression and behavioral disturbances in children with conduct disorder, oppositional defiant disorder, and other disruptive disorders, developmentally delayed adolescents, and mentally retarded subjects of various ages.^40-42 Children and adolescents appear to be more sensitive than adults to risperidone’s side effects such as weight gain, EPS, and pancreatitis.

Personality disorders

Antipsychotics have been recommended for paranoid ideas and psychotic-like symptoms in borderline personality disorder and in paranoid personality disorder.⁴³

Olanzapine. A 24-week, double-blind study found low-dose olanzapine (mean dosage 5.3 mg/d) more effective than placebo for anxiety, interpersonal sensitivity, paranoia, and anger/hostility in women with borderline personality disorder.⁴⁴

In another double-blind study, 12 weeks of olanzapine therapy (mean 6.9 mg/d) was more effective than placebo for inappropriate anger in borderline personality disorder, as measured by a modified Clinical Global Impression scale.⁴⁵

Others. Anger and hostility improved more with aripiprazole, 15 mg/d, than with placebo in an 8-week double-blind study of patients with borderline personality disorder.⁴⁶ Quetiapine, risperidone, ziprasidone, and clozapine have shown efficacy in open-label studies and case reports.

Related resources

• Boos J. Off label use–label off use? Ann Oncol 2003;14(1):1-5.
  
• Blum RS. Legal considerations in off-label medication prescribing. Arch Intern Med 2002;162(15):1777-9.
  
• Jeste DV, Dolder CR. Treatment of non-schizophrenic disorders: focus on atypical antipsychotics. J Psychiatr Res 2004;38(1):73-103.
  
• Food and Drug Administration. Searchable catalog of FDA-approved drug products. www.accessdata.fda.gov/scripts/cder/drugsatfda.
  

• Aripiprazole • Abilify
  
• Chlorpromazine • Thorazine
  
• Citalopram • Celexa
  
• Clozapine • Clozaril
  
• Divalproex • Depakote
  
• Fluoxetine • Prozac
  
• Haloperidol • Haldol
  
• Nortriptyline • Pamelor, Aventyl
  
• Olanzapine • Zyprexa
  
• Olanzapine/fluoxetine • Symbyax
  
• Paroxetine • Paxil
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Thioridazine • Mellaril
  
• Ziprasidone • Geodon
  

Dr. Trémeau receives grant/research support from Eli Lilly and Company.

Dr. Citrome receives grant/research support from AstraZeneca, Barr Laboratories, Bristol-Myers Squibb, Eli Lilly and Company, Janssen Research Foundation, and Pfizer; is a consultant to Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Jazz Pharmaceuticals, and GlaxoSmithKline; and is a speaker for Abbott Laboratories, AstraZeneca, Eli Lilly and Company, and Pfizer.

Controlled clinical trial results can help you make two prescribing decisions:

• Is an antipsychotic the right choice for this patient?
  
• If yes, which agent?
  

Prescribing antipsychotics off-label can be worthwhile when a patient gets better, but even then two worries remain:

• Most uses of antipsychotics for nonpsychotic illness are not evidence-based.
  
• This practice may expose clinicians to liability if the patient gets worse.
  

Consider the use of second-generation antipsychotics (SGAs) to manage acute behaviors in patients with dementia. The FDA ordered a black box warning in 2005 that SGAs may increase mortality risk in older patients. In October, the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer’s Disease (CATIE-AD) reported that SGAs’ side effects offset their benefits when compared with placebo (see Will CATIE-AD change dementia treatment?).¹

What do you do when FDA-approved drugs fail to help your patient with dementia, unipolar depression, anxiety disorders, or other nonpsychotic symptoms, and SGAs may be the next consideration? The answers lie in managing side effects and knowing which antipsychotic uses are supported by data from controlled clinical trials, which we review here.

Box 1

Prescribing considerations

For a variety of reasons (Box 1), SGAs have rapidly assumed a major role in treating nonpsychotic disorders. Thirty-one percent of psychotropics are dispensed off-label,² and Buckley³ reported in a 3-state survey that 70% of SGA prescriptions were written for indications other than schizophrenia.

Using antipsychotics for nonpsychotic symptoms is a longstanding clinical practice. In schizophrenia patients, antipsychotics have been shown to improve psychotic and nonpsychotic symptoms: agitation, violence, negative symptoms, social isolation, depression, suicidality, anxiety, insomnia, poor appetite, compulsions, cognition, smoking, alcohol and drug use, polydipsia, tardive dyskinesia, and tardive dystonia. Some clinicians may view these reports as evidence that antipsychotics might relieve these symptoms in patients with nonpsychotic disorders as well, but the issue is more complicated than that (Box 2).⁴

Caveats. SGAs do offer clinicians unique tools; no other class of psychotropics can claim efficacy in psychotic disorders, bipolar disorder, depression, and other disorders we describe in this review. On the other hand:

• Although some SGAs are approved for bipolar disorder and one was recently approved to treat irritability in autism (Table 1), most SGA uses in nonpsychotic disorders are off-label and supported by few—if any—large, randomized, controlled trials.
  
• Antipsychotics can cause the very symptoms they relieve, including depression, obsessive-compulsive disorder (OCD), anxiety, poorer cognition, agitation, mania, insomnia, and abnormal movements.
  
• Few controlled studies have compared SGAs to usual first-line treatments; most have evaluated SGAs as adjuncts to other psychotropics—such as serotonin reuptake inhibitors (SRIs)—for patients with treatment-resistant disorders.
  
• Published head-to-head studies have rarely compared the efficacy of various SGAs in treating nonpsychotic disorders.
  
• Long-term safety studies of SGAs for nonpsychotic indications have not been done.
  

Table 1

Bipolar and other nonpsychotic indications FDA-approved for SGAs

Prescribing decisions. SGA’s potential adverse effects complicate clinical decision-making. First you must decide whether to use an SGA for your patient with a nonpsychotic disorder.

Box 2

• patient history and clinical characteristics
  
• potential side effects
  
• individual therapeutic response to previous medications.
  

Table 2

SGA uses in nonpsychotic disorders supported by evidence
from published double-blind clinical trials*

Dementia

Most Alzheimer’s patients—75% to 90%—experience behavioral problems during this progressive dementia. Double-blind studies have found risperidone (mean dosage ~1 mg/d) and olanzapine (mean dosage 5 to 10 mg/d) effective in reducing agitation and aggression, even in nonpsychotic patients with Alzheimer’s disease or vascular dementia.^5,6 Quetiapine, ≤100 mg/d, was not more effective than placebo in reducing agitation.⁷ One study comparing IM olanzapine with IM lorazepam and placebo in acute agitation found both active treatments more effective than placebo.⁸

CATIE-AD—sponsored by the National Institute of Mental Health—compared olanzapine, risperidone, and quetiapine with placebo in 421 outpatients with behavioral symptoms such as psychosis, agitation, or aggressiveness.¹ No significant differences were seen in overall effectiveness (measured as discontinuation for any cause⁹), although patients receiving olanzapine (mean dosage 5.5 mg/d) or risperidone (mean dosage 1 mg/d) had lower discontinuation rates for lack of efficacy than those receiving placebo.

Unfortunately, the results of the first phase of CATIE-AD provide no clear guidance on the therapeutic strategy to use in dementia. Its findings do suggest two secondary conclusions, however, about using SGAs for patients with dementia:

• Because quetiapine, mean dosage 56.5 mg/d, was not more effective than placebo on any measures, consider higher dosages when using this agent.
  
• Close attention to preventing and treating SGAs’ side effects is the key to effectively treating agitation and psychosis in dementia.
  

Recommendation. Nonpharmacologic interventions are an important part of treating behavioral problems in patients with dementia.^13,14 Antipsychotics—particularly SGAs—have shown efficacy for psychosis and agitation in these patients and remain the first therapeutic option. The CATIE-AD investigators recommend that clinicians evaluate potential risks and benefits of pharmacotherapy and discuss these with patients and caregivers.¹ Also:

• Consider which SGAs have the lowest risk of causing side effects for an individual patient.
  
• Start with low dosages and increase as needed, based on efficacy and tolerability.
  

Bipolar disorder

Acute mania. Five SGAs—aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone—are FDA-approved for acute mania (Table 1). Large double-blind studies supporting this indication show that SGAs have efficacy in treating mania as monotherapy and in combination with lithium or divalproex.¹⁵ These clinical trials included patients who were not psychotic at baseline.

Antipsychotic dosages in these studies were within the ranges used in schizophrenia treatment studies. Combining an SGA with lithium or divalproex generally yields greater reductions in mania rating scale scores, higher response rates, and higher remission rates than using lithium or divalproex alone. No published study has compared SGAs with each other in mania, but differences in efficacy among these compounds are likely to be small.¹⁶

Bipolar depression. SGAs’ efficacy in bipolar depression has been evaluated in double-blind studies, and quetiapine and the olanzapine/fluoxetine combination are FDA-approved for this indication.

