Case-Based Review

CASE: Delusions and threats

For over 20 months, Ms. I, age 48, sends a psychiatric resident letters and postcards that total approximately 3,000 pages and come from dozens of return addresses. Ms. I expresses romantic feelings toward the resident and believes that he was her physician and prescribed medications, including “mood stabilizers.” The resident never treated Ms. I; to his knowledge, he has never interacted with her.

Ms. I describes the resident’s refusal to continue treating her as “abandonment” and states that she is contemplating self-harm because of this rejection. In her letters, Ms. I admits that she was a long-term patient in a state psychiatric hospital in her home state and suffers from persistent auditory hallucinations. She also wants a romantic relationship with the resident and repeatedly threatens the resident’s female acquaintances and former romantic partners whose relationships she had surmised from news articles available on the Internet. Ms. I also threatens to strangle the resident. The resident sends her multiple written requests that she cease contact, but they are not acknowledged.

The authors’ observations

Stalking—repeated, unwanted attention or communication that would cause a reasonable person fear—is a serious threat for many psychiatric clinicians.¹ Prevalence rates among mental health care providers range from 3% to 21%.^2,3 Most stalkers have engaged in previous stalking behavior.³

Being stalked is highly distressing,⁴ and mental health professionals often do not reveal such experiences to colleagues.⁵ Irrational feelings of guilt or embarrassment, such as being thought to have poorly managed interactions with the stalker, often motivate a self-imposed silence (Table 1).⁶ This isolation may foster anxiety, interfere with receiving problem-solving advice, and increase physical vulnerability. In the case involving Ms. I, the psychiatric resident’s primary responsibility is safeguarding his own physical and psychological welfare.

Clinicians who work in a hospital or other institutional setting who are being stalked should inform their supervisors and the facility’s security personnel. Security personnel may be able to gather data about the stalker, decrease the stalker’s ability to communicate with the victim, and reduce unwanted physical access to the victim by distributing a photo of the stalker or installing a camera or receptionist-controlled door lock in patient entryways. Security personnel also may collaborate with local law enforcement. Having a third party respond to a stalker’s aggressive behavior—rather than the victim responding directly—avoids rewarding the stalker, which may generate further unwanted contact.⁷ Any intervention by the victim may increase the risk of violence, creating an “intervention dilemma.” Resnick⁸ argues that before deciding how best to address the stalker’s behavior, a stalking victim must “first separate the risk of continued stalking from the risk that the stalker will commit a violent act.”

Mental health professionals in private practice who are being stalked should consider retaining an attorney. An attorney often can maintain privacy of communications regarding the stalker via the attorney-client and attorney-work product privileges, which may help during legal proceedings.

Table 1

Factors that can impede psychiatrists from reporting stalking

RESPONSE: Involving police

Over 2 months, Ms. I phones the resident’s home 105 times (the resident screens the calls). During 1 call, she states that she is hidden in a closet in her home and will hurt herself unless the resident “resumes” her psychiatric care. The resident contacts police in his city and Ms. I’s community, but authorities are reluctant to act when he acknowledges that he is not Ms. I’s psychiatrist and does not know her. Police officers in Ms. I’s hometown tell the resident no one answered the door when they visited her home. They state that they would enter the residence forcibly only if Ms. I’s physician or a family member asked them to do so, and because the resident admits that he is not her psychiatrist, they cannot take further action. Ms. I leaves the resident a phone message several hours later to inform him she is safe.

The authors’ observations

Stalking-induced countertransference responses may lead a psychiatrist to unwittingly place himself in harm’s way. For example, intense rage at a stalker’s request for treatment may generate guilt that motivates the psychiatrist to agree to treat the stalker. Feelings of helplessness may produce a frantic desire to do something even when such activity is ill-advised. Psychiatrists may develop a tolerance for antisocial or threatening behavior—which is common in mental health settings—and could accept unnecessary risks.

A psychiatrist who is being stalked may be able to assist a mentally ill stalker in a way that does not create a duty to treat and does not expose the psychiatrist to harm, such as contacting a mobile crisis intervention team, a mental health professional who recently treated the stalker, a family member of the stalker, or law enforcement personnel. A psychiatrist who is thrust from the role of helper to victim and must protect his or her own well-being instead of attending to a patient’s welfare is prone to suffer substantial countertransference distress.

The situation with Ms. I was particularly challenging because the resident did not know her complete history and therefore had little information to gauge how likely she was to act on her aggressive threats. Factors that predict future violence include:

• a history of violence
• significant prior criminality
• young age at first arrest
• concomitant substance abuse
• male sex.⁹

Unfortunately, other than sex, this data regarding Ms. I could not be readily obtained.

A psychiatrist’s duty

Although sympathetic to his stalker’s distress, the resident did not want to treat this woman, nor was he ethically or legally obligated to do so. An individual’s wish to be treated by a particular psychiatrist does not create a duty for the psychiatrist to satisfy this wish.¹⁰ State-based “Good Samaritan” laws encourage physicians to assist those in acute need by shielding them from liability, as long as they reasonably act within the scope of their expertise.¹¹ However, they do not require a physician to care for an individual in acute need. A delusional wish for treatment or a false belief of already being in treatment does not create a duty to care for a person.

OUTCOME: Seeking help

Ms. I’s phone calls and letters continue. The resident discusses the situation with his associate residency director, who refers him to the hospital’s legal and investigative staffs. Based on advice from the hospital’s private investigator, the resident sends Ms. I a formal “cease and desist” letter that threatens her with legal action and possible jail time. The staff at the front desk of the clinic where the resident works and the hospital’s security department are instructed to watch for a visitor with Ms. I’s name and description, although the hospital’s investigator is unable to obtain a photograph of her. Shortly after the resident sends the letter, Ms. I ceases communication.

The authors’ observations

This case is unusual because most stalking victims know their stalkers. Identifying a stalker’s motivation can be helpful in formulating a risk assessment. One classification system recognizes 5 categories of stalkers: rejected, intimacy seeking, incompetent, resentful, and predatory (Table 2).¹ Rejected stalkers appear to pose the greatest risk of violence and homicide.⁸ However, all stalkers may pose a risk of violence and therefore all stalking behavior should be treated seriously.

Table 2

Classification of stalkers

Responding to a stalker

The approach should be tailored to the stalker’s characteristics.¹² Silence—ie, lack of acknowledgement of a stalker’s intrusions—is one tactic.¹³ Consistent and persistent lack of engagement may bore the stalker, but also may provoke frustration or narcissistic or paranoia-fueled rage, and increased efforts to interact with the mental health professional. Other responses include:

• obtaining a protection or restraining order
• promoting the stalker’s participation in adversarial civil litigation, such as a lawsuit
• issuing verbal counterthreats.

Restraining orders are controversial and assessments of their effectiveness vary.¹⁴ How well a restraining order works may depend on the stalker’s:

• ability to appreciate reality, and how likely he or she is to experience anxiety when confronted with adverse consequences of his or her actions
• how consistently, rapidly, and harshly the criminal justice system responds to violations of restraining orders.

Restraining orders also may provide the victim a false sense of security.¹⁵ One of her letters revealed that Ms. I violated a criminal plea arrangement years earlier, which suggests she was capable of violating a restraining order.

Litigation. A stalker may initiate civil litigation against the victim to feel that he or she has an impact on the victim, which may reduce the stalker’s risk of violence if he or she is emotionally engaged in the litigation. Based on the authors’ experience, as long as the stalker is talking, he or she generally is less likely to act out violently and terminate a satisfying process. Adversarial civil litigation could give a stalker the opportunity to be “close” to the victim and a means of expressing aggressive wishes. The benefit of litigation lasts only as long as the case persists and the stalker believes he or she may prevail. In one of her letters, Ms. I bragged that she had represented herself as a pro se litigant in a complex civil matter, suggesting that she might be constructively channeled into litigation.

Promoting litigation carries significant risk.¹⁶ Being a defendant in pro se litigation may be emotionally and financially stressful. This approach may be desirable if the psychiatrist’s institution is willing to offer substantial support. For example, an institution may provide legal assistance—including helping to defray the cost of litigation—and litigation-related scheduling flexibility. An attorney may serve as a boundary between the victim and the pro se litigant’s sometimes ceaseless, time-devouring, anxiety-inducing legal maneuvers.

Counterthreats. Warning a stalker that he or she will face severe civil and criminal consequences if his or her behavior continues can make clear that his or her conduct is unacceptable.¹⁷ Such warnings may be delivered verbally or in writing by a legal representative, law enforcement personnel, a private security agent, or the victim.

Issuing a counterthreat can be risky. Stalkers with antisocial or narcissistic personality features may perceive a counterthreat as narcissistically diminishing, and to save face will escalate their stalking in retaliation. Avoid counterthreats if you believe the stalker might be psychotic because destabilizing such an individual—such as by precipitating a short psychotic episode—may increase unpredictability and diminish their responsive to interventions.

Ms. I’s contact with the resident lasted approximately 20 months, slightly less than the average 26 months reported in a survey of mental health professionals.³ Because stalkers are unpredictable, the psychiatric resident remains cautious.

Related Resources

• National Center for Victims of Crime. Stalking resource center. www.victimsofcrime.org/our-programs/stalking-resource-center.
• Mullen PE, Pathé M, Purcell R. Stalkers and their victims. New York, NY: Cambridge University Press; 2009.

Disclosure

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

CASE: Delusions and threats

For over 20 months, Ms. I, age 48, sends a psychiatric resident letters and postcards that total approximately 3,000 pages and come from dozens of return addresses. Ms. I expresses romantic feelings toward the resident and believes that he was her physician and prescribed medications, including “mood stabilizers.” The resident never treated Ms. I; to his knowledge, he has never interacted with her.

Ms. I describes the resident’s refusal to continue treating her as “abandonment” and states that she is contemplating self-harm because of this rejection. In her letters, Ms. I admits that she was a long-term patient in a state psychiatric hospital in her home state and suffers from persistent auditory hallucinations. She also wants a romantic relationship with the resident and repeatedly threatens the resident’s female acquaintances and former romantic partners whose relationships she had surmised from news articles available on the Internet. Ms. I also threatens to strangle the resident. The resident sends her multiple written requests that she cease contact, but they are not acknowledged.

The authors’ observations

Stalking—repeated, unwanted attention or communication that would cause a reasonable person fear—is a serious threat for many psychiatric clinicians.¹ Prevalence rates among mental health care providers range from 3% to 21%.^2,3 Most stalkers have engaged in previous stalking behavior.³

Being stalked is highly distressing,⁴ and mental health professionals often do not reveal such experiences to colleagues.⁵ Irrational feelings of guilt or embarrassment, such as being thought to have poorly managed interactions with the stalker, often motivate a self-imposed silence (Table 1).⁶ This isolation may foster anxiety, interfere with receiving problem-solving advice, and increase physical vulnerability. In the case involving Ms. I, the psychiatric resident’s primary responsibility is safeguarding his own physical and psychological welfare.

Clinicians who work in a hospital or other institutional setting who are being stalked should inform their supervisors and the facility’s security personnel. Security personnel may be able to gather data about the stalker, decrease the stalker’s ability to communicate with the victim, and reduce unwanted physical access to the victim by distributing a photo of the stalker or installing a camera or receptionist-controlled door lock in patient entryways. Security personnel also may collaborate with local law enforcement. Having a third party respond to a stalker’s aggressive behavior—rather than the victim responding directly—avoids rewarding the stalker, which may generate further unwanted contact.⁷ Any intervention by the victim may increase the risk of violence, creating an “intervention dilemma.” Resnick⁸ argues that before deciding how best to address the stalker’s behavior, a stalking victim must “first separate the risk of continued stalking from the risk that the stalker will commit a violent act.”

Mental health professionals in private practice who are being stalked should consider retaining an attorney. An attorney often can maintain privacy of communications regarding the stalker via the attorney-client and attorney-work product privileges, which may help during legal proceedings.

Table 1

Factors that can impede psychiatrists from reporting stalking

RESPONSE: Involving police

Over 2 months, Ms. I phones the resident’s home 105 times (the resident screens the calls). During 1 call, she states that she is hidden in a closet in her home and will hurt herself unless the resident “resumes” her psychiatric care. The resident contacts police in his city and Ms. I’s community, but authorities are reluctant to act when he acknowledges that he is not Ms. I’s psychiatrist and does not know her. Police officers in Ms. I’s hometown tell the resident no one answered the door when they visited her home. They state that they would enter the residence forcibly only if Ms. I’s physician or a family member asked them to do so, and because the resident admits that he is not her psychiatrist, they cannot take further action. Ms. I leaves the resident a phone message several hours later to inform him she is safe.

The authors’ observations

Stalking-induced countertransference responses may lead a psychiatrist to unwittingly place himself in harm’s way. For example, intense rage at a stalker’s request for treatment may generate guilt that motivates the psychiatrist to agree to treat the stalker. Feelings of helplessness may produce a frantic desire to do something even when such activity is ill-advised. Psychiatrists may develop a tolerance for antisocial or threatening behavior—which is common in mental health settings—and could accept unnecessary risks.

A psychiatrist who is being stalked may be able to assist a mentally ill stalker in a way that does not create a duty to treat and does not expose the psychiatrist to harm, such as contacting a mobile crisis intervention team, a mental health professional who recently treated the stalker, a family member of the stalker, or law enforcement personnel. A psychiatrist who is thrust from the role of helper to victim and must protect his or her own well-being instead of attending to a patient’s welfare is prone to suffer substantial countertransference distress.

The situation with Ms. I was particularly challenging because the resident did not know her complete history and therefore had little information to gauge how likely she was to act on her aggressive threats. Factors that predict future violence include:

• a history of violence
• significant prior criminality
• young age at first arrest
• concomitant substance abuse
• male sex.⁹

Unfortunately, other than sex, this data regarding Ms. I could not be readily obtained.

A psychiatrist’s duty

Although sympathetic to his stalker’s distress, the resident did not want to treat this woman, nor was he ethically or legally obligated to do so. An individual’s wish to be treated by a particular psychiatrist does not create a duty for the psychiatrist to satisfy this wish.¹⁰ State-based “Good Samaritan” laws encourage physicians to assist those in acute need by shielding them from liability, as long as they reasonably act within the scope of their expertise.¹¹ However, they do not require a physician to care for an individual in acute need. A delusional wish for treatment or a false belief of already being in treatment does not create a duty to care for a person.

OUTCOME: Seeking help

Ms. I’s phone calls and letters continue. The resident discusses the situation with his associate residency director, who refers him to the hospital’s legal and investigative staffs. Based on advice from the hospital’s private investigator, the resident sends Ms. I a formal “cease and desist” letter that threatens her with legal action and possible jail time. The staff at the front desk of the clinic where the resident works and the hospital’s security department are instructed to watch for a visitor with Ms. I’s name and description, although the hospital’s investigator is unable to obtain a photograph of her. Shortly after the resident sends the letter, Ms. I ceases communication.

The authors’ observations

This case is unusual because most stalking victims know their stalkers. Identifying a stalker’s motivation can be helpful in formulating a risk assessment. One classification system recognizes 5 categories of stalkers: rejected, intimacy seeking, incompetent, resentful, and predatory (Table 2).¹ Rejected stalkers appear to pose the greatest risk of violence and homicide.⁸ However, all stalkers may pose a risk of violence and therefore all stalking behavior should be treated seriously.

Table 2

Classification of stalkers

Responding to a stalker

The approach should be tailored to the stalker’s characteristics.¹² Silence—ie, lack of acknowledgement of a stalker’s intrusions—is one tactic.¹³ Consistent and persistent lack of engagement may bore the stalker, but also may provoke frustration or narcissistic or paranoia-fueled rage, and increased efforts to interact with the mental health professional. Other responses include:

• obtaining a protection or restraining order
• promoting the stalker’s participation in adversarial civil litigation, such as a lawsuit
• issuing verbal counterthreats.

Restraining orders are controversial and assessments of their effectiveness vary.¹⁴ How well a restraining order works may depend on the stalker’s:

• ability to appreciate reality, and how likely he or she is to experience anxiety when confronted with adverse consequences of his or her actions
• how consistently, rapidly, and harshly the criminal justice system responds to violations of restraining orders.

Restraining orders also may provide the victim a false sense of security.¹⁵ One of her letters revealed that Ms. I violated a criminal plea arrangement years earlier, which suggests she was capable of violating a restraining order.

Litigation. A stalker may initiate civil litigation against the victim to feel that he or she has an impact on the victim, which may reduce the stalker’s risk of violence if he or she is emotionally engaged in the litigation. Based on the authors’ experience, as long as the stalker is talking, he or she generally is less likely to act out violently and terminate a satisfying process. Adversarial civil litigation could give a stalker the opportunity to be “close” to the victim and a means of expressing aggressive wishes. The benefit of litigation lasts only as long as the case persists and the stalker believes he or she may prevail. In one of her letters, Ms. I bragged that she had represented herself as a pro se litigant in a complex civil matter, suggesting that she might be constructively channeled into litigation.

Promoting litigation carries significant risk.¹⁶ Being a defendant in pro se litigation may be emotionally and financially stressful. This approach may be desirable if the psychiatrist’s institution is willing to offer substantial support. For example, an institution may provide legal assistance—including helping to defray the cost of litigation—and litigation-related scheduling flexibility. An attorney may serve as a boundary between the victim and the pro se litigant’s sometimes ceaseless, time-devouring, anxiety-inducing legal maneuvers.

