Mrs. X, age 43, gravida 4 para 1, is a married woman of sub-Saharan African heritage with a history of idiopathic hypertension, uterine leiomyomas, and multiple spontaneous miscarriages. She has no psychiatric history and had never been evaluated by a mental health professional. Mrs. X is well known to the hospital’s emergency room and obstetrics and gynecology services for several presentations claiming to be pregnant, continuously, over the last 11 months, despite evidence—several negative serum beta human chorionic gonadotropin (ß-hCG) tests and transvaginal sonograms—to the contrary.

Mrs. X reports that after feeling ill for “a few days,” she began to believe that she was “losing [her] mucous plug” and needed urgent evaluation in preparation for the delivery of her “child.” She again is given a ß-hCG test, which is negative, as well as a negative transvaginal sonogram.

Mrs. X’s blood pressure is 220/113 mm Hg, and she emergently receives captopril, 25 mg sublingually, which lowers her systolic blood pressure to 194 mm Hg. The internal medicine team learns that Mrs. X stopped taking her blood pressure medications, lisinopril and hydrochlorothiazide, approximately 2 weeks earlier because she “didn’t want it [the antihypertensive agents] to hurt [her] baby.”

What explains Mrs. X’s belief that she is pregnant?

a) polycystic ovary syndrome (PCOS)
b) delusional disorder
c) bipolar I disorder
d) somatic symptom disorder

The authors’ observations

Pseudocyesis is a psychosomatic condition with an estimated incidence of 1 in 160 maternity admissions in many African countries and 1 in 22,000 in the United States.¹ According to DSM-5, pseudocyesis is a false belief of being pregnant along with signs and symptoms of pregnancy.²

Pseudocyesis is more common in:

• developing countries
• areas of low socioeconomic status with minimal education
• societies that place great importance on childbirth
• areas with low access to care.³

The primary presenting symptoms are changes in menses, enlarging abdomen, awareness of fetal movement, enlarged and tender breasts, galactorrhea, and weight gain.⁴

The exact pathophysiology of the disorder has not been determined, but we believe the psychosomatic hypothesis offers the most compelling explanation. According to this hypothesis, intense social pressures, such as an overwhelming desire to become pregnant because of cultural considerations, personal reasons, or both, could alter the normal function of the hypothalamic-pituitary-ovarian axis,⁵ which could result in physical manifestations of pregnancy. Tarín et al¹ found that rodents with chronic psychosocial stress had decreased brain norepinephrine and dopamine activity and elevated plasma levels of norepinephrine. This can translate to human models, in which a deficit or dysfunction of catecholaminergic activity in the brain could lead to increased pulsatile gonadotropin-releasing hormone, luteinizing hormone (LH), prolactin, and an elevated LH:follicle-stimulating hormone ratio.¹ These endocrine changes could induce traits found in most women with pseudocyesis, such as hypomenorrhea or amenorrhea, diurnal or nocturnal hyperprolactinemia (or both), and galactorrhea.¹

How would you approach Mrs. X’s care?

a) confront her with the negative pregnancy tests
b) admit her to the inpatient psychiatric unit
c) begin antipsychotic therapy
d) discharge her with outpatient follow-up

EVALUATION A curse on her

Although Mrs. X initially refused to see the psychiatry team, she is more receptive on hospital Day 3. Mrs. X reports that she and her husband had been trying to have a child since they were married 17 years earlier. She had a child with another man before she met her husband, causing her in-laws in Africa to become suspicious that she is intentionally not producing a child for her husband. She had 3 spontaneous abortions since her marriage; these added stress to the relationship because the couple would feel elated when learning of a pregnancy and increasingly devastated with each miscarriage.

Mrs. X reports that she and her husband have been seeing a number of reproductive endocrinologists for 7 years to try to become pregnant. She reports feeling that these physicians are not listening to her or giving her adequate treatment, which is why she has not been able to become pregnant. At the time of the evaluation, she reports that she is pregnant, and the tests have been negative because her mother-in-law placed a “curse” on her. This “curse” caused the baby to be invisible to the laboratory tests and sonograms.

During the psychiatric evaluation, Mrs. X displays her protuberant abdomen and says that she feels the fetus kicking. In addition, she also reports amenorrhea and breast tenderness and engorgement.

During her hospital stay, Mrs. X’s mental status exam does not demonstrate signs or symptoms of a mood disorder, bipolar disorder, or psychosis. Nonetheless, she remains delusional and holds to her fixed false belief of being pregnant. She refuses to be swayed by evidence that she is not pregnant. Despite this, clinicians build enough rapport that Mrs. X agrees to follow up with psychiatry in the outpatient clinic after discharge.

The internal medicine team is apprehensive that Mrs. X will continue to refuse anti­hypertensive medications out of concern that the medications would harm her pregnancy, as she had in the hospital. She remains hypertensive, with average systolic blood pressure in the 180 to 200 mm Hg range; however, after much discussion with her and her family members, she agrees to try amlodipine, 5 mg/d, a category C drug. She says that she will adhere to the medication if she does not experience any side effects.

Mrs. X is discharged on hospital Day 4 to outpatient follow-up.

 

The authors’ observations

When considering a diagnosis of pseudocyesis, the condition should be distinguished from others with similar presentations. Before beginning a psychiatric evaluation, a normal pregnancy must be ruled out. This is easily done with a positive urine or serum ß-hCG and an abdominal or transvaginal ultrasound. Pseudocyesis can be differentiated from:

• delusion of pregnancy (sometimes referred to as psychotic pregnancy)—a delusional disorder often seen in psychotic illness without any physical manifestations of pregnancy
• pseudopregnancy (sometimes referred to as erroneous pseudocyesis), another rare condition in which signs and symptoms of pregnancy are manifested^1,6,7 but the patient does not have a delusion of pregnancy.

Pseudocyesis, in contrast, comprises the delusion of pregnancy and physical manifestations.² These distinctions could be difficult to make clinically; for example, an increase in abdominal girth could be a result of pseudocyesis or obesity. In the setting of physical manifestations of pregnancy, a diagnosis of pseudocyesis is more likely  (Table¹).

Patients with pseudocyesis exhibit subjective and objective findings of pregnancy, such as abdominal distension, enlarged breasts, enhanced pigmentation, lordotic posture, cessation of menses, morning sickness, and weight gain.^8,9 Furthermore, approximately 1% of pseudocyesis patients have false labor, as Mrs. X did.¹⁰ Typically, the duration of these symptoms range from a few weeks to 9 months. In some cases, symptoms can last longer¹¹; at admission, Mrs. X reported that she was 11 months pregnant. She saw nothing wrong with this assertion, despite knowing that human gestation lasts 9 months.

In delusion of pregnancy, a patient might exhibit abdominal distension and cessation of menses but have no other objective findings of pregnancy.⁷ Rather than being a somatoform disorder such as pseudocyesis, a delusion of pregnancy is a symptom of psychosis or, rarely, dementia.¹²

Pseudopregnancy is a somatic state resembling pregnancy that can arise from a variety of medical conditions. A full medical workup and intensive mental status and cognitive evaluation are necessary for diagnostic clarity. Although the pathology and workup of delusional pregnancy is beyond the scope of this article, we suggest Seeman¹³ for a review and Chatterjee et al¹⁴ and Tarín et al¹ for guidance on making the diagnosis.

Theories about pathophysiology

As with many psychosomatic conditions, the pathological process of pseudocyesis originally was thought of in a psychodynamic context. Several psychodynamic theories have been proposed, including instances in which the internal desire to be pregnant is strong enough to induce a series of physiological changes akin to the state of pregnancy.⁶

Other examiners of pseudocyesis have noted its development from fears and societal pressure, including the loss of companionship or “womanhood.”^6,9 Last, the tenuous interplay of desire for a child and substantial fear of pregnancy appears to play a role in many cases.^9-11 Rosenberg et al¹⁵ reported on a teenager with pseudocyesis who desired to be pregnant to appease her husband and family, but feared pregnancy and the implications of having a child at such a young age. As this team wrote, “this pregnancy sans child fulfilled the needs of the entire family, at least temporarily.”¹⁵

Prevailing modern theories behind the somatic presentations of these patients hinge on an imbalance of the hypothalamic-pituitary-adrenal axis.⁹ Although this remains the area of ongoing research, most literature has not shown a consistent change or trend in laboratory levels of hormones associated with pseudocyesis.¹⁶ Tarín et al,¹ however, did show a similar hormonal profile between patients with pseudocyesis and those with PCOS. Although urine or serum pregnancy testing and ultrasonography are indicated to rule out pseudopregnancy, we see no benefit in obtaining other lab work in most cases beyond that of a general medical workup, because such evaluations are not helpful in diagnosis or treatment.

Mrs. X’s abdomen was protuberant and she displayed the typical linea nigra of pregnancy. Many authors have theorized the physiological mechanism behind the abdominal enlargement to include contraction of the diaphragm, which reduces the abdominal cavity and forces the bowel outwards. As abdominal fat increases, the patient becomes constipated, and the bowel becomes distended.^10,16 Although the cause of our patient’s abdominal enlargement was not pursued, we note that the literature reported that the abdominal enlargement disappears when the patient is under general anesthesia.^10,16,17

Characteristics of pseudocyesis

Bivin and Klinger’s 1937 compilation of >400 cases of pseudocyesis over nearly 200 years remains a landmark in the study of this condition.¹⁸ In their analysis, patients range in age from 20 to 44; >75% were married. The authors noted that many of the women they studied had borne children previously. Further social and psychological studies came from this breakthrough article, which shed light on the dynamics of pseudocyesis in many patients with the condition.

 

According to Koic,¹¹ pseudocyesis is a form of conversion disorder with underlying depression. This theory is based on literature reports of patients displaying similar personal, cultural, and social factors. These similarities, although not comprehensive, are paramount in both the diagnosis and treatment of this condition.

Often, pseudocyesis presents in patients with lower education and socioeconomic status.^1,3,11 This is particularly true in developing nations in sub-Saharan Africa and the Indian subcontinent. Case reports, cross-sectional, and longitudinal studies from these developing nations in particular note the extremely high stress placed on women to produce children for their husbands and family in male-dominated society; it is common for a woman to be rejected by her husband and family if she is unable to reproduce.³

The effect of a lower level of education on development of pseudocyesis appears to be multifactorial:

• Lack of understanding of the human body and reproductive health can lead to misperception of signs of pregnancy and bodily changes
• Low education correlates with poor earnings and worse prenatal care; delayed or no prenatal care also has been associated with an increased incidence of pseudocyesis.³

In Ouj’s study of pseudocyesis in Nigeria, the author postulated that an educated woman does not endure the same stress of fertility as an uneducated woman; she is already respected in her society and will not be rejected if she does not have children.³

Mrs. X’s ethnic background and continued close ties with sub-Saharan Africa are notable: Her background is one that is typically associated with pseudocyesis. She is from an developing country, did not complete higher education, was ostracized by her mother-in-law because of her inability to conceive, and was told several times, during her visits to Ghana, that she was indeed pregnant.

