Current Psychiatry

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

Comparing prazosin and quetiapine. A historical prospective cohort study of 237 veterans with PTSD receiving prazosin or quetiapine for nighttime PTSD symptoms demonstrated that although the 2 drugs have similar efficacy (defined as symptomatic improvement) for short-term, 6-month treatment (61% vs 62%; P=.54), a higher percentage of patients continued prazosin long-term (3 to 6 years) than those taking quetiapine (48% vs 24%; P < .001).²³ Twenty-five percent of patients taking quetiapine switched to prazosin during the study, and approximately one-half of these patients remained on prazosin until the study’s end. Only 8% of prazosin patients switched to quetiapine, and none continued this therapy until study end.²³ Patients in the quetiapine group were more likely to discontinue the drug because of lack of efficacy (13% vs 3%; P=.03) and adverse effects (35% vs 18%; P=.008), specifically sedation (21% vs 2%; P < .001) and metabolic effects (9% vs 0%; P=.014), compared with prazosin. Although this trial may be the only published comparison study of prazosin and quetiapine, its methodological quality has been questioned, which makes it difficult to draw definitive conclusions.

Metabolic syndrome—elevated diastolic blood pressure, increased waist circumference, and low high-density lipoprotein cholesterol—is common among PTSD patients treated with antipsychotics.²⁴ This syndrome may be caused by medications, lifestyle factors, or long-term overactivation of stress-response pathways. A retrospective chart review at a community mental health center revealed that patients taking even low doses of quetiapine for insomnia gained an average of 5 lbs (P=.037).²⁵ Another retrospective chart review at 2 military hospitals reported that patients receiving low-dose quetiapine (≤100 mg/d) gained an average of slightly less than 1 lb per month, which adds up to approximately 10 lbs per year (P < .001).²⁶ The benefit of using atypical antipsychotics may be outweighed by metabolic risks such as obesity, new-onset diabetes, and dyslipidemia.²⁷

Prazosin is considered a first-line treatment for sleep disturbances and nightmares in PTSD because of its superior long-term efficacy and decreased adverse effects compared with quetiapine.

Related Resources

• American Psychiatric Association. Practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Arlington, VA: American Psychiatric Publishing, Inc.; 2004.
• Veterans Affairs/Department of Defense clinical practice guidelines. Management of traumatic stress disorder and acute stress reaction. www.healthquality.va.gov/Post_Traumatic_Stress_Disorder_PTSD.asp.

Drug Brand Names

• Prazosin • Minipress
• Quetiapine • Seroquel
• Sertraline • Zoloft
• Ziprasidone • Geodon

Disclosure

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

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

Comparing prazosin and quetiapine. A historical prospective cohort study of 237 veterans with PTSD receiving prazosin or quetiapine for nighttime PTSD symptoms demonstrated that although the 2 drugs have similar efficacy (defined as symptomatic improvement) for short-term, 6-month treatment (61% vs 62%; P=.54), a higher percentage of patients continued prazosin long-term (3 to 6 years) than those taking quetiapine (48% vs 24%; P < .001).²³ Twenty-five percent of patients taking quetiapine switched to prazosin during the study, and approximately one-half of these patients remained on prazosin until the study’s end. Only 8% of prazosin patients switched to quetiapine, and none continued this therapy until study end.²³ Patients in the quetiapine group were more likely to discontinue the drug because of lack of efficacy (13% vs 3%; P=.03) and adverse effects (35% vs 18%; P=.008), specifically sedation (21% vs 2%; P < .001) and metabolic effects (9% vs 0%; P=.014), compared with prazosin. Although this trial may be the only published comparison study of prazosin and quetiapine, its methodological quality has been questioned, which makes it difficult to draw definitive conclusions.