Counterthreats. Warning a stalker that he or she will face severe civil and criminal consequences if his or her behavior continues can make clear that his or her conduct is unacceptable.¹⁷ Such warnings may be delivered verbally or in writing by a legal representative, law enforcement personnel, a private security agent, or the victim.

Issuing a counterthreat can be risky. Stalkers with antisocial or narcissistic personality features may perceive a counterthreat as narcissistically diminishing, and to save face will escalate their stalking in retaliation. Avoid counterthreats if you believe the stalker might be psychotic because destabilizing such an individual—such as by precipitating a short psychotic episode—may increase unpredictability and diminish their responsive to interventions.

Ms. I’s contact with the resident lasted approximately 20 months, slightly less than the average 26 months reported in a survey of mental health professionals.³ Because stalkers are unpredictable, the psychiatric resident remains cautious.

Related Resources

• National Center for Victims of Crime. Stalking resource center. www.victimsofcrime.org/our-programs/stalking-resource-center.
• Mullen PE, Pathé M, Purcell R. Stalkers and their victims. New York, NY: Cambridge University Press; 2009.

Disclosure

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

CASE: Delusions and threats

For over 20 months, Ms. I, age 48, sends a psychiatric resident letters and postcards that total approximately 3,000 pages and come from dozens of return addresses. Ms. I expresses romantic feelings toward the resident and believes that he was her physician and prescribed medications, including “mood stabilizers.” The resident never treated Ms. I; to his knowledge, he has never interacted with her.

Ms. I describes the resident’s refusal to continue treating her as “abandonment” and states that she is contemplating self-harm because of this rejection. In her letters, Ms. I admits that she was a long-term patient in a state psychiatric hospital in her home state and suffers from persistent auditory hallucinations. She also wants a romantic relationship with the resident and repeatedly threatens the resident’s female acquaintances and former romantic partners whose relationships she had surmised from news articles available on the Internet. Ms. I also threatens to strangle the resident. The resident sends her multiple written requests that she cease contact, but they are not acknowledged.

The authors’ observations

Stalking—repeated, unwanted attention or communication that would cause a reasonable person fear—is a serious threat for many psychiatric clinicians.¹ Prevalence rates among mental health care providers range from 3% to 21%.^2,3 Most stalkers have engaged in previous stalking behavior.³

Being stalked is highly distressing,⁴ and mental health professionals often do not reveal such experiences to colleagues.⁵ Irrational feelings of guilt or embarrassment, such as being thought to have poorly managed interactions with the stalker, often motivate a self-imposed silence (Table 1).⁶ This isolation may foster anxiety, interfere with receiving problem-solving advice, and increase physical vulnerability. In the case involving Ms. I, the psychiatric resident’s primary responsibility is safeguarding his own physical and psychological welfare.

Clinicians who work in a hospital or other institutional setting who are being stalked should inform their supervisors and the facility’s security personnel. Security personnel may be able to gather data about the stalker, decrease the stalker’s ability to communicate with the victim, and reduce unwanted physical access to the victim by distributing a photo of the stalker or installing a camera or receptionist-controlled door lock in patient entryways. Security personnel also may collaborate with local law enforcement. Having a third party respond to a stalker’s aggressive behavior—rather than the victim responding directly—avoids rewarding the stalker, which may generate further unwanted contact.⁷ Any intervention by the victim may increase the risk of violence, creating an “intervention dilemma.” Resnick⁸ argues that before deciding how best to address the stalker’s behavior, a stalking victim must “first separate the risk of continued stalking from the risk that the stalker will commit a violent act.”

Mental health professionals in private practice who are being stalked should consider retaining an attorney. An attorney often can maintain privacy of communications regarding the stalker via the attorney-client and attorney-work product privileges, which may help during legal proceedings.

Table 1

Factors that can impede psychiatrists from reporting stalking

RESPONSE: Involving police

Over 2 months, Ms. I phones the resident’s home 105 times (the resident screens the calls). During 1 call, she states that she is hidden in a closet in her home and will hurt herself unless the resident “resumes” her psychiatric care. The resident contacts police in his city and Ms. I’s community, but authorities are reluctant to act when he acknowledges that he is not Ms. I’s psychiatrist and does not know her. Police officers in Ms. I’s hometown tell the resident no one answered the door when they visited her home. They state that they would enter the residence forcibly only if Ms. I’s physician or a family member asked them to do so, and because the resident admits that he is not her psychiatrist, they cannot take further action. Ms. I leaves the resident a phone message several hours later to inform him she is safe.

The authors’ observations

Stalking-induced countertransference responses may lead a psychiatrist to unwittingly place himself in harm’s way. For example, intense rage at a stalker’s request for treatment may generate guilt that motivates the psychiatrist to agree to treat the stalker. Feelings of helplessness may produce a frantic desire to do something even when such activity is ill-advised. Psychiatrists may develop a tolerance for antisocial or threatening behavior—which is common in mental health settings—and could accept unnecessary risks.

A psychiatrist who is being stalked may be able to assist a mentally ill stalker in a way that does not create a duty to treat and does not expose the psychiatrist to harm, such as contacting a mobile crisis intervention team, a mental health professional who recently treated the stalker, a family member of the stalker, or law enforcement personnel. A psychiatrist who is thrust from the role of helper to victim and must protect his or her own well-being instead of attending to a patient’s welfare is prone to suffer substantial countertransference distress.

The situation with Ms. I was particularly challenging because the resident did not know her complete history and therefore had little information to gauge how likely she was to act on her aggressive threats. Factors that predict future violence include:

• a history of violence
• significant prior criminality
• young age at first arrest
• concomitant substance abuse
• male sex.⁹

Unfortunately, other than sex, this data regarding Ms. I could not be readily obtained.

A psychiatrist’s duty

Although sympathetic to his stalker’s distress, the resident did not want to treat this woman, nor was he ethically or legally obligated to do so. An individual’s wish to be treated by a particular psychiatrist does not create a duty for the psychiatrist to satisfy this wish.¹⁰ State-based “Good Samaritan” laws encourage physicians to assist those in acute need by shielding them from liability, as long as they reasonably act within the scope of their expertise.¹¹ However, they do not require a physician to care for an individual in acute need. A delusional wish for treatment or a false belief of already being in treatment does not create a duty to care for a person.

OUTCOME: Seeking help

Ms. I’s phone calls and letters continue. The resident discusses the situation with his associate residency director, who refers him to the hospital’s legal and investigative staffs. Based on advice from the hospital’s private investigator, the resident sends Ms. I a formal “cease and desist” letter that threatens her with legal action and possible jail time. The staff at the front desk of the clinic where the resident works and the hospital’s security department are instructed to watch for a visitor with Ms. I’s name and description, although the hospital’s investigator is unable to obtain a photograph of her. Shortly after the resident sends the letter, Ms. I ceases communication.

The authors’ observations

This case is unusual because most stalking victims know their stalkers. Identifying a stalker’s motivation can be helpful in formulating a risk assessment. One classification system recognizes 5 categories of stalkers: rejected, intimacy seeking, incompetent, resentful, and predatory (Table 2).¹ Rejected stalkers appear to pose the greatest risk of violence and homicide.⁸ However, all stalkers may pose a risk of violence and therefore all stalking behavior should be treated seriously.

Table 2

Classification of stalkers

Responding to a stalker

The approach should be tailored to the stalker’s characteristics.¹² Silence—ie, lack of acknowledgement of a stalker’s intrusions—is one tactic.¹³ Consistent and persistent lack of engagement may bore the stalker, but also may provoke frustration or narcissistic or paranoia-fueled rage, and increased efforts to interact with the mental health professional. Other responses include:

• obtaining a protection or restraining order
• promoting the stalker’s participation in adversarial civil litigation, such as a lawsuit
• issuing verbal counterthreats.

Restraining orders are controversial and assessments of their effectiveness vary.¹⁴ How well a restraining order works may depend on the stalker’s:

• ability to appreciate reality, and how likely he or she is to experience anxiety when confronted with adverse consequences of his or her actions
• how consistently, rapidly, and harshly the criminal justice system responds to violations of restraining orders.

Restraining orders also may provide the victim a false sense of security.¹⁵ One of her letters revealed that Ms. I violated a criminal plea arrangement years earlier, which suggests she was capable of violating a restraining order.

Litigation. A stalker may initiate civil litigation against the victim to feel that he or she has an impact on the victim, which may reduce the stalker’s risk of violence if he or she is emotionally engaged in the litigation. Based on the authors’ experience, as long as the stalker is talking, he or she generally is less likely to act out violently and terminate a satisfying process. Adversarial civil litigation could give a stalker the opportunity to be “close” to the victim and a means of expressing aggressive wishes. The benefit of litigation lasts only as long as the case persists and the stalker believes he or she may prevail. In one of her letters, Ms. I bragged that she had represented herself as a pro se litigant in a complex civil matter, suggesting that she might be constructively channeled into litigation.

Promoting litigation carries significant risk.¹⁶ Being a defendant in pro se litigation may be emotionally and financially stressful. This approach may be desirable if the psychiatrist’s institution is willing to offer substantial support. For example, an institution may provide legal assistance—including helping to defray the cost of litigation—and litigation-related scheduling flexibility. An attorney may serve as a boundary between the victim and the pro se litigant’s sometimes ceaseless, time-devouring, anxiety-inducing legal maneuvers.

Counterthreats. Warning a stalker that he or she will face severe civil and criminal consequences if his or her behavior continues can make clear that his or her conduct is unacceptable.¹⁷ Such warnings may be delivered verbally or in writing by a legal representative, law enforcement personnel, a private security agent, or the victim.

Issuing a counterthreat can be risky. Stalkers with antisocial or narcissistic personality features may perceive a counterthreat as narcissistically diminishing, and to save face will escalate their stalking in retaliation. Avoid counterthreats if you believe the stalker might be psychotic because destabilizing such an individual—such as by precipitating a short psychotic episode—may increase unpredictability and diminish their responsive to interventions.

Ms. I’s contact with the resident lasted approximately 20 months, slightly less than the average 26 months reported in a survey of mental health professionals.³ Because stalkers are unpredictable, the psychiatric resident remains cautious.

Related Resources

• National Center for Victims of Crime. Stalking resource center. www.victimsofcrime.org/our-programs/stalking-resource-center.
• Mullen PE, Pathé M, Purcell R. Stalkers and their victims. New York, NY: Cambridge University Press; 2009.

Disclosure

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

Mrs. A, age 68, has a 40-year history of schizoaffective disorder with comorbid anxiety disorder not otherwise specified, type 2 diabetes mellitus, and hypertension. She takes furosemide, 40 mg/d, lisinopril, 20 mg/d, and metformin, 2,000 mg/d, for hypertension and diabetes; lorazepam, 1.5 mg/d, and paroxetine, 40 mg/d, for anxiety; and quetiapine extended release, 800 mg/d, for psychotic features and mood dysregulation with schizoaffective disorder. Mrs. A’s husband died 5 years ago and she lives alone in a senior care facility. Mrs. A uses a weekly pill reminder box because her residential facility does not monitor medication adherence. She sees her psychiatrist once a month and her primary care provider every 3 months. She has no history of illicit drug, alcohol, or tobacco use.

Two weeks ago, Mrs. A was found leaning against the wall in a hallway, complaining of dizziness and disorientation, and unable to find her way back to her apartment. In the emergency department, her serum potassium is low (3.0 mEq/L; normal range: 3.5 to 5.0), fasting glucose is elevated (110 mg/dL; range: 65 to 99), and ECG reveals a prolonged QTc interval of 530 milliseconds. Before this episode, Mrs. A had been medically stable without mood or psychotic symptoms, although her daughter reported medication self-administration was becoming difficult.

Exposure to psychotropics carries a risk of QTc prolongation. The QT interval is an ECG measure of ventricular depolarization and repolarization. The QTc designation indicates a correction for heart rate with increasing heart rate correlating with a shorter QT interval. Readings of 440 milliseconds are considered normal.¹ QTc prolongation is defined as >450 milliseconds for men and >470 milliseconds for women.² An increase in the QT interval is a predictor of serious cardiac events.³

Antidepressants and antipsychotics have been associated with QTc prolongation. When identifying agents that could disrupt cardiac conduction, clinicians need to consider whether the drug’s molecular structure, receptor affinity, or pharmacologic effects are most critical.² Although these may be important, patient-specific variables that increase the risk of QTc prolongation may have greater impact. These include:

• age >65
• female sex
• electrolyte imbalances (specifically low serum potassium and magnesium levels)
• high or toxic serum levels of the suspected drug
• preexisting cardiovascular impairment, such as bradycardia.^4,5

Other risk factors include concurrent use of an agent with similar cardiovascular effects or one that competes for metabolism (either enzymatic or at the binding site), physiologic limitations such as renal insufficiency, and medication changes that may increase or decrease psychotropic clearance.^4,6 Geriatric patients with dementia have an increased risk for cardiovascular-related death.^7,8

Antidepressants

Among tricyclic antidepressants, most reports of QTc prolongation involve amitriptyline and maprotiline.⁹ Risk factors include demographics (eg, female sex, age), personal or family history (congenital long QT syndrome, cardiovascular disease), and concurrent conditions or drug use, particularly those associated with QTc prolongation.³ Desipramine and nortriptyline also have been identified as high-risk agents.¹⁰

QTc prolongation has been reported with all selective serotonin reuptake inhibitors at plasma concentrations above the therapeutic level.¹¹ Fluoxetine-associated QTc prolongation was limited to cases of overdose or when additional risk factors were reported.⁴ QTc prolongation from psychotropics could increase the risk of torsades de pointes, according to an analysis of the FDA Adverse Event Reporting System.¹² In 2011, the FDA reported an increased risk of abnormal heart rhythms—including QTc prolongation—with citalopram doses >40 mg/d.¹³ Although cases of QTc prolongation with paroxetine have not been reported,¹¹ the Arizona Center for Education and Research on Therapeutics lists paroxetine with other agents that may increase the risk for QTc prolongation with concurrent use of medications that may prolong QTc interval.¹⁴ Venlafaxine doses >300 mg/d may require additional cardiac monitoring.^5,12 Data from venlafaxine poisoning case reports found a positive correlation between dose and QTc prolongation.¹⁵ In a review of toxicology database information, Wenzel-Seifert et al⁴ found extended QT interval with citalopram, fluoxetine, and venlafaxine at toxic doses or in the presence of additional risk factors such as sex, older age, or personal or family history of congenital long QT syndrome or cardiovascular disease.

Antipsychotics

Case reports, case series, and research trials have evaluated the risk of QTc prolongation with antipsychotics (Table).^1,2,4,16,17 The first-generation antipsychotics thioridazine,^4,16,18 mesoridazine,^16,18 chlorpromazine,¹⁹ and haloperidol³ warrant cardiac monitoring. The QTc prolongation effects of thioridazine and its active metabolite mesoridazine are well-documented and thioridazine-mediated QTc prolongation increases are dose-dependent.^4,18 ECG monitoring is recommended with IV haloperidol, which is used for delirium in adults.²⁰ QTc prolongation has been associated with long-term ziprasidone use more often than with risperidone, olanzapine, or quetiapine.¹⁹ Ziprasidone prolongs the QTc interval an average of 20 milliseconds,²¹ which could represent a clinically significant change. QTc prolongation for iloperidone is comparable to ziprasidone and haloperidol.²² There is some evidence that aripiprazole may shorten, rather than prolong, the QTc interval.^4,17

Cardiovascular adverse effects associated with clozapine—including QTc prolongation—are dose-dependent.³ Olanzapine prolongs QTc interval, although the mean change is less than with other agents unless other variables were present, such as:

• concomitant use of medications that may prolong QTc interval (ie, amantadine, hydroxyzine, or tamoxifen²)
• preexisting cardiovascular conduction disorders
• higher doses (>40 mg/d).^3,23

In 17 case reports of cardiac changes associated with quetiapine use, doses ranged from 100 mg/d²⁴ to an overdose of 36 g/d.²⁵ Only 1 patient death was reported secondary to overdose and preexisting dysrhythmia and hypertension.²⁶ QTc prolongation associated with risperidone was minor¹ based on oral doses in the normal therapeutic range and incidences of overdose.¹⁰ Paliperidone²⁷ and lurasidone²⁸ are associated with clinically insignificant QTc prolongation. Changes in QTc interval were positively correlated with asenapine dose, although at the highest dose of 40 mg/d, the increase was <5 milliseconds.²⁹

Mrs. A presents with a number of risk factors for QTc prolongation, including older age, female sex, and psychiatric and medical comorbidities that require medication. A pill count revealed that she was taking more than the prescribed daily doses of her medications. During the interview, Mrs. A said that if she missed her medication time, she would take them when she remembered. If she could not remember if she took her pills, she would take them again. Her physicians will explore strategies to increase medication adherence.

Table

Examples of QTc prolongation associated with select antipsychotics^a

Related Resources

• De Hert M, Detraux J, van Winkel R, et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8(2):114-126.
• Vieweg WV, Wood MA, Fernandez A, et al. Proarrhythmic risk with antipsychotic and antidepressant drugs: implications in the elderly. Drugs Aging. 2009;26(12):997-1012.
• Sandson NB, Armstrong SC, Cozza KL. An overview of psychotropic drug-drug interactions. Psychosomatics. 2005;46(5):464-494.