Olanzapine plus fluoxetine was more effective in improving depressive symptoms than olanzapine alone in a double-blind study of 833 adults with depressive symptoms of bipolar I disorder, as measured by Montgomery-Åsburg Depression Rating Scale (MADRS) scores. Olanzapine alone was more effective than placebo. Mean dosages were olanzapine, 7.4 mg/d, and fluoxetine, 39.3 mg/d, in combination therapy and olanzapine, 9.7 mg/d, as monotherapy.

MADRS scores indicated that combination therapy—but not olanzapine alone—improved core depressive symptoms such as sadness, lassitude, inability to feel, and pessimistic thoughts.¹⁷

Quetiapine. A double-blind, placebo-controlled trial (BOLDER I) evaluated quetiapine in 542 outpatients experiencing a major depressive episode associated with bipolar I or II disorder. After 8 weeks, quetiapine at 300 or 600 mg/d was more effective than placebo in reducing depressive symptoms, as measured by MADRS score changes.

Response rates were 58% with quetiapine and 36% with placebo; remission rates were 53% with quetiapine and 28% with placebo. Most symptoms, including core depression items, improved significantly with quetiapine, compared with placebo.¹⁸ Results of a second double-blind study (BOLDER II) have been presented at conferences but have not been fully published.

Risperidone. A smaller double-blind study compared risperidone plus placebo, paroxetine plus placebo, and risperidone plus paroxetine in 30 patients in the depressed phase of bipolar I or II disorder. Patients continued taking mood stabilizers during the study. After 12 weeks, depressive symptoms improved significantly in all three groups, with no significant differences.¹⁹

Maintenance therapy. Olanzapine and aripiprazole are FDA-approved for maintenance therapy in bipolar disorder (Table 1).

Unipolar depression

FGAs have shown efficacy in depression in multiple controlled studies.²⁰ SGAs have been evaluated mostly as add-on therapies in antidepressant-resistant depression.

Olanzapine. Shelton et al²¹ compared olanzapine monotherapy, fluoxetine monotherapy, and combined treatment in 34 nonpsychotic, treatment-resistant depressed subjects. Olanzapine plus fluoxetine was more effective than either agent alone. A subsequent double-blind study, however, showed similar efficacy after 8 weeks among the three treatments and nortriptyline monotherapy. Patients in the double-blind trial appeared to respond more rapidly to combined treatment than to the monotherapies.²²

Risperidone. A multiphase study of the efficacy of risperidone augmentation in treatment-resistant major depression began when 489 outpatients (2% with psychotic symptoms) received open-label citalopram, 20 to 60 mg/d. After 4 to 6 weeks, 386 nonresponders entered the augmentation phase with open-label risperidone, 0.25 to 2 mg/d. After 4 to 6 weeks of combination therapy, 241 (63%) patients whose symptoms resolved entered a double-blind discontinuation phase, in which they were randomly assigned to augmentation with risperidone or placebo, while on citalopram.

Median time to relapse during the double-blind phase was 102 days with risperidone augmentation and 85 days with placebo—not a statistically significant difference. Relapse rates after 24 weeks were 53.3% and 54.6%, respectively.²³ This study showed that the improvement observed after adding risperidone was not sustained over time.

Quetiapine. In a prospective single-blind study, paroxetine augmented with quetiapine, 200 mg/d, was compared to paroxetine alone in major depression with anxiety.²⁴ Combination therapy was more effective in improving anxiety and depression symptoms.

Others. Open-label, add-on studies indicate that aripiprazole and ziprasidone can improve treatment-resistant depression.^25-27

Anxiety disorders

OCD. SGAs also have been investigated as augmentation therapy for patients with OCD resistant to SRIs. A single-blind study of 27 patients found adjunctive quetiapine more effective than placebo in improving OCD symptoms.²⁸ SGAs were more effective than placebo as augmentation therapy to SRIs for treatment-refractory OCD in double-blind, placebo-controlled studies using mean dosages of:

• risperidone, 2.2 mg/d
  
• olanzapine, 11 mg/d
  
• quetiapine, 300 mg/d.^29-31
  

In other trials:

• A small double-blind study of patients with social anxiety disorder found olanzapine monotherapy more effective than placebo.³⁴
  
• Low-dose risperidone (mean dosage 1.1 mg/d) improved core symptoms of generalized anxiety disorder in a 5-week, double-blind, placebo-controlled trial.³⁵
  
• Some authors have reported clinical improvement of panic disorder with olanzapine augmentation.³⁶
  

Developmental disorders

Antipsychotics represent one-third of all filled psychotropic prescriptions for individuals with pervasive developmental disorders (PDD).³⁷ Haloperidol and thioridazine are the only two FDA-approved FGAs for severe behavioral problems in PDD (and for hyperactivity with conduct disorders). Recently, risperidone received FDA approval for the treatment of irritability associated with autistic disorder in children.

Risperidone—the most-studied SGA in the PDD population—has shown efficacy in autism and in PDD not otherwise specified. Risperidone at dosages >3 mg/d improved repetitive behavior and aggression in adult patients.³⁸

In children with autism, risperidone can improve tantrums, aggression, and self-injury. In a study of risperidone’s effect on autism’s core symptoms, the authors reported improvements in repetitive and stereotyped behavior but not in social relatedness or verbal communication.³⁹

Double-blind studies have shown positive effects on aggression and behavioral disturbances in children with conduct disorder, oppositional defiant disorder, and other disruptive disorders, developmentally delayed adolescents, and mentally retarded subjects of various ages.^40-42 Children and adolescents appear to be more sensitive than adults to risperidone’s side effects such as weight gain, EPS, and pancreatitis.

Personality disorders

Antipsychotics have been recommended for paranoid ideas and psychotic-like symptoms in borderline personality disorder and in paranoid personality disorder.⁴³

Olanzapine. A 24-week, double-blind study found low-dose olanzapine (mean dosage 5.3 mg/d) more effective than placebo for anxiety, interpersonal sensitivity, paranoia, and anger/hostility in women with borderline personality disorder.⁴⁴

In another double-blind study, 12 weeks of olanzapine therapy (mean 6.9 mg/d) was more effective than placebo for inappropriate anger in borderline personality disorder, as measured by a modified Clinical Global Impression scale.⁴⁵

Others. Anger and hostility improved more with aripiprazole, 15 mg/d, than with placebo in an 8-week double-blind study of patients with borderline personality disorder.⁴⁶ Quetiapine, risperidone, ziprasidone, and clozapine have shown efficacy in open-label studies and case reports.

Related resources

• Boos J. Off label use–label off use? Ann Oncol 2003;14(1):1-5.
  
• Blum RS. Legal considerations in off-label medication prescribing. Arch Intern Med 2002;162(15):1777-9.
  
• Jeste DV, Dolder CR. Treatment of non-schizophrenic disorders: focus on atypical antipsychotics. J Psychiatr Res 2004;38(1):73-103.
  
• Food and Drug Administration. Searchable catalog of FDA-approved drug products. www.accessdata.fda.gov/scripts/cder/drugsatfda.
  

• Aripiprazole • Abilify
  
• Chlorpromazine • Thorazine
  
• Citalopram • Celexa
  
• Clozapine • Clozaril
  
• Divalproex • Depakote
  
• Fluoxetine • Prozac
  
• Haloperidol • Haldol
  
• Nortriptyline • Pamelor, Aventyl
  
• Olanzapine • Zyprexa
  
• Olanzapine/fluoxetine • Symbyax
  
• Paroxetine • Paxil
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Thioridazine • Mellaril
  
• Ziprasidone • Geodon
  

Dr. Trémeau receives grant/research support from Eli Lilly and Company.

Dr. Citrome receives grant/research support from AstraZeneca, Barr Laboratories, Bristol-Myers Squibb, Eli Lilly and Company, Janssen Research Foundation, and Pfizer; is a consultant to Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Jazz Pharmaceuticals, and GlaxoSmithKline; and is a speaker for Abbott Laboratories, AstraZeneca, Eli Lilly and Company, and Pfizer.

Controlled clinical trial results can help you make two prescribing decisions:

• Is an antipsychotic the right choice for this patient?
  
• If yes, which agent?
  

Prescribing antipsychotics off-label can be worthwhile when a patient gets better, but even then two worries remain:

• Most uses of antipsychotics for nonpsychotic illness are not evidence-based.
  
• This practice may expose clinicians to liability if the patient gets worse.
  