Metabolic syndrome—elevated diastolic blood pressure, increased waist circumference, and low high-density lipoprotein cholesterol—is common among PTSD patients treated with antipsychotics.²⁴ This syndrome may be caused by medications, lifestyle factors, or long-term overactivation of stress-response pathways. A retrospective chart review at a community mental health center revealed that patients taking even low doses of quetiapine for insomnia gained an average of 5 lbs (P=.037).²⁵ Another retrospective chart review at 2 military hospitals reported that patients receiving low-dose quetiapine (≤100 mg/d) gained an average of slightly less than 1 lb per month, which adds up to approximately 10 lbs per year (P < .001).²⁶ The benefit of using atypical antipsychotics may be outweighed by metabolic risks such as obesity, new-onset diabetes, and dyslipidemia.²⁷

Prazosin is considered a first-line treatment for sleep disturbances and nightmares in PTSD because of its superior long-term efficacy and decreased adverse effects compared with quetiapine.

Related Resources

• American Psychiatric Association. Practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Arlington, VA: American Psychiatric Publishing, Inc.; 2004.
• Veterans Affairs/Department of Defense clinical practice guidelines. Management of traumatic stress disorder and acute stress reaction. www.healthquality.va.gov/Post_Traumatic_Stress_Disorder_PTSD.asp.

Drug Brand Names

• Prazosin • Minipress
• Quetiapine • Seroquel
• Sertraline • Zoloft
• Ziprasidone • Geodon

Disclosure

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

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

Comparing prazosin and quetiapine. A historical prospective cohort study of 237 veterans with PTSD receiving prazosin or quetiapine for nighttime PTSD symptoms demonstrated that although the 2 drugs have similar efficacy (defined as symptomatic improvement) for short-term, 6-month treatment (61% vs 62%; P=.54), a higher percentage of patients continued prazosin long-term (3 to 6 years) than those taking quetiapine (48% vs 24%; P < .001).²³ Twenty-five percent of patients taking quetiapine switched to prazosin during the study, and approximately one-half of these patients remained on prazosin until the study’s end. Only 8% of prazosin patients switched to quetiapine, and none continued this therapy until study end.²³ Patients in the quetiapine group were more likely to discontinue the drug because of lack of efficacy (13% vs 3%; P=.03) and adverse effects (35% vs 18%; P=.008), specifically sedation (21% vs 2%; P < .001) and metabolic effects (9% vs 0%; P=.014), compared with prazosin. Although this trial may be the only published comparison study of prazosin and quetiapine, its methodological quality has been questioned, which makes it difficult to draw definitive conclusions.

Metabolic syndrome—elevated diastolic blood pressure, increased waist circumference, and low high-density lipoprotein cholesterol—is common among PTSD patients treated with antipsychotics.²⁴ This syndrome may be caused by medications, lifestyle factors, or long-term overactivation of stress-response pathways. A retrospective chart review at a community mental health center revealed that patients taking even low doses of quetiapine for insomnia gained an average of 5 lbs (P=.037).²⁵ Another retrospective chart review at 2 military hospitals reported that patients receiving low-dose quetiapine (≤100 mg/d) gained an average of slightly less than 1 lb per month, which adds up to approximately 10 lbs per year (P < .001).²⁶ The benefit of using atypical antipsychotics may be outweighed by metabolic risks such as obesity, new-onset diabetes, and dyslipidemia.²⁷

Prazosin is considered a first-line treatment for sleep disturbances and nightmares in PTSD because of its superior long-term efficacy and decreased adverse effects compared with quetiapine.

Related Resources

• American Psychiatric Association. Practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Arlington, VA: American Psychiatric Publishing, Inc.; 2004.
• Veterans Affairs/Department of Defense clinical practice guidelines. Management of traumatic stress disorder and acute stress reaction. www.healthquality.va.gov/Post_Traumatic_Stress_Disorder_PTSD.asp.

Drug Brand Names

• Prazosin • Minipress
• Quetiapine • Seroquel
• Sertraline • Zoloft
• Ziprasidone • Geodon

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

Dear Dr. Mossman:
Could providing a “curbside” consultation to a colleague leave me medico legally vulnerable if an adverse event leads to a malpractice lawsuit? If so, what can I do to address this risk?—Submitted by “Dr. W”

Medicine is a collaborative profession. Surgeons often combine skills to perform complex operations together, and specialists pool their expertise when they collectively manage patients with several medical problems. Doctors share their knowledge when they give lectures to medical audiences, write reports to referring physicians, or respond verbally to colleagues’ requests for information or advice.¹