Drug Brand Names

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Asenapine • Saphris
• Chlorpromazine • Thorazine
• Citalopram • Celexa
• Clozapine • Clozaril
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Furosemide • Lasix
• Haloperidol • Haldol
• Hydroxyzine • Atarax, Vistaril
• Iloperidone • Fanapt
• Lisinopril • Prinivil, Zestril
• Lorazepam • Ativan
• Lurasidone • Latuda
• Maprotiline • Ludiomil
• Mesoridazine • Serentil
• Metformin • Glucophage
• Nortriptyline • Pamelor
• Olanzapine • Zyprexa
• Paliperidone • Invega
• Paroxetine • Paxil
• Pimozide • Orap
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Tamoxifen • Nolvadex, Soltamox
• Thioridazine • Mellaril
• Venlafaxine • Effexor
• Ziprasidone • Geodon

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. No similar work by the authors is under review or in press. No funding was requested or received in conjunction with this manuscript.

Mrs. A, age 68, has a 40-year history of schizoaffective disorder with comorbid anxiety disorder not otherwise specified, type 2 diabetes mellitus, and hypertension. She takes furosemide, 40 mg/d, lisinopril, 20 mg/d, and metformin, 2,000 mg/d, for hypertension and diabetes; lorazepam, 1.5 mg/d, and paroxetine, 40 mg/d, for anxiety; and quetiapine extended release, 800 mg/d, for psychotic features and mood dysregulation with schizoaffective disorder. Mrs. A’s husband died 5 years ago and she lives alone in a senior care facility. Mrs. A uses a weekly pill reminder box because her residential facility does not monitor medication adherence. She sees her psychiatrist once a month and her primary care provider every 3 months. She has no history of illicit drug, alcohol, or tobacco use.

Two weeks ago, Mrs. A was found leaning against the wall in a hallway, complaining of dizziness and disorientation, and unable to find her way back to her apartment. In the emergency department, her serum potassium is low (3.0 mEq/L; normal range: 3.5 to 5.0), fasting glucose is elevated (110 mg/dL; range: 65 to 99), and ECG reveals a prolonged QTc interval of 530 milliseconds. Before this episode, Mrs. A had been medically stable without mood or psychotic symptoms, although her daughter reported medication self-administration was becoming difficult.

Exposure to psychotropics carries a risk of QTc prolongation. The QT interval is an ECG measure of ventricular depolarization and repolarization. The QTc designation indicates a correction for heart rate with increasing heart rate correlating with a shorter QT interval. Readings of 440 milliseconds are considered normal.¹ QTc prolongation is defined as >450 milliseconds for men and >470 milliseconds for women.² An increase in the QT interval is a predictor of serious cardiac events.³

Antidepressants and antipsychotics have been associated with QTc prolongation. When identifying agents that could disrupt cardiac conduction, clinicians need to consider whether the drug’s molecular structure, receptor affinity, or pharmacologic effects are most critical.² Although these may be important, patient-specific variables that increase the risk of QTc prolongation may have greater impact. These include:

• age >65
• female sex
• electrolyte imbalances (specifically low serum potassium and magnesium levels)
• high or toxic serum levels of the suspected drug
• preexisting cardiovascular impairment, such as bradycardia.^4,5

Other risk factors include concurrent use of an agent with similar cardiovascular effects or one that competes for metabolism (either enzymatic or at the binding site), physiologic limitations such as renal insufficiency, and medication changes that may increase or decrease psychotropic clearance.^4,6 Geriatric patients with dementia have an increased risk for cardiovascular-related death.^7,8

Antidepressants

Among tricyclic antidepressants, most reports of QTc prolongation involve amitriptyline and maprotiline.⁹ Risk factors include demographics (eg, female sex, age), personal or family history (congenital long QT syndrome, cardiovascular disease), and concurrent conditions or drug use, particularly those associated with QTc prolongation.³ Desipramine and nortriptyline also have been identified as high-risk agents.¹⁰

QTc prolongation has been reported with all selective serotonin reuptake inhibitors at plasma concentrations above the therapeutic level.¹¹ Fluoxetine-associated QTc prolongation was limited to cases of overdose or when additional risk factors were reported.⁴ QTc prolongation from psychotropics could increase the risk of torsades de pointes, according to an analysis of the FDA Adverse Event Reporting System.¹² In 2011, the FDA reported an increased risk of abnormal heart rhythms—including QTc prolongation—with citalopram doses >40 mg/d.¹³ Although cases of QTc prolongation with paroxetine have not been reported,¹¹ the Arizona Center for Education and Research on Therapeutics lists paroxetine with other agents that may increase the risk for QTc prolongation with concurrent use of medications that may prolong QTc interval.¹⁴ Venlafaxine doses >300 mg/d may require additional cardiac monitoring.^5,12 Data from venlafaxine poisoning case reports found a positive correlation between dose and QTc prolongation.¹⁵ In a review of toxicology database information, Wenzel-Seifert et al⁴ found extended QT interval with citalopram, fluoxetine, and venlafaxine at toxic doses or in the presence of additional risk factors such as sex, older age, or personal or family history of congenital long QT syndrome or cardiovascular disease.

Antipsychotics

Case reports, case series, and research trials have evaluated the risk of QTc prolongation with antipsychotics (Table).^1,2,4,16,17 The first-generation antipsychotics thioridazine,^4,16,18 mesoridazine,^16,18 chlorpromazine,¹⁹ and haloperidol³ warrant cardiac monitoring. The QTc prolongation effects of thioridazine and its active metabolite mesoridazine are well-documented and thioridazine-mediated QTc prolongation increases are dose-dependent.^4,18 ECG monitoring is recommended with IV haloperidol, which is used for delirium in adults.²⁰ QTc prolongation has been associated with long-term ziprasidone use more often than with risperidone, olanzapine, or quetiapine.¹⁹ Ziprasidone prolongs the QTc interval an average of 20 milliseconds,²¹ which could represent a clinically significant change. QTc prolongation for iloperidone is comparable to ziprasidone and haloperidol.²² There is some evidence that aripiprazole may shorten, rather than prolong, the QTc interval.^4,17

Cardiovascular adverse effects associated with clozapine—including QTc prolongation—are dose-dependent.³ Olanzapine prolongs QTc interval, although the mean change is less than with other agents unless other variables were present, such as:

• concomitant use of medications that may prolong QTc interval (ie, amantadine, hydroxyzine, or tamoxifen²)
• preexisting cardiovascular conduction disorders
• higher doses (>40 mg/d).^3,23

In 17 case reports of cardiac changes associated with quetiapine use, doses ranged from 100 mg/d²⁴ to an overdose of 36 g/d.²⁵ Only 1 patient death was reported secondary to overdose and preexisting dysrhythmia and hypertension.²⁶ QTc prolongation associated with risperidone was minor¹ based on oral doses in the normal therapeutic range and incidences of overdose.¹⁰ Paliperidone²⁷ and lurasidone²⁸ are associated with clinically insignificant QTc prolongation. Changes in QTc interval were positively correlated with asenapine dose, although at the highest dose of 40 mg/d, the increase was <5 milliseconds.²⁹

Mrs. A presents with a number of risk factors for QTc prolongation, including older age, female sex, and psychiatric and medical comorbidities that require medication. A pill count revealed that she was taking more than the prescribed daily doses of her medications. During the interview, Mrs. A said that if she missed her medication time, she would take them when she remembered. If she could not remember if she took her pills, she would take them again. Her physicians will explore strategies to increase medication adherence.

Table

Examples of QTc prolongation associated with select antipsychotics^a

Related Resources

• De Hert M, Detraux J, van Winkel R, et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8(2):114-126.
• Vieweg WV, Wood MA, Fernandez A, et al. Proarrhythmic risk with antipsychotic and antidepressant drugs: implications in the elderly. Drugs Aging. 2009;26(12):997-1012.
• Sandson NB, Armstrong SC, Cozza KL. An overview of psychotropic drug-drug interactions. Psychosomatics. 2005;46(5):464-494.

Drug Brand Names

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Asenapine • Saphris
• Chlorpromazine • Thorazine
• Citalopram • Celexa
• Clozapine • Clozaril
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Furosemide • Lasix
• Haloperidol • Haldol
• Hydroxyzine • Atarax, Vistaril
• Iloperidone • Fanapt
• Lisinopril • Prinivil, Zestril
• Lorazepam • Ativan
• Lurasidone • Latuda
• Maprotiline • Ludiomil
• Mesoridazine • Serentil
• Metformin • Glucophage
• Nortriptyline • Pamelor
• Olanzapine • Zyprexa
• Paliperidone • Invega
• Paroxetine • Paxil
• Pimozide • Orap
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Tamoxifen • Nolvadex, Soltamox
• Thioridazine • Mellaril
• Venlafaxine • Effexor
• Ziprasidone • Geodon

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. No similar work by the authors is under review or in press. No funding was requested or received in conjunction with this manuscript.

Mrs. A, age 68, has a 40-year history of schizoaffective disorder with comorbid anxiety disorder not otherwise specified, type 2 diabetes mellitus, and hypertension. She takes furosemide, 40 mg/d, lisinopril, 20 mg/d, and metformin, 2,000 mg/d, for hypertension and diabetes; lorazepam, 1.5 mg/d, and paroxetine, 40 mg/d, for anxiety; and quetiapine extended release, 800 mg/d, for psychotic features and mood dysregulation with schizoaffective disorder. Mrs. A’s husband died 5 years ago and she lives alone in a senior care facility. Mrs. A uses a weekly pill reminder box because her residential facility does not monitor medication adherence. She sees her psychiatrist once a month and her primary care provider every 3 months. She has no history of illicit drug, alcohol, or tobacco use.

Two weeks ago, Mrs. A was found leaning against the wall in a hallway, complaining of dizziness and disorientation, and unable to find her way back to her apartment. In the emergency department, her serum potassium is low (3.0 mEq/L; normal range: 3.5 to 5.0), fasting glucose is elevated (110 mg/dL; range: 65 to 99), and ECG reveals a prolonged QTc interval of 530 milliseconds. Before this episode, Mrs. A had been medically stable without mood or psychotic symptoms, although her daughter reported medication self-administration was becoming difficult.

Exposure to psychotropics carries a risk of QTc prolongation. The QT interval is an ECG measure of ventricular depolarization and repolarization. The QTc designation indicates a correction for heart rate with increasing heart rate correlating with a shorter QT interval. Readings of 440 milliseconds are considered normal.¹ QTc prolongation is defined as >450 milliseconds for men and >470 milliseconds for women.² An increase in the QT interval is a predictor of serious cardiac events.³

Antidepressants and antipsychotics have been associated with QTc prolongation. When identifying agents that could disrupt cardiac conduction, clinicians need to consider whether the drug’s molecular structure, receptor affinity, or pharmacologic effects are most critical.² Although these may be important, patient-specific variables that increase the risk of QTc prolongation may have greater impact. These include:

• age >65
• female sex
• electrolyte imbalances (specifically low serum potassium and magnesium levels)
• high or toxic serum levels of the suspected drug
• preexisting cardiovascular impairment, such as bradycardia.^4,5

Other risk factors include concurrent use of an agent with similar cardiovascular effects or one that competes for metabolism (either enzymatic or at the binding site), physiologic limitations such as renal insufficiency, and medication changes that may increase or decrease psychotropic clearance.^4,6 Geriatric patients with dementia have an increased risk for cardiovascular-related death.^7,8

Antidepressants

Among tricyclic antidepressants, most reports of QTc prolongation involve amitriptyline and maprotiline.⁹ Risk factors include demographics (eg, female sex, age), personal or family history (congenital long QT syndrome, cardiovascular disease), and concurrent conditions or drug use, particularly those associated with QTc prolongation.³ Desipramine and nortriptyline also have been identified as high-risk agents.¹⁰

QTc prolongation has been reported with all selective serotonin reuptake inhibitors at plasma concentrations above the therapeutic level.¹¹ Fluoxetine-associated QTc prolongation was limited to cases of overdose or when additional risk factors were reported.⁴ QTc prolongation from psychotropics could increase the risk of torsades de pointes, according to an analysis of the FDA Adverse Event Reporting System.¹² In 2011, the FDA reported an increased risk of abnormal heart rhythms—including QTc prolongation—with citalopram doses >40 mg/d.¹³ Although cases of QTc prolongation with paroxetine have not been reported,¹¹ the Arizona Center for Education and Research on Therapeutics lists paroxetine with other agents that may increase the risk for QTc prolongation with concurrent use of medications that may prolong QTc interval.¹⁴ Venlafaxine doses >300 mg/d may require additional cardiac monitoring.^5,12 Data from venlafaxine poisoning case reports found a positive correlation between dose and QTc prolongation.¹⁵ In a review of toxicology database information, Wenzel-Seifert et al⁴ found extended QT interval with citalopram, fluoxetine, and venlafaxine at toxic doses or in the presence of additional risk factors such as sex, older age, or personal or family history of congenital long QT syndrome or cardiovascular disease.

Antipsychotics

Case reports, case series, and research trials have evaluated the risk of QTc prolongation with antipsychotics (Table).^1,2,4,16,17 The first-generation antipsychotics thioridazine,^4,16,18 mesoridazine,^16,18 chlorpromazine,¹⁹ and haloperidol³ warrant cardiac monitoring. The QTc prolongation effects of thioridazine and its active metabolite mesoridazine are well-documented and thioridazine-mediated QTc prolongation increases are dose-dependent.^4,18 ECG monitoring is recommended with IV haloperidol, which is used for delirium in adults.²⁰ QTc prolongation has been associated with long-term ziprasidone use more often than with risperidone, olanzapine, or quetiapine.¹⁹ Ziprasidone prolongs the QTc interval an average of 20 milliseconds,²¹ which could represent a clinically significant change. QTc prolongation for iloperidone is comparable to ziprasidone and haloperidol.²² There is some evidence that aripiprazole may shorten, rather than prolong, the QTc interval.^4,17

Cardiovascular adverse effects associated with clozapine—including QTc prolongation—are dose-dependent.³ Olanzapine prolongs QTc interval, although the mean change is less than with other agents unless other variables were present, such as:

• concomitant use of medications that may prolong QTc interval (ie, amantadine, hydroxyzine, or tamoxifen²)
• preexisting cardiovascular conduction disorders
• higher doses (>40 mg/d).^3,23

In 17 case reports of cardiac changes associated with quetiapine use, doses ranged from 100 mg/d²⁴ to an overdose of 36 g/d.²⁵ Only 1 patient death was reported secondary to overdose and preexisting dysrhythmia and hypertension.²⁶ QTc prolongation associated with risperidone was minor¹ based on oral doses in the normal therapeutic range and incidences of overdose.¹⁰ Paliperidone²⁷ and lurasidone²⁸ are associated with clinically insignificant QTc prolongation. Changes in QTc interval were positively correlated with asenapine dose, although at the highest dose of 40 mg/d, the increase was <5 milliseconds.²⁹

Mrs. A presents with a number of risk factors for QTc prolongation, including older age, female sex, and psychiatric and medical comorbidities that require medication. A pill count revealed that she was taking more than the prescribed daily doses of her medications. During the interview, Mrs. A said that if she missed her medication time, she would take them when she remembered. If she could not remember if she took her pills, she would take them again. Her physicians will explore strategies to increase medication adherence.

Table

Examples of QTc prolongation associated with select antipsychotics^a

Related Resources

• De Hert M, Detraux J, van Winkel R, et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8(2):114-126.
• Vieweg WV, Wood MA, Fernandez A, et al. Proarrhythmic risk with antipsychotic and antidepressant drugs: implications in the elderly. Drugs Aging. 2009;26(12):997-1012.
• Sandson NB, Armstrong SC, Cozza KL. An overview of psychotropic drug-drug interactions. Psychosomatics. 2005;46(5):464-494.

Drug Brand Names

• Amantadine • Symmetrel
• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Asenapine • Saphris
• Chlorpromazine • Thorazine
• Citalopram • Celexa
• Clozapine • Clozaril
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Furosemide • Lasix
• Haloperidol • Haldol
• Hydroxyzine • Atarax, Vistaril
• Iloperidone • Fanapt
• Lisinopril • Prinivil, Zestril
• Lorazepam • Ativan
• Lurasidone • Latuda
• Maprotiline • Ludiomil
• Mesoridazine • Serentil
• Metformin • Glucophage
• Nortriptyline • Pamelor
• Olanzapine • Zyprexa
• Paliperidone • Invega
• Paroxetine • Paxil
• Pimozide • Orap
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Tamoxifen • Nolvadex, Soltamox
• Thioridazine • Mellaril
• Venlafaxine • Effexor
• Ziprasidone • Geodon

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. No similar work by the authors is under review or in press. No funding was requested or received in conjunction with this manuscript.

CASE: Unexplained panic

Mr. J, age 35, is a married, unemployed musician who presents for outpatient treatment for panic attacks. He experienced his first panic attack at his oldest son’s baptism 12 years ago, but does not know why it occurred at that moment. He rarely has panic attacks now, but wants to continue medication management. He denies depressive symptoms, saying, “I’m the most optimistic person in the world.” Mr. J tried several medications for his panic attacks before clonazepam, 2 mg/d, proved effective, but always has been vehemently opposed to antidepressants. Despite his insistence that he needs only medication management, Mr. J chooses to enroll in a resident-run psychotherapy clinic.