Consider the use of second-generation antipsychotics (SGAs) to manage acute behaviors in patients with dementia. The FDA ordered a black box warning in 2005 that SGAs may increase mortality risk in older patients. In October, the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer’s Disease (CATIE-AD) reported that SGAs’ side effects offset their benefits when compared with placebo (see Will CATIE-AD change dementia treatment?).¹

What do you do when FDA-approved drugs fail to help your patient with dementia, unipolar depression, anxiety disorders, or other nonpsychotic symptoms, and SGAs may be the next consideration? The answers lie in managing side effects and knowing which antipsychotic uses are supported by data from controlled clinical trials, which we review here.

Box 1

Prescribing considerations

For a variety of reasons (Box 1), SGAs have rapidly assumed a major role in treating nonpsychotic disorders. Thirty-one percent of psychotropics are dispensed off-label,² and Buckley³ reported in a 3-state survey that 70% of SGA prescriptions were written for indications other than schizophrenia.

Using antipsychotics for nonpsychotic symptoms is a longstanding clinical practice. In schizophrenia patients, antipsychotics have been shown to improve psychotic and nonpsychotic symptoms: agitation, violence, negative symptoms, social isolation, depression, suicidality, anxiety, insomnia, poor appetite, compulsions, cognition, smoking, alcohol and drug use, polydipsia, tardive dyskinesia, and tardive dystonia. Some clinicians may view these reports as evidence that antipsychotics might relieve these symptoms in patients with nonpsychotic disorders as well, but the issue is more complicated than that (Box 2).⁴

Caveats. SGAs do offer clinicians unique tools; no other class of psychotropics can claim efficacy in psychotic disorders, bipolar disorder, depression, and other disorders we describe in this review. On the other hand:

• Although some SGAs are approved for bipolar disorder and one was recently approved to treat irritability in autism (Table 1), most SGA uses in nonpsychotic disorders are off-label and supported by few—if any—large, randomized, controlled trials.
  
• Antipsychotics can cause the very symptoms they relieve, including depression, obsessive-compulsive disorder (OCD), anxiety, poorer cognition, agitation, mania, insomnia, and abnormal movements.
  
• Few controlled studies have compared SGAs to usual first-line treatments; most have evaluated SGAs as adjuncts to other psychotropics—such as serotonin reuptake inhibitors (SRIs)—for patients with treatment-resistant disorders.
  
• Published head-to-head studies have rarely compared the efficacy of various SGAs in treating nonpsychotic disorders.
  
• Long-term safety studies of SGAs for nonpsychotic indications have not been done.
  

Table 1

Bipolar and other nonpsychotic indications FDA-approved for SGAs

Prescribing decisions. SGA’s potential adverse effects complicate clinical decision-making. First you must decide whether to use an SGA for your patient with a nonpsychotic disorder.

Box 2

• patient history and clinical characteristics
  
• potential side effects
  
• individual therapeutic response to previous medications.
  

Table 2

SGA uses in nonpsychotic disorders supported by evidence
from published double-blind clinical trials*

Dementia

Most Alzheimer’s patients—75% to 90%—experience behavioral problems during this progressive dementia. Double-blind studies have found risperidone (mean dosage ~1 mg/d) and olanzapine (mean dosage 5 to 10 mg/d) effective in reducing agitation and aggression, even in nonpsychotic patients with Alzheimer’s disease or vascular dementia.^5,6 Quetiapine, ≤100 mg/d, was not more effective than placebo in reducing agitation.⁷ One study comparing IM olanzapine with IM lorazepam and placebo in acute agitation found both active treatments more effective than placebo.⁸

CATIE-AD—sponsored by the National Institute of Mental Health—compared olanzapine, risperidone, and quetiapine with placebo in 421 outpatients with behavioral symptoms such as psychosis, agitation, or aggressiveness.¹ No significant differences were seen in overall effectiveness (measured as discontinuation for any cause⁹), although patients receiving olanzapine (mean dosage 5.5 mg/d) or risperidone (mean dosage 1 mg/d) had lower discontinuation rates for lack of efficacy than those receiving placebo.

Unfortunately, the results of the first phase of CATIE-AD provide no clear guidance on the therapeutic strategy to use in dementia. Its findings do suggest two secondary conclusions, however, about using SGAs for patients with dementia:

• Because quetiapine, mean dosage 56.5 mg/d, was not more effective than placebo on any measures, consider higher dosages when using this agent.
  
• Close attention to preventing and treating SGAs’ side effects is the key to effectively treating agitation and psychosis in dementia.
  

Recommendation. Nonpharmacologic interventions are an important part of treating behavioral problems in patients with dementia.^13,14 Antipsychotics—particularly SGAs—have shown efficacy for psychosis and agitation in these patients and remain the first therapeutic option. The CATIE-AD investigators recommend that clinicians evaluate potential risks and benefits of pharmacotherapy and discuss these with patients and caregivers.¹ Also:

• Consider which SGAs have the lowest risk of causing side effects for an individual patient.
  
• Start with low dosages and increase as needed, based on efficacy and tolerability.
  

Bipolar disorder

Acute mania. Five SGAs—aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone—are FDA-approved for acute mania (Table 1). Large double-blind studies supporting this indication show that SGAs have efficacy in treating mania as monotherapy and in combination with lithium or divalproex.¹⁵ These clinical trials included patients who were not psychotic at baseline.

Antipsychotic dosages in these studies were within the ranges used in schizophrenia treatment studies. Combining an SGA with lithium or divalproex generally yields greater reductions in mania rating scale scores, higher response rates, and higher remission rates than using lithium or divalproex alone. No published study has compared SGAs with each other in mania, but differences in efficacy among these compounds are likely to be small.¹⁶

Bipolar depression. SGAs’ efficacy in bipolar depression has been evaluated in double-blind studies, and quetiapine and the olanzapine/fluoxetine combination are FDA-approved for this indication.

Olanzapine plus fluoxetine was more effective in improving depressive symptoms than olanzapine alone in a double-blind study of 833 adults with depressive symptoms of bipolar I disorder, as measured by Montgomery-Åsburg Depression Rating Scale (MADRS) scores. Olanzapine alone was more effective than placebo. Mean dosages were olanzapine, 7.4 mg/d, and fluoxetine, 39.3 mg/d, in combination therapy and olanzapine, 9.7 mg/d, as monotherapy.

MADRS scores indicated that combination therapy—but not olanzapine alone—improved core depressive symptoms such as sadness, lassitude, inability to feel, and pessimistic thoughts.¹⁷

Quetiapine. A double-blind, placebo-controlled trial (BOLDER I) evaluated quetiapine in 542 outpatients experiencing a major depressive episode associated with bipolar I or II disorder. After 8 weeks, quetiapine at 300 or 600 mg/d was more effective than placebo in reducing depressive symptoms, as measured by MADRS score changes.

Response rates were 58% with quetiapine and 36% with placebo; remission rates were 53% with quetiapine and 28% with placebo. Most symptoms, including core depression items, improved significantly with quetiapine, compared with placebo.¹⁸ Results of a second double-blind study (BOLDER II) have been presented at conferences but have not been fully published.

Risperidone. A smaller double-blind study compared risperidone plus placebo, paroxetine plus placebo, and risperidone plus paroxetine in 30 patients in the depressed phase of bipolar I or II disorder. Patients continued taking mood stabilizers during the study. After 12 weeks, depressive symptoms improved significantly in all three groups, with no significant differences.¹⁹

Maintenance therapy. Olanzapine and aripiprazole are FDA-approved for maintenance therapy in bipolar disorder (Table 1).

Unipolar depression

FGAs have shown efficacy in depression in multiple controlled studies.²⁰ SGAs have been evaluated mostly as add-on therapies in antidepressant-resistant depression.

Olanzapine. Shelton et al²¹ compared olanzapine monotherapy, fluoxetine monotherapy, and combined treatment in 34 nonpsychotic, treatment-resistant depressed subjects. Olanzapine plus fluoxetine was more effective than either agent alone. A subsequent double-blind study, however, showed similar efficacy after 8 weeks among the three treatments and nortriptyline monotherapy. Patients in the double-blind trial appeared to respond more rapidly to combined treatment than to the monotherapies.²²

Risperidone. A multiphase study of the efficacy of risperidone augmentation in treatment-resistant major depression began when 489 outpatients (2% with psychotic symptoms) received open-label citalopram, 20 to 60 mg/d. After 4 to 6 weeks, 386 nonresponders entered the augmentation phase with open-label risperidone, 0.25 to 2 mg/d. After 4 to 6 weeks of combination therapy, 241 (63%) patients whose symptoms resolved entered a double-blind discontinuation phase, in which they were randomly assigned to augmentation with risperidone or placebo, while on citalopram.