Doctors use the phrase “curbside consult” to refer (with humor and self-deprecation) to informal conversations with colleagues about patients’ medical management—advice-seeking that falls short of asking a colleague to make recommendations based on a formal, personal examination. Many physicians seek or provide curbside advice several times a month.² Curbside consults transmit knowledge and cement professional bonds among physicians, making them “an integral part of our medical culture.”³

More than a dozen legal decisions mention curbside consultations. Judges think informal information-sharing improves medical practice and don’t want doctors to stop soliciting ideas or offering suggestions because they fear lawsuits.^4,5 However, courts have found that, under certain conditions, giving advice can create liability for a bad outcome, even though the doctor never met the patient who was harmed.

In this article, we’ll look at:

• when such liability might occur, and
• what you can do to minimize it.

A doctor-patient relationship?

Legally, doctors are obligated to provide competent care for just 1 group of people: their patients. Therefore, to decide if plaintiffs could pursue malpractice claims in cases where doctors offered comments about patients they did not personally examine, courts have asked whether the circumstances, actions undertaken, or nature of information that was exchanged created a professional relationship.

Reynolds v Decatur Memorial Hospital⁴ describes an informal consultation that did not create a physician-patient relationship. In this case, a boy was admitted to a hospital after he had fallen. The treating pediatrician telephoned a neurosurgeon, who asked whether the boy’s neck was stiff, discussed diagnostic possibilities with the pediatrician, and suggested doing a lumbar puncture. The neurosurgeon offered to see the boy if requested, but he never did, and he did not bill for the telephone consultation. Guillain-Barré syndrome was first suspected, but a spinal cord injury was discovered after the boy—who developed quadriplegia—was transferred to another hospital.

In a subsequent lawsuit, the boy’s mother claimed her son’s paralysis resulted from negligence by the first hospital and its doctors, but the trial court dismissed the case against the neurosurgeon. Affirming the trial court’s ruling, an Illinois appeals court explained that the neurosurgeon had not been asked to provide medical services, conduct tests, or interpret test results. “A doctor who gives an informal opinion at the request of a treating physician does not owe a duty of care to the patient whose case was discussed,” the Reynolds court said.

Campbell v Haber⁶ describes circumstances that differed slightly from those described in the Reynolds decision but appeared to create a doctor-patient relationship. Campbell concerned a patient who came to an emergency room (ER) complaining of chest pain. The ER physician’s findings indicated possible heart muscle damage, so he telephoned a cardiologist (whom the ER doctor believed was “on call”) and described the patient’s symptoms and test results. The cardiologist thought the test results were not consistent with a cardiac event. The ER physician told the patient and his wife about the cardiologist’s opinion and, relying on what the cardiologist said, discharged the patient. Shortly after, the patient had a heart attack.

The patient sued not just the ER physician, but the cardiologist, who sought dismissal from the suit because he never saw the patient, had no treatment relationship with him, and never billed for services. However, the trial judge ruled that the patient could sue the cardiologist and the appellate court agreed, saying that a jury had to decide whether the cardiologist had incurred a doctor-patient relationship and might be liable. “An implied physician-patient relationship may arise when a physician gives advice to a patient,” the appeals court said, “even if that advice is communicated through another health care professional.”

Telling the difference

So what differentiates a no-liability curbside consult from a medical discussion that creates a doctor-patient duty and potential for liability for adverse results?

You create a physician-patient relationship when you assume responsibility to diagnose or treat someone.⁷ Although typically this requires an in-person encounter with a patient, it can happen indirectly—electronically (through e-mail), by telephone, or through a family member or another professional. But if you do nothing that implies consent to act for the patient’s benefit, you should have no actual malpractice liability if something goes wrong.^3,8 As a Kansas Supreme Court decision explains, you “cannot be liable for medical malpractice” if you “merely consult with a treating physician and [do] nothing more.”⁵

Several legal cases discuss doctors’ efforts to extricate themselves from lawsuits arising from clinical encounters that the doctors mistakenly thought were just curbside consults. Table 1^8-12 lists situations in which talking about patients goes beyond just being “curbsided.”