Mrs. X noted a strong desire to conceive for her husband and family and carried with her perhaps an even stronger fear of loss of marriage and female identity—which has been bolstered by the importance placed on the woman’s raison d’être in the family by her cultural upbringing.^3,6,9-11,15 What Mrs. X never made clear, however, was whether she wanted another child at her age and in the setting of having many friends and rewarding full-time employment.

Epidemiology of pseudocyesis worldwide has been evaluated in a handful of studies. As compiled by Cohen,⁸ the prevalence of pseudocyesis in Boston, Massachusetts, was 1/22,000 births, whereas it was dramatically higher in Sudan (1/160 women who had previously been managed for reproductive failure).¹ This discrepancy in prevalance is consistent with current theories on patient characteristics that lead to increased incidence of pseudocyesis in underdeveloped nations. A 1951 study at an academic hospital in Philadelphia, Pennsylvania, noted 27 cases of pseudocyesis in maternity admissions during the study period—an incidence of 1 in 250.¹⁹ Of note, 85% of cases were of African American heritage; in 89% of cases, the woman had been trying to conceive for as long as 17 years.

Avoiding confrontation

Initially, Mrs. X was resistant to talking with a psychiatrist; this is consistent with studies showing that a patient can be suspicious and even hostile when a clinician attempts to engage her in mental health treatment.^10,16 The patient interprets the physical sensations she experiences during pseudocyesis, for example, as a real pregnancy, a perception that is contradicted by medical testing.

It is important to understand this conflict and to avoid confronting the patient directly about false beliefs; confrontation has been shown to be detrimental to patient recovery. Instead, offer the patient alternatives to her symptoms (ie, sensations of abdominal movement also can be caused by indigestion), while not directly discounting her experiences.^6,9 Indeed, from early on in the study of pseudocyesis, there have been many reports of resolution of symptoms when the physician helped the patient understand that she is not pregnant.^20,21

OUTCOME Supportive therapy

Mrs. X is seen for outpatient psychiatry follow-up several weeks after hospitalization. She acknowledges that, although she still thought pregnancy is possible, she is willing to entertain the idea that there could be another medical explanation for her symptoms.

Mrs. X is provided with supportive therapy techniques, and her marital and societal stressors are discussed. Psychotropic medications are considered, but eventually deemed unnecessary; the treatment team is concerned that Mrs. X, who remains wary of mental health providers, would view the offer of medication as offensive.

Mrs. X is seen in the gynecology clinic approximately 2 weeks later; there, a diagnosis of secondary anovulation is made and a workup for PCOS initiated.

Subsequent review of the medical record states that, during further follow-up with gynecology, Mrs. X no longer believes that she is pregnant.

 

Mrs. X, age 43, gravida 4 para 1, is a married woman of sub-Saharan African heritage with a history of idiopathic hypertension, uterine leiomyomas, and multiple spontaneous miscarriages. She has no psychiatric history and had never been evaluated by a mental health professional. Mrs. X is well known to the hospital’s emergency room and obstetrics and gynecology services for several presentations claiming to be pregnant, continuously, over the last 11 months, despite evidence—several negative serum beta human chorionic gonadotropin (ß-hCG) tests and transvaginal sonograms—to the contrary.

Mrs. X reports that after feeling ill for “a few days,” she began to believe that she was “losing [her] mucous plug” and needed urgent evaluation in preparation for the delivery of her “child.” She again is given a ß-hCG test, which is negative, as well as a negative transvaginal sonogram.

Mrs. X’s blood pressure is 220/113 mm Hg, and she emergently receives captopril, 25 mg sublingually, which lowers her systolic blood pressure to 194 mm Hg. The internal medicine team learns that Mrs. X stopped taking her blood pressure medications, lisinopril and hydrochlorothiazide, approximately 2 weeks earlier because she “didn’t want it [the antihypertensive agents] to hurt [her] baby.”

What explains Mrs. X’s belief that she is pregnant?

a) polycystic ovary syndrome (PCOS)
b) delusional disorder
c) bipolar I disorder
d) somatic symptom disorder

The authors’ observations

Pseudocyesis is a psychosomatic condition with an estimated incidence of 1 in 160 maternity admissions in many African countries and 1 in 22,000 in the United States.¹ According to DSM-5, pseudocyesis is a false belief of being pregnant along with signs and symptoms of pregnancy.²

Pseudocyesis is more common in:

• developing countries
• areas of low socioeconomic status with minimal education
• societies that place great importance on childbirth
• areas with low access to care.³

The primary presenting symptoms are changes in menses, enlarging abdomen, awareness of fetal movement, enlarged and tender breasts, galactorrhea, and weight gain.⁴

The exact pathophysiology of the disorder has not been determined, but we believe the psychosomatic hypothesis offers the most compelling explanation. According to this hypothesis, intense social pressures, such as an overwhelming desire to become pregnant because of cultural considerations, personal reasons, or both, could alter the normal function of the hypothalamic-pituitary-ovarian axis,⁵ which could result in physical manifestations of pregnancy. Tarín et al¹ found that rodents with chronic psychosocial stress had decreased brain norepinephrine and dopamine activity and elevated plasma levels of norepinephrine. This can translate to human models, in which a deficit or dysfunction of catecholaminergic activity in the brain could lead to increased pulsatile gonadotropin-releasing hormone, luteinizing hormone (LH), prolactin, and an elevated LH:follicle-stimulating hormone ratio.¹ These endocrine changes could induce traits found in most women with pseudocyesis, such as hypomenorrhea or amenorrhea, diurnal or nocturnal hyperprolactinemia (or both), and galactorrhea.¹

How would you approach Mrs. X’s care?

a) confront her with the negative pregnancy tests
b) admit her to the inpatient psychiatric unit
c) begin antipsychotic therapy
d) discharge her with outpatient follow-up

EVALUATION A curse on her

Although Mrs. X initially refused to see the psychiatry team, she is more receptive on hospital Day 3. Mrs. X reports that she and her husband had been trying to have a child since they were married 17 years earlier. She had a child with another man before she met her husband, causing her in-laws in Africa to become suspicious that she is intentionally not producing a child for her husband. She had 3 spontaneous abortions since her marriage; these added stress to the relationship because the couple would feel elated when learning of a pregnancy and increasingly devastated with each miscarriage.

Mrs. X reports that she and her husband have been seeing a number of reproductive endocrinologists for 7 years to try to become pregnant. She reports feeling that these physicians are not listening to her or giving her adequate treatment, which is why she has not been able to become pregnant. At the time of the evaluation, she reports that she is pregnant, and the tests have been negative because her mother-in-law placed a “curse” on her. This “curse” caused the baby to be invisible to the laboratory tests and sonograms.

During the psychiatric evaluation, Mrs. X displays her protuberant abdomen and says that she feels the fetus kicking. In addition, she also reports amenorrhea and breast tenderness and engorgement.

During her hospital stay, Mrs. X’s mental status exam does not demonstrate signs or symptoms of a mood disorder, bipolar disorder, or psychosis. Nonetheless, she remains delusional and holds to her fixed false belief of being pregnant. She refuses to be swayed by evidence that she is not pregnant. Despite this, clinicians build enough rapport that Mrs. X agrees to follow up with psychiatry in the outpatient clinic after discharge.

The internal medicine team is apprehensive that Mrs. X will continue to refuse anti­hypertensive medications out of concern that the medications would harm her pregnancy, as she had in the hospital. She remains hypertensive, with average systolic blood pressure in the 180 to 200 mm Hg range; however, after much discussion with her and her family members, she agrees to try amlodipine, 5 mg/d, a category C drug. She says that she will adhere to the medication if she does not experience any side effects.

Mrs. X is discharged on hospital Day 4 to outpatient follow-up.

 

The authors’ observations

When considering a diagnosis of pseudocyesis, the condition should be distinguished from others with similar presentations. Before beginning a psychiatric evaluation, a normal pregnancy must be ruled out. This is easily done with a positive urine or serum ß-hCG and an abdominal or transvaginal ultrasound. Pseudocyesis can be differentiated from:

• delusion of pregnancy (sometimes referred to as psychotic pregnancy)—a delusional disorder often seen in psychotic illness without any physical manifestations of pregnancy
• pseudopregnancy (sometimes referred to as erroneous pseudocyesis), another rare condition in which signs and symptoms of pregnancy are manifested^1,6,7 but the patient does not have a delusion of pregnancy.

Pseudocyesis, in contrast, comprises the delusion of pregnancy and physical manifestations.² These distinctions could be difficult to make clinically; for example, an increase in abdominal girth could be a result of pseudocyesis or obesity. In the setting of physical manifestations of pregnancy, a diagnosis of pseudocyesis is more likely  (Table¹).

Patients with pseudocyesis exhibit subjective and objective findings of pregnancy, such as abdominal distension, enlarged breasts, enhanced pigmentation, lordotic posture, cessation of menses, morning sickness, and weight gain.^8,9 Furthermore, approximately 1% of pseudocyesis patients have false labor, as Mrs. X did.¹⁰ Typically, the duration of these symptoms range from a few weeks to 9 months. In some cases, symptoms can last longer¹¹; at admission, Mrs. X reported that she was 11 months pregnant. She saw nothing wrong with this assertion, despite knowing that human gestation lasts 9 months.

In delusion of pregnancy, a patient might exhibit abdominal distension and cessation of menses but have no other objective findings of pregnancy.⁷ Rather than being a somatoform disorder such as pseudocyesis, a delusion of pregnancy is a symptom of psychosis or, rarely, dementia.¹²

Pseudopregnancy is a somatic state resembling pregnancy that can arise from a variety of medical conditions. A full medical workup and intensive mental status and cognitive evaluation are necessary for diagnostic clarity. Although the pathology and workup of delusional pregnancy is beyond the scope of this article, we suggest Seeman¹³ for a review and Chatterjee et al¹⁴ and Tarín et al¹ for guidance on making the diagnosis.