In sessions, Mr. J describes his father, who also has panic disorder, as a powerful figure who is physically and emotionally abusive, but also charismatic, charming, and “impossible not to love.” However, Mr. J felt his father was impossible to live with, and moved out at age 18 to marry his high school sweetheart. They have 3 children, ages 12, 10, and 8. Mr. J worked for his father at his construction company, but was not able to satisfy him or live up to his standards so he quit because he was tired of being cut down and emasculated.

Mr. J’s parents divorced 15 years ago after his mother had an affair with her husband’s friend. His father learned of the affair and threatened his wife with a handgun. Although Mr. J and his mother were close before her affair, he has been unable to forgive or empathize with her, and rarely speaks to her. Mr. J’s mother could not protect him from his father’s abuse, and later compounded her failure by abandoning her husband and son through her sexual affair. Growing up with a father he did not respect or get comfort from and sharing a common fear and alliance with his mother likely made it difficult for Mr. J to navigate his Oedipal phase,¹ and made her abandonment even more painful.

When Mr. J was 6 years old, he was molested by one of his father’s friends. His father stabbed the man in the shoulder when he found out about the molestation and received probation. Although Mr. J knows he was molested, he does not remember it and has repressed most of his childhood.

The authors’ observations

I (JF) wanted to discuss with Mr. J why his first panic attack occurred during such a symbolic occasion. His panic could be the result of a struggle between a murderous wish toward his father and paternal protective instinct toward his son. The baptism placed his son in a highly vulnerable position, which reminded Mr. J of his own vulnerability and impotent rage toward his father. Anxiety often results when an individual has 2 opposing wishes,² and a murderous wish often is involved when anxiety progresses to panic. Getting to the root of this with Mr. J could allow for further psychological growth.³ His murderous wishes and fantasies are ego-dystonic, and panic could be a way of punishing himself for these thoughts. When Mr. J identified himself as his son during the baptism, he likely was flooded with thoughts that his defenses were no longer able to repress. Seeing his son submerged in the baptismal font brought back an aspect of his own life that he had completely split off from consciousness, and likely will take time to process. Considering the current therapeutic dynamic, I decided that it was not the best time to address this potential conflict; however, I could have chosen a manualized form of psychodynamic psychotherapy for panic disorder.⁴  See Table 1 for an outline of the phases of psychodynamic psychotherapy for panic disorder.

Although Mr. J’s initial willingness to discuss his past was encouraging, he refused to schedule more than 1 session every 4 weeks. He also began to keep the content of our sessions superficial, which caused me angst because he seemed to be withholding information and would not come more frequently. Although I was not proud of my feelings, I had to be honest with myself that I had started to dislike Mr. J.

Table 1

Psychodynamic psychotherapy for panic disorder

Countertransference reactions

Countertransference is a therapist's emotional reaction to a patient. Just as patients form reactions based on past relationships brought to present, therapists develop similar reactions.⁵ Noting one’s countertransference provides a window into how the patient’s thoughts and actions evoke feelings in others. It also can shed light on an aspect of the doctor-patient relationship that may have gone unnoticed.²

Countertransference hatred can occur when a therapist begins to dislike a patient. Typically, patients with borderline personality disorder, masochistic tendencies, or suicidality arouse strong countertransference reactions⁶; however, any patient can evoke these emotions. This type of hateful patient can precipitate antitherapeutic feelings such as aversion or malice that can be a major obstacle to treatment.⁷ Aversion leads the therapist to withdraw from the patient, and malice can trigger cruel impulses.

Maltsberger and Buie⁷ identified 5 defenses therapists may use to combat countertransference hatred (Table 2). When treating Mr. J, I used several of these defenses, including projection and turning against the self to protect myself from this challenging patient. In turning against the self, I became doubtful and critical of my skills and increasingly submissive to Mr. J. Additionally, I projected this countertransference hatred onto Mr. J, focusing on the negative transference that he brought to our therapeutic encounters. On an unconscious level, I may have feared retribution from Mr. J.

I became so frustrated with Mr. J that I reduced the frequency of our sessions to once every 6 weeks, which I realized could be evidence of my feelings regarding Mr. J’s minimization and avoidant style.

Table 2

Defenses against countertransference hate

TREATMENT: A breakthrough

Mr. J presents with obvious unease at the first visit after we had decreased the frequency of our sessions. At this point, Mr. J opens up to me. He says he has not been truthful with me, and has had worsening depression, anhedonia, and agoraphobia over the past year. He also reveals that he has homosexual fantasies that he cannot stop, which disturb him because he says he is heterosexual. He agrees to come once a week, and reluctantly admits that he desperately needs help.

Although Mr. J only takes clonazepam and citalopram, 20 mg/d, which I prescribed after he admitted to depression and anxiety, he has hyperlipidemia and a family history of heart disease. In addition to being a musician and working at his father’s construction company, he has worked as a security guard, bounty hunter, and computer technician. His careers have been solitary in nature, and, with the exception of computer work, permitted an outlet for aggression. However, he recently started taking online college classes and wants to become a music teacher because he feels he has a lot to offer children as a result of his life experiences. His fantasy of being a teacher shows considerably less aggression, and could be a sign of psychological growth.

Mr. J is struggling financially and his home is on the verge of foreclosure. Early in treatment he told me that he stopped paying his mortgage, but demonstrated blind optimism that things would “work out.” I asked if this was a wise decision, but he seemed confident and dismissive of my concerns. Although he now struggles with this situation, I consider this healthier than his constant pseudo-happy state, and a sign of psychological development.⁸ Despite his financial stressors, he wants to pursue his dream of being a famous musician, and says he “could never work a 9-to-5 job in a cubicle.”

The authors’ observations

I do not think it’s a coincidence that Mr. J stopped minimizing his symptoms when we decreased the frequency of his sessions. I had viewed our sessions as unproductive and blamed Mr. J for wasting both of our time with his resistance and minimization and had begun to dislike him. I felt impotent because he had been controlling each session with long, elaborate stories that had little relevance to his panic attacks, and I could not redirect him or get him to focus on pertinent issues. It was as if I was an audience for him, and provided nothing useful. However, I was interested in these superficial stories because Mr. J was charming and engaging. He likely reenacted his relationship with his father with me. Mr. J’s superficial relationship with me caused me to dislike him, and, similar to his father, reject him. This rejection likely was damaging because I was unable to anticipate his needs, which would have been to increase—rather than decrease—the frequency of our sessions. Just like his father, I was not able to take care of him.

Mr. J is deeply conflicted about his father. He states that his father “is a monster who instills fear and intimidation into everyone around him, but he’s charismatic, and I’ll always love him.” His view of his domineering father likely developed into a castration anxiety because he was afraid of competing for his mother’s love, contributing to a muddled sexual identity. This was intensified when Mr. J was sexually abused; he may have been stimulated by the molestation, adding to his confusion. Although Mr. J has repressed the abuse and split off most of his childhood, he suffers from shame, guilt, and depression because of his ego-dystonic homosexual fantasies. Homosexuality is at odds with his self-image and contributes to his anxiety and panic attacks. He cannot adequately discharge this dangerous libidinal energy, and as he becomes more conscious of it, his anxiety intensifies.

OUTCOME: Overcoming fear

As Mr. J sits crying in my office, he says he hasn’t cried in front of another man in years. I wonder aloud what his father would think of this situation. His states that his father does not respect any type of weakness and probably would “knock his teeth in.” Overcoming this fear of opening up will be a goal of Mr. J’s treatment. His unbridled optimism borders on pathologic, and is a defense against reality.⁸ Additionally, his reluctance to accept that he is suffering from depression, which he perceives as a weakness, will be a struggle throughout therapy. He likely will continue to minimize his symptoms when possible, making the true depths of his illness difficult to grasp.

Related Resources

• Waska R. Using countertransference: analytic contact, projective identification, and transference phantasy states. Am J Psychother. 2008;62(4):333-351.
• Gabbard GO, Litowitz BE, Williams P. Textbook of psychoanalysis. Arlington, VA: American Psychiatric Publishing, Inc; 2011.

Drug Brand Names

• Citalopram • Celexa
• Clonazepam • Klonopin

Disclosure

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

CASE: Unexplained panic

Mr. J, age 35, is a married, unemployed musician who presents for outpatient treatment for panic attacks. He experienced his first panic attack at his oldest son’s baptism 12 years ago, but does not know why it occurred at that moment. He rarely has panic attacks now, but wants to continue medication management. He denies depressive symptoms, saying, “I’m the most optimistic person in the world.” Mr. J tried several medications for his panic attacks before clonazepam, 2 mg/d, proved effective, but always has been vehemently opposed to antidepressants. Despite his insistence that he needs only medication management, Mr. J chooses to enroll in a resident-run psychotherapy clinic.

In sessions, Mr. J describes his father, who also has panic disorder, as a powerful figure who is physically and emotionally abusive, but also charismatic, charming, and “impossible not to love.” However, Mr. J felt his father was impossible to live with, and moved out at age 18 to marry his high school sweetheart. They have 3 children, ages 12, 10, and 8. Mr. J worked for his father at his construction company, but was not able to satisfy him or live up to his standards so he quit because he was tired of being cut down and emasculated.

Mr. J’s parents divorced 15 years ago after his mother had an affair with her husband’s friend. His father learned of the affair and threatened his wife with a handgun. Although Mr. J and his mother were close before her affair, he has been unable to forgive or empathize with her, and rarely speaks to her. Mr. J’s mother could not protect him from his father’s abuse, and later compounded her failure by abandoning her husband and son through her sexual affair. Growing up with a father he did not respect or get comfort from and sharing a common fear and alliance with his mother likely made it difficult for Mr. J to navigate his Oedipal phase,¹ and made her abandonment even more painful.

When Mr. J was 6 years old, he was molested by one of his father’s friends. His father stabbed the man in the shoulder when he found out about the molestation and received probation. Although Mr. J knows he was molested, he does not remember it and has repressed most of his childhood.

The authors’ observations

I (JF) wanted to discuss with Mr. J why his first panic attack occurred during such a symbolic occasion. His panic could be the result of a struggle between a murderous wish toward his father and paternal protective instinct toward his son. The baptism placed his son in a highly vulnerable position, which reminded Mr. J of his own vulnerability and impotent rage toward his father. Anxiety often results when an individual has 2 opposing wishes,² and a murderous wish often is involved when anxiety progresses to panic. Getting to the root of this with Mr. J could allow for further psychological growth.³ His murderous wishes and fantasies are ego-dystonic, and panic could be a way of punishing himself for these thoughts. When Mr. J identified himself as his son during the baptism, he likely was flooded with thoughts that his defenses were no longer able to repress. Seeing his son submerged in the baptismal font brought back an aspect of his own life that he had completely split off from consciousness, and likely will take time to process. Considering the current therapeutic dynamic, I decided that it was not the best time to address this potential conflict; however, I could have chosen a manualized form of psychodynamic psychotherapy for panic disorder.⁴  See Table 1 for an outline of the phases of psychodynamic psychotherapy for panic disorder.

Although Mr. J’s initial willingness to discuss his past was encouraging, he refused to schedule more than 1 session every 4 weeks. He also began to keep the content of our sessions superficial, which caused me angst because he seemed to be withholding information and would not come more frequently. Although I was not proud of my feelings, I had to be honest with myself that I had started to dislike Mr. J.

Table 1

Psychodynamic psychotherapy for panic disorder

Countertransference reactions

Countertransference is a therapist's emotional reaction to a patient. Just as patients form reactions based on past relationships brought to present, therapists develop similar reactions.⁵ Noting one’s countertransference provides a window into how the patient’s thoughts and actions evoke feelings in others. It also can shed light on an aspect of the doctor-patient relationship that may have gone unnoticed.²

Countertransference hatred can occur when a therapist begins to dislike a patient. Typically, patients with borderline personality disorder, masochistic tendencies, or suicidality arouse strong countertransference reactions⁶; however, any patient can evoke these emotions. This type of hateful patient can precipitate antitherapeutic feelings such as aversion or malice that can be a major obstacle to treatment.⁷ Aversion leads the therapist to withdraw from the patient, and malice can trigger cruel impulses.

Maltsberger and Buie⁷ identified 5 defenses therapists may use to combat countertransference hatred (Table 2). When treating Mr. J, I used several of these defenses, including projection and turning against the self to protect myself from this challenging patient. In turning against the self, I became doubtful and critical of my skills and increasingly submissive to Mr. J. Additionally, I projected this countertransference hatred onto Mr. J, focusing on the negative transference that he brought to our therapeutic encounters. On an unconscious level, I may have feared retribution from Mr. J.

I became so frustrated with Mr. J that I reduced the frequency of our sessions to once every 6 weeks, which I realized could be evidence of my feelings regarding Mr. J’s minimization and avoidant style.

Table 2

Defenses against countertransference hate

TREATMENT: A breakthrough

Mr. J presents with obvious unease at the first visit after we had decreased the frequency of our sessions. At this point, Mr. J opens up to me. He says he has not been truthful with me, and has had worsening depression, anhedonia, and agoraphobia over the past year. He also reveals that he has homosexual fantasies that he cannot stop, which disturb him because he says he is heterosexual. He agrees to come once a week, and reluctantly admits that he desperately needs help.

Although Mr. J only takes clonazepam and citalopram, 20 mg/d, which I prescribed after he admitted to depression and anxiety, he has hyperlipidemia and a family history of heart disease. In addition to being a musician and working at his father’s construction company, he has worked as a security guard, bounty hunter, and computer technician. His careers have been solitary in nature, and, with the exception of computer work, permitted an outlet for aggression. However, he recently started taking online college classes and wants to become a music teacher because he feels he has a lot to offer children as a result of his life experiences. His fantasy of being a teacher shows considerably less aggression, and could be a sign of psychological growth.

Mr. J is struggling financially and his home is on the verge of foreclosure. Early in treatment he told me that he stopped paying his mortgage, but demonstrated blind optimism that things would “work out.” I asked if this was a wise decision, but he seemed confident and dismissive of my concerns. Although he now struggles with this situation, I consider this healthier than his constant pseudo-happy state, and a sign of psychological development.⁸ Despite his financial stressors, he wants to pursue his dream of being a famous musician, and says he “could never work a 9-to-5 job in a cubicle.”

The authors’ observations

I do not think it’s a coincidence that Mr. J stopped minimizing his symptoms when we decreased the frequency of his sessions. I had viewed our sessions as unproductive and blamed Mr. J for wasting both of our time with his resistance and minimization and had begun to dislike him. I felt impotent because he had been controlling each session with long, elaborate stories that had little relevance to his panic attacks, and I could not redirect him or get him to focus on pertinent issues. It was as if I was an audience for him, and provided nothing useful. However, I was interested in these superficial stories because Mr. J was charming and engaging. He likely reenacted his relationship with his father with me. Mr. J’s superficial relationship with me caused me to dislike him, and, similar to his father, reject him. This rejection likely was damaging because I was unable to anticipate his needs, which would have been to increase—rather than decrease—the frequency of our sessions. Just like his father, I was not able to take care of him.

Mr. J is deeply conflicted about his father. He states that his father “is a monster who instills fear and intimidation into everyone around him, but he’s charismatic, and I’ll always love him.” His view of his domineering father likely developed into a castration anxiety because he was afraid of competing for his mother’s love, contributing to a muddled sexual identity. This was intensified when Mr. J was sexually abused; he may have been stimulated by the molestation, adding to his confusion. Although Mr. J has repressed the abuse and split off most of his childhood, he suffers from shame, guilt, and depression because of his ego-dystonic homosexual fantasies. Homosexuality is at odds with his self-image and contributes to his anxiety and panic attacks. He cannot adequately discharge this dangerous libidinal energy, and as he becomes more conscious of it, his anxiety intensifies.

OUTCOME: Overcoming fear

As Mr. J sits crying in my office, he says he hasn’t cried in front of another man in years. I wonder aloud what his father would think of this situation. His states that his father does not respect any type of weakness and probably would “knock his teeth in.” Overcoming this fear of opening up will be a goal of Mr. J’s treatment. His unbridled optimism borders on pathologic, and is a defense against reality.⁸ Additionally, his reluctance to accept that he is suffering from depression, which he perceives as a weakness, will be a struggle throughout therapy. He likely will continue to minimize his symptoms when possible, making the true depths of his illness difficult to grasp.

Related Resources

• Waska R. Using countertransference: analytic contact, projective identification, and transference phantasy states. Am J Psychother. 2008;62(4):333-351.
• Gabbard GO, Litowitz BE, Williams P. Textbook of psychoanalysis. Arlington, VA: American Psychiatric Publishing, Inc; 2011.

Drug Brand Names

• Citalopram • Celexa
• Clonazepam • Klonopin

Disclosure

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

CASE: Unexplained panic

Mr. J, age 35, is a married, unemployed musician who presents for outpatient treatment for panic attacks. He experienced his first panic attack at his oldest son’s baptism 12 years ago, but does not know why it occurred at that moment. He rarely has panic attacks now, but wants to continue medication management. He denies depressive symptoms, saying, “I’m the most optimistic person in the world.” Mr. J tried several medications for his panic attacks before clonazepam, 2 mg/d, proved effective, but always has been vehemently opposed to antidepressants. Despite his insistence that he needs only medication management, Mr. J chooses to enroll in a resident-run psychotherapy clinic.