Table 1

When it’s not a ‘curbside consultation’

How to respond

Should you decline to provide curbside consultations to keep yourself out of lawsuits? Some authors think so, pointing out that informally transmitted clinical data may be faulty, which means you may give bad advice based on incomplete information or a verbal misunderstanding.^13-16 These authors suggest that if you’re curbsided you should ask to see the patient for a formal consultation, decline to give informal advice, or provide a response that lacks specifics.

Other authors feel that these approaches are needlessly cautious and would harm patients by impeding doctors’ ability to help and learn from each other.^3,17 These authors think the risk of incurring liability from a curbside consult is low. Also, getting advice from a colleague is a valuable risk management strategy; it helps you make sure you’re on the right track, and it shows you are a thoughtful clinician whose patients benefit from your own and your colleagues’ medical expertise.

Even if you’re comfortable soliciting and providing curbside advice, sometimes circumstances make it wise to follow-up an informal initial inquiry with a formal consultation. Table 2^3,17 lists examples of when you should follow-up with a formal consultation.

Table 2

Considerations that favor formal consultation

Documentation

Experts disagree about whether the requesting or receiving physician should document a curbside consultation, and if so, how. On one hand, making a notation in a patient’s record documents the treating doctor’s diligence and may provide a measure of liability protection in a malpractice action. Doing this, however, exposes the identity of the consultant, who might be named among the defendants in a lawsuit.

One commonly recommended strategy is to request the consultant’s permission before identifying him or her in the record,^13,16,17 a position that is defensible on grounds of courtesy alone. But omitting a consultant’s name from record does not guarantee that the consultant’s involvement won’t be discovered in the course of litigation.³ For example, treating doctors who get sued often are asked during their depositions about whether they talked with anyone about the case, and they have to answer honestly.

If a consulted doctor makes written notes, it might suggest that the consultation was more than the sort of informal information-sharing implied by the term “curbside.” However, in the unlikely event that a lawsuit arose and included the consultant as a defendant, documentation of advice given would help the consultant recall and defend what was said.

Related Resources

• Grant-Kels JM, Kels BD. The curbside consultation: legal, moral, and ethical considerations. J Am Acad Dermatol. 2012;66(5):827-829.
• Kreichelt R, Hilbert ML, Shinn D. Minimizing the legal risk with ‘curbside’ consultation. J Healthc Risk Manag. 2008;28(1):27-29.
• Atkinson L. Curbside consults: what is your liability risk? Iowa Med. 2003;93(4):15.

Disclosure

Dr. Mossman reports 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

Dear Dr. Mossman:
Could providing a “curbside” consultation to a colleague leave me medico legally vulnerable if an adverse event leads to a malpractice lawsuit? If so, what can I do to address this risk?—Submitted by “Dr. W”

Medicine is a collaborative profession. Surgeons often combine skills to perform complex operations together, and specialists pool their expertise when they collectively manage patients with several medical problems. Doctors share their knowledge when they give lectures to medical audiences, write reports to referring physicians, or respond verbally to colleagues’ requests for information or advice.¹

Doctors use the phrase “curbside consult” to refer (with humor and self-deprecation) to informal conversations with colleagues about patients’ medical management—advice-seeking that falls short of asking a colleague to make recommendations based on a formal, personal examination. Many physicians seek or provide curbside advice several times a month.² Curbside consults transmit knowledge and cement professional bonds among physicians, making them “an integral part of our medical culture.”³

More than a dozen legal decisions mention curbside consultations. Judges think informal information-sharing improves medical practice and don’t want doctors to stop soliciting ideas or offering suggestions because they fear lawsuits.^4,5 However, courts have found that, under certain conditions, giving advice can create liability for a bad outcome, even though the doctor never met the patient who was harmed.

In this article, we’ll look at:

• when such liability might occur, and
• what you can do to minimize it.

A doctor-patient relationship?

Legally, doctors are obligated to provide competent care for just 1 group of people: their patients. Therefore, to decide if plaintiffs could pursue malpractice claims in cases where doctors offered comments about patients they did not personally examine, courts have asked whether the circumstances, actions undertaken, or nature of information that was exchanged created a professional relationship.