Theories about pathophysiology

As with many psychosomatic conditions, the pathological process of pseudocyesis originally was thought of in a psychodynamic context. Several psychodynamic theories have been proposed, including instances in which the internal desire to be pregnant is strong enough to induce a series of physiological changes akin to the state of pregnancy.⁶

Other examiners of pseudocyesis have noted its development from fears and societal pressure, including the loss of companionship or “womanhood.”^6,9 Last, the tenuous interplay of desire for a child and substantial fear of pregnancy appears to play a role in many cases.^9-11 Rosenberg et al¹⁵ reported on a teenager with pseudocyesis who desired to be pregnant to appease her husband and family, but feared pregnancy and the implications of having a child at such a young age. As this team wrote, “this pregnancy sans child fulfilled the needs of the entire family, at least temporarily.”¹⁵

Prevailing modern theories behind the somatic presentations of these patients hinge on an imbalance of the hypothalamic-pituitary-adrenal axis.⁹ Although this remains the area of ongoing research, most literature has not shown a consistent change or trend in laboratory levels of hormones associated with pseudocyesis.¹⁶ Tarín et al,¹ however, did show a similar hormonal profile between patients with pseudocyesis and those with PCOS. Although urine or serum pregnancy testing and ultrasonography are indicated to rule out pseudopregnancy, we see no benefit in obtaining other lab work in most cases beyond that of a general medical workup, because such evaluations are not helpful in diagnosis or treatment.

Mrs. X’s abdomen was protuberant and she displayed the typical linea nigra of pregnancy. Many authors have theorized the physiological mechanism behind the abdominal enlargement to include contraction of the diaphragm, which reduces the abdominal cavity and forces the bowel outwards. As abdominal fat increases, the patient becomes constipated, and the bowel becomes distended.^10,16 Although the cause of our patient’s abdominal enlargement was not pursued, we note that the literature reported that the abdominal enlargement disappears when the patient is under general anesthesia.^10,16,17

Characteristics of pseudocyesis

Bivin and Klinger’s 1937 compilation of >400 cases of pseudocyesis over nearly 200 years remains a landmark in the study of this condition.¹⁸ In their analysis, patients range in age from 20 to 44; >75% were married. The authors noted that many of the women they studied had borne children previously. Further social and psychological studies came from this breakthrough article, which shed light on the dynamics of pseudocyesis in many patients with the condition.

 

According to Koic,¹¹ pseudocyesis is a form of conversion disorder with underlying depression. This theory is based on literature reports of patients displaying similar personal, cultural, and social factors. These similarities, although not comprehensive, are paramount in both the diagnosis and treatment of this condition.

Often, pseudocyesis presents in patients with lower education and socioeconomic status.^1,3,11 This is particularly true in developing nations in sub-Saharan Africa and the Indian subcontinent. Case reports, cross-sectional, and longitudinal studies from these developing nations in particular note the extremely high stress placed on women to produce children for their husbands and family in male-dominated society; it is common for a woman to be rejected by her husband and family if she is unable to reproduce.³

The effect of a lower level of education on development of pseudocyesis appears to be multifactorial:

• Lack of understanding of the human body and reproductive health can lead to misperception of signs of pregnancy and bodily changes
• Low education correlates with poor earnings and worse prenatal care; delayed or no prenatal care also has been associated with an increased incidence of pseudocyesis.³

In Ouj’s study of pseudocyesis in Nigeria, the author postulated that an educated woman does not endure the same stress of fertility as an uneducated woman; she is already respected in her society and will not be rejected if she does not have children.³

Mrs. X’s ethnic background and continued close ties with sub-Saharan Africa are notable: Her background is one that is typically associated with pseudocyesis. She is from an developing country, did not complete higher education, was ostracized by her mother-in-law because of her inability to conceive, and was told several times, during her visits to Ghana, that she was indeed pregnant.

Mrs. X noted a strong desire to conceive for her husband and family and carried with her perhaps an even stronger fear of loss of marriage and female identity—which has been bolstered by the importance placed on the woman’s raison d’être in the family by her cultural upbringing.^3,6,9-11,15 What Mrs. X never made clear, however, was whether she wanted another child at her age and in the setting of having many friends and rewarding full-time employment.

Epidemiology of pseudocyesis worldwide has been evaluated in a handful of studies. As compiled by Cohen,⁸ the prevalence of pseudocyesis in Boston, Massachusetts, was 1/22,000 births, whereas it was dramatically higher in Sudan (1/160 women who had previously been managed for reproductive failure).¹ This discrepancy in prevalance is consistent with current theories on patient characteristics that lead to increased incidence of pseudocyesis in underdeveloped nations. A 1951 study at an academic hospital in Philadelphia, Pennsylvania, noted 27 cases of pseudocyesis in maternity admissions during the study period—an incidence of 1 in 250.¹⁹ Of note, 85% of cases were of African American heritage; in 89% of cases, the woman had been trying to conceive for as long as 17 years.

Avoiding confrontation

Initially, Mrs. X was resistant to talking with a psychiatrist; this is consistent with studies showing that a patient can be suspicious and even hostile when a clinician attempts to engage her in mental health treatment.^10,16 The patient interprets the physical sensations she experiences during pseudocyesis, for example, as a real pregnancy, a perception that is contradicted by medical testing.

It is important to understand this conflict and to avoid confronting the patient directly about false beliefs; confrontation has been shown to be detrimental to patient recovery. Instead, offer the patient alternatives to her symptoms (ie, sensations of abdominal movement also can be caused by indigestion), while not directly discounting her experiences.^6,9 Indeed, from early on in the study of pseudocyesis, there have been many reports of resolution of symptoms when the physician helped the patient understand that she is not pregnant.^20,21

OUTCOME Supportive therapy

Mrs. X is seen for outpatient psychiatry follow-up several weeks after hospitalization. She acknowledges that, although she still thought pregnancy is possible, she is willing to entertain the idea that there could be another medical explanation for her symptoms.

Mrs. X is provided with supportive therapy techniques, and her marital and societal stressors are discussed. Psychotropic medications are considered, but eventually deemed unnecessary; the treatment team is concerned that Mrs. X, who remains wary of mental health providers, would view the offer of medication as offensive.

Mrs. X is seen in the gynecology clinic approximately 2 weeks later; there, a diagnosis of secondary anovulation is made and a workup for PCOS initiated.

Subsequent review of the medical record states that, during further follow-up with gynecology, Mrs. X no longer believes that she is pregnant.

 

Mrs. X, age 43, gravida 4 para 1, is a married woman of sub-Saharan African heritage with a history of idiopathic hypertension, uterine leiomyomas, and multiple spontaneous miscarriages. She has no psychiatric history and had never been evaluated by a mental health professional. Mrs. X is well known to the hospital’s emergency room and obstetrics and gynecology services for several presentations claiming to be pregnant, continuously, over the last 11 months, despite evidence—several negative serum beta human chorionic gonadotropin (ß-hCG) tests and transvaginal sonograms—to the contrary.

Mrs. X reports that after feeling ill for “a few days,” she began to believe that she was “losing [her] mucous plug” and needed urgent evaluation in preparation for the delivery of her “child.” She again is given a ß-hCG test, which is negative, as well as a negative transvaginal sonogram.

Mrs. X’s blood pressure is 220/113 mm Hg, and she emergently receives captopril, 25 mg sublingually, which lowers her systolic blood pressure to 194 mm Hg. The internal medicine team learns that Mrs. X stopped taking her blood pressure medications, lisinopril and hydrochlorothiazide, approximately 2 weeks earlier because she “didn’t want it [the antihypertensive agents] to hurt [her] baby.”

What explains Mrs. X’s belief that she is pregnant?

a) polycystic ovary syndrome (PCOS)
b) delusional disorder
c) bipolar I disorder
d) somatic symptom disorder

The authors’ observations

Pseudocyesis is a psychosomatic condition with an estimated incidence of 1 in 160 maternity admissions in many African countries and 1 in 22,000 in the United States.¹ According to DSM-5, pseudocyesis is a false belief of being pregnant along with signs and symptoms of pregnancy.²

Pseudocyesis is more common in:

• developing countries
• areas of low socioeconomic status with minimal education
• societies that place great importance on childbirth
• areas with low access to care.³

The primary presenting symptoms are changes in menses, enlarging abdomen, awareness of fetal movement, enlarged and tender breasts, galactorrhea, and weight gain.⁴

The exact pathophysiology of the disorder has not been determined, but we believe the psychosomatic hypothesis offers the most compelling explanation. According to this hypothesis, intense social pressures, such as an overwhelming desire to become pregnant because of cultural considerations, personal reasons, or both, could alter the normal function of the hypothalamic-pituitary-ovarian axis,⁵ which could result in physical manifestations of pregnancy. Tarín et al¹ found that rodents with chronic psychosocial stress had decreased brain norepinephrine and dopamine activity and elevated plasma levels of norepinephrine. This can translate to human models, in which a deficit or dysfunction of catecholaminergic activity in the brain could lead to increased pulsatile gonadotropin-releasing hormone, luteinizing hormone (LH), prolactin, and an elevated LH:follicle-stimulating hormone ratio.¹ These endocrine changes could induce traits found in most women with pseudocyesis, such as hypomenorrhea or amenorrhea, diurnal or nocturnal hyperprolactinemia (or both), and galactorrhea.¹

How would you approach Mrs. X’s care?

a) confront her with the negative pregnancy tests
b) admit her to the inpatient psychiatric unit
c) begin antipsychotic therapy
d) discharge her with outpatient follow-up

EVALUATION A curse on her

Although Mrs. X initially refused to see the psychiatry team, she is more receptive on hospital Day 3. Mrs. X reports that she and her husband had been trying to have a child since they were married 17 years earlier. She had a child with another man before she met her husband, causing her in-laws in Africa to become suspicious that she is intentionally not producing a child for her husband. She had 3 spontaneous abortions since her marriage; these added stress to the relationship because the couple would feel elated when learning of a pregnancy and increasingly devastated with each miscarriage.

Mrs. X reports that she and her husband have been seeing a number of reproductive endocrinologists for 7 years to try to become pregnant. She reports feeling that these physicians are not listening to her or giving her adequate treatment, which is why she has not been able to become pregnant. At the time of the evaluation, she reports that she is pregnant, and the tests have been negative because her mother-in-law placed a “curse” on her. This “curse” caused the baby to be invisible to the laboratory tests and sonograms.

During the psychiatric evaluation, Mrs. X displays her protuberant abdomen and says that she feels the fetus kicking. In addition, she also reports amenorrhea and breast tenderness and engorgement.

During her hospital stay, Mrs. X’s mental status exam does not demonstrate signs or symptoms of a mood disorder, bipolar disorder, or psychosis. Nonetheless, she remains delusional and holds to her fixed false belief of being pregnant. She refuses to be swayed by evidence that she is not pregnant. Despite this, clinicians build enough rapport that Mrs. X agrees to follow up with psychiatry in the outpatient clinic after discharge.

The internal medicine team is apprehensive that Mrs. X will continue to refuse anti­hypertensive medications out of concern that the medications would harm her pregnancy, as she had in the hospital. She remains hypertensive, with average systolic blood pressure in the 180 to 200 mm Hg range; however, after much discussion with her and her family members, she agrees to try amlodipine, 5 mg/d, a category C drug. She says that she will adhere to the medication if she does not experience any side effects.

Mrs. X is discharged on hospital Day 4 to outpatient follow-up.