In sessions, Mr. J describes his father, who also has panic disorder, as a powerful figure who is physically and emotionally abusive, but also charismatic, charming, and “impossible not to love.” However, Mr. J felt his father was impossible to live with, and moved out at age 18 to marry his high school sweetheart. They have 3 children, ages 12, 10, and 8. Mr. J worked for his father at his construction company, but was not able to satisfy him or live up to his standards so he quit because he was tired of being cut down and emasculated.

Mr. J’s parents divorced 15 years ago after his mother had an affair with her husband’s friend. His father learned of the affair and threatened his wife with a handgun. Although Mr. J and his mother were close before her affair, he has been unable to forgive or empathize with her, and rarely speaks to her. Mr. J’s mother could not protect him from his father’s abuse, and later compounded her failure by abandoning her husband and son through her sexual affair. Growing up with a father he did not respect or get comfort from and sharing a common fear and alliance with his mother likely made it difficult for Mr. J to navigate his Oedipal phase,¹ and made her abandonment even more painful.

When Mr. J was 6 years old, he was molested by one of his father’s friends. His father stabbed the man in the shoulder when he found out about the molestation and received probation. Although Mr. J knows he was molested, he does not remember it and has repressed most of his childhood.

The authors’ observations

I (JF) wanted to discuss with Mr. J why his first panic attack occurred during such a symbolic occasion. His panic could be the result of a struggle between a murderous wish toward his father and paternal protective instinct toward his son. The baptism placed his son in a highly vulnerable position, which reminded Mr. J of his own vulnerability and impotent rage toward his father. Anxiety often results when an individual has 2 opposing wishes,² and a murderous wish often is involved when anxiety progresses to panic. Getting to the root of this with Mr. J could allow for further psychological growth.³ His murderous wishes and fantasies are ego-dystonic, and panic could be a way of punishing himself for these thoughts. When Mr. J identified himself as his son during the baptism, he likely was flooded with thoughts that his defenses were no longer able to repress. Seeing his son submerged in the baptismal font brought back an aspect of his own life that he had completely split off from consciousness, and likely will take time to process. Considering the current therapeutic dynamic, I decided that it was not the best time to address this potential conflict; however, I could have chosen a manualized form of psychodynamic psychotherapy for panic disorder.⁴  See Table 1 for an outline of the phases of psychodynamic psychotherapy for panic disorder.

Although Mr. J’s initial willingness to discuss his past was encouraging, he refused to schedule more than 1 session every 4 weeks. He also began to keep the content of our sessions superficial, which caused me angst because he seemed to be withholding information and would not come more frequently. Although I was not proud of my feelings, I had to be honest with myself that I had started to dislike Mr. J.

Table 1

Psychodynamic psychotherapy for panic disorder

Countertransference reactions

Countertransference is a therapist's emotional reaction to a patient. Just as patients form reactions based on past relationships brought to present, therapists develop similar reactions.⁵ Noting one’s countertransference provides a window into how the patient’s thoughts and actions evoke feelings in others. It also can shed light on an aspect of the doctor-patient relationship that may have gone unnoticed.²

Countertransference hatred can occur when a therapist begins to dislike a patient. Typically, patients with borderline personality disorder, masochistic tendencies, or suicidality arouse strong countertransference reactions⁶; however, any patient can evoke these emotions. This type of hateful patient can precipitate antitherapeutic feelings such as aversion or malice that can be a major obstacle to treatment.⁷ Aversion leads the therapist to withdraw from the patient, and malice can trigger cruel impulses.

Maltsberger and Buie⁷ identified 5 defenses therapists may use to combat countertransference hatred (Table 2). When treating Mr. J, I used several of these defenses, including projection and turning against the self to protect myself from this challenging patient. In turning against the self, I became doubtful and critical of my skills and increasingly submissive to Mr. J. Additionally, I projected this countertransference hatred onto Mr. J, focusing on the negative transference that he brought to our therapeutic encounters. On an unconscious level, I may have feared retribution from Mr. J.

I became so frustrated with Mr. J that I reduced the frequency of our sessions to once every 6 weeks, which I realized could be evidence of my feelings regarding Mr. J’s minimization and avoidant style.

Table 2

Defenses against countertransference hate

TREATMENT: A breakthrough

Mr. J presents with obvious unease at the first visit after we had decreased the frequency of our sessions. At this point, Mr. J opens up to me. He says he has not been truthful with me, and has had worsening depression, anhedonia, and agoraphobia over the past year. He also reveals that he has homosexual fantasies that he cannot stop, which disturb him because he says he is heterosexual. He agrees to come once a week, and reluctantly admits that he desperately needs help.

Although Mr. J only takes clonazepam and citalopram, 20 mg/d, which I prescribed after he admitted to depression and anxiety, he has hyperlipidemia and a family history of heart disease. In addition to being a musician and working at his father’s construction company, he has worked as a security guard, bounty hunter, and computer technician. His careers have been solitary in nature, and, with the exception of computer work, permitted an outlet for aggression. However, he recently started taking online college classes and wants to become a music teacher because he feels he has a lot to offer children as a result of his life experiences. His fantasy of being a teacher shows considerably less aggression, and could be a sign of psychological growth.

Mr. J is struggling financially and his home is on the verge of foreclosure. Early in treatment he told me that he stopped paying his mortgage, but demonstrated blind optimism that things would “work out.” I asked if this was a wise decision, but he seemed confident and dismissive of my concerns. Although he now struggles with this situation, I consider this healthier than his constant pseudo-happy state, and a sign of psychological development.⁸ Despite his financial stressors, he wants to pursue his dream of being a famous musician, and says he “could never work a 9-to-5 job in a cubicle.”

The authors’ observations

I do not think it’s a coincidence that Mr. J stopped minimizing his symptoms when we decreased the frequency of his sessions. I had viewed our sessions as unproductive and blamed Mr. J for wasting both of our time with his resistance and minimization and had begun to dislike him. I felt impotent because he had been controlling each session with long, elaborate stories that had little relevance to his panic attacks, and I could not redirect him or get him to focus on pertinent issues. It was as if I was an audience for him, and provided nothing useful. However, I was interested in these superficial stories because Mr. J was charming and engaging. He likely reenacted his relationship with his father with me. Mr. J’s superficial relationship with me caused me to dislike him, and, similar to his father, reject him. This rejection likely was damaging because I was unable to anticipate his needs, which would have been to increase—rather than decrease—the frequency of our sessions. Just like his father, I was not able to take care of him.

Mr. J is deeply conflicted about his father. He states that his father “is a monster who instills fear and intimidation into everyone around him, but he’s charismatic, and I’ll always love him.” His view of his domineering father likely developed into a castration anxiety because he was afraid of competing for his mother’s love, contributing to a muddled sexual identity. This was intensified when Mr. J was sexually abused; he may have been stimulated by the molestation, adding to his confusion. Although Mr. J has repressed the abuse and split off most of his childhood, he suffers from shame, guilt, and depression because of his ego-dystonic homosexual fantasies. Homosexuality is at odds with his self-image and contributes to his anxiety and panic attacks. He cannot adequately discharge this dangerous libidinal energy, and as he becomes more conscious of it, his anxiety intensifies.

OUTCOME: Overcoming fear

As Mr. J sits crying in my office, he says he hasn’t cried in front of another man in years. I wonder aloud what his father would think of this situation. His states that his father does not respect any type of weakness and probably would “knock his teeth in.” Overcoming this fear of opening up will be a goal of Mr. J’s treatment. His unbridled optimism borders on pathologic, and is a defense against reality.⁸ Additionally, his reluctance to accept that he is suffering from depression, which he perceives as a weakness, will be a struggle throughout therapy. He likely will continue to minimize his symptoms when possible, making the true depths of his illness difficult to grasp.

Related Resources

• Waska R. Using countertransference: analytic contact, projective identification, and transference phantasy states. Am J Psychother. 2008;62(4):333-351.
• Gabbard GO, Litowitz BE, Williams P. Textbook of psychoanalysis. Arlington, VA: American Psychiatric Publishing, Inc; 2011.

Drug Brand Names

• Citalopram • Celexa
• Clonazepam • Klonopin

Disclosure

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

Discuss this article at www.facebook.com/CurrentPsychiatry

CASE: Agitated and paranoid

Mr. E, age 55, presents to the emergency department (ED) with a 2-week history of altered mental status (AMS). His wife reports, “He was normal one day and the next day he was not.” Mr. E also presents with sleep disturbance, decreased appetite and speech, and a 20-lb weight loss. His family reports no recent stressors or head trauma. Mr. E is agitated in the ED and receives a single dose of IV haloperidol, 5 mg. He exhibits paranoia and is afraid to get a CT scan. The medical team attempts a lumbar puncture (LP), but Mr. E does not cooperate.

His laboratory values are: potassium, 3.0 mEq/L; creatinine, 1.60 mg/dL; calcium, 10.6 mg/dL; thyroid-stimulating hormone, 0.177 IU/L; vitamin B12, >1500 pg/mL; folate, >20 ng/mL; and creatine kinase, 281 U/L. Urine drug screen is positive for benzodiazepines and opiates, neither of which was prescribed, and blood alcohol is negative.

Mr. E is admitted for further workup of AMS. His daughter-in-law states that Mr. E is an alcoholic and she is concerned that he may have mixed drugs and alcohol. The medical service starts Mr. E on empiric antimicrobials—vancomycin, ceftriaxone, and acyclovir—because of his AMS, and performs an LP to rule out intracranial pathology. His LP results are unremarkable.

Mr. E appears to be confused during psychiatric evaluation. He requests to be “hypnotized on a helicopter to find out what is wrong with me.” His wife states that Mr. E drank vodka daily but decreased his alcohol consumption after surgery 5 months ago. Before his current admission, he was drinking approximately half a glass of vodka every few days, according to his wife. Mr. E says he has no prior psychiatric admissions. During the mental status exam, his eye contact is poor, with latency of response to questions, thought blocking, and psychomotor retardation. He is alert, oriented to time, place, and person, and cooperative. He cannot concentrate or focus during the interview. He denies suicidal or homicidal ideation.

The authors’ observations

Mr. E appeared to be delirious, as evidenced by the sudden onset of waxing and waning changes in consciousness, attention deficits, and cognition. He also had a history of daily alcohol use and decreased his alcohol intake after a surgery 5 months ago, which puts him at risk for Wernicke’s encephalopathy.^1-3 The type of surgery and whether he received adequate thiamine supplementation at that time was unclear. Because Mr. E is older, he has a higher risk of mortality and morbidity from delirium.^4,5 We started Mr. E on quetiapine, 50 mg/d, for delirium and an IV lorazepam taper, starting at 2 mg every 8 hours, because the extent of his alcohol and benzodiazepine use was unclear—we weren’t sure how forthcoming he was about his alcohol use. He received IV thiamine supplementation followed by oral thiamine, 100 mg/d.

The authors’ recommendations

We requested a neurology consult, EEG, CSF cultures, and brain MRI (Table 1).⁶ EEG, chest radiography, thyroid scan, and CT scan were normal and MRI showed no acute intracranial process. However, there was a redemonstration of increased T1 signal seen within the bilateral basal ganglia and relative diminutive appearance to the bilateral mamillary bodies, which suggests possible liver disease and/or alcohol abuse. These findings were unchanged from an MRI Mr. E received 10 years ago, were consistent with his history of alcohol abuse, and may indicate an underlying predisposition to delirium. A CT scan of the abdomen showed hepatic cirrhosis with prominent, tortuous vessels of the upper abdomen, subtle ill-defined hypodensity of the anterior aspect of the liver, and an enlarged spleen.

Mr. E’s mental functioning did not improve with quetiapine and lorazepam. Further evaluation revealed a negative human immunodeficiency virus test and normal heavy metals, ammonia, ceruloplasmin, and thiamine. We suspected limbic encephalitis because of Mr. E’s memory problems and behavioral and psychiatric manifestations,⁷ but CSF was unremarkable and limbic encephalitis workup of CSF and paraneoplastic antibody panel were negative.

Mr. E’s primary care physician stated that at an appointment 1 month ago, Mr. E was alert, oriented, and conversational with normal thought processing. At that time he had presented with rectal bleeding, occult blood in his stool, and an unintentional 25-lb weight loss over 2 months. It was not clear if his weight loss was caused by poor nutrition—which is common among chronic alcoholics—or an occult disease process.

After 10 days, Mr. E was discharged home from the medicine service with no clear cause of his AMS.

Table 1

Suggested workup for altered mental status

EVALUATION: Worsening behavior

One week later, Mr. E presents to the ED with continued AMS and worsening behavior at home. Two days ago, he attempted to strangle his dog and cut himself with a knife. His paranoia was worsening and his oral intake continued to decrease. In the ED, Mr. E does not want a chest radiograph because, “I don’t like radiation contaminating my body”; his family stated that he had been suspicious of radiography all of his life. He receives empiric ceftriaxone because of a possible urinary tract infection. Urine culture is positive for Pseudomonas aeruginosa and he is switched to ciprofloxacin. Mr. E is admitted for further workup.

Mr. E’s mother states, “I think this change in behavior is related to my son drinking alcohol for 20 years. This is exactly how he acted when he was on drugs. I think he is having a flashback.” She also reports her son purchased multiple chemicals—the details of which are unclear—that he left lying around the house.

His wife says that after discharge a week ago, Mr. E was stable for 1 or 2 days and then “he started going downhill.” He became more paranoid and he started talking about cameras watching him in his house. Mr. E took quetiapine, 50 mg/d, for a few days, then refused because he thought there was something in the medication. Mr. E’s family feels that at times he is responding to internal stimuli. He makes statements about his DNA being changed and reports that he has 2 wives and the wife in the room was not the real one, which suggests Capgras syndrome. His wife provides a home medication list that includes vitamin B complex, vitamins B12, E, and C, a multivitamin, zinc, magnesium, fish oil, garlic, calcium, glucosamine, chondroitin, herbal supplements, and gingko. The psychiatry team recommends switching from quetiapine to olanzapine, 15 mg/d, because Mr. E was paranoid about taking quetiapine.

We determine that Mr. E does not have medical decision-making capacity.

Because his symptoms do not improve, Mr. E is transferred to the psychiatric intensive care unit. His mental status shows little change while there. Neuropsychiatric testing shows only “cognitive deficits.” He shows signs consistent with neurologic dysfunction in terms of stimulus-bound responding and perseveration, which is compatible with the bilateral basal ganglia lesion seen on MRI. However, some of his behaviors suggest psychiatric and motivationally driven or manipulative etiology. During this testing he was difficult to evaluate and needed to be convinced to engage. At times he was illogical and at other times he showed good focus and recall. It is difficult to draw more definitive conclusions and Mr. E is discharged home with minor improvement in his symptoms. He didn’t attend follow-up appointments. During a courtesy call a few months after his admission, his wife revealed that Mr. E had died after shooting himself. It is unclear if it was an accident or suicide.

The authors’ observations

Mr. E’s diagnosis remains unclear (for a summary of his clinical course, see Table 2). Although his initial presentation was consistent with delirium, the lack of an identifiable medical cause, prolonged time course, and lack of improvement with dopamine blocking agents suggest additional diagnoses such as Wernicke-Korsakoff syndrome, rapidly progressive dementia, or a substance-induced disorder. He displayed paranoia and bizarre delusions, which would suggest a thought disorder. However, he also had a history of substance use. A few months after we saw Mr. E, “bath salt” (methylenedioxypyrovalerone) abuse gained national attention. Patients with bath salt intoxication present with confusion, paranoia, and behavioral disturbances as well as a prolonged course.⁸

Mr. E’s CT and MRI scans, history of alcohol use, and cirrhosis also point to Wernicke-Korsakoff syndrome as an underlying diagnosis. It is unclear whether Mr. E experienced alcohol withdrawal and IV glucose without adequate thiamine replacement during a prior surgery. However, MRI findings were unchanged from a previous study 10 years ago.

It is puzzling whether Mr. E’s AMS was a first psychotic break, a result of drug and alcohol use, rapidly progressing dementia, or another neurologic problem that we have not identified. Our tentative diagnosis was Wernicke-Korsakoff syndrome because of his history of alcohol use and imaging findings.

Although we used a multidisciplinary team approach that included psychiatry, internal medicine, neurology, neuropsychology, and an aggressive and thorough workup, we could not establish a definitive diagnosis. Unsolved cases such as this can leave patients and clinicians frustrated and may lead to unfavorable outcomes. Additional resources such as a telephone call after the first missed appointment may have been warranted.

Table 2

Mr. E’s clinical course

Related Resources

• Kaufman DM. Clinical neurology for psychiatrists. 6th ed. Philadelphia, PA: Saunders Elsevier; 2007.
• Sidhu KS, Balon R, Ajluni V, et al. Standard EEG and the difficult-to-assess mental status. Ann Clin Psychiatry. 2009;21(2):103-108.