Median time to relapse during the double-blind phase was 102 days with risperidone augmentation and 85 days with placebo—not a statistically significant difference. Relapse rates after 24 weeks were 53.3% and 54.6%, respectively.²³ This study showed that the improvement observed after adding risperidone was not sustained over time.

Quetiapine. In a prospective single-blind study, paroxetine augmented with quetiapine, 200 mg/d, was compared to paroxetine alone in major depression with anxiety.²⁴ Combination therapy was more effective in improving anxiety and depression symptoms.

Others. Open-label, add-on studies indicate that aripiprazole and ziprasidone can improve treatment-resistant depression.^25-27

Anxiety disorders

OCD. SGAs also have been investigated as augmentation therapy for patients with OCD resistant to SRIs. A single-blind study of 27 patients found adjunctive quetiapine more effective than placebo in improving OCD symptoms.²⁸ SGAs were more effective than placebo as augmentation therapy to SRIs for treatment-refractory OCD in double-blind, placebo-controlled studies using mean dosages of:

• risperidone, 2.2 mg/d
  
• olanzapine, 11 mg/d
  
• quetiapine, 300 mg/d.^29-31
  

In other trials:

• A small double-blind study of patients with social anxiety disorder found olanzapine monotherapy more effective than placebo.³⁴
  
• Low-dose risperidone (mean dosage 1.1 mg/d) improved core symptoms of generalized anxiety disorder in a 5-week, double-blind, placebo-controlled trial.³⁵
  
• Some authors have reported clinical improvement of panic disorder with olanzapine augmentation.³⁶
  

Developmental disorders

Antipsychotics represent one-third of all filled psychotropic prescriptions for individuals with pervasive developmental disorders (PDD).³⁷ Haloperidol and thioridazine are the only two FDA-approved FGAs for severe behavioral problems in PDD (and for hyperactivity with conduct disorders). Recently, risperidone received FDA approval for the treatment of irritability associated with autistic disorder in children.

Risperidone—the most-studied SGA in the PDD population—has shown efficacy in autism and in PDD not otherwise specified. Risperidone at dosages >3 mg/d improved repetitive behavior and aggression in adult patients.³⁸

In children with autism, risperidone can improve tantrums, aggression, and self-injury. In a study of risperidone’s effect on autism’s core symptoms, the authors reported improvements in repetitive and stereotyped behavior but not in social relatedness or verbal communication.³⁹

Double-blind studies have shown positive effects on aggression and behavioral disturbances in children with conduct disorder, oppositional defiant disorder, and other disruptive disorders, developmentally delayed adolescents, and mentally retarded subjects of various ages.^40-42 Children and adolescents appear to be more sensitive than adults to risperidone’s side effects such as weight gain, EPS, and pancreatitis.

Personality disorders

Antipsychotics have been recommended for paranoid ideas and psychotic-like symptoms in borderline personality disorder and in paranoid personality disorder.⁴³

Olanzapine. A 24-week, double-blind study found low-dose olanzapine (mean dosage 5.3 mg/d) more effective than placebo for anxiety, interpersonal sensitivity, paranoia, and anger/hostility in women with borderline personality disorder.⁴⁴

In another double-blind study, 12 weeks of olanzapine therapy (mean 6.9 mg/d) was more effective than placebo for inappropriate anger in borderline personality disorder, as measured by a modified Clinical Global Impression scale.⁴⁵

Others. Anger and hostility improved more with aripiprazole, 15 mg/d, than with placebo in an 8-week double-blind study of patients with borderline personality disorder.⁴⁶ Quetiapine, risperidone, ziprasidone, and clozapine have shown efficacy in open-label studies and case reports.

Related resources

• Boos J. Off label use–label off use? Ann Oncol 2003;14(1):1-5.
  
• Blum RS. Legal considerations in off-label medication prescribing. Arch Intern Med 2002;162(15):1777-9.
  
• Jeste DV, Dolder CR. Treatment of non-schizophrenic disorders: focus on atypical antipsychotics. J Psychiatr Res 2004;38(1):73-103.
  
• Food and Drug Administration. Searchable catalog of FDA-approved drug products. www.accessdata.fda.gov/scripts/cder/drugsatfda.
  

• Aripiprazole • Abilify
  
• Chlorpromazine • Thorazine
  
• Citalopram • Celexa
  
• Clozapine • Clozaril
  
• Divalproex • Depakote
  
• Fluoxetine • Prozac
  
• Haloperidol • Haldol
  
• Nortriptyline • Pamelor, Aventyl
  
• Olanzapine • Zyprexa
  
• Olanzapine/fluoxetine • Symbyax
  
• Paroxetine • Paxil
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Thioridazine • Mellaril
  
• Ziprasidone • Geodon
  

Dr. Trémeau receives grant/research support from Eli Lilly and Company.

Dr. Citrome receives grant/research support from AstraZeneca, Barr Laboratories, Bristol-Myers Squibb, Eli Lilly and Company, Janssen Research Foundation, and Pfizer; is a consultant to Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Jazz Pharmaceuticals, and GlaxoSmithKline; and is a speaker for Abbott Laboratories, AstraZeneca, Eli Lilly and Company, and Pfizer.

Emergency admissions to psychiatric units usually are hectic, with ample opportunities to miss valuable clinical information. In these circumstances, failing to identify key features of the patient’s preadmission history can waste time and misinform treatment.

In our experience, psychiatric inpatients show characteristic trajectories and can be grouped into 6 categories based on preadmission course. Identifying which category best describes a particular patient can help direct your assessment and predict appropriate treatment (Table 1).

Table 1

Treatment planning at psychiatric admission: 6 patient categories*

Why this system?

In busy academic psychiatry departments—with rotating inpatient attending physicians and multiple outpatient providers—inpatient teams need a treatment framework that will decrease redundant assessments, unnecessary laboratory exams, and diagnostic confusion. We developed the following guide for residents, medical students, and attending physicians who practice in our 20-bed inpatient unit in an urban public hospital, where beds are always at a premium.

No controlled data support this approach. It does not consider predictors of length of stay—such as diagnoses or if patients have suicidal thoughts or behavioral disturbances. This model can be used across a broad range of diagnostic, symptomatic, and behavioral presentations, however, and our residents have found it helps them organize inpatient care.

Category 1: first-time admissions

Patients who never have had psychiatric treatment and are admitted to an inpatient unit usually are experiencing an index psychotic or mood episode. They represent a small fraction of all admitted patients but deserve the most comprehensive medical and psychiatric evaluation. The goal is to establish an accurate diagnosis, which will determine the treatment course.

Evaluation. Obtain a clinical history from the patient and from individuals with corroborating information. Do a comprehensive physical examination, and order a baseline laboratory evaluation, including a complete blood count with differential, comprehensive metabolic panel (CMP), thyroid-stimulating hormone (TSH), and toxicology screen. Add other laboratory tests as indicated by the history and physical exam.

Always obtain brain CT or MRI for an atypical psychosis and probably even for a typical presentation of an index psychotic episode. CT and/or MRI are indicated if mental status, physical, or neurologic examinations reveal focal neurologic deficits.

Order an EEG if you suspect seizures—especially complex partial seizures—or metabolic encephalopathy. Order a lumbar puncture with cerebrospinal fluid analysis and culture if CNS infection is a possibility.

Neuropsychological tests. Psychological testing may include personality tests such as the Minnesota Multiphasic Personality Inventory (MMPI-2) or Millon Clinical Multiaxial Inventory-III and rating scales and instruments to quantify symptom severity (Table 2).

Always administer a Mini-Mental State Examination (MMSE) to assess for cognitive impairment, and use the Blessed Dementia Scale (BDS) if needed.

For suspected delirium, consider the Delirium Rating Scale (DRS) or the updated version, DRS-98. Further neuropsychological testing may be indicated if the patient shows cognitive dysfunction, as may be seen in delirium or dementia (Table 3).

Table 2

How severe are psychiatric symptoms? Consider these rating scales

Tests for patients with cognitive dysfunction, as in delirium or dementia

Categories 2 & 3: readmission for nonadherence

Without outpatient follow-up. Although inpatients are almost always referred for outpatient care after discharge, many do not keep even one outpatient appointment. Patients who have no outpatient follow-up after discharge are twice as likely to be rehospitalized the same year, compared with patients who kept at least one outpatient appointment.¹

With outpatient follow-up. Patients who relapse and are readmitted after a period of outpatient treatment probably account for the largest group of psychiatric inpatients. Reasons why outpatients become nonadherent² and relapse after a period of stable remission are legion (Table 4).^3-10

Table 4

Factors that interfere with patient adherence to psychiatric treatment

Patients being readmitted often are less-than-honest about treatment adherence, so seek corroboration from family, case managers, other caregivers, or outpatient clinicians. Measuring blood levels of medications or hormones (such as prolactin) that are influenced by medications may help you gauge adherence.