 

The authors’ observations

When considering a diagnosis of pseudocyesis, the condition should be distinguished from others with similar presentations. Before beginning a psychiatric evaluation, a normal pregnancy must be ruled out. This is easily done with a positive urine or serum ß-hCG and an abdominal or transvaginal ultrasound. Pseudocyesis can be differentiated from:

• delusion of pregnancy (sometimes referred to as psychotic pregnancy)—a delusional disorder often seen in psychotic illness without any physical manifestations of pregnancy
• pseudopregnancy (sometimes referred to as erroneous pseudocyesis), another rare condition in which signs and symptoms of pregnancy are manifested^1,6,7 but the patient does not have a delusion of pregnancy.

Pseudocyesis, in contrast, comprises the delusion of pregnancy and physical manifestations.² These distinctions could be difficult to make clinically; for example, an increase in abdominal girth could be a result of pseudocyesis or obesity. In the setting of physical manifestations of pregnancy, a diagnosis of pseudocyesis is more likely  (Table¹).

Patients with pseudocyesis exhibit subjective and objective findings of pregnancy, such as abdominal distension, enlarged breasts, enhanced pigmentation, lordotic posture, cessation of menses, morning sickness, and weight gain.^8,9 Furthermore, approximately 1% of pseudocyesis patients have false labor, as Mrs. X did.¹⁰ Typically, the duration of these symptoms range from a few weeks to 9 months. In some cases, symptoms can last longer¹¹; at admission, Mrs. X reported that she was 11 months pregnant. She saw nothing wrong with this assertion, despite knowing that human gestation lasts 9 months.

In delusion of pregnancy, a patient might exhibit abdominal distension and cessation of menses but have no other objective findings of pregnancy.⁷ Rather than being a somatoform disorder such as pseudocyesis, a delusion of pregnancy is a symptom of psychosis or, rarely, dementia.¹²

Pseudopregnancy is a somatic state resembling pregnancy that can arise from a variety of medical conditions. A full medical workup and intensive mental status and cognitive evaluation are necessary for diagnostic clarity. Although the pathology and workup of delusional pregnancy is beyond the scope of this article, we suggest Seeman¹³ for a review and Chatterjee et al¹⁴ and Tarín et al¹ for guidance on making the diagnosis.

Theories about pathophysiology

As with many psychosomatic conditions, the pathological process of pseudocyesis originally was thought of in a psychodynamic context. Several psychodynamic theories have been proposed, including instances in which the internal desire to be pregnant is strong enough to induce a series of physiological changes akin to the state of pregnancy.⁶

Other examiners of pseudocyesis have noted its development from fears and societal pressure, including the loss of companionship or “womanhood.”^6,9 Last, the tenuous interplay of desire for a child and substantial fear of pregnancy appears to play a role in many cases.^9-11 Rosenberg et al¹⁵ reported on a teenager with pseudocyesis who desired to be pregnant to appease her husband and family, but feared pregnancy and the implications of having a child at such a young age. As this team wrote, “this pregnancy sans child fulfilled the needs of the entire family, at least temporarily.”¹⁵

Prevailing modern theories behind the somatic presentations of these patients hinge on an imbalance of the hypothalamic-pituitary-adrenal axis.⁹ Although this remains the area of ongoing research, most literature has not shown a consistent change or trend in laboratory levels of hormones associated with pseudocyesis.¹⁶ Tarín et al,¹ however, did show a similar hormonal profile between patients with pseudocyesis and those with PCOS. Although urine or serum pregnancy testing and ultrasonography are indicated to rule out pseudopregnancy, we see no benefit in obtaining other lab work in most cases beyond that of a general medical workup, because such evaluations are not helpful in diagnosis or treatment.

Mrs. X’s abdomen was protuberant and she displayed the typical linea nigra of pregnancy. Many authors have theorized the physiological mechanism behind the abdominal enlargement to include contraction of the diaphragm, which reduces the abdominal cavity and forces the bowel outwards. As abdominal fat increases, the patient becomes constipated, and the bowel becomes distended.^10,16 Although the cause of our patient’s abdominal enlargement was not pursued, we note that the literature reported that the abdominal enlargement disappears when the patient is under general anesthesia.^10,16,17

Characteristics of pseudocyesis

Bivin and Klinger’s 1937 compilation of >400 cases of pseudocyesis over nearly 200 years remains a landmark in the study of this condition.¹⁸ In their analysis, patients range in age from 20 to 44; >75% were married. The authors noted that many of the women they studied had borne children previously. Further social and psychological studies came from this breakthrough article, which shed light on the dynamics of pseudocyesis in many patients with the condition.

 

According to Koic,¹¹ pseudocyesis is a form of conversion disorder with underlying depression. This theory is based on literature reports of patients displaying similar personal, cultural, and social factors. These similarities, although not comprehensive, are paramount in both the diagnosis and treatment of this condition.

Often, pseudocyesis presents in patients with lower education and socioeconomic status.^1,3,11 This is particularly true in developing nations in sub-Saharan Africa and the Indian subcontinent. Case reports, cross-sectional, and longitudinal studies from these developing nations in particular note the extremely high stress placed on women to produce children for their husbands and family in male-dominated society; it is common for a woman to be rejected by her husband and family if she is unable to reproduce.³

The effect of a lower level of education on development of pseudocyesis appears to be multifactorial:

• Lack of understanding of the human body and reproductive health can lead to misperception of signs of pregnancy and bodily changes
• Low education correlates with poor earnings and worse prenatal care; delayed or no prenatal care also has been associated with an increased incidence of pseudocyesis.³

In Ouj’s study of pseudocyesis in Nigeria, the author postulated that an educated woman does not endure the same stress of fertility as an uneducated woman; she is already respected in her society and will not be rejected if she does not have children.³

Mrs. X’s ethnic background and continued close ties with sub-Saharan Africa are notable: Her background is one that is typically associated with pseudocyesis. She is from an developing country, did not complete higher education, was ostracized by her mother-in-law because of her inability to conceive, and was told several times, during her visits to Ghana, that she was indeed pregnant.

Mrs. X noted a strong desire to conceive for her husband and family and carried with her perhaps an even stronger fear of loss of marriage and female identity—which has been bolstered by the importance placed on the woman’s raison d’être in the family by her cultural upbringing.^3,6,9-11,15 What Mrs. X never made clear, however, was whether she wanted another child at her age and in the setting of having many friends and rewarding full-time employment.

Epidemiology of pseudocyesis worldwide has been evaluated in a handful of studies. As compiled by Cohen,⁸ the prevalence of pseudocyesis in Boston, Massachusetts, was 1/22,000 births, whereas it was dramatically higher in Sudan (1/160 women who had previously been managed for reproductive failure).¹ This discrepancy in prevalance is consistent with current theories on patient characteristics that lead to increased incidence of pseudocyesis in underdeveloped nations. A 1951 study at an academic hospital in Philadelphia, Pennsylvania, noted 27 cases of pseudocyesis in maternity admissions during the study period—an incidence of 1 in 250.¹⁹ Of note, 85% of cases were of African American heritage; in 89% of cases, the woman had been trying to conceive for as long as 17 years.

Avoiding confrontation

Initially, Mrs. X was resistant to talking with a psychiatrist; this is consistent with studies showing that a patient can be suspicious and even hostile when a clinician attempts to engage her in mental health treatment.^10,16 The patient interprets the physical sensations she experiences during pseudocyesis, for example, as a real pregnancy, a perception that is contradicted by medical testing.

It is important to understand this conflict and to avoid confronting the patient directly about false beliefs; confrontation has been shown to be detrimental to patient recovery. Instead, offer the patient alternatives to her symptoms (ie, sensations of abdominal movement also can be caused by indigestion), while not directly discounting her experiences.^6,9 Indeed, from early on in the study of pseudocyesis, there have been many reports of resolution of symptoms when the physician helped the patient understand that she is not pregnant.^20,21

OUTCOME Supportive therapy

Mrs. X is seen for outpatient psychiatry follow-up several weeks after hospitalization. She acknowledges that, although she still thought pregnancy is possible, she is willing to entertain the idea that there could be another medical explanation for her symptoms.

Mrs. X is provided with supportive therapy techniques, and her marital and societal stressors are discussed. Psychotropic medications are considered, but eventually deemed unnecessary; the treatment team is concerned that Mrs. X, who remains wary of mental health providers, would view the offer of medication as offensive.

Mrs. X is seen in the gynecology clinic approximately 2 weeks later; there, a diagnosis of secondary anovulation is made and a workup for PCOS initiated.

Subsequent review of the medical record states that, during further follow-up with gynecology, Mrs. X no longer believes that she is pregnant.

 

Pimavanserin is a potent 5-HT2A inverse agonist and 5-HT2C inverse agonist, with 5-fold greater affinity for the 5-HT2A receptor.¹ Although antagonists block agonist actions at the receptor site, inverse agonists reduce the level of baseline constitutive activity seen in many G protein-coupled receptors. This medication is FDA approved for treating hallucinations and delusions associated with Parkinson’s disease (PD) psychosis (Table 1).¹

In the pivotal 6-week clinical trial, pimavanserin significantly reduced positive symptoms seen in PD patients with psychosis (effect size = 0.50), with no evident impairment of motor function.² Only 2 adverse effects occurred in ≥5% of pimavanserin-treated patients and at ≥2 times the rate of placebo: peripheral edema (7% vs 3% for placebo) and confusion (6% vs 3% for placebo). There was a mean increase in the QTc of 7.3 milliseconds compared with placebo in the pivotal phase III study.

Clinical implications

Despite numerous developments in the pharmacotherapeutics of psychotic disorders, patients with psychosis related to PD previously responded in a robust manner to only 1 antipsychotic, low-dosage clozapine (mean effect size, 0.80),² with numerous failed trials for other atypical antipsychotics, including quetiapine.^3,4 The pathophysiology of psychosis in PD patients is not related to dopamine agonist treatment, but is caused by the accumulation of cortical Lewy body burden, which results in loss of serotonergic signaling from dorsal raphe neurons. The net effect is up-regulation of postsynaptic 5-HT2A receptors.⁵ Psychosis is the most common cause of nursing home placement among PD patients without dementia.⁶

Receptor blocking. Based on the finding that clozapine in low dosages acts at 5-HT2A receptors,⁷ pimavanserin was designed to be a potent 5-HT2A inverse agonist, with more than 5-fold higher selectivity over 5-HT2C receptors, and no appreciable affinity for other serotonergic, adrenergic, dopaminergic, muscarinic, or histaminergic receptors⁸ (Table 2). The concept that 5-HT2A receptor stimulation can cause psychosis with prominent visual hallucinations is known from studies of LSD and other hallucinogenic compounds whose activity is blocked by 5-HT2A antagonists.