Reynolds v Decatur Memorial Hospital⁴ describes an informal consultation that did not create a physician-patient relationship. In this case, a boy was admitted to a hospital after he had fallen. The treating pediatrician telephoned a neurosurgeon, who asked whether the boy’s neck was stiff, discussed diagnostic possibilities with the pediatrician, and suggested doing a lumbar puncture. The neurosurgeon offered to see the boy if requested, but he never did, and he did not bill for the telephone consultation. Guillain-Barré syndrome was first suspected, but a spinal cord injury was discovered after the boy—who developed quadriplegia—was transferred to another hospital.

In a subsequent lawsuit, the boy’s mother claimed her son’s paralysis resulted from negligence by the first hospital and its doctors, but the trial court dismissed the case against the neurosurgeon. Affirming the trial court’s ruling, an Illinois appeals court explained that the neurosurgeon had not been asked to provide medical services, conduct tests, or interpret test results. “A doctor who gives an informal opinion at the request of a treating physician does not owe a duty of care to the patient whose case was discussed,” the Reynolds court said.

Campbell v Haber⁶ describes circumstances that differed slightly from those described in the Reynolds decision but appeared to create a doctor-patient relationship. Campbell concerned a patient who came to an emergency room (ER) complaining of chest pain. The ER physician’s findings indicated possible heart muscle damage, so he telephoned a cardiologist (whom the ER doctor believed was “on call”) and described the patient’s symptoms and test results. The cardiologist thought the test results were not consistent with a cardiac event. The ER physician told the patient and his wife about the cardiologist’s opinion and, relying on what the cardiologist said, discharged the patient. Shortly after, the patient had a heart attack.

The patient sued not just the ER physician, but the cardiologist, who sought dismissal from the suit because he never saw the patient, had no treatment relationship with him, and never billed for services. However, the trial judge ruled that the patient could sue the cardiologist and the appellate court agreed, saying that a jury had to decide whether the cardiologist had incurred a doctor-patient relationship and might be liable. “An implied physician-patient relationship may arise when a physician gives advice to a patient,” the appeals court said, “even if that advice is communicated through another health care professional.”

Telling the difference

So what differentiates a no-liability curbside consult from a medical discussion that creates a doctor-patient duty and potential for liability for adverse results?

You create a physician-patient relationship when you assume responsibility to diagnose or treat someone.⁷ Although typically this requires an in-person encounter with a patient, it can happen indirectly—electronically (through e-mail), by telephone, or through a family member or another professional. But if you do nothing that implies consent to act for the patient’s benefit, you should have no actual malpractice liability if something goes wrong.^3,8 As a Kansas Supreme Court decision explains, you “cannot be liable for medical malpractice” if you “merely consult with a treating physician and [do] nothing more.”⁵

Several legal cases discuss doctors’ efforts to extricate themselves from lawsuits arising from clinical encounters that the doctors mistakenly thought were just curbside consults. Table 1^8-12 lists situations in which talking about patients goes beyond just being “curbsided.”

Table 1

When it’s not a ‘curbside consultation’

How to respond

Should you decline to provide curbside consultations to keep yourself out of lawsuits? Some authors think so, pointing out that informally transmitted clinical data may be faulty, which means you may give bad advice based on incomplete information or a verbal misunderstanding.^13-16 These authors suggest that if you’re curbsided you should ask to see the patient for a formal consultation, decline to give informal advice, or provide a response that lacks specifics.

Other authors feel that these approaches are needlessly cautious and would harm patients by impeding doctors’ ability to help and learn from each other.^3,17 These authors think the risk of incurring liability from a curbside consult is low. Also, getting advice from a colleague is a valuable risk management strategy; it helps you make sure you’re on the right track, and it shows you are a thoughtful clinician whose patients benefit from your own and your colleagues’ medical expertise.

Even if you’re comfortable soliciting and providing curbside advice, sometimes circumstances make it wise to follow-up an informal initial inquiry with a formal consultation. Table 2^3,17 lists examples of when you should follow-up with a formal consultation.

Table 2

Considerations that favor formal consultation

Documentation

Experts disagree about whether the requesting or receiving physician should document a curbside consultation, and if so, how. On one hand, making a notation in a patient’s record documents the treating doctor’s diligence and may provide a measure of liability protection in a malpractice action. Doing this, however, exposes the identity of the consultant, who might be named among the defendants in a lawsuit.