Promote treatment adherence. After you re-establish treatment, the second goal is to promote future adherence. Contact the outpatient psychiatrist to explore the patient’s involvement with outpatient care.

If the patient was nonadherent because of poor insight or misconceptions about the medication—such as fear of dependence, stigma of mental illness, or denial—educate the patient and family/caregivers. If patient and family education prove ineffective or are not possible, consider depot psychotropics.

For nonadherence caused by side effects, consider changing the dosage or rhythm of administration. Simplified dosing schedules might help. Pay close attention to drug-drug interactions with nonpsychotropic medications.

Because drug or alcohol abuse is a common reason for outpatient nonadherence,^7,8 consider chemical-dependency treatment programs for patients with addictions or those whose nondependent substance use causes psychiatric relapse.

Links to outpatient care. In an ideal system, the links between inpatient and outpatient treatment would be seamless. Many real world systems do not work as well, however. Too often patients are admitted and discharged before the outpatient doctor has heard of the admission.

Three inpatient interventions have been shown to more than triple the likelihood for successful linkage to outpatient care:

• communication between inpatient and outpatient clinicians about discharge plans
  
• patients starting outpatient programs before discharge
  
• involving family during the hospital stay.⁶
  

Category 4: readmission after stressful event

Even in patients who have been completely adherent with outpatient treatment, a sudden stressful life event can exacerbate psychiatric symptoms and require inpatient care. Examples include:

• death of a family member
  
• departure of a trusted caregiver
  
• onset of an intercurrent medical illness
  
• loss of a job or other financial hardship
  
• loss of housing
  
• anniversary of a traumatic life event.
  

Although we are trained to look for a “precipitating event” in formulating psychiatric illness, patients might be unable to talk about such preadmission changes. If this information is not readily available, symptomatic deterioration may be misinterpreted as treatment nonadherence, incorrect diagnosis, or other etiology.

Treatment goals. For a patient who has deteriorated because of a psychosocial change, the goal of admission is to address this stressor and return the patient to function. These patients do not require extensive medical or psychiatric assessment, and their previously successful psychotropics probably do not need to be changed.

Patients in this category typically do not need or benefit from diagnostic reassessment or comprehensive laboratory, radiologic, or psychological investigations. Even so, consider the possibility that the patient might be experiencing a comorbid medical illness, drug side effect, or other biomedical change, even in cases of an apparent intercurrent stressful event.

Inpatient treatment is supportive, encompassing grief work and individual and group therapy. Involve the social worker immediately to address adverse changes in the patient’s income, financial status, and residential circumstances.

Continue previous outpatient medications, and modify dosages if indicated by symptom severity. Patients in this group usually require only short hospital stays until the acute symptoms recede and they rebuild sufficient coping skills to address the new stressors.

Category 5: progressive deterioration

Patients who worsen despite adherence with out-patient treatment and have not experienced a new psychosocial stressor are difficult to treat. Similar to patients with an index psychotic episode, deteriorating patients require extensive re-evaluation of diagnosis and treatment trajectory going back several years.

As described for category 1 patients, perform an extensive physical and laboratory examination, psychological testing, and additional or specialized radiologic testing such as MRI, fMRI, SPECT, or (if possible) PET, as needed. Focus on the possibility of diagnostic reassignment and/or the presence of comorbidities. Seek clinical consultation, especially if academic specialty programs are available in the vicinity. Consultation from medical, neurology, and neuropsychology colleagues can help clarify diagnostic possibilities.

Unlike patients in categories 2, 3, and 4, deteriorating patients often require wholesale changes in medication management because:

• adherence with previous regimens has not produced ongoing remission
  
• illness is worse or progressive and requires a new or more intensive approach.
  

Category 6: malingering

Resnick¹¹ characterized 5 motivations for malingering psychosis and probably mental illness in general (Table 5). Psychiatric malingerers fall into two categories:

• those who have no illness but fake one
  
• those who have mental illness but grossly exaggerate the intensity and gravity of symptoms for secondary gain.
  

In general, malingering patients should not be hospitalized. If malingering is discovered after admission, discharge those without illness. In those with psychiatric illness, exaggerating symptoms may represent comorbid illness (especially Axis II disorders) or increased dependency because of a psychosocial change, such as loss of housing.

Address the latter with psychosocial support and social work/case management services, as with patients in category 4.

Table 5

5 motivations for psychiatric malingering

5 clinical factors that suggest malingering

• Cuffel BJ, Held M, Goldman W. Predictive models and the effectiveness of strategies for improving outpatient follow-up under managed care. Psychiatr Serv 2002;53(11):1438-43.
  
• Lien L. Are readmission rates influenced by how psychiatric services are organized? Nord J Psychiatry 2002;56(1):23-8.
  
• Maruish ME, ed. The use of psychological testing for treatment planning and outcomes assessment, 3rd ed. Mahwah, NJ: Lawrence Erlbaum Assoc; 2004.
  

Emergency admissions to psychiatric units usually are hectic, with ample opportunities to miss valuable clinical information. In these circumstances, failing to identify key features of the patient’s preadmission history can waste time and misinform treatment.

In our experience, psychiatric inpatients show characteristic trajectories and can be grouped into 6 categories based on preadmission course. Identifying which category best describes a particular patient can help direct your assessment and predict appropriate treatment (Table 1).

Table 1

Treatment planning at psychiatric admission: 6 patient categories*

Why this system?

In busy academic psychiatry departments—with rotating inpatient attending physicians and multiple outpatient providers—inpatient teams need a treatment framework that will decrease redundant assessments, unnecessary laboratory exams, and diagnostic confusion. We developed the following guide for residents, medical students, and attending physicians who practice in our 20-bed inpatient unit in an urban public hospital, where beds are always at a premium.

No controlled data support this approach. It does not consider predictors of length of stay—such as diagnoses or if patients have suicidal thoughts or behavioral disturbances. This model can be used across a broad range of diagnostic, symptomatic, and behavioral presentations, however, and our residents have found it helps them organize inpatient care.

Category 1: first-time admissions

Patients who never have had psychiatric treatment and are admitted to an inpatient unit usually are experiencing an index psychotic or mood episode. They represent a small fraction of all admitted patients but deserve the most comprehensive medical and psychiatric evaluation. The goal is to establish an accurate diagnosis, which will determine the treatment course.

Evaluation. Obtain a clinical history from the patient and from individuals with corroborating information. Do a comprehensive physical examination, and order a baseline laboratory evaluation, including a complete blood count with differential, comprehensive metabolic panel (CMP), thyroid-stimulating hormone (TSH), and toxicology screen. Add other laboratory tests as indicated by the history and physical exam.

Always obtain brain CT or MRI for an atypical psychosis and probably even for a typical presentation of an index psychotic episode. CT and/or MRI are indicated if mental status, physical, or neurologic examinations reveal focal neurologic deficits.

Order an EEG if you suspect seizures—especially complex partial seizures—or metabolic encephalopathy. Order a lumbar puncture with cerebrospinal fluid analysis and culture if CNS infection is a possibility.

Neuropsychological tests. Psychological testing may include personality tests such as the Minnesota Multiphasic Personality Inventory (MMPI-2) or Millon Clinical Multiaxial Inventory-III and rating scales and instruments to quantify symptom severity (Table 2).

Always administer a Mini-Mental State Examination (MMSE) to assess for cognitive impairment, and use the Blessed Dementia Scale (BDS) if needed.

For suspected delirium, consider the Delirium Rating Scale (DRS) or the updated version, DRS-98. Further neuropsychological testing may be indicated if the patient shows cognitive dysfunction, as may be seen in delirium or dementia (Table 3).

Table 2

How severe are psychiatric symptoms? Consider these rating scales

Tests for patients with cognitive dysfunction, as in delirium or dementia

Categories 2 & 3: readmission for nonadherence

Without outpatient follow-up. Although inpatients are almost always referred for outpatient care after discharge, many do not keep even one outpatient appointment. Patients who have no outpatient follow-up after discharge are twice as likely to be rehospitalized the same year, compared with patients who kept at least one outpatient appointment.¹

With outpatient follow-up. Patients who relapse and are readmitted after a period of outpatient treatment probably account for the largest group of psychiatric inpatients. Reasons why outpatients become nonadherent² and relapse after a period of stable remission are legion (Table 4).^3-10

Table 4

Factors that interfere with patient adherence to psychiatric treatment

Patients being readmitted often are less-than-honest about treatment adherence, so seek corroboration from family, case managers, other caregivers, or outpatient clinicians. Measuring blood levels of medications or hormones (such as prolactin) that are influenced by medications may help you gauge adherence.