As an agent devoid of dopamine D2 antagonism, pimavanserin carries no risk of exacerbating motor symptoms, which was commonly seen with most atypical antipsychotics studied for psychosis in PD patients, except for clozapine and quetiapine.³ Although quetiapine did not cause motor effects, it proved ineffective in multiple studies (n = 153), likely because of the near absence of potent 5-HT2A binding.⁴

Pimavanserin also lacks:

• the hematologic monitoring requirement of clozapine
• clozapine’s risks of sedation, orthostasis, and anticholinergic and metabolic adverse effects.

Pimavanserin is significantly more potent than other non-antipsychotic psychotropics at the 5-HT2Areceptor, including doxepin (26 nM), trazodone (36 nM), and mirtazapine (60 nM).

Use in psychosis associated with PD. Recommended dosage is 34 mg once daily without titration (with or without food), based on results from a phase III clinical trial² (because of the FDA breakthrough therapy designation for this compound, only 1 phase III trial was required). Pimavanserin produced significant improvement on the PD-adapted Scale for the Assessment of Positive Symptoms (SAPS-PD), a 9-item instrument extracted from the larger SAPS used in schizophrenia research. Specifically, pimavanserin was effective for both the hallucinations and delusions components of the SAPS-PD.

Pharmacologic profile, adverse effects. Pimavanserin lacks affinity for receptors other than 5-HT2A and 5-HT2C, leading to an absence of significant anticholinergic effects, orthostasis, or sedation in clinical trials.² In all short-term clinical trials, the only common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were peripheral edema (7% vs 2% placebo) and confusional state (6% vs 3% placebo).² More than 300 patients have been treated for >6 months, >270 have been treated for at least 12 months, and >150 have been treated for at least 24 months with no adverse effects other than those seen in the short-term trials.¹

There is a measurable impact on cardiac conduction seen in phase III data and in the thorough QT study. In the thorough QT study, 252 healthy participants received multiple dosages in a randomized, double-blind manner with positive controls.¹ The maximum mean change from baseline was 13.5 milliseconds at dosages twice the recommended dosage, and the upper limit of the 90% CI was only slightly greater at 16.6 milliseconds. Subsequent kinetic analyses suggested concentration-dependent QTc interval prolongation in the therapeutic range, with a recommendation to halve the daily dosage in patients taking potent cytochrome P450 (CYP) 3A4 inhibitors.

In the 6-week, placebo-controlled effectiveness studies, mean increases in QTc interval were in the range of 5 to 8 milliseconds. There were sporadic reports of QTcF values ≥500 milliseconds, or changes from baseline QTc values ≥60 milliseconds in pimavanserin-treated participants, although the incidence generally was the same for pimavanserin and placebo groups. There were no reports of torsades de pointes or any differences from placebo in the incidence of adverse reactions associated with delayed ventricular repolarization.

 

How it works

The theory behind development of pimavanserin rests in the finding that low-dosage clozapine (6.25 to 50 mg/d) was effective for PD patients with psychosis (effect size 0.80).⁸ Although clozapine has high affinity for multiple sites, including histamine H1 receptors (Ki = 1.13 nM), α-1A and a α-2C adrenergic receptors (Ki = 1.62 nM and 6 nM, respectively), 5-HT2A receptors (Ki = 5.35 nM), and muscarinic M1 receptors (Ki = 6 nM), the hypothesized primary mechanism of clozapine’s effectiveness for PD psychosis at low dosages focused on the 5-HT2Areceptor. This idea was based on the knowledge that hallucinogens such as mescaline, psilocybin, and LSD are 5-HT2A agonists.⁹ This hallucinogenic activity can be blocked with 5-HT2A antagonists. Because of pimavanserin’s binding profile, the compound was studied as a treatment for psychosis in PD patients.

Pharmacokinetics

Pimavanserin demonstrates dose-proportional pharmacokinetics after a single oral dose as much as 7.5 times the recommended dosage. The pharmacokinetics of pimavanserin were similar in study participants (mean age, 72.4) and healthy controls, and a high-fat meal had no impact on the maximum blood levels (Cmax) or total drug exposure (area under the curve [AUC]).

The mean plasma half-lives for pimavanserin and its metabolite N-desmethyl-pimavanserin (AC-279) are 57 hours and 200 hours, respectively. Although the metabolite appears active in in vitro assays, it does not cross the blood-brain barrier to any appreciable extent, therefore contributing little to the clinical effect. The median time to maximum concentration (Tmax) of pimavanserin is 6 hours with a range of 4 to 24 hours, while the median Tmax of the primary metabolite AC-279 is 6 hours. The bioavailability of pimavanserin in an oral tablet or solution essentially is identical.

Pimavanserin is primarily metabolized via CYP3A4 to AC-279, and strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, indinavir) increase pimavanserin Cmax by 1.5-fold, and AUC by 3-fold. In patients taking strong CYP3A4 inhibitors, the dosage of pimavanserin should be reduced by 50% to 17 mg/d. Conversely, patients on CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin) should be monitored for lack of efficacy; consider a dosage increase as necessary. Neither pimavanserin nor its metabolite, AC-279, are inhibitors or inducers of major CYP enzymes or drug transporters.

Efficacy in PD psychosis

Study 1. This 6-week, fixed dosage, double-blind, placebo-controlled trial was performed in adult PD patients age ≥40 with PD psychosis.² Participants had to have (1) a PD diagnosis for at least 1 year and (2) psychotic symptoms that developed after diagnosis. Psychotic symptoms had to be present for at least 1 month, occurring at least weekly in the month before screening, and severe enough to warrant antipsychotic treatment. Baseline Mini-Mental State Examination score had to be ≥21 out of 30, with no evidence of delirium. Patients with dementia preceding or concurrent with the PD diagnosis were excluded. Antipsychotic treatments were not permitted during the trial.

After a 2-week nonpharmacotherapeutic lead-in phase that included a brief, daily psychosocial intervention by a caregiver, 199 patients who still met severity criteria were randomly allocated in a 1:1 manner to pimavanserin (34 mg of active drug, reported in the paper as 40 mg of pimavanserin tartrate) or matched placebo. Based on kinetic modeling and earlier clinical data, lower dosages (ie, 17 mg) were not explored, because they achieved only 50% of the steady state plasma levels thought to be required for efficacy.

The primary outcome was assessed by central, independent raters using the PD-adapted SAPS-PD. The efficacy analysis included 95 pimavanserin-treated individuals and 90 taking placebo. Baseline SAPS-PD scores were 14.7 ± 5.55 in the placebo group, and 15.9 ± 6.12 in the pimavanserin arm. Participants had a mean age of 72.4 and 94% white ethnicity across both cohorts; 42% of the placebo group and 33% of the pimavanserin group were female. Antipsychotic exposure in the 21 days prior to study entry were reported in 17% (n = 15) and 19% (n = 18) of the placebo and pimavanserin groups, respectively, with the most common agent being quetiapine (13 of 15, placebo, 16 of 18, pimavanserin). Approximately one-third of all participants were taking a cholinesterase inhibitor throughout the study.

Efficacy outcome. Pimavanserin was associated with a 5.79-point decrease in SAPS-PD scores compared with 2.73-point decrease for placebo (difference −3.06, 95% CI −4.91 to −1.20; P = .001). The effect size for this difference (Cohen’s d) was 0.50. The significant effect of pimavanserin vs placebo also was seen in separate analyses of the SAPS-PD subscore for hallucinations and delusions (effect size 0.50), and individually for hallucinations (effect size 0.45) and delusions (effect size 0.33). Separation from placebo appeared after the second week of pimavanserin treatment, and continued through the end of the study. There is unpublished data showing efficacy through week 10, and longer term, uncontrolled data consistent with sustained response. An exploratory analysis of caregiver burden demonstrated an effect size of 0.50.

 

Tolerability

The discontinuation rate because of adverse events for pimavanserin and placebo-treated patients was 10 patients in the pimavanserin group (4 due to psychotic symptoms within 10 days of starting the study drug) compared with 2 in the placebo group. There was no evidence of motor worsening in either group, demonstrated by the score on part II of the Unified Parkinson’s Disease Rating Scale (UPDRS) that captures self-reported activities of daily living, or on UPDRS part III (motor examination). Pimavanserin has no contraindications.

Unique clinical issues

Binding properties. Pimavanserin possesses potent 5-HT2A inverse agonist properties required to manage psychosis in PD patients, but lacks clozapine’s affinities for α-1 adrenergic, muscarinic, or histaminergic receptors that contribute to clozapine’s poor tolerability. Moreover, pimavanserin has no appreciable affinity for dopaminergic receptors, and therefore does not induce motor adverse effects.

Clozapine aside, all available atypical antipsychotics have proved ineffective for psychosis in PD patients, and most caused significant motor worsening.³ Although quetiapine does not cause motor effects, it has been shown to be ineffective for psychosis in PD patients in multiple trials.⁴

The effect size for clozapine response is large (0.80) in PD patients with psychosis, but tolerability issues and administrative burdens regarding patient and prescriber registration and routine hematological monitoring pose significant clinical barriers. Clozapine also lacks an FDA indication for this purpose, which may pose a hurdle to its use in certain treatment settings.

Why Rx? The reasons to prescribe pimavanserin for PD patients with psychosis likely include:

• absence of tolerability issues seen with the only other effective agent, clozapine
• lack of motor effects
• lack of administrative and monitoring burden related to clozapine prescribing
• only agent with FDA approval for hallucinations and delusions in PD patients with psychosis.

Dosing

The recommended dosage of pimavanserin is 34 mg/d administered as a single dose with or without food. There is no need for titration, and none was performed in the pivotal clinical trial. Given the long half-life (57 hours), steady state is not achieved until day 12, therefore initiation with a lower dosage might prolong the time to efficacy. There is no dosage adjustment required in patients with mild or moderate renal impairment, but pimavanserin treatment is not recommended in patients with severe renal impairment. Pimavanserin has not been evaluated in patients with hepatic impairment (using Child-Pugh criteria), and is not recommended for these patients.

Other key aspects of dosing to keep in mind.

• Because pimavanserin is metabolized primarily by CYP3A4, dosage adjustment is required in the presence of a strong CYP3A4 inhibitor; the recommended dosage is 17 mg/d when administered concomitantly with a strong CYP3A4 inhibitor.
• Because data are not available regarding concomitant use of pimavanserin with CYP3A4 inducers, patients should be monitored for lack of efficacy during concomitant use with a CYP3A4 inducer, and consideration given to a dosage increase.

Use in pregnancy and lactation. There are no data on the use of pimavanserin in pregnant women, but no developmental effects were seen when the drug was administered orally at 10 or 12 times the maximum recommended human dosage to rats or rabbits during organogenesis. Pimavanserin was not teratogenic in pregnant rats and rabbits. There is no information regarding the presence of pimavanserin in human breast milk.