Drug Brand Names

• Acyclovir • Zovirax
• Ceftriaxone • Rocephin
• Ciprofloxacin • Cipro
• Haloperidol • Haldol
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Thiamine • Betaxin
• Vancomycin • Vancocin

Disclosure

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

Discuss this article at www.facebook.com/CurrentPsychiatry

CASE: Agitated and paranoid

Mr. E, age 55, presents to the emergency department (ED) with a 2-week history of altered mental status (AMS). His wife reports, “He was normal one day and the next day he was not.” Mr. E also presents with sleep disturbance, decreased appetite and speech, and a 20-lb weight loss. His family reports no recent stressors or head trauma. Mr. E is agitated in the ED and receives a single dose of IV haloperidol, 5 mg. He exhibits paranoia and is afraid to get a CT scan. The medical team attempts a lumbar puncture (LP), but Mr. E does not cooperate.

His laboratory values are: potassium, 3.0 mEq/L; creatinine, 1.60 mg/dL; calcium, 10.6 mg/dL; thyroid-stimulating hormone, 0.177 IU/L; vitamin B12, >1500 pg/mL; folate, >20 ng/mL; and creatine kinase, 281 U/L. Urine drug screen is positive for benzodiazepines and opiates, neither of which was prescribed, and blood alcohol is negative.

Mr. E is admitted for further workup of AMS. His daughter-in-law states that Mr. E is an alcoholic and she is concerned that he may have mixed drugs and alcohol. The medical service starts Mr. E on empiric antimicrobials—vancomycin, ceftriaxone, and acyclovir—because of his AMS, and performs an LP to rule out intracranial pathology. His LP results are unremarkable.

Mr. E appears to be confused during psychiatric evaluation. He requests to be “hypnotized on a helicopter to find out what is wrong with me.” His wife states that Mr. E drank vodka daily but decreased his alcohol consumption after surgery 5 months ago. Before his current admission, he was drinking approximately half a glass of vodka every few days, according to his wife. Mr. E says he has no prior psychiatric admissions. During the mental status exam, his eye contact is poor, with latency of response to questions, thought blocking, and psychomotor retardation. He is alert, oriented to time, place, and person, and cooperative. He cannot concentrate or focus during the interview. He denies suicidal or homicidal ideation.

The authors’ observations

Mr. E appeared to be delirious, as evidenced by the sudden onset of waxing and waning changes in consciousness, attention deficits, and cognition. He also had a history of daily alcohol use and decreased his alcohol intake after a surgery 5 months ago, which puts him at risk for Wernicke’s encephalopathy.^1-3 The type of surgery and whether he received adequate thiamine supplementation at that time was unclear. Because Mr. E is older, he has a higher risk of mortality and morbidity from delirium.^4,5 We started Mr. E on quetiapine, 50 mg/d, for delirium and an IV lorazepam taper, starting at 2 mg every 8 hours, because the extent of his alcohol and benzodiazepine use was unclear—we weren’t sure how forthcoming he was about his alcohol use. He received IV thiamine supplementation followed by oral thiamine, 100 mg/d.

The authors’ recommendations

We requested a neurology consult, EEG, CSF cultures, and brain MRI (Table 1).⁶ EEG, chest radiography, thyroid scan, and CT scan were normal and MRI showed no acute intracranial process. However, there was a redemonstration of increased T1 signal seen within the bilateral basal ganglia and relative diminutive appearance to the bilateral mamillary bodies, which suggests possible liver disease and/or alcohol abuse. These findings were unchanged from an MRI Mr. E received 10 years ago, were consistent with his history of alcohol abuse, and may indicate an underlying predisposition to delirium. A CT scan of the abdomen showed hepatic cirrhosis with prominent, tortuous vessels of the upper abdomen, subtle ill-defined hypodensity of the anterior aspect of the liver, and an enlarged spleen.

Mr. E’s mental functioning did not improve with quetiapine and lorazepam. Further evaluation revealed a negative human immunodeficiency virus test and normal heavy metals, ammonia, ceruloplasmin, and thiamine. We suspected limbic encephalitis because of Mr. E’s memory problems and behavioral and psychiatric manifestations,⁷ but CSF was unremarkable and limbic encephalitis workup of CSF and paraneoplastic antibody panel were negative.

Mr. E’s primary care physician stated that at an appointment 1 month ago, Mr. E was alert, oriented, and conversational with normal thought processing. At that time he had presented with rectal bleeding, occult blood in his stool, and an unintentional 25-lb weight loss over 2 months. It was not clear if his weight loss was caused by poor nutrition—which is common among chronic alcoholics—or an occult disease process.

After 10 days, Mr. E was discharged home from the medicine service with no clear cause of his AMS.

Table 1

Suggested workup for altered mental status

EVALUATION: Worsening behavior

One week later, Mr. E presents to the ED with continued AMS and worsening behavior at home. Two days ago, he attempted to strangle his dog and cut himself with a knife. His paranoia was worsening and his oral intake continued to decrease. In the ED, Mr. E does not want a chest radiograph because, “I don’t like radiation contaminating my body”; his family stated that he had been suspicious of radiography all of his life. He receives empiric ceftriaxone because of a possible urinary tract infection. Urine culture is positive for Pseudomonas aeruginosa and he is switched to ciprofloxacin. Mr. E is admitted for further workup.

Mr. E’s mother states, “I think this change in behavior is related to my son drinking alcohol for 20 years. This is exactly how he acted when he was on drugs. I think he is having a flashback.” She also reports her son purchased multiple chemicals—the details of which are unclear—that he left lying around the house.

His wife says that after discharge a week ago, Mr. E was stable for 1 or 2 days and then “he started going downhill.” He became more paranoid and he started talking about cameras watching him in his house. Mr. E took quetiapine, 50 mg/d, for a few days, then refused because he thought there was something in the medication. Mr. E’s family feels that at times he is responding to internal stimuli. He makes statements about his DNA being changed and reports that he has 2 wives and the wife in the room was not the real one, which suggests Capgras syndrome. His wife provides a home medication list that includes vitamin B complex, vitamins B12, E, and C, a multivitamin, zinc, magnesium, fish oil, garlic, calcium, glucosamine, chondroitin, herbal supplements, and gingko. The psychiatry team recommends switching from quetiapine to olanzapine, 15 mg/d, because Mr. E was paranoid about taking quetiapine.

We determine that Mr. E does not have medical decision-making capacity.

Because his symptoms do not improve, Mr. E is transferred to the psychiatric intensive care unit. His mental status shows little change while there. Neuropsychiatric testing shows only “cognitive deficits.” He shows signs consistent with neurologic dysfunction in terms of stimulus-bound responding and perseveration, which is compatible with the bilateral basal ganglia lesion seen on MRI. However, some of his behaviors suggest psychiatric and motivationally driven or manipulative etiology. During this testing he was difficult to evaluate and needed to be convinced to engage. At times he was illogical and at other times he showed good focus and recall. It is difficult to draw more definitive conclusions and Mr. E is discharged home with minor improvement in his symptoms. He didn’t attend follow-up appointments. During a courtesy call a few months after his admission, his wife revealed that Mr. E had died after shooting himself. It is unclear if it was an accident or suicide.

The authors’ observations

Mr. E’s diagnosis remains unclear (for a summary of his clinical course, see Table 2). Although his initial presentation was consistent with delirium, the lack of an identifiable medical cause, prolonged time course, and lack of improvement with dopamine blocking agents suggest additional diagnoses such as Wernicke-Korsakoff syndrome, rapidly progressive dementia, or a substance-induced disorder. He displayed paranoia and bizarre delusions, which would suggest a thought disorder. However, he also had a history of substance use. A few months after we saw Mr. E, “bath salt” (methylenedioxypyrovalerone) abuse gained national attention. Patients with bath salt intoxication present with confusion, paranoia, and behavioral disturbances as well as a prolonged course.⁸

Mr. E’s CT and MRI scans, history of alcohol use, and cirrhosis also point to Wernicke-Korsakoff syndrome as an underlying diagnosis. It is unclear whether Mr. E experienced alcohol withdrawal and IV glucose without adequate thiamine replacement during a prior surgery. However, MRI findings were unchanged from a previous study 10 years ago.

It is puzzling whether Mr. E’s AMS was a first psychotic break, a result of drug and alcohol use, rapidly progressing dementia, or another neurologic problem that we have not identified. Our tentative diagnosis was Wernicke-Korsakoff syndrome because of his history of alcohol use and imaging findings.

Although we used a multidisciplinary team approach that included psychiatry, internal medicine, neurology, neuropsychology, and an aggressive and thorough workup, we could not establish a definitive diagnosis. Unsolved cases such as this can leave patients and clinicians frustrated and may lead to unfavorable outcomes. Additional resources such as a telephone call after the first missed appointment may have been warranted.

Table 2

Mr. E’s clinical course

Related Resources

• Kaufman DM. Clinical neurology for psychiatrists. 6th ed. Philadelphia, PA: Saunders Elsevier; 2007.
• Sidhu KS, Balon R, Ajluni V, et al. Standard EEG and the difficult-to-assess mental status. Ann Clin Psychiatry. 2009;21(2):103-108.

Drug Brand Names

• Acyclovir • Zovirax
• Ceftriaxone • Rocephin
• Ciprofloxacin • Cipro
• Haloperidol • Haldol
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Thiamine • Betaxin
• Vancomycin • Vancocin

Disclosure

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

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CASE: Agitated and paranoid

Mr. E, age 55, presents to the emergency department (ED) with a 2-week history of altered mental status (AMS). His wife reports, “He was normal one day and the next day he was not.” Mr. E also presents with sleep disturbance, decreased appetite and speech, and a 20-lb weight loss. His family reports no recent stressors or head trauma. Mr. E is agitated in the ED and receives a single dose of IV haloperidol, 5 mg. He exhibits paranoia and is afraid to get a CT scan. The medical team attempts a lumbar puncture (LP), but Mr. E does not cooperate.

His laboratory values are: potassium, 3.0 mEq/L; creatinine, 1.60 mg/dL; calcium, 10.6 mg/dL; thyroid-stimulating hormone, 0.177 IU/L; vitamin B12, >1500 pg/mL; folate, >20 ng/mL; and creatine kinase, 281 U/L. Urine drug screen is positive for benzodiazepines and opiates, neither of which was prescribed, and blood alcohol is negative.

Mr. E is admitted for further workup of AMS. His daughter-in-law states that Mr. E is an alcoholic and she is concerned that he may have mixed drugs and alcohol. The medical service starts Mr. E on empiric antimicrobials—vancomycin, ceftriaxone, and acyclovir—because of his AMS, and performs an LP to rule out intracranial pathology. His LP results are unremarkable.

Mr. E appears to be confused during psychiatric evaluation. He requests to be “hypnotized on a helicopter to find out what is wrong with me.” His wife states that Mr. E drank vodka daily but decreased his alcohol consumption after surgery 5 months ago. Before his current admission, he was drinking approximately half a glass of vodka every few days, according to his wife. Mr. E says he has no prior psychiatric admissions. During the mental status exam, his eye contact is poor, with latency of response to questions, thought blocking, and psychomotor retardation. He is alert, oriented to time, place, and person, and cooperative. He cannot concentrate or focus during the interview. He denies suicidal or homicidal ideation.

The authors’ observations

Mr. E appeared to be delirious, as evidenced by the sudden onset of waxing and waning changes in consciousness, attention deficits, and cognition. He also had a history of daily alcohol use and decreased his alcohol intake after a surgery 5 months ago, which puts him at risk for Wernicke’s encephalopathy.^1-3 The type of surgery and whether he received adequate thiamine supplementation at that time was unclear. Because Mr. E is older, he has a higher risk of mortality and morbidity from delirium.^4,5 We started Mr. E on quetiapine, 50 mg/d, for delirium and an IV lorazepam taper, starting at 2 mg every 8 hours, because the extent of his alcohol and benzodiazepine use was unclear—we weren’t sure how forthcoming he was about his alcohol use. He received IV thiamine supplementation followed by oral thiamine, 100 mg/d.

The authors’ recommendations

We requested a neurology consult, EEG, CSF cultures, and brain MRI (Table 1).⁶ EEG, chest radiography, thyroid scan, and CT scan were normal and MRI showed no acute intracranial process. However, there was a redemonstration of increased T1 signal seen within the bilateral basal ganglia and relative diminutive appearance to the bilateral mamillary bodies, which suggests possible liver disease and/or alcohol abuse. These findings were unchanged from an MRI Mr. E received 10 years ago, were consistent with his history of alcohol abuse, and may indicate an underlying predisposition to delirium. A CT scan of the abdomen showed hepatic cirrhosis with prominent, tortuous vessels of the upper abdomen, subtle ill-defined hypodensity of the anterior aspect of the liver, and an enlarged spleen.

Mr. E’s mental functioning did not improve with quetiapine and lorazepam. Further evaluation revealed a negative human immunodeficiency virus test and normal heavy metals, ammonia, ceruloplasmin, and thiamine. We suspected limbic encephalitis because of Mr. E’s memory problems and behavioral and psychiatric manifestations,⁷ but CSF was unremarkable and limbic encephalitis workup of CSF and paraneoplastic antibody panel were negative.

Mr. E’s primary care physician stated that at an appointment 1 month ago, Mr. E was alert, oriented, and conversational with normal thought processing. At that time he had presented with rectal bleeding, occult blood in his stool, and an unintentional 25-lb weight loss over 2 months. It was not clear if his weight loss was caused by poor nutrition—which is common among chronic alcoholics—or an occult disease process.

After 10 days, Mr. E was discharged home from the medicine service with no clear cause of his AMS.

Table 1

Suggested workup for altered mental status

EVALUATION: Worsening behavior

One week later, Mr. E presents to the ED with continued AMS and worsening behavior at home. Two days ago, he attempted to strangle his dog and cut himself with a knife. His paranoia was worsening and his oral intake continued to decrease. In the ED, Mr. E does not want a chest radiograph because, “I don’t like radiation contaminating my body”; his family stated that he had been suspicious of radiography all of his life. He receives empiric ceftriaxone because of a possible urinary tract infection. Urine culture is positive for Pseudomonas aeruginosa and he is switched to ciprofloxacin. Mr. E is admitted for further workup.

Mr. E’s mother states, “I think this change in behavior is related to my son drinking alcohol for 20 years. This is exactly how he acted when he was on drugs. I think he is having a flashback.” She also reports her son purchased multiple chemicals—the details of which are unclear—that he left lying around the house.

His wife says that after discharge a week ago, Mr. E was stable for 1 or 2 days and then “he started going downhill.” He became more paranoid and he started talking about cameras watching him in his house. Mr. E took quetiapine, 50 mg/d, for a few days, then refused because he thought there was something in the medication. Mr. E’s family feels that at times he is responding to internal stimuli. He makes statements about his DNA being changed and reports that he has 2 wives and the wife in the room was not the real one, which suggests Capgras syndrome. His wife provides a home medication list that includes vitamin B complex, vitamins B12, E, and C, a multivitamin, zinc, magnesium, fish oil, garlic, calcium, glucosamine, chondroitin, herbal supplements, and gingko. The psychiatry team recommends switching from quetiapine to olanzapine, 15 mg/d, because Mr. E was paranoid about taking quetiapine.

We determine that Mr. E does not have medical decision-making capacity.

Because his symptoms do not improve, Mr. E is transferred to the psychiatric intensive care unit. His mental status shows little change while there. Neuropsychiatric testing shows only “cognitive deficits.” He shows signs consistent with neurologic dysfunction in terms of stimulus-bound responding and perseveration, which is compatible with the bilateral basal ganglia lesion seen on MRI. However, some of his behaviors suggest psychiatric and motivationally driven or manipulative etiology. During this testing he was difficult to evaluate and needed to be convinced to engage. At times he was illogical and at other times he showed good focus and recall. It is difficult to draw more definitive conclusions and Mr. E is discharged home with minor improvement in his symptoms. He didn’t attend follow-up appointments. During a courtesy call a few months after his admission, his wife revealed that Mr. E had died after shooting himself. It is unclear if it was an accident or suicide.

The authors’ observations

Mr. E’s diagnosis remains unclear (for a summary of his clinical course, see Table 2). Although his initial presentation was consistent with delirium, the lack of an identifiable medical cause, prolonged time course, and lack of improvement with dopamine blocking agents suggest additional diagnoses such as Wernicke-Korsakoff syndrome, rapidly progressive dementia, or a substance-induced disorder. He displayed paranoia and bizarre delusions, which would suggest a thought disorder. However, he also had a history of substance use. A few months after we saw Mr. E, “bath salt” (methylenedioxypyrovalerone) abuse gained national attention. Patients with bath salt intoxication present with confusion, paranoia, and behavioral disturbances as well as a prolonged course.⁸

Mr. E’s CT and MRI scans, history of alcohol use, and cirrhosis also point to Wernicke-Korsakoff syndrome as an underlying diagnosis. It is unclear whether Mr. E experienced alcohol withdrawal and IV glucose without adequate thiamine replacement during a prior surgery. However, MRI findings were unchanged from a previous study 10 years ago.

It is puzzling whether Mr. E’s AMS was a first psychotic break, a result of drug and alcohol use, rapidly progressing dementia, or another neurologic problem that we have not identified. Our tentative diagnosis was Wernicke-Korsakoff syndrome because of his history of alcohol use and imaging findings.

Although we used a multidisciplinary team approach that included psychiatry, internal medicine, neurology, neuropsychology, and an aggressive and thorough workup, we could not establish a definitive diagnosis. Unsolved cases such as this can leave patients and clinicians frustrated and may lead to unfavorable outcomes. Additional resources such as a telephone call after the first missed appointment may have been warranted.

Table 2

Mr. E’s clinical course

Related Resources

• Kaufman DM. Clinical neurology for psychiatrists. 6th ed. Philadelphia, PA: Saunders Elsevier; 2007.
• Sidhu KS, Balon R, Ajluni V, et al. Standard EEG and the difficult-to-assess mental status. Ann Clin Psychiatry. 2009;21(2):103-108.

Drug Brand Names

• Acyclovir • Zovirax
• Ceftriaxone • Rocephin
• Ciprofloxacin • Cipro
• Haloperidol • Haldol
• Lorazepam • Ativan
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Thiamine • Betaxin
• Vancomycin • Vancocin

Disclosure

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

CASE: Medication sensitivity

Mrs. C, age 48, is admitted to a tertiary care inpatient mood disorder unit for evaluation of severe depression characterized by depressed mood, anhedonia, and insomnia. Her initial Hamilton Rating Scale for Depression 17-Item (HRSD-17) score is 30, indicating severe depression. Her medications are fluoxetine, 10 mg/d, and diazepam, 0.5 mg/d.

Mrs. C describes a 10-month history of depression and extreme anxiety in the context of several psychosocial stressors. Her father recently died and she is having difficulty with the demands of administering her father’s estate. She is intensely obsessive and focused on nihilistic themes, her diagnosis, somatic themes, and medications side effects. Her husband confirms our observations. No history or current symptoms of typical compulsions (eg, washing hands or checking doors) are elicited. She has limited insight into her obsessive tendencies.

Mrs. C had no psychiatric history before her depressive and obsessive symptoms developed 10 months ago. However, in the past 10 months, she has been hospitalized in a psychiatric facility twice. She also received a series of 8 electroconvulsive therapy treatments, but reported minimal improvement of her depressive symptoms. Mrs. C had a few cognitive-behavioral therapy (CBT) sessions with a psychotherapist, but she said they didn’t help much.

Mrs. C has substantial difficulty adhering to medications, even at subtherapeutic doses. She states she is “extremely sensitive” to all medications. Mrs. C says she develops dizziness, increased anxiety, insomnia, nausea, and other vague reactions whenever she attempts to increase her psychotropics to therapeutic doses. She took sertraline, 10 mg/d, for 4 days, but discontinued it because of unspecified side effects. She then received escitalopram, 2.5 mg/d, for 10 days, but again stopped it because of vague side effects. She was taking paroxetine, 10 mg/d, for 2 days, but experienced vomiting and discontinued the drug. She tried venlafaxine at a low dose and also discontinued it because of vomiting. Mrs. C stayed on mirtazapine, 22.5 mg/d, for 3 months, but stopped it because of lack of efficacy and she was unwilling to increase the dose. Other unsuccessful trials include citalopram and doxepin. Mrs. C is hesitant to try another medication or increase to therapeutic doses any of the previous medications.

The authors’ observations

Before initiating another treatment, the treatment team considered Mrs. C’s pervasive medication intolerance. Her enzymatic activity may be genetically compromised, which could lead to high blood levels of medications and significant side effects when she takes very low doses. Individual variations in response to psychotropics are influenced by genetic factors.¹ Variants in the cytochrome P450 (CYP450) genes produce enzymes with increased activity, normal activity, reduced activity, or no activity, creating phenotypes of ultrarapid metabolizers, extensive metabolizers, intermediate metabolizers, and poor metabolizers, respectively. These genetic variations can affect blood levels of medications that employ these enzymes in their metabolic pathways.² Mrs. C could be a poor metabolizer of common CYP450 variant enzymes, which led to her exquisite sensitivity to psychotropics. We felt this was a reasonable hypothesis given her tumultuous 10-month course of psychiatric treatment and multiple failed medication trials.

An alternative hypothesis is that Mrs. C’s somatic obsessions about drug side effects were the primary clinical issue that led to her severe medication intolerance. Mrs. C spends hours questioning the inpatient staff about her diagnosis (eg, “Are you sure I don’t have bipolar disorder?”), medications (eg, “Are you sure this medication won’t make me sick?”), somatic themes (eg, “Are you sure I don’t have Meniere’s disease with all my dizziness?”), and nihilistic themes (eg, “What if I never get better?”). Mrs. C’s husband attested that she has spent hours researching her new medications on the Internet and reading the medication handouts from the pharmacy. She admits to mentally cycling through the DSM-IV-TR criteria for hours at a time to “figure out” if she has bipolar disorder (BD).

We initiated pharmacogenomic testing to help distinguish between these hypotheses. Mrs. C’s results are presented in Table 1. Genotype results were applied using an interpretive algorithm (Figure) in which 26 psychiatric medications were placed in categories of “use as directed” (green column), “use with caution” (yellow column), and “use with caution or more frequent monitoring” (red column). The algorithm incorporates the genetic information with the known pharmacologic profile for each of the medications in the panel. Highlights of Mrs. C’s interpretive report are shown in Table 2.

Table 1

Mrs. C’s genotype results

Figure

Genotype-phenotype integration into Mrs. C’s interpretive report

  Table 2

Mrs. C’s pharmacogenomic-based interpretive report

The authors’ observations

Mrs. C’s genotype might explain some sensitivity to medications metabolized by CYP2D6 (eg, venlafaxine, paroxetine, fluoxetine), but does not explain her acute sensitivity to all of the medications she has taken. For example, she is an extensive metabolizer for CYP2C19, which metabolizes escitalopram; therefore, it is unlikely escitalopram, 2.5 mg/d, would result in high blood levels and side effects.³ Regardless of the next step in treatment, we deemed her somatic obsessions to be the most important clinical issue. It seems unlikely that Mrs. C would adhere to any medication regimen until this underlying problem was addressed.

The focus of treatment shifted to Mrs. C’s obsessions about her medications and their side effects. Mrs. C was fixated on the content of her obsessions (eg, medications, side effects) rather than the process of her obsessional thinking. The goal was to help Mrs. C identify, label, and ultimately create distance from her obsessive thoughts associated with side effects. The treatment team employed an acceptance and commitment therapy (ACT) model of observing and defusing thoughts in the inpatient setting (Table 3).⁴ ACT is based on mindfulness and committed, values-based action.⁵ When patients are “fused” with their thoughts, they believe these thoughts are important and representative of reality. In Mrs. C’s case, she fused with the concept that her medications were making her sick and the idea that she may have BD. The treatment team thought these fused thoughts were the major problem that resulted in 10 months of protracted illness.

Conversely, in a “defused” state, patients can separate from their thoughts and observe them as disparate sounds, words, stories, or bits of language. The goal is to observe and allow the patient’s thoughts to simply be thoughts rather than trying to determine if they are “true.” Mrs. C was fused with the idea that her medications were making her ill, so this belief became the story underlying her obsessional thinking. Helping her disengage from this story became the focus of her treatment.

Table 3

6 core principles of acceptance and commitment therapy

Results guide pharmacotherapy

In addition to helping change the focus of Mrs. C’s psychotherapy, we used the pharmacogenomic results to guide medication treatment. We initially prescribed fluvoxamine, 50 mg/d, because her partially compromised CYP2D6 pathway probably would play only a minor role in metabolizing the drug.¹ Smoking induces CYP1A2, which is fluvoxamine’s primary metabolic pathway; however, Mrs. C does not smoke.⁶ When we saw Mrs. C in January 2009, the author (JGW) was unaware of any available genetic testing for CYP1A2, although now such testing is clinically available.

Mirtazapine is in the “use as directed” category for Mrs. C’s genotype (Table 2) and was the only medication she had adhered to at a therapeutic dose for more than a few days. However, she indicated that she would not adhere to this medication if we prescribed it again. Duloxetine also is in the “use as directed” category; however, given the entire clinical picture, we chose fluvoxamine because of Mrs. C’s obsessive symptomatology and because she had never reached a therapeutic dose of a selective serotonin reuptake inhibitor.

OUTCOME: Obsessions abate

Given Mrs. C’s lack of insight, we initiate a family approach to help broach the topic of obsessions as the focus of treatment. With her husband’s help, she participates in defusion techniques as an inpatient and follows up with an acceptance-based psychotherapist after discharge. After we share the pharmacogenomic information with Mrs. C, she agrees to try fluvoxamine, which is titrated to 100 mg/d. She maintains this dose at her 4-week follow-up visit. Notably, this was only the second time Mrs. C adhered to a medication trial since illness onset. Upon admission, Mrs. C had an HRSD-17 score of 30, indicating severe depression; at 4 weeks, her HRSD-17 score is 8, indicating mild depression.

The authors’ observations

In a complementary case, the author (JGW) consulted on a patient who was taking paroxetine and experiencing anorgasmia, weight gain, and loss of libido. Pharmacogenomic testing revealed that the patient was a poor metabolizer of CYP2D6. Paroxetine is substantially metabolized by CYP2D6; therefore, it was likely that high blood levels were contributing to the side effects.^3,7 The key clinical distinction is that although this patient was bothered by intrusive side effects, he was not fixated on them like Mrs. C. His pharmacogenomic test results were used to identify a metabolic issue that was causing the side effects. This is in contrast with Mrs. C, for whom the pharmacogenomic information ruled out a metabolic issue as the primary problem and helped guide the next step in treatment.

Mrs. C’s case illustrates how pharmacogenomics and ACT complemented each other to create a desirable outcome. Pharmacogenomic testing originally was developed as a safety mechanism for medication choice and dosing, but clinical applications have grown as astute clinicians utilize it to help care for their patients.⁸ ACT can be a powerful tool for patients who have difficulties creating distance from their thoughts. Both pharmacogenomic testing and ACT are noninvasive interventions that can be implemented as part of a multi-faceted treatment approach.

Related Resources

• Hayes SC, Strosahl KD, Wilson KG. Acceptance and commitment therapy: The process and practice of mindful change. 2nd ed. New York, NY: The Guilford Press; 2011.
• Mrazek DA. Psychiatric pharmacogenomics. New York, NY: Oxford University Press; 2010.

Drug Brand Names

• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Bupropion • Wellbutrin, Zyban
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Desipramine • Norpramin
• Diazepam • Valium
• Doxepin • Adapin, Silenor
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Lithium • Eskalith, Lithobid
• Mirtazapine • Remeron
• Olanzapine • Zyprexa
• Nortriptyline • Pamelor
• Paroxetine • Paxil
• Perphenazine • Trilafon
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Trazodone • Desyrel, Oleptro
• Venlafaxine • Effexor
• Ziprasidone • Geodon

Disclosure

The authors are employed by AssureRx Health, Inc., the provider of the pharmacogenomic testing used in this article.

CASE: Medication sensitivity

Mrs. C, age 48, is admitted to a tertiary care inpatient mood disorder unit for evaluation of severe depression characterized by depressed mood, anhedonia, and insomnia. Her initial Hamilton Rating Scale for Depression 17-Item (HRSD-17) score is 30, indicating severe depression. Her medications are fluoxetine, 10 mg/d, and diazepam, 0.5 mg/d.

Mrs. C describes a 10-month history of depression and extreme anxiety in the context of several psychosocial stressors. Her father recently died and she is having difficulty with the demands of administering her father’s estate. She is intensely obsessive and focused on nihilistic themes, her diagnosis, somatic themes, and medications side effects. Her husband confirms our observations. No history or current symptoms of typical compulsions (eg, washing hands or checking doors) are elicited. She has limited insight into her obsessive tendencies.

Mrs. C had no psychiatric history before her depressive and obsessive symptoms developed 10 months ago. However, in the past 10 months, she has been hospitalized in a psychiatric facility twice. She also received a series of 8 electroconvulsive therapy treatments, but reported minimal improvement of her depressive symptoms. Mrs. C had a few cognitive-behavioral therapy (CBT) sessions with a psychotherapist, but she said they didn’t help much.

Mrs. C has substantial difficulty adhering to medications, even at subtherapeutic doses. She states she is “extremely sensitive” to all medications. Mrs. C says she develops dizziness, increased anxiety, insomnia, nausea, and other vague reactions whenever she attempts to increase her psychotropics to therapeutic doses. She took sertraline, 10 mg/d, for 4 days, but discontinued it because of unspecified side effects. She then received escitalopram, 2.5 mg/d, for 10 days, but again stopped it because of vague side effects. She was taking paroxetine, 10 mg/d, for 2 days, but experienced vomiting and discontinued the drug. She tried venlafaxine at a low dose and also discontinued it because of vomiting. Mrs. C stayed on mirtazapine, 22.5 mg/d, for 3 months, but stopped it because of lack of efficacy and she was unwilling to increase the dose. Other unsuccessful trials include citalopram and doxepin. Mrs. C is hesitant to try another medication or increase to therapeutic doses any of the previous medications.

The authors’ observations

Before initiating another treatment, the treatment team considered Mrs. C’s pervasive medication intolerance. Her enzymatic activity may be genetically compromised, which could lead to high blood levels of medications and significant side effects when she takes very low doses. Individual variations in response to psychotropics are influenced by genetic factors.¹ Variants in the cytochrome P450 (CYP450) genes produce enzymes with increased activity, normal activity, reduced activity, or no activity, creating phenotypes of ultrarapid metabolizers, extensive metabolizers, intermediate metabolizers, and poor metabolizers, respectively. These genetic variations can affect blood levels of medications that employ these enzymes in their metabolic pathways.² Mrs. C could be a poor metabolizer of common CYP450 variant enzymes, which led to her exquisite sensitivity to psychotropics. We felt this was a reasonable hypothesis given her tumultuous 10-month course of psychiatric treatment and multiple failed medication trials.

An alternative hypothesis is that Mrs. C’s somatic obsessions about drug side effects were the primary clinical issue that led to her severe medication intolerance. Mrs. C spends hours questioning the inpatient staff about her diagnosis (eg, “Are you sure I don’t have bipolar disorder?”), medications (eg, “Are you sure this medication won’t make me sick?”), somatic themes (eg, “Are you sure I don’t have Meniere’s disease with all my dizziness?”), and nihilistic themes (eg, “What if I never get better?”). Mrs. C’s husband attested that she has spent hours researching her new medications on the Internet and reading the medication handouts from the pharmacy. She admits to mentally cycling through the DSM-IV-TR criteria for hours at a time to “figure out” if she has bipolar disorder (BD).

We initiated pharmacogenomic testing to help distinguish between these hypotheses. Mrs. C’s results are presented in Table 1. Genotype results were applied using an interpretive algorithm (Figure) in which 26 psychiatric medications were placed in categories of “use as directed” (green column), “use with caution” (yellow column), and “use with caution or more frequent monitoring” (red column). The algorithm incorporates the genetic information with the known pharmacologic profile for each of the medications in the panel. Highlights of Mrs. C’s interpretive report are shown in Table 2.

Table 1

Mrs. C’s genotype results

Figure

Genotype-phenotype integration into Mrs. C’s interpretive report

  Table 2

Mrs. C’s pharmacogenomic-based interpretive report

The authors’ observations

Mrs. C’s genotype might explain some sensitivity to medications metabolized by CYP2D6 (eg, venlafaxine, paroxetine, fluoxetine), but does not explain her acute sensitivity to all of the medications she has taken. For example, she is an extensive metabolizer for CYP2C19, which metabolizes escitalopram; therefore, it is unlikely escitalopram, 2.5 mg/d, would result in high blood levels and side effects.³ Regardless of the next step in treatment, we deemed her somatic obsessions to be the most important clinical issue. It seems unlikely that Mrs. C would adhere to any medication regimen until this underlying problem was addressed.

The focus of treatment shifted to Mrs. C’s obsessions about her medications and their side effects. Mrs. C was fixated on the content of her obsessions (eg, medications, side effects) rather than the process of her obsessional thinking. The goal was to help Mrs. C identify, label, and ultimately create distance from her obsessive thoughts associated with side effects. The treatment team employed an acceptance and commitment therapy (ACT) model of observing and defusing thoughts in the inpatient setting (Table 3).⁴ ACT is based on mindfulness and committed, values-based action.⁵ When patients are “fused” with their thoughts, they believe these thoughts are important and representative of reality. In Mrs. C’s case, she fused with the concept that her medications were making her sick and the idea that she may have BD. The treatment team thought these fused thoughts were the major problem that resulted in 10 months of protracted illness.

Conversely, in a “defused” state, patients can separate from their thoughts and observe them as disparate sounds, words, stories, or bits of language. The goal is to observe and allow the patient’s thoughts to simply be thoughts rather than trying to determine if they are “true.” Mrs. C was fused with the idea that her medications were making her ill, so this belief became the story underlying her obsessional thinking. Helping her disengage from this story became the focus of her treatment.

Table 3

6 core principles of acceptance and commitment therapy

Results guide pharmacotherapy

In addition to helping change the focus of Mrs. C’s psychotherapy, we used the pharmacogenomic results to guide medication treatment. We initially prescribed fluvoxamine, 50 mg/d, because her partially compromised CYP2D6 pathway probably would play only a minor role in metabolizing the drug.¹ Smoking induces CYP1A2, which is fluvoxamine’s primary metabolic pathway; however, Mrs. C does not smoke.⁶ When we saw Mrs. C in January 2009, the author (JGW) was unaware of any available genetic testing for CYP1A2, although now such testing is clinically available.