Promote treatment adherence. After you re-establish treatment, the second goal is to promote future adherence. Contact the outpatient psychiatrist to explore the patient’s involvement with outpatient care.

If the patient was nonadherent because of poor insight or misconceptions about the medication—such as fear of dependence, stigma of mental illness, or denial—educate the patient and family/caregivers. If patient and family education prove ineffective or are not possible, consider depot psychotropics.

For nonadherence caused by side effects, consider changing the dosage or rhythm of administration. Simplified dosing schedules might help. Pay close attention to drug-drug interactions with nonpsychotropic medications.

Because drug or alcohol abuse is a common reason for outpatient nonadherence,^7,8 consider chemical-dependency treatment programs for patients with addictions or those whose nondependent substance use causes psychiatric relapse.

Links to outpatient care. In an ideal system, the links between inpatient and outpatient treatment would be seamless. Many real world systems do not work as well, however. Too often patients are admitted and discharged before the outpatient doctor has heard of the admission.

Three inpatient interventions have been shown to more than triple the likelihood for successful linkage to outpatient care:

• communication between inpatient and outpatient clinicians about discharge plans
  
• patients starting outpatient programs before discharge
  
• involving family during the hospital stay.⁶
  

Category 4: readmission after stressful event

Even in patients who have been completely adherent with outpatient treatment, a sudden stressful life event can exacerbate psychiatric symptoms and require inpatient care. Examples include:

• death of a family member
  
• departure of a trusted caregiver
  
• onset of an intercurrent medical illness
  
• loss of a job or other financial hardship
  
• loss of housing
  
• anniversary of a traumatic life event.
  

Although we are trained to look for a “precipitating event” in formulating psychiatric illness, patients might be unable to talk about such preadmission changes. If this information is not readily available, symptomatic deterioration may be misinterpreted as treatment nonadherence, incorrect diagnosis, or other etiology.

Treatment goals. For a patient who has deteriorated because of a psychosocial change, the goal of admission is to address this stressor and return the patient to function. These patients do not require extensive medical or psychiatric assessment, and their previously successful psychotropics probably do not need to be changed.

Patients in this category typically do not need or benefit from diagnostic reassessment or comprehensive laboratory, radiologic, or psychological investigations. Even so, consider the possibility that the patient might be experiencing a comorbid medical illness, drug side effect, or other biomedical change, even in cases of an apparent intercurrent stressful event.

Inpatient treatment is supportive, encompassing grief work and individual and group therapy. Involve the social worker immediately to address adverse changes in the patient’s income, financial status, and residential circumstances.

Continue previous outpatient medications, and modify dosages if indicated by symptom severity. Patients in this group usually require only short hospital stays until the acute symptoms recede and they rebuild sufficient coping skills to address the new stressors.

Category 5: progressive deterioration

Patients who worsen despite adherence with out-patient treatment and have not experienced a new psychosocial stressor are difficult to treat. Similar to patients with an index psychotic episode, deteriorating patients require extensive re-evaluation of diagnosis and treatment trajectory going back several years.

As described for category 1 patients, perform an extensive physical and laboratory examination, psychological testing, and additional or specialized radiologic testing such as MRI, fMRI, SPECT, or (if possible) PET, as needed. Focus on the possibility of diagnostic reassignment and/or the presence of comorbidities. Seek clinical consultation, especially if academic specialty programs are available in the vicinity. Consultation from medical, neurology, and neuropsychology colleagues can help clarify diagnostic possibilities.

Unlike patients in categories 2, 3, and 4, deteriorating patients often require wholesale changes in medication management because:

• adherence with previous regimens has not produced ongoing remission
  
• illness is worse or progressive and requires a new or more intensive approach.
  

Category 6: malingering

Resnick¹¹ characterized 5 motivations for malingering psychosis and probably mental illness in general (Table 5). Psychiatric malingerers fall into two categories:

• those who have no illness but fake one
  
• those who have mental illness but grossly exaggerate the intensity and gravity of symptoms for secondary gain.
  

In general, malingering patients should not be hospitalized. If malingering is discovered after admission, discharge those without illness. In those with psychiatric illness, exaggerating symptoms may represent comorbid illness (especially Axis II disorders) or increased dependency because of a psychosocial change, such as loss of housing.

Address the latter with psychosocial support and social work/case management services, as with patients in category 4.

Table 5

5 motivations for psychiatric malingering

5 clinical factors that suggest malingering

• Cuffel BJ, Held M, Goldman W. Predictive models and the effectiveness of strategies for improving outpatient follow-up under managed care. Psychiatr Serv 2002;53(11):1438-43.
  
• Lien L. Are readmission rates influenced by how psychiatric services are organized? Nord J Psychiatry 2002;56(1):23-8.
  
• Maruish ME, ed. The use of psychological testing for treatment planning and outcomes assessment, 3rd ed. Mahwah, NJ: Lawrence Erlbaum Assoc; 2004.
  

Emergency admissions to psychiatric units usually are hectic, with ample opportunities to miss valuable clinical information. In these circumstances, failing to identify key features of the patient’s preadmission history can waste time and misinform treatment.

In our experience, psychiatric inpatients show characteristic trajectories and can be grouped into 6 categories based on preadmission course. Identifying which category best describes a particular patient can help direct your assessment and predict appropriate treatment (Table 1).

Table 1

Treatment planning at psychiatric admission: 6 patient categories*

Why this system?

In busy academic psychiatry departments—with rotating inpatient attending physicians and multiple outpatient providers—inpatient teams need a treatment framework that will decrease redundant assessments, unnecessary laboratory exams, and diagnostic confusion. We developed the following guide for residents, medical students, and attending physicians who practice in our 20-bed inpatient unit in an urban public hospital, where beds are always at a premium.

No controlled data support this approach. It does not consider predictors of length of stay—such as diagnoses or if patients have suicidal thoughts or behavioral disturbances. This model can be used across a broad range of diagnostic, symptomatic, and behavioral presentations, however, and our residents have found it helps them organize inpatient care.

Category 1: first-time admissions

Patients who never have had psychiatric treatment and are admitted to an inpatient unit usually are experiencing an index psychotic or mood episode. They represent a small fraction of all admitted patients but deserve the most comprehensive medical and psychiatric evaluation. The goal is to establish an accurate diagnosis, which will determine the treatment course.

Evaluation. Obtain a clinical history from the patient and from individuals with corroborating information. Do a comprehensive physical examination, and order a baseline laboratory evaluation, including a complete blood count with differential, comprehensive metabolic panel (CMP), thyroid-stimulating hormone (TSH), and toxicology screen. Add other laboratory tests as indicated by the history and physical exam.

Always obtain brain CT or MRI for an atypical psychosis and probably even for a typical presentation of an index psychotic episode. CT and/or MRI are indicated if mental status, physical, or neurologic examinations reveal focal neurologic deficits.

Order an EEG if you suspect seizures—especially complex partial seizures—or metabolic encephalopathy. Order a lumbar puncture with cerebrospinal fluid analysis and culture if CNS infection is a possibility.

Neuropsychological tests. Psychological testing may include personality tests such as the Minnesota Multiphasic Personality Inventory (MMPI-2) or Millon Clinical Multiaxial Inventory-III and rating scales and instruments to quantify symptom severity (Table 2).

Always administer a Mini-Mental State Examination (MMSE) to assess for cognitive impairment, and use the Blessed Dementia Scale (BDS) if needed.

For suspected delirium, consider the Delirium Rating Scale (DRS) or the updated version, DRS-98. Further neuropsychological testing may be indicated if the patient shows cognitive dysfunction, as may be seen in delirium or dementia (Table 3).

Table 2

How severe are psychiatric symptoms? Consider these rating scales

Tests for patients with cognitive dysfunction, as in delirium or dementia

Categories 2 & 3: readmission for nonadherence

Without outpatient follow-up. Although inpatients are almost always referred for outpatient care after discharge, many do not keep even one outpatient appointment. Patients who have no outpatient follow-up after discharge are twice as likely to be rehospitalized the same year, compared with patients who kept at least one outpatient appointment.¹

With outpatient follow-up. Patients who relapse and are readmitted after a period of outpatient treatment probably account for the largest group of psychiatric inpatients. Reasons why outpatients become nonadherent² and relapse after a period of stable remission are legion (Table 4).^3-10

Table 4

Factors that interfere with patient adherence to psychiatric treatment

Patients being readmitted often are less-than-honest about treatment adherence, so seek corroboration from family, case managers, other caregivers, or outpatient clinicians. Measuring blood levels of medications or hormones (such as prolactin) that are influenced by medications may help you gauge adherence.