Geriatric patients. No dosage adjustment is required for older patients. The study population in the pivotal trial was mean age 72.4 years.

Summing up

Before development of pimavanserin, clozapine was the only effective treatment for psychosis in PD patients. Despite clozapine’s robust effects across several trials, patients often were given ineffective medications, such as quetiapine, because of the administrative and tolerability barriers posed by clozapine use. Because psychosis is the most common cause of nursing home placement in non-demented PD patients, an agent with demonstrated efficacy and without the adverse effect profile of clozapine or monitoring requirements represents an enormous advance in the treatment of psychosis in PD patients.

Pimavanserin is a potent 5-HT2A inverse agonist and 5-HT2C inverse agonist, with 5-fold greater affinity for the 5-HT2A receptor.¹ Although antagonists block agonist actions at the receptor site, inverse agonists reduce the level of baseline constitutive activity seen in many G protein-coupled receptors. This medication is FDA approved for treating hallucinations and delusions associated with Parkinson’s disease (PD) psychosis (Table 1).¹

In the pivotal 6-week clinical trial, pimavanserin significantly reduced positive symptoms seen in PD patients with psychosis (effect size = 0.50), with no evident impairment of motor function.² Only 2 adverse effects occurred in ≥5% of pimavanserin-treated patients and at ≥2 times the rate of placebo: peripheral edema (7% vs 3% for placebo) and confusion (6% vs 3% for placebo). There was a mean increase in the QTc of 7.3 milliseconds compared with placebo in the pivotal phase III study.

Clinical implications

Despite numerous developments in the pharmacotherapeutics of psychotic disorders, patients with psychosis related to PD previously responded in a robust manner to only 1 antipsychotic, low-dosage clozapine (mean effect size, 0.80),² with numerous failed trials for other atypical antipsychotics, including quetiapine.^3,4 The pathophysiology of psychosis in PD patients is not related to dopamine agonist treatment, but is caused by the accumulation of cortical Lewy body burden, which results in loss of serotonergic signaling from dorsal raphe neurons. The net effect is up-regulation of postsynaptic 5-HT2A receptors.⁵ Psychosis is the most common cause of nursing home placement among PD patients without dementia.⁶

Receptor blocking. Based on the finding that clozapine in low dosages acts at 5-HT2A receptors,⁷ pimavanserin was designed to be a potent 5-HT2A inverse agonist, with more than 5-fold higher selectivity over 5-HT2C receptors, and no appreciable affinity for other serotonergic, adrenergic, dopaminergic, muscarinic, or histaminergic receptors⁸ (Table 2). The concept that 5-HT2A receptor stimulation can cause psychosis with prominent visual hallucinations is known from studies of LSD and other hallucinogenic compounds whose activity is blocked by 5-HT2A antagonists.

As an agent devoid of dopamine D2 antagonism, pimavanserin carries no risk of exacerbating motor symptoms, which was commonly seen with most atypical antipsychotics studied for psychosis in PD patients, except for clozapine and quetiapine.³ Although quetiapine did not cause motor effects, it proved ineffective in multiple studies (n = 153), likely because of the near absence of potent 5-HT2A binding.⁴

Pimavanserin also lacks:

• the hematologic monitoring requirement of clozapine
• clozapine’s risks of sedation, orthostasis, and anticholinergic and metabolic adverse effects.

Pimavanserin is significantly more potent than other non-antipsychotic psychotropics at the 5-HT2Areceptor, including doxepin (26 nM), trazodone (36 nM), and mirtazapine (60 nM).

Use in psychosis associated with PD. Recommended dosage is 34 mg once daily without titration (with or without food), based on results from a phase III clinical trial² (because of the FDA breakthrough therapy designation for this compound, only 1 phase III trial was required). Pimavanserin produced significant improvement on the PD-adapted Scale for the Assessment of Positive Symptoms (SAPS-PD), a 9-item instrument extracted from the larger SAPS used in schizophrenia research. Specifically, pimavanserin was effective for both the hallucinations and delusions components of the SAPS-PD.

Pharmacologic profile, adverse effects. Pimavanserin lacks affinity for receptors other than 5-HT2A and 5-HT2C, leading to an absence of significant anticholinergic effects, orthostasis, or sedation in clinical trials.² In all short-term clinical trials, the only common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were peripheral edema (7% vs 2% placebo) and confusional state (6% vs 3% placebo).² More than 300 patients have been treated for >6 months, >270 have been treated for at least 12 months, and >150 have been treated for at least 24 months with no adverse effects other than those seen in the short-term trials.¹

There is a measurable impact on cardiac conduction seen in phase III data and in the thorough QT study. In the thorough QT study, 252 healthy participants received multiple dosages in a randomized, double-blind manner with positive controls.¹ The maximum mean change from baseline was 13.5 milliseconds at dosages twice the recommended dosage, and the upper limit of the 90% CI was only slightly greater at 16.6 milliseconds. Subsequent kinetic analyses suggested concentration-dependent QTc interval prolongation in the therapeutic range, with a recommendation to halve the daily dosage in patients taking potent cytochrome P450 (CYP) 3A4 inhibitors.

In the 6-week, placebo-controlled effectiveness studies, mean increases in QTc interval were in the range of 5 to 8 milliseconds. There were sporadic reports of QTcF values ≥500 milliseconds, or changes from baseline QTc values ≥60 milliseconds in pimavanserin-treated participants, although the incidence generally was the same for pimavanserin and placebo groups. There were no reports of torsades de pointes or any differences from placebo in the incidence of adverse reactions associated with delayed ventricular repolarization.

 

How it works

The theory behind development of pimavanserin rests in the finding that low-dosage clozapine (6.25 to 50 mg/d) was effective for PD patients with psychosis (effect size 0.80).⁸ Although clozapine has high affinity for multiple sites, including histamine H1 receptors (Ki = 1.13 nM), α-1A and a α-2C adrenergic receptors (Ki = 1.62 nM and 6 nM, respectively), 5-HT2A receptors (Ki = 5.35 nM), and muscarinic M1 receptors (Ki = 6 nM), the hypothesized primary mechanism of clozapine’s effectiveness for PD psychosis at low dosages focused on the 5-HT2Areceptor. This idea was based on the knowledge that hallucinogens such as mescaline, psilocybin, and LSD are 5-HT2A agonists.⁹ This hallucinogenic activity can be blocked with 5-HT2A antagonists. Because of pimavanserin’s binding profile, the compound was studied as a treatment for psychosis in PD patients.

Pharmacokinetics

Pimavanserin demonstrates dose-proportional pharmacokinetics after a single oral dose as much as 7.5 times the recommended dosage. The pharmacokinetics of pimavanserin were similar in study participants (mean age, 72.4) and healthy controls, and a high-fat meal had no impact on the maximum blood levels (Cmax) or total drug exposure (area under the curve [AUC]).

The mean plasma half-lives for pimavanserin and its metabolite N-desmethyl-pimavanserin (AC-279) are 57 hours and 200 hours, respectively. Although the metabolite appears active in in vitro assays, it does not cross the blood-brain barrier to any appreciable extent, therefore contributing little to the clinical effect. The median time to maximum concentration (Tmax) of pimavanserin is 6 hours with a range of 4 to 24 hours, while the median Tmax of the primary metabolite AC-279 is 6 hours. The bioavailability of pimavanserin in an oral tablet or solution essentially is identical.

Pimavanserin is primarily metabolized via CYP3A4 to AC-279, and strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, indinavir) increase pimavanserin Cmax by 1.5-fold, and AUC by 3-fold. In patients taking strong CYP3A4 inhibitors, the dosage of pimavanserin should be reduced by 50% to 17 mg/d. Conversely, patients on CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin) should be monitored for lack of efficacy; consider a dosage increase as necessary. Neither pimavanserin nor its metabolite, AC-279, are inhibitors or inducers of major CYP enzymes or drug transporters.

Efficacy in PD psychosis

Study 1. This 6-week, fixed dosage, double-blind, placebo-controlled trial was performed in adult PD patients age ≥40 with PD psychosis.² Participants had to have (1) a PD diagnosis for at least 1 year and (2) psychotic symptoms that developed after diagnosis. Psychotic symptoms had to be present for at least 1 month, occurring at least weekly in the month before screening, and severe enough to warrant antipsychotic treatment. Baseline Mini-Mental State Examination score had to be ≥21 out of 30, with no evidence of delirium. Patients with dementia preceding or concurrent with the PD diagnosis were excluded. Antipsychotic treatments were not permitted during the trial.

After a 2-week nonpharmacotherapeutic lead-in phase that included a brief, daily psychosocial intervention by a caregiver, 199 patients who still met severity criteria were randomly allocated in a 1:1 manner to pimavanserin (34 mg of active drug, reported in the paper as 40 mg of pimavanserin tartrate) or matched placebo. Based on kinetic modeling and earlier clinical data, lower dosages (ie, 17 mg) were not explored, because they achieved only 50% of the steady state plasma levels thought to be required for efficacy.

The primary outcome was assessed by central, independent raters using the PD-adapted SAPS-PD. The efficacy analysis included 95 pimavanserin-treated individuals and 90 taking placebo. Baseline SAPS-PD scores were 14.7 ± 5.55 in the placebo group, and 15.9 ± 6.12 in the pimavanserin arm. Participants had a mean age of 72.4 and 94% white ethnicity across both cohorts; 42% of the placebo group and 33% of the pimavanserin group were female. Antipsychotic exposure in the 21 days prior to study entry were reported in 17% (n = 15) and 19% (n = 18) of the placebo and pimavanserin groups, respectively, with the most common agent being quetiapine (13 of 15, placebo, 16 of 18, pimavanserin). Approximately one-third of all participants were taking a cholinesterase inhibitor throughout the study.

Efficacy outcome. Pimavanserin was associated with a 5.79-point decrease in SAPS-PD scores compared with 2.73-point decrease for placebo (difference −3.06, 95% CI −4.91 to −1.20; P = .001). The effect size for this difference (Cohen’s d) was 0.50. The significant effect of pimavanserin vs placebo also was seen in separate analyses of the SAPS-PD subscore for hallucinations and delusions (effect size 0.50), and individually for hallucinations (effect size 0.45) and delusions (effect size 0.33). Separation from placebo appeared after the second week of pimavanserin treatment, and continued through the end of the study. There is unpublished data showing efficacy through week 10, and longer term, uncontrolled data consistent with sustained response. An exploratory analysis of caregiver burden demonstrated an effect size of 0.50.

 

Tolerability

The discontinuation rate because of adverse events for pimavanserin and placebo-treated patients was 10 patients in the pimavanserin group (4 due to psychotic symptoms within 10 days of starting the study drug) compared with 2 in the placebo group. There was no evidence of motor worsening in either group, demonstrated by the score on part II of the Unified Parkinson’s Disease Rating Scale (UPDRS) that captures self-reported activities of daily living, or on UPDRS part III (motor examination). Pimavanserin has no contraindications.