One commonly recommended strategy is to request the consultant’s permission before identifying him or her in the record,^13,16,17 a position that is defensible on grounds of courtesy alone. But omitting a consultant’s name from record does not guarantee that the consultant’s involvement won’t be discovered in the course of litigation.³ For example, treating doctors who get sued often are asked during their depositions about whether they talked with anyone about the case, and they have to answer honestly.

If a consulted doctor makes written notes, it might suggest that the consultation was more than the sort of informal information-sharing implied by the term “curbside.” However, in the unlikely event that a lawsuit arose and included the consultant as a defendant, documentation of advice given would help the consultant recall and defend what was said.

Related Resources

• Grant-Kels JM, Kels BD. The curbside consultation: legal, moral, and ethical considerations. J Am Acad Dermatol. 2012;66(5):827-829.
• Kreichelt R, Hilbert ML, Shinn D. Minimizing the legal risk with ‘curbside’ consultation. J Healthc Risk Manag. 2008;28(1):27-29.
• Atkinson L. Curbside consults: what is your liability risk? Iowa Med. 2003;93(4):15.

Disclosure

Dr. Mossman reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

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Dear Dr. Mossman:
Could providing a “curbside” consultation to a colleague leave me medico legally vulnerable if an adverse event leads to a malpractice lawsuit? If so, what can I do to address this risk?—Submitted by “Dr. W”

Medicine is a collaborative profession. Surgeons often combine skills to perform complex operations together, and specialists pool their expertise when they collectively manage patients with several medical problems. Doctors share their knowledge when they give lectures to medical audiences, write reports to referring physicians, or respond verbally to colleagues’ requests for information or advice.¹

Doctors use the phrase “curbside consult” to refer (with humor and self-deprecation) to informal conversations with colleagues about patients’ medical management—advice-seeking that falls short of asking a colleague to make recommendations based on a formal, personal examination. Many physicians seek or provide curbside advice several times a month.² Curbside consults transmit knowledge and cement professional bonds among physicians, making them “an integral part of our medical culture.”³

More than a dozen legal decisions mention curbside consultations. Judges think informal information-sharing improves medical practice and don’t want doctors to stop soliciting ideas or offering suggestions because they fear lawsuits.^4,5 However, courts have found that, under certain conditions, giving advice can create liability for a bad outcome, even though the doctor never met the patient who was harmed.

In this article, we’ll look at:

• when such liability might occur, and
• what you can do to minimize it.

A doctor-patient relationship?

Legally, doctors are obligated to provide competent care for just 1 group of people: their patients. Therefore, to decide if plaintiffs could pursue malpractice claims in cases where doctors offered comments about patients they did not personally examine, courts have asked whether the circumstances, actions undertaken, or nature of information that was exchanged created a professional relationship.

Reynolds v Decatur Memorial Hospital⁴ describes an informal consultation that did not create a physician-patient relationship. In this case, a boy was admitted to a hospital after he had fallen. The treating pediatrician telephoned a neurosurgeon, who asked whether the boy’s neck was stiff, discussed diagnostic possibilities with the pediatrician, and suggested doing a lumbar puncture. The neurosurgeon offered to see the boy if requested, but he never did, and he did not bill for the telephone consultation. Guillain-Barré syndrome was first suspected, but a spinal cord injury was discovered after the boy—who developed quadriplegia—was transferred to another hospital.

In a subsequent lawsuit, the boy’s mother claimed her son’s paralysis resulted from negligence by the first hospital and its doctors, but the trial court dismissed the case against the neurosurgeon. Affirming the trial court’s ruling, an Illinois appeals court explained that the neurosurgeon had not been asked to provide medical services, conduct tests, or interpret test results. “A doctor who gives an informal opinion at the request of a treating physician does not owe a duty of care to the patient whose case was discussed,” the Reynolds court said.