Promote treatment adherence. After you re-establish treatment, the second goal is to promote future adherence. Contact the outpatient psychiatrist to explore the patient’s involvement with outpatient care.

If the patient was nonadherent because of poor insight or misconceptions about the medication—such as fear of dependence, stigma of mental illness, or denial—educate the patient and family/caregivers. If patient and family education prove ineffective or are not possible, consider depot psychotropics.

For nonadherence caused by side effects, consider changing the dosage or rhythm of administration. Simplified dosing schedules might help. Pay close attention to drug-drug interactions with nonpsychotropic medications.

Because drug or alcohol abuse is a common reason for outpatient nonadherence,^7,8 consider chemical-dependency treatment programs for patients with addictions or those whose nondependent substance use causes psychiatric relapse.

Links to outpatient care. In an ideal system, the links between inpatient and outpatient treatment would be seamless. Many real world systems do not work as well, however. Too often patients are admitted and discharged before the outpatient doctor has heard of the admission.

Three inpatient interventions have been shown to more than triple the likelihood for successful linkage to outpatient care:

• communication between inpatient and outpatient clinicians about discharge plans
  
• patients starting outpatient programs before discharge
  
• involving family during the hospital stay.⁶
  

Category 4: readmission after stressful event

Even in patients who have been completely adherent with outpatient treatment, a sudden stressful life event can exacerbate psychiatric symptoms and require inpatient care. Examples include:

• death of a family member
  
• departure of a trusted caregiver
  
• onset of an intercurrent medical illness
  
• loss of a job or other financial hardship
  
• loss of housing
  
• anniversary of a traumatic life event.
  

Although we are trained to look for a “precipitating event” in formulating psychiatric illness, patients might be unable to talk about such preadmission changes. If this information is not readily available, symptomatic deterioration may be misinterpreted as treatment nonadherence, incorrect diagnosis, or other etiology.

Treatment goals. For a patient who has deteriorated because of a psychosocial change, the goal of admission is to address this stressor and return the patient to function. These patients do not require extensive medical or psychiatric assessment, and their previously successful psychotropics probably do not need to be changed.

Patients in this category typically do not need or benefit from diagnostic reassessment or comprehensive laboratory, radiologic, or psychological investigations. Even so, consider the possibility that the patient might be experiencing a comorbid medical illness, drug side effect, or other biomedical change, even in cases of an apparent intercurrent stressful event.

Inpatient treatment is supportive, encompassing grief work and individual and group therapy. Involve the social worker immediately to address adverse changes in the patient’s income, financial status, and residential circumstances.

Continue previous outpatient medications, and modify dosages if indicated by symptom severity. Patients in this group usually require only short hospital stays until the acute symptoms recede and they rebuild sufficient coping skills to address the new stressors.

Category 5: progressive deterioration

Patients who worsen despite adherence with out-patient treatment and have not experienced a new psychosocial stressor are difficult to treat. Similar to patients with an index psychotic episode, deteriorating patients require extensive re-evaluation of diagnosis and treatment trajectory going back several years.

As described for category 1 patients, perform an extensive physical and laboratory examination, psychological testing, and additional or specialized radiologic testing such as MRI, fMRI, SPECT, or (if possible) PET, as needed. Focus on the possibility of diagnostic reassignment and/or the presence of comorbidities. Seek clinical consultation, especially if academic specialty programs are available in the vicinity. Consultation from medical, neurology, and neuropsychology colleagues can help clarify diagnostic possibilities.

Unlike patients in categories 2, 3, and 4, deteriorating patients often require wholesale changes in medication management because:

• adherence with previous regimens has not produced ongoing remission
  
• illness is worse or progressive and requires a new or more intensive approach.
  

Category 6: malingering

Resnick¹¹ characterized 5 motivations for malingering psychosis and probably mental illness in general (Table 5). Psychiatric malingerers fall into two categories:

• those who have no illness but fake one
  
• those who have mental illness but grossly exaggerate the intensity and gravity of symptoms for secondary gain.
  

In general, malingering patients should not be hospitalized. If malingering is discovered after admission, discharge those without illness. In those with psychiatric illness, exaggerating symptoms may represent comorbid illness (especially Axis II disorders) or increased dependency because of a psychosocial change, such as loss of housing.

Address the latter with psychosocial support and social work/case management services, as with patients in category 4.

Table 5

5 motivations for psychiatric malingering

5 clinical factors that suggest malingering

• Cuffel BJ, Held M, Goldman W. Predictive models and the effectiveness of strategies for improving outpatient follow-up under managed care. Psychiatr Serv 2002;53(11):1438-43.
  
• Lien L. Are readmission rates influenced by how psychiatric services are organized? Nord J Psychiatry 2002;56(1):23-8.
  
• Maruish ME, ed. The use of psychological testing for treatment planning and outcomes assessment, 3rd ed. Mahwah, NJ: Lawrence Erlbaum Assoc; 2004.
  

Personal digital assistant (PDA)-based drug reference software can help you make informed point-of-care prescription decisions, but accuracy, usability, and comprehensiveness vary greatly among programs.

This article looks at the benefits and drawbacks of popular PDA drug reference programs and offers advice on choosing the right one for your practice.

PDA Program benefits

Equipping your PDA with drug reference software makes prescription information portable and accessible. PDA-based drug guides also:

• are easy to update. Most PDA-based systems automatically update as part of routine synchronization procedures between the device and its host computer, keeping the information up-to-date. This is an important feature as some drug databases are updated daily.
• list potential side effects. Most programs list all potential medication side effects and distinguish between common and uncommon adverse events.
• list possible drug-drug interactions. This feature gives PDA-based drug guides a clear advantage over print textbooks. Users enter two or more medications, and the program searches for potential interactions between them.
• list interactions with alternative medications. Many databases include herbal supplements and other nontraditional pharmaceuticals.
• offer additional tools, such as medical calculators, treatment algorithms, and other handy features.

Drawbacks

Because PDA screens are so small, PDA-based drug guides must compromise between level of detail and ease of use. Unlike standard drug reference books, for example, PDA programs rarely list rates of side effects or comparisons with placebo.

PDA-based drug guides usually do not display references or analyses of the data behind the lists. For example, many programs provide dosing suggestions for special populations—such as the elderly, medically ill, and children—but the basis for these dose adjustments often is unclear or does not jibe with other programs. Most PDA drug software excludes other specific information, such as the evidence behind drug indications.

Researchers’ ratings

Some PDA-based drug databases, such as mobilePDR, evolved from written pharmacy databases. Others, such as ePharmacopoeia or Epocrates, were developed from more-general reference tools aimed at students and physicians. Overall, the former type of drug guide is more comprehensive and the latter is easier to use, although all PDA drug software offers some degree of comprehensiveness and usability.

PDA-based programs differ greatly, however, and the following researchers have explored the differences.

• Enders et al¹ in 2001 rated Lexi-Drugs Platinum the most comprehensive and accurate among nine programs.
• Galt and colleagues,² placing more weight on safety concerns than ease of use, in 2005 also rated Lexi-Drugs Platinum number one among 11 programs.
• Clauson et al³ in 2004 rated Lexi-Drugs number one among 10 programs, but noted that other products were catching up.
• Knollmann et al⁴ in 2004 rated 11 PDA-based drug databases on ease of use, comprehensiveness, and accuracy. They entered three pairs of drug names into each program; one pair included an herbal supplement.
• Perkins et al⁵ in 2004 entered 37 pairs of drug names into eight programs to test their ability to detect drug-drug interactions. They found that Epocrates offered the best combination of sensitivity (identifying all potential interactions) and specificity (reporting only important interactions). Lexi-Drugs had perfect sensitivity but comparatively poor specificity.

Which program should you choose?

No PDA-based drug reference will provide everything you need, so be clear on what you desire most when choosing a program:

• If drug safety is your primary concern, Lexi-Drugs might be best, although it tends to report clinically insignificant interactions.
• If you want only clinically significant interactions, consider Epocrates or Epocrates RX Pro.
• If a comprehensive database is critical, Clinical Pharmacology OnHand has the most extensive drug database.
• If you’re looking for the best combination of accuracy, comprehensiveness, and physician-friendly features, Lexi-Drugs and PEPID PDC might be most effective, though Epocrates is also a reasonable performer.
• If you wish to understand the evidence behind each recommendation, books and online pharmaceutical references remain better options.

Cost is another factor. This might explain why Epocrates—which offers a free version for physicians and medical students—is more popular than Lexi-Drugs, which is one of the most expensive programs at $70 for the basic version and $285 for the comprehensive suite. Most programs have two options: a less expensive—or even free—drug database that costs up to $75 and a suite of features such as treatment algorithms or diagnosis databases that range from $60 to almost $300.