Unique clinical issues

Binding properties. Pimavanserin possesses potent 5-HT2A inverse agonist properties required to manage psychosis in PD patients, but lacks clozapine’s affinities for α-1 adrenergic, muscarinic, or histaminergic receptors that contribute to clozapine’s poor tolerability. Moreover, pimavanserin has no appreciable affinity for dopaminergic receptors, and therefore does not induce motor adverse effects.

Clozapine aside, all available atypical antipsychotics have proved ineffective for psychosis in PD patients, and most caused significant motor worsening.³ Although quetiapine does not cause motor effects, it has been shown to be ineffective for psychosis in PD patients in multiple trials.⁴

The effect size for clozapine response is large (0.80) in PD patients with psychosis, but tolerability issues and administrative burdens regarding patient and prescriber registration and routine hematological monitoring pose significant clinical barriers. Clozapine also lacks an FDA indication for this purpose, which may pose a hurdle to its use in certain treatment settings.

Why Rx? The reasons to prescribe pimavanserin for PD patients with psychosis likely include:

• absence of tolerability issues seen with the only other effective agent, clozapine
• lack of motor effects
• lack of administrative and monitoring burden related to clozapine prescribing
• only agent with FDA approval for hallucinations and delusions in PD patients with psychosis.

Dosing

The recommended dosage of pimavanserin is 34 mg/d administered as a single dose with or without food. There is no need for titration, and none was performed in the pivotal clinical trial. Given the long half-life (57 hours), steady state is not achieved until day 12, therefore initiation with a lower dosage might prolong the time to efficacy. There is no dosage adjustment required in patients with mild or moderate renal impairment, but pimavanserin treatment is not recommended in patients with severe renal impairment. Pimavanserin has not been evaluated in patients with hepatic impairment (using Child-Pugh criteria), and is not recommended for these patients.

Other key aspects of dosing to keep in mind.

• Because pimavanserin is metabolized primarily by CYP3A4, dosage adjustment is required in the presence of a strong CYP3A4 inhibitor; the recommended dosage is 17 mg/d when administered concomitantly with a strong CYP3A4 inhibitor.
• Because data are not available regarding concomitant use of pimavanserin with CYP3A4 inducers, patients should be monitored for lack of efficacy during concomitant use with a CYP3A4 inducer, and consideration given to a dosage increase.

Use in pregnancy and lactation. There are no data on the use of pimavanserin in pregnant women, but no developmental effects were seen when the drug was administered orally at 10 or 12 times the maximum recommended human dosage to rats or rabbits during organogenesis. Pimavanserin was not teratogenic in pregnant rats and rabbits. There is no information regarding the presence of pimavanserin in human breast milk.

Geriatric patients. No dosage adjustment is required for older patients. The study population in the pivotal trial was mean age 72.4 years.

Summing up

Before development of pimavanserin, clozapine was the only effective treatment for psychosis in PD patients. Despite clozapine’s robust effects across several trials, patients often were given ineffective medications, such as quetiapine, because of the administrative and tolerability barriers posed by clozapine use. Because psychosis is the most common cause of nursing home placement in non-demented PD patients, an agent with demonstrated efficacy and without the adverse effect profile of clozapine or monitoring requirements represents an enormous advance in the treatment of psychosis in PD patients.

Pimavanserin is a potent 5-HT2A inverse agonist and 5-HT2C inverse agonist, with 5-fold greater affinity for the 5-HT2A receptor.¹ Although antagonists block agonist actions at the receptor site, inverse agonists reduce the level of baseline constitutive activity seen in many G protein-coupled receptors. This medication is FDA approved for treating hallucinations and delusions associated with Parkinson’s disease (PD) psychosis (Table 1).¹

In the pivotal 6-week clinical trial, pimavanserin significantly reduced positive symptoms seen in PD patients with psychosis (effect size = 0.50), with no evident impairment of motor function.² Only 2 adverse effects occurred in ≥5% of pimavanserin-treated patients and at ≥2 times the rate of placebo: peripheral edema (7% vs 3% for placebo) and confusion (6% vs 3% for placebo). There was a mean increase in the QTc of 7.3 milliseconds compared with placebo in the pivotal phase III study.

Clinical implications

Despite numerous developments in the pharmacotherapeutics of psychotic disorders, patients with psychosis related to PD previously responded in a robust manner to only 1 antipsychotic, low-dosage clozapine (mean effect size, 0.80),² with numerous failed trials for other atypical antipsychotics, including quetiapine.^3,4 The pathophysiology of psychosis in PD patients is not related to dopamine agonist treatment, but is caused by the accumulation of cortical Lewy body burden, which results in loss of serotonergic signaling from dorsal raphe neurons. The net effect is up-regulation of postsynaptic 5-HT2A receptors.⁵ Psychosis is the most common cause of nursing home placement among PD patients without dementia.⁶

Receptor blocking. Based on the finding that clozapine in low dosages acts at 5-HT2A receptors,⁷ pimavanserin was designed to be a potent 5-HT2A inverse agonist, with more than 5-fold higher selectivity over 5-HT2C receptors, and no appreciable affinity for other serotonergic, adrenergic, dopaminergic, muscarinic, or histaminergic receptors⁸ (Table 2). The concept that 5-HT2A receptor stimulation can cause psychosis with prominent visual hallucinations is known from studies of LSD and other hallucinogenic compounds whose activity is blocked by 5-HT2A antagonists.

As an agent devoid of dopamine D2 antagonism, pimavanserin carries no risk of exacerbating motor symptoms, which was commonly seen with most atypical antipsychotics studied for psychosis in PD patients, except for clozapine and quetiapine.³ Although quetiapine did not cause motor effects, it proved ineffective in multiple studies (n = 153), likely because of the near absence of potent 5-HT2A binding.⁴

Pimavanserin also lacks:

• the hematologic monitoring requirement of clozapine
• clozapine’s risks of sedation, orthostasis, and anticholinergic and metabolic adverse effects.

Pimavanserin is significantly more potent than other non-antipsychotic psychotropics at the 5-HT2Areceptor, including doxepin (26 nM), trazodone (36 nM), and mirtazapine (60 nM).

Use in psychosis associated with PD. Recommended dosage is 34 mg once daily without titration (with or without food), based on results from a phase III clinical trial² (because of the FDA breakthrough therapy designation for this compound, only 1 phase III trial was required). Pimavanserin produced significant improvement on the PD-adapted Scale for the Assessment of Positive Symptoms (SAPS-PD), a 9-item instrument extracted from the larger SAPS used in schizophrenia research. Specifically, pimavanserin was effective for both the hallucinations and delusions components of the SAPS-PD.

Pharmacologic profile, adverse effects. Pimavanserin lacks affinity for receptors other than 5-HT2A and 5-HT2C, leading to an absence of significant anticholinergic effects, orthostasis, or sedation in clinical trials.² In all short-term clinical trials, the only common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were peripheral edema (7% vs 2% placebo) and confusional state (6% vs 3% placebo).² More than 300 patients have been treated for >6 months, >270 have been treated for at least 12 months, and >150 have been treated for at least 24 months with no adverse effects other than those seen in the short-term trials.¹

There is a measurable impact on cardiac conduction seen in phase III data and in the thorough QT study. In the thorough QT study, 252 healthy participants received multiple dosages in a randomized, double-blind manner with positive controls.¹ The maximum mean change from baseline was 13.5 milliseconds at dosages twice the recommended dosage, and the upper limit of the 90% CI was only slightly greater at 16.6 milliseconds. Subsequent kinetic analyses suggested concentration-dependent QTc interval prolongation in the therapeutic range, with a recommendation to halve the daily dosage in patients taking potent cytochrome P450 (CYP) 3A4 inhibitors.

In the 6-week, placebo-controlled effectiveness studies, mean increases in QTc interval were in the range of 5 to 8 milliseconds. There were sporadic reports of QTcF values ≥500 milliseconds, or changes from baseline QTc values ≥60 milliseconds in pimavanserin-treated participants, although the incidence generally was the same for pimavanserin and placebo groups. There were no reports of torsades de pointes or any differences from placebo in the incidence of adverse reactions associated with delayed ventricular repolarization.

 

How it works

The theory behind development of pimavanserin rests in the finding that low-dosage clozapine (6.25 to 50 mg/d) was effective for PD patients with psychosis (effect size 0.80).⁸ Although clozapine has high affinity for multiple sites, including histamine H1 receptors (Ki = 1.13 nM), α-1A and a α-2C adrenergic receptors (Ki = 1.62 nM and 6 nM, respectively), 5-HT2A receptors (Ki = 5.35 nM), and muscarinic M1 receptors (Ki = 6 nM), the hypothesized primary mechanism of clozapine’s effectiveness for PD psychosis at low dosages focused on the 5-HT2Areceptor. This idea was based on the knowledge that hallucinogens such as mescaline, psilocybin, and LSD are 5-HT2A agonists.⁹ This hallucinogenic activity can be blocked with 5-HT2A antagonists. Because of pimavanserin’s binding profile, the compound was studied as a treatment for psychosis in PD patients.

Pharmacokinetics

Pimavanserin demonstrates dose-proportional pharmacokinetics after a single oral dose as much as 7.5 times the recommended dosage. The pharmacokinetics of pimavanserin were similar in study participants (mean age, 72.4) and healthy controls, and a high-fat meal had no impact on the maximum blood levels (Cmax) or total drug exposure (area under the curve [AUC]).

The mean plasma half-lives for pimavanserin and its metabolite N-desmethyl-pimavanserin (AC-279) are 57 hours and 200 hours, respectively. Although the metabolite appears active in in vitro assays, it does not cross the blood-brain barrier to any appreciable extent, therefore contributing little to the clinical effect. The median time to maximum concentration (Tmax) of pimavanserin is 6 hours with a range of 4 to 24 hours, while the median Tmax of the primary metabolite AC-279 is 6 hours. The bioavailability of pimavanserin in an oral tablet or solution essentially is identical.

Pimavanserin is primarily metabolized via CYP3A4 to AC-279, and strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, indinavir) increase pimavanserin Cmax by 1.5-fold, and AUC by 3-fold. In patients taking strong CYP3A4 inhibitors, the dosage of pimavanserin should be reduced by 50% to 17 mg/d. Conversely, patients on CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin) should be monitored for lack of efficacy; consider a dosage increase as necessary. Neither pimavanserin nor its metabolite, AC-279, are inhibitors or inducers of major CYP enzymes or drug transporters.