Mirtazapine is in the “use as directed” category for Mrs. C’s genotype (Table 2) and was the only medication she had adhered to at a therapeutic dose for more than a few days. However, she indicated that she would not adhere to this medication if we prescribed it again. Duloxetine also is in the “use as directed” category; however, given the entire clinical picture, we chose fluvoxamine because of Mrs. C’s obsessive symptomatology and because she had never reached a therapeutic dose of a selective serotonin reuptake inhibitor.

OUTCOME: Obsessions abate

Given Mrs. C’s lack of insight, we initiate a family approach to help broach the topic of obsessions as the focus of treatment. With her husband’s help, she participates in defusion techniques as an inpatient and follows up with an acceptance-based psychotherapist after discharge. After we share the pharmacogenomic information with Mrs. C, she agrees to try fluvoxamine, which is titrated to 100 mg/d. She maintains this dose at her 4-week follow-up visit. Notably, this was only the second time Mrs. C adhered to a medication trial since illness onset. Upon admission, Mrs. C had an HRSD-17 score of 30, indicating severe depression; at 4 weeks, her HRSD-17 score is 8, indicating mild depression.

The authors’ observations

In a complementary case, the author (JGW) consulted on a patient who was taking paroxetine and experiencing anorgasmia, weight gain, and loss of libido. Pharmacogenomic testing revealed that the patient was a poor metabolizer of CYP2D6. Paroxetine is substantially metabolized by CYP2D6; therefore, it was likely that high blood levels were contributing to the side effects.^3,7 The key clinical distinction is that although this patient was bothered by intrusive side effects, he was not fixated on them like Mrs. C. His pharmacogenomic test results were used to identify a metabolic issue that was causing the side effects. This is in contrast with Mrs. C, for whom the pharmacogenomic information ruled out a metabolic issue as the primary problem and helped guide the next step in treatment.

Mrs. C’s case illustrates how pharmacogenomics and ACT complemented each other to create a desirable outcome. Pharmacogenomic testing originally was developed as a safety mechanism for medication choice and dosing, but clinical applications have grown as astute clinicians utilize it to help care for their patients.⁸ ACT can be a powerful tool for patients who have difficulties creating distance from their thoughts. Both pharmacogenomic testing and ACT are noninvasive interventions that can be implemented as part of a multi-faceted treatment approach.

Related Resources

• Hayes SC, Strosahl KD, Wilson KG. Acceptance and commitment therapy: The process and practice of mindful change. 2nd ed. New York, NY: The Guilford Press; 2011.
• Mrazek DA. Psychiatric pharmacogenomics. New York, NY: Oxford University Press; 2010.

Drug Brand Names

• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Bupropion • Wellbutrin, Zyban
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Desipramine • Norpramin
• Diazepam • Valium
• Doxepin • Adapin, Silenor
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Lithium • Eskalith, Lithobid
• Mirtazapine • Remeron
• Olanzapine • Zyprexa
• Nortriptyline • Pamelor
• Paroxetine • Paxil
• Perphenazine • Trilafon
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Trazodone • Desyrel, Oleptro
• Venlafaxine • Effexor
• Ziprasidone • Geodon

Disclosure

The authors are employed by AssureRx Health, Inc., the provider of the pharmacogenomic testing used in this article.

CASE: Medication sensitivity

Mrs. C, age 48, is admitted to a tertiary care inpatient mood disorder unit for evaluation of severe depression characterized by depressed mood, anhedonia, and insomnia. Her initial Hamilton Rating Scale for Depression 17-Item (HRSD-17) score is 30, indicating severe depression. Her medications are fluoxetine, 10 mg/d, and diazepam, 0.5 mg/d.

Mrs. C describes a 10-month history of depression and extreme anxiety in the context of several psychosocial stressors. Her father recently died and she is having difficulty with the demands of administering her father’s estate. She is intensely obsessive and focused on nihilistic themes, her diagnosis, somatic themes, and medications side effects. Her husband confirms our observations. No history or current symptoms of typical compulsions (eg, washing hands or checking doors) are elicited. She has limited insight into her obsessive tendencies.

Mrs. C had no psychiatric history before her depressive and obsessive symptoms developed 10 months ago. However, in the past 10 months, she has been hospitalized in a psychiatric facility twice. She also received a series of 8 electroconvulsive therapy treatments, but reported minimal improvement of her depressive symptoms. Mrs. C had a few cognitive-behavioral therapy (CBT) sessions with a psychotherapist, but she said they didn’t help much.

Mrs. C has substantial difficulty adhering to medications, even at subtherapeutic doses. She states she is “extremely sensitive” to all medications. Mrs. C says she develops dizziness, increased anxiety, insomnia, nausea, and other vague reactions whenever she attempts to increase her psychotropics to therapeutic doses. She took sertraline, 10 mg/d, for 4 days, but discontinued it because of unspecified side effects. She then received escitalopram, 2.5 mg/d, for 10 days, but again stopped it because of vague side effects. She was taking paroxetine, 10 mg/d, for 2 days, but experienced vomiting and discontinued the drug. She tried venlafaxine at a low dose and also discontinued it because of vomiting. Mrs. C stayed on mirtazapine, 22.5 mg/d, for 3 months, but stopped it because of lack of efficacy and she was unwilling to increase the dose. Other unsuccessful trials include citalopram and doxepin. Mrs. C is hesitant to try another medication or increase to therapeutic doses any of the previous medications.

The authors’ observations

Before initiating another treatment, the treatment team considered Mrs. C’s pervasive medication intolerance. Her enzymatic activity may be genetically compromised, which could lead to high blood levels of medications and significant side effects when she takes very low doses. Individual variations in response to psychotropics are influenced by genetic factors.¹ Variants in the cytochrome P450 (CYP450) genes produce enzymes with increased activity, normal activity, reduced activity, or no activity, creating phenotypes of ultrarapid metabolizers, extensive metabolizers, intermediate metabolizers, and poor metabolizers, respectively. These genetic variations can affect blood levels of medications that employ these enzymes in their metabolic pathways.² Mrs. C could be a poor metabolizer of common CYP450 variant enzymes, which led to her exquisite sensitivity to psychotropics. We felt this was a reasonable hypothesis given her tumultuous 10-month course of psychiatric treatment and multiple failed medication trials.

An alternative hypothesis is that Mrs. C’s somatic obsessions about drug side effects were the primary clinical issue that led to her severe medication intolerance. Mrs. C spends hours questioning the inpatient staff about her diagnosis (eg, “Are you sure I don’t have bipolar disorder?”), medications (eg, “Are you sure this medication won’t make me sick?”), somatic themes (eg, “Are you sure I don’t have Meniere’s disease with all my dizziness?”), and nihilistic themes (eg, “What if I never get better?”). Mrs. C’s husband attested that she has spent hours researching her new medications on the Internet and reading the medication handouts from the pharmacy. She admits to mentally cycling through the DSM-IV-TR criteria for hours at a time to “figure out” if she has bipolar disorder (BD).

We initiated pharmacogenomic testing to help distinguish between these hypotheses. Mrs. C’s results are presented in Table 1. Genotype results were applied using an interpretive algorithm (Figure) in which 26 psychiatric medications were placed in categories of “use as directed” (green column), “use with caution” (yellow column), and “use with caution or more frequent monitoring” (red column). The algorithm incorporates the genetic information with the known pharmacologic profile for each of the medications in the panel. Highlights of Mrs. C’s interpretive report are shown in Table 2.

Table 1

Mrs. C’s genotype results

Figure

Genotype-phenotype integration into Mrs. C’s interpretive report

  Table 2

Mrs. C’s pharmacogenomic-based interpretive report

The authors’ observations

Mrs. C’s genotype might explain some sensitivity to medications metabolized by CYP2D6 (eg, venlafaxine, paroxetine, fluoxetine), but does not explain her acute sensitivity to all of the medications she has taken. For example, she is an extensive metabolizer for CYP2C19, which metabolizes escitalopram; therefore, it is unlikely escitalopram, 2.5 mg/d, would result in high blood levels and side effects.³ Regardless of the next step in treatment, we deemed her somatic obsessions to be the most important clinical issue. It seems unlikely that Mrs. C would adhere to any medication regimen until this underlying problem was addressed.

The focus of treatment shifted to Mrs. C’s obsessions about her medications and their side effects. Mrs. C was fixated on the content of her obsessions (eg, medications, side effects) rather than the process of her obsessional thinking. The goal was to help Mrs. C identify, label, and ultimately create distance from her obsessive thoughts associated with side effects. The treatment team employed an acceptance and commitment therapy (ACT) model of observing and defusing thoughts in the inpatient setting (Table 3).⁴ ACT is based on mindfulness and committed, values-based action.⁵ When patients are “fused” with their thoughts, they believe these thoughts are important and representative of reality. In Mrs. C’s case, she fused with the concept that her medications were making her sick and the idea that she may have BD. The treatment team thought these fused thoughts were the major problem that resulted in 10 months of protracted illness.

Conversely, in a “defused” state, patients can separate from their thoughts and observe them as disparate sounds, words, stories, or bits of language. The goal is to observe and allow the patient’s thoughts to simply be thoughts rather than trying to determine if they are “true.” Mrs. C was fused with the idea that her medications were making her ill, so this belief became the story underlying her obsessional thinking. Helping her disengage from this story became the focus of her treatment.

Table 3

6 core principles of acceptance and commitment therapy

Results guide pharmacotherapy

In addition to helping change the focus of Mrs. C’s psychotherapy, we used the pharmacogenomic results to guide medication treatment. We initially prescribed fluvoxamine, 50 mg/d, because her partially compromised CYP2D6 pathway probably would play only a minor role in metabolizing the drug.¹ Smoking induces CYP1A2, which is fluvoxamine’s primary metabolic pathway; however, Mrs. C does not smoke.⁶ When we saw Mrs. C in January 2009, the author (JGW) was unaware of any available genetic testing for CYP1A2, although now such testing is clinically available.

Mirtazapine is in the “use as directed” category for Mrs. C’s genotype (Table 2) and was the only medication she had adhered to at a therapeutic dose for more than a few days. However, she indicated that she would not adhere to this medication if we prescribed it again. Duloxetine also is in the “use as directed” category; however, given the entire clinical picture, we chose fluvoxamine because of Mrs. C’s obsessive symptomatology and because she had never reached a therapeutic dose of a selective serotonin reuptake inhibitor.

OUTCOME: Obsessions abate

Given Mrs. C’s lack of insight, we initiate a family approach to help broach the topic of obsessions as the focus of treatment. With her husband’s help, she participates in defusion techniques as an inpatient and follows up with an acceptance-based psychotherapist after discharge. After we share the pharmacogenomic information with Mrs. C, she agrees to try fluvoxamine, which is titrated to 100 mg/d. She maintains this dose at her 4-week follow-up visit. Notably, this was only the second time Mrs. C adhered to a medication trial since illness onset. Upon admission, Mrs. C had an HRSD-17 score of 30, indicating severe depression; at 4 weeks, her HRSD-17 score is 8, indicating mild depression.

The authors’ observations

In a complementary case, the author (JGW) consulted on a patient who was taking paroxetine and experiencing anorgasmia, weight gain, and loss of libido. Pharmacogenomic testing revealed that the patient was a poor metabolizer of CYP2D6. Paroxetine is substantially metabolized by CYP2D6; therefore, it was likely that high blood levels were contributing to the side effects.^3,7 The key clinical distinction is that although this patient was bothered by intrusive side effects, he was not fixated on them like Mrs. C. His pharmacogenomic test results were used to identify a metabolic issue that was causing the side effects. This is in contrast with Mrs. C, for whom the pharmacogenomic information ruled out a metabolic issue as the primary problem and helped guide the next step in treatment.

Mrs. C’s case illustrates how pharmacogenomics and ACT complemented each other to create a desirable outcome. Pharmacogenomic testing originally was developed as a safety mechanism for medication choice and dosing, but clinical applications have grown as astute clinicians utilize it to help care for their patients.⁸ ACT can be a powerful tool for patients who have difficulties creating distance from their thoughts. Both pharmacogenomic testing and ACT are noninvasive interventions that can be implemented as part of a multi-faceted treatment approach.

Related Resources

• Hayes SC, Strosahl KD, Wilson KG. Acceptance and commitment therapy: The process and practice of mindful change. 2nd ed. New York, NY: The Guilford Press; 2011.
• Mrazek DA. Psychiatric pharmacogenomics. New York, NY: Oxford University Press; 2010.

Drug Brand Names

• Amitriptyline • Elavil
• Aripiprazole • Abilify
• Bupropion • Wellbutrin, Zyban
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clozapine • Clozaril
• Desipramine • Norpramin
• Diazepam • Valium
• Doxepin • Adapin, Silenor
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Imipramine • Tofranil
• Lithium • Eskalith, Lithobid
• Mirtazapine • Remeron
• Olanzapine • Zyprexa
• Nortriptyline • Pamelor
• Paroxetine • Paxil
• Perphenazine • Trilafon
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Sertraline • Zoloft
• Trazodone • Desyrel, Oleptro
• Venlafaxine • Effexor
• Ziprasidone • Geodon

Disclosure

The authors are employed by AssureRx Health, Inc., the provider of the pharmacogenomic testing used in this article.

Mr. S, a 45-year-old veteran, was diagnosed with posttraumatic stress disorder (PTSD) 18 years ago after a tour of duty in the Persian Gulf. He had combat-related flashbacks triggered by the smell of gasoline or smoke from a fire, was easily startled, and began to isolate himself socially. However, his symptoms improved when he started volunteering at his local Veterans Affairs Medical Center. After he lost his job 3 years ago, Mr. S started experiencing flashbacks. He was irritable, easily startled, and avoided things that reminded him of his time in the Persian Gulf. His psychiatrist prescribed sertraline, titrated to 200 mg/d. The drug reduced the severity of his avoidance and hyperarousal symptoms and improved his mood.

During a clinic visit, Mr. S says he is doing well and can fall asleep at night but is having recurring nightmares about traumatic events that occurred during combat. These nightmares wake him up and have become more frequent, occurring once per night for the past month. Mr. S says he has been watching more news programs about conflicts in Afghanistan and Iraq since the nightmares began. His psychiatrist starts quetiapine, 50 mg at bedtime for 7 nights then 100 mg at bedtime, but after 6 weeks Mr. S says his nightmares continue.

PTSD occurs in approximately 19% of Vietnam war combat veterans¹ and 14% of service members returning from Iraq and Afghanistan.² PTSD symptoms are classified into clusters: intrusive/re-experiencing; avoidant/numbing; and hyperarousal.³ Nightmares are part of the intrusive/re-experiencing cluster, which is Criterion B in DSM-IV-TR. See Table 1 for a description of DSM-IV-TR PTSD criteria. Among PTSD patients, 50% to 70% report PTSD-associated nightmares.⁴ Despite adequate treatment targeted to improve PTSD’s core symptoms, symptoms such as sleep disturbances or nightmares often persist.

Table 1

DSM-IV-TR diagnostic criteria for posttraumatic stress disorder

Nightmares and other sleep disturbances are associated with significant distress and daytime impairment and can interfere with PTSD recovery^4-8 by disrupting sleep-dependent processing of emotional experiences and causing repeated resensitization to trauma cues (Table 2).⁸

Table 2

Psychosocial consequences of sleep disruption in PTSD

Few randomized controlled medication trials specifically address PTSD-related nightmares. Most PTSD studies do not examine sleep outcomes as a primary measure, and comprehensive literature reviews could not offer evidence-based recommendations.^9,10 The American Academy of Sleep Medicine (AASM) also noted a paucity of PTSD studies that identified nightmares as a primary outcome measure.¹¹ See Table 3 for a list of recommended medication options for PTSD-associated nightmares.

Table 3

Recommended medication treatments for PTSD-associated nightmares

CASE CONTINUED: Medication change, improvement

After reviewing AASM’s treatment recommendations, we prescribe prazosin, 1 mg at bedtime for 7 nights, then increase by 1 mg at bedtime each week until Mr. S’s nightmares improve. He reports a substantial improvement in nightmare severity and frequency after a few weeks of treatment with prazosin, 5 mg at bedtime.

Prazosin

Prazosin is an α1-adrenergic receptor antagonist with good CNS penetrability. The rationale for reducing adrenergic activity to address intrusive PTSD symptoms has been well documented.^12,13 In open-label trials,^14-18 a chart review,¹⁹ and placebo-controlled trials,^20-22prazosin reduced trauma nightmares and improved sleep quality and global clinical status more than placebo (Table 4). In these studies, prazosin doses ranged from 1 to 20 mg/d, with an average of 3 mg at bedtime and a starting dose of 1 mg. Prazosin is the only agent recommended in the AASM’s Best Practice Guide for treating PTSD-related nightmares.¹¹

Table 4

RCTs of prazosin for trauma-related nightmares

Atypical antipsychotics

Atypical antipsychotics have been used to reduce nightmares in PTSD; however, most of the evidence from studies evaluated in the AASM’s Best Practice Guide were considered to be low quality.¹¹ Quetiapine and ziprasidone were not included in the AASM review. See (Table 5) for a review of the evidence for atypical antipsychotics for treating PTSD nightmares.

Table 5

Combat-related nightmares: Evidence for atypical antipsychotics