Personal experience is the best way to determine which product is best. Most manufacturers let you try their programs before buying.

Related resources

Chan CH, Luo JS, Kennedy RS. Concise Guide to Computers in Clinical Psychiatry. Washington DC: American Psychiatric Press; 2002

American Association for Technology in Psychiatry. www.techpsych.org

Personal digital assistant (PDA)-based drug reference software can help you make informed point-of-care prescription decisions, but accuracy, usability, and comprehensiveness vary greatly among programs.

This article looks at the benefits and drawbacks of popular PDA drug reference programs and offers advice on choosing the right one for your practice.

PDA Program benefits

Equipping your PDA with drug reference software makes prescription information portable and accessible. PDA-based drug guides also:

• are easy to update. Most PDA-based systems automatically update as part of routine synchronization procedures between the device and its host computer, keeping the information up-to-date. This is an important feature as some drug databases are updated daily.
• list potential side effects. Most programs list all potential medication side effects and distinguish between common and uncommon adverse events.
• list possible drug-drug interactions. This feature gives PDA-based drug guides a clear advantage over print textbooks. Users enter two or more medications, and the program searches for potential interactions between them.
• list interactions with alternative medications. Many databases include herbal supplements and other nontraditional pharmaceuticals.
• offer additional tools, such as medical calculators, treatment algorithms, and other handy features.

Drawbacks

Because PDA screens are so small, PDA-based drug guides must compromise between level of detail and ease of use. Unlike standard drug reference books, for example, PDA programs rarely list rates of side effects or comparisons with placebo.

PDA-based drug guides usually do not display references or analyses of the data behind the lists. For example, many programs provide dosing suggestions for special populations—such as the elderly, medically ill, and children—but the basis for these dose adjustments often is unclear or does not jibe with other programs. Most PDA drug software excludes other specific information, such as the evidence behind drug indications.

Researchers’ ratings

Some PDA-based drug databases, such as mobilePDR, evolved from written pharmacy databases. Others, such as ePharmacopoeia or Epocrates, were developed from more-general reference tools aimed at students and physicians. Overall, the former type of drug guide is more comprehensive and the latter is easier to use, although all PDA drug software offers some degree of comprehensiveness and usability.

PDA-based programs differ greatly, however, and the following researchers have explored the differences.

• Enders et al¹ in 2001 rated Lexi-Drugs Platinum the most comprehensive and accurate among nine programs.
• Galt and colleagues,² placing more weight on safety concerns than ease of use, in 2005 also rated Lexi-Drugs Platinum number one among 11 programs.
• Clauson et al³ in 2004 rated Lexi-Drugs number one among 10 programs, but noted that other products were catching up.
• Knollmann et al⁴ in 2004 rated 11 PDA-based drug databases on ease of use, comprehensiveness, and accuracy. They entered three pairs of drug names into each program; one pair included an herbal supplement.
• Perkins et al⁵ in 2004 entered 37 pairs of drug names into eight programs to test their ability to detect drug-drug interactions. They found that Epocrates offered the best combination of sensitivity (identifying all potential interactions) and specificity (reporting only important interactions). Lexi-Drugs had perfect sensitivity but comparatively poor specificity.

Which program should you choose?

No PDA-based drug reference will provide everything you need, so be clear on what you desire most when choosing a program:

• If drug safety is your primary concern, Lexi-Drugs might be best, although it tends to report clinically insignificant interactions.
• If you want only clinically significant interactions, consider Epocrates or Epocrates RX Pro.
• If a comprehensive database is critical, Clinical Pharmacology OnHand has the most extensive drug database.
• If you’re looking for the best combination of accuracy, comprehensiveness, and physician-friendly features, Lexi-Drugs and PEPID PDC might be most effective, though Epocrates is also a reasonable performer.
• If you wish to understand the evidence behind each recommendation, books and online pharmaceutical references remain better options.

Cost is another factor. This might explain why Epocrates—which offers a free version for physicians and medical students—is more popular than Lexi-Drugs, which is one of the most expensive programs at $70 for the basic version and $285 for the comprehensive suite. Most programs have two options: a less expensive—or even free—drug database that costs up to $75 and a suite of features such as treatment algorithms or diagnosis databases that range from $60 to almost $300.

Personal experience is the best way to determine which product is best. Most manufacturers let you try their programs before buying.

Related resources

Chan CH, Luo JS, Kennedy RS. Concise Guide to Computers in Clinical Psychiatry. Washington DC: American Psychiatric Press; 2002

American Association for Technology in Psychiatry. www.techpsych.org

Personal digital assistant (PDA)-based drug reference software can help you make informed point-of-care prescription decisions, but accuracy, usability, and comprehensiveness vary greatly among programs.

This article looks at the benefits and drawbacks of popular PDA drug reference programs and offers advice on choosing the right one for your practice.

PDA Program benefits

Equipping your PDA with drug reference software makes prescription information portable and accessible. PDA-based drug guides also:

• are easy to update. Most PDA-based systems automatically update as part of routine synchronization procedures between the device and its host computer, keeping the information up-to-date. This is an important feature as some drug databases are updated daily.
• list potential side effects. Most programs list all potential medication side effects and distinguish between common and uncommon adverse events.
• list possible drug-drug interactions. This feature gives PDA-based drug guides a clear advantage over print textbooks. Users enter two or more medications, and the program searches for potential interactions between them.
• list interactions with alternative medications. Many databases include herbal supplements and other nontraditional pharmaceuticals.
• offer additional tools, such as medical calculators, treatment algorithms, and other handy features.

Drawbacks

Because PDA screens are so small, PDA-based drug guides must compromise between level of detail and ease of use. Unlike standard drug reference books, for example, PDA programs rarely list rates of side effects or comparisons with placebo.

PDA-based drug guides usually do not display references or analyses of the data behind the lists. For example, many programs provide dosing suggestions for special populations—such as the elderly, medically ill, and children—but the basis for these dose adjustments often is unclear or does not jibe with other programs. Most PDA drug software excludes other specific information, such as the evidence behind drug indications.

Researchers’ ratings

Some PDA-based drug databases, such as mobilePDR, evolved from written pharmacy databases. Others, such as ePharmacopoeia or Epocrates, were developed from more-general reference tools aimed at students and physicians. Overall, the former type of drug guide is more comprehensive and the latter is easier to use, although all PDA drug software offers some degree of comprehensiveness and usability.

PDA-based programs differ greatly, however, and the following researchers have explored the differences.

• Enders et al¹ in 2001 rated Lexi-Drugs Platinum the most comprehensive and accurate among nine programs.
• Galt and colleagues,² placing more weight on safety concerns than ease of use, in 2005 also rated Lexi-Drugs Platinum number one among 11 programs.
• Clauson et al³ in 2004 rated Lexi-Drugs number one among 10 programs, but noted that other products were catching up.
• Knollmann et al⁴ in 2004 rated 11 PDA-based drug databases on ease of use, comprehensiveness, and accuracy. They entered three pairs of drug names into each program; one pair included an herbal supplement.
• Perkins et al⁵ in 2004 entered 37 pairs of drug names into eight programs to test their ability to detect drug-drug interactions. They found that Epocrates offered the best combination of sensitivity (identifying all potential interactions) and specificity (reporting only important interactions). Lexi-Drugs had perfect sensitivity but comparatively poor specificity.

Which program should you choose?

No PDA-based drug reference will provide everything you need, so be clear on what you desire most when choosing a program:

• If drug safety is your primary concern, Lexi-Drugs might be best, although it tends to report clinically insignificant interactions.
• If you want only clinically significant interactions, consider Epocrates or Epocrates RX Pro.
• If a comprehensive database is critical, Clinical Pharmacology OnHand has the most extensive drug database.
• If you’re looking for the best combination of accuracy, comprehensiveness, and physician-friendly features, Lexi-Drugs and PEPID PDC might be most effective, though Epocrates is also a reasonable performer.
• If you wish to understand the evidence behind each recommendation, books and online pharmaceutical references remain better options.

Cost is another factor. This might explain why Epocrates—which offers a free version for physicians and medical students—is more popular than Lexi-Drugs, which is one of the most expensive programs at $70 for the basic version and $285 for the comprehensive suite. Most programs have two options: a less expensive—or even free—drug database that costs up to $75 and a suite of features such as treatment algorithms or diagnosis databases that range from $60 to almost $300.

Personal experience is the best way to determine which product is best. Most manufacturers let you try their programs before buying.

Related resources

Chan CH, Luo JS, Kennedy RS. Concise Guide to Computers in Clinical Psychiatry. Washington DC: American Psychiatric Press; 2002

American Association for Technology in Psychiatry. www.techpsych.org