Efficacy in PD psychosis

Study 1. This 6-week, fixed dosage, double-blind, placebo-controlled trial was performed in adult PD patients age ≥40 with PD psychosis.² Participants had to have (1) a PD diagnosis for at least 1 year and (2) psychotic symptoms that developed after diagnosis. Psychotic symptoms had to be present for at least 1 month, occurring at least weekly in the month before screening, and severe enough to warrant antipsychotic treatment. Baseline Mini-Mental State Examination score had to be ≥21 out of 30, with no evidence of delirium. Patients with dementia preceding or concurrent with the PD diagnosis were excluded. Antipsychotic treatments were not permitted during the trial.

After a 2-week nonpharmacotherapeutic lead-in phase that included a brief, daily psychosocial intervention by a caregiver, 199 patients who still met severity criteria were randomly allocated in a 1:1 manner to pimavanserin (34 mg of active drug, reported in the paper as 40 mg of pimavanserin tartrate) or matched placebo. Based on kinetic modeling and earlier clinical data, lower dosages (ie, 17 mg) were not explored, because they achieved only 50% of the steady state plasma levels thought to be required for efficacy.

The primary outcome was assessed by central, independent raters using the PD-adapted SAPS-PD. The efficacy analysis included 95 pimavanserin-treated individuals and 90 taking placebo. Baseline SAPS-PD scores were 14.7 ± 5.55 in the placebo group, and 15.9 ± 6.12 in the pimavanserin arm. Participants had a mean age of 72.4 and 94% white ethnicity across both cohorts; 42% of the placebo group and 33% of the pimavanserin group were female. Antipsychotic exposure in the 21 days prior to study entry were reported in 17% (n = 15) and 19% (n = 18) of the placebo and pimavanserin groups, respectively, with the most common agent being quetiapine (13 of 15, placebo, 16 of 18, pimavanserin). Approximately one-third of all participants were taking a cholinesterase inhibitor throughout the study.

Efficacy outcome. Pimavanserin was associated with a 5.79-point decrease in SAPS-PD scores compared with 2.73-point decrease for placebo (difference −3.06, 95% CI −4.91 to −1.20; P = .001). The effect size for this difference (Cohen’s d) was 0.50. The significant effect of pimavanserin vs placebo also was seen in separate analyses of the SAPS-PD subscore for hallucinations and delusions (effect size 0.50), and individually for hallucinations (effect size 0.45) and delusions (effect size 0.33). Separation from placebo appeared after the second week of pimavanserin treatment, and continued through the end of the study. There is unpublished data showing efficacy through week 10, and longer term, uncontrolled data consistent with sustained response. An exploratory analysis of caregiver burden demonstrated an effect size of 0.50.

 

Tolerability

The discontinuation rate because of adverse events for pimavanserin and placebo-treated patients was 10 patients in the pimavanserin group (4 due to psychotic symptoms within 10 days of starting the study drug) compared with 2 in the placebo group. There was no evidence of motor worsening in either group, demonstrated by the score on part II of the Unified Parkinson’s Disease Rating Scale (UPDRS) that captures self-reported activities of daily living, or on UPDRS part III (motor examination). Pimavanserin has no contraindications.

Unique clinical issues

Binding properties. Pimavanserin possesses potent 5-HT2A inverse agonist properties required to manage psychosis in PD patients, but lacks clozapine’s affinities for α-1 adrenergic, muscarinic, or histaminergic receptors that contribute to clozapine’s poor tolerability. Moreover, pimavanserin has no appreciable affinity for dopaminergic receptors, and therefore does not induce motor adverse effects.

Clozapine aside, all available atypical antipsychotics have proved ineffective for psychosis in PD patients, and most caused significant motor worsening.³ Although quetiapine does not cause motor effects, it has been shown to be ineffective for psychosis in PD patients in multiple trials.⁴

The effect size for clozapine response is large (0.80) in PD patients with psychosis, but tolerability issues and administrative burdens regarding patient and prescriber registration and routine hematological monitoring pose significant clinical barriers. Clozapine also lacks an FDA indication for this purpose, which may pose a hurdle to its use in certain treatment settings.

Why Rx? The reasons to prescribe pimavanserin for PD patients with psychosis likely include:

• absence of tolerability issues seen with the only other effective agent, clozapine
• lack of motor effects
• lack of administrative and monitoring burden related to clozapine prescribing
• only agent with FDA approval for hallucinations and delusions in PD patients with psychosis.

Dosing

The recommended dosage of pimavanserin is 34 mg/d administered as a single dose with or without food. There is no need for titration, and none was performed in the pivotal clinical trial. Given the long half-life (57 hours), steady state is not achieved until day 12, therefore initiation with a lower dosage might prolong the time to efficacy. There is no dosage adjustment required in patients with mild or moderate renal impairment, but pimavanserin treatment is not recommended in patients with severe renal impairment. Pimavanserin has not been evaluated in patients with hepatic impairment (using Child-Pugh criteria), and is not recommended for these patients.

Other key aspects of dosing to keep in mind.

• Because pimavanserin is metabolized primarily by CYP3A4, dosage adjustment is required in the presence of a strong CYP3A4 inhibitor; the recommended dosage is 17 mg/d when administered concomitantly with a strong CYP3A4 inhibitor.
• Because data are not available regarding concomitant use of pimavanserin with CYP3A4 inducers, patients should be monitored for lack of efficacy during concomitant use with a CYP3A4 inducer, and consideration given to a dosage increase.

Use in pregnancy and lactation. There are no data on the use of pimavanserin in pregnant women, but no developmental effects were seen when the drug was administered orally at 10 or 12 times the maximum recommended human dosage to rats or rabbits during organogenesis. Pimavanserin was not teratogenic in pregnant rats and rabbits. There is no information regarding the presence of pimavanserin in human breast milk.

Geriatric patients. No dosage adjustment is required for older patients. The study population in the pivotal trial was mean age 72.4 years.

Summing up

Before development of pimavanserin, clozapine was the only effective treatment for psychosis in PD patients. Despite clozapine’s robust effects across several trials, patients often were given ineffective medications, such as quetiapine, because of the administrative and tolerability barriers posed by clozapine use. Because psychosis is the most common cause of nursing home placement in non-demented PD patients, an agent with demonstrated efficacy and without the adverse effect profile of clozapine or monitoring requirements represents an enormous advance in the treatment of psychosis in PD patients.

Most adults want to have happy romantic relationships. But meeting eligible companions and finding the time to date can feel nearly impossible to many physicians, especially residents, whose 80-hour work weeks limit opportunities to meet potential partners.¹

So it’s no surprise that Dr. R’s friends have suggested that she try online dating. If she does, she would be far from alone: 15% of U.S. adults have sought relationships online, and one-fourth of people in their 20s have used a mobile dating app.^2,3 Online dating might work well for Dr. R, too. Between 2005 and 2012, more than one-third of U.S. marriages started online, and these marriages seemed happier and ended in separation or divorce less often than marriages that started in more traditional ways.⁴

Online dating is just one example of how “the permeation of online and social media into everyday life is placing doctors in new situations that they find difficult to navigate.”⁵ Many physicians—psychiatrists among them—date online. Yet, like Dr. R, physicians are cautious about using social media because of worries about public exposure and legal concerns.⁵ Moreover, medical associations haven’t developed guidelines that would help physicians reconcile their professional and personal lives if they seek companionship online.⁶

Although we don’t have complete answers to Dr. R’s questions, we have gathered some ideas and information that she might find helpful. Read on as we explore:

• potential benefits for psychiatrists who try online dating
• problems when physicians use social media
• how to minimize mishaps if you seek companionship online.

Advantages and benefits

Online dating is most popular among young adults. But singles and divorcees of all ages, sexual orientations, and backgrounds are increasingly seeking long-term relationships with internet-based dating tools rather than hoping to meet people through family, friends, church, and the workplace. It has become common—and no longer stigmatizing—for couples to say they met online.^2,7

A dating Web site or app is a simple, fast, low-investment way to increase your opportunities to meet other singles and to make contact with more potential partners than you would meet otherwise. This is particularly helpful for people in thinner dating markets (eg, gays, lesbians, middle-age heterosexuals, and rural dwellers) or people seeking a companion of a particular type or lifestyle.^7,8 Many internet dating tools claim that their matching algorithms can increase your chances of meeting someone you will find compatible (although research questions whether the algorithms really work⁸). Dating sites and apps also let users engage in brief, computer-mediated communications that can foster greater attraction and comfort before meeting for a first date.⁸

Appeal to psychiatrists

Online dating may have special appeal to young psychiatrists such as Dr. R. Oddly enough, being a mental health professional can leave you socially isolated. Many people react cautiously when they learn you are a psychiatrist—they think you are evaluating them (and let’s face it: often, this is true).⁹ Psychiatrists should be cordial but circumspect in conducting work relationships, which limits the type and amount of social life they might generate in the setting where many people meet their future spouses.¹⁰

Online dating can help single psychiatrists overcome these barriers. Scientifically minded physicians can find plenty of research-grounded advice for improving online dating chances.^11-14 Two medical researchers even published a meta-analysis of evidence-based methods that can improve the chances of converting online contacts to a first date.¹⁵

Caution: Hazards ahead

When seeking romance online, psychiatrists shouldn’t forget their professional obligations, including the duty to maintain clear boundaries between their social and work lives.¹⁶ If Dr. R decides to try online dating, she will be making it possible for curious patients to gain access to some of her personal information. She will have to figure out how to avoid jeopardizing her professional reputation or inadvertently opening the door to sexual misconduct.¹⁷

Boundaries online. Psychiatrists use the term “boundaries” to refer to how they structure appointments and monitor their behavior during therapy to keep the treatment relationship free of personal, sexual, and romantic influences. Keeping one’s emotional life out of treatment helps prevent exploitation of patients and fosters a sense of safety and assurance that the physician is acting solely with the patient’s interest in mind. Breaching boundaries in ways that exploit patients or serve the doctor’s needs can undermine treatment, harm patients, and result in serious professional consequences.¹⁸

 

Maintaining appropriate boundaries can be challenging for psychiatrists who want to date online because the outside-the-office context can muddy the distinction between one’s professional and personal identity. Online dating environments make it easier for physicians to inadvertently initiate social or romantic interactions with people they have treated but don’t recognize (something the authors know has happened to colleagues). Additionally, the internet’s anonymity leaves users vulnerable to being lured into interactions with someone who is using a fictional online persona—an activity colloquially called “catfishing.”¹⁹

Although patients may play an active role in boundary breaches, the physician bears sole responsibility for maintaining proper limits within the therapeutic relationship.¹⁸ For many psychiatrists, innocuous but non-professional interactions with patients have been the first steps down a “slippery slope” toward serious boundary violations, including sexual contact—an activity that both the American Medical Association (AMA) and the American Psychiatric Association deem categorically unethical and that can lead to malpractice lawsuits, sanctions by medical license boards, and (in some jurisdictions) criminal prosecution.²⁰ When using social media and online dating tools, psychiatrists should avoid even seemingly minor boundary violations