Campbell v Haber⁶ describes circumstances that differed slightly from those described in the Reynolds decision but appeared to create a doctor-patient relationship. Campbell concerned a patient who came to an emergency room (ER) complaining of chest pain. The ER physician’s findings indicated possible heart muscle damage, so he telephoned a cardiologist (whom the ER doctor believed was “on call”) and described the patient’s symptoms and test results. The cardiologist thought the test results were not consistent with a cardiac event. The ER physician told the patient and his wife about the cardiologist’s opinion and, relying on what the cardiologist said, discharged the patient. Shortly after, the patient had a heart attack.

The patient sued not just the ER physician, but the cardiologist, who sought dismissal from the suit because he never saw the patient, had no treatment relationship with him, and never billed for services. However, the trial judge ruled that the patient could sue the cardiologist and the appellate court agreed, saying that a jury had to decide whether the cardiologist had incurred a doctor-patient relationship and might be liable. “An implied physician-patient relationship may arise when a physician gives advice to a patient,” the appeals court said, “even if that advice is communicated through another health care professional.”

Telling the difference

So what differentiates a no-liability curbside consult from a medical discussion that creates a doctor-patient duty and potential for liability for adverse results?

You create a physician-patient relationship when you assume responsibility to diagnose or treat someone.⁷ Although typically this requires an in-person encounter with a patient, it can happen indirectly—electronically (through e-mail), by telephone, or through a family member or another professional. But if you do nothing that implies consent to act for the patient’s benefit, you should have no actual malpractice liability if something goes wrong.^3,8 As a Kansas Supreme Court decision explains, you “cannot be liable for medical malpractice” if you “merely consult with a treating physician and [do] nothing more.”⁵

Several legal cases discuss doctors’ efforts to extricate themselves from lawsuits arising from clinical encounters that the doctors mistakenly thought were just curbside consults. Table 1^8-12 lists situations in which talking about patients goes beyond just being “curbsided.”

Table 1

When it’s not a ‘curbside consultation’

How to respond

Should you decline to provide curbside consultations to keep yourself out of lawsuits? Some authors think so, pointing out that informally transmitted clinical data may be faulty, which means you may give bad advice based on incomplete information or a verbal misunderstanding.^13-16 These authors suggest that if you’re curbsided you should ask to see the patient for a formal consultation, decline to give informal advice, or provide a response that lacks specifics.

Other authors feel that these approaches are needlessly cautious and would harm patients by impeding doctors’ ability to help and learn from each other.^3,17 These authors think the risk of incurring liability from a curbside consult is low. Also, getting advice from a colleague is a valuable risk management strategy; it helps you make sure you’re on the right track, and it shows you are a thoughtful clinician whose patients benefit from your own and your colleagues’ medical expertise.

Even if you’re comfortable soliciting and providing curbside advice, sometimes circumstances make it wise to follow-up an informal initial inquiry with a formal consultation. Table 2^3,17 lists examples of when you should follow-up with a formal consultation.

Table 2

Considerations that favor formal consultation

Documentation

Experts disagree about whether the requesting or receiving physician should document a curbside consultation, and if so, how. On one hand, making a notation in a patient’s record documents the treating doctor’s diligence and may provide a measure of liability protection in a malpractice action. Doing this, however, exposes the identity of the consultant, who might be named among the defendants in a lawsuit.

One commonly recommended strategy is to request the consultant’s permission before identifying him or her in the record,^13,16,17 a position that is defensible on grounds of courtesy alone. But omitting a consultant’s name from record does not guarantee that the consultant’s involvement won’t be discovered in the course of litigation.³ For example, treating doctors who get sued often are asked during their depositions about whether they talked with anyone about the case, and they have to answer honestly.

If a consulted doctor makes written notes, it might suggest that the consultation was more than the sort of informal information-sharing implied by the term “curbside.” However, in the unlikely event that a lawsuit arose and included the consultant as a defendant, documentation of advice given would help the consultant recall and defend what was said.

Related Resources

• Grant-Kels JM, Kels BD. The curbside consultation: legal, moral, and ethical considerations. J Am Acad Dermatol. 2012;66(5):827-829.
• Kreichelt R, Hilbert ML, Shinn D. Minimizing the legal risk with ‘curbside’ consultation. J Healthc Risk Manag. 2008;28(1):27-29.
• Atkinson L. Curbside consults: what is your liability risk? Iowa Med. 2003;93(4):15.

Disclosure

Dr. Mossman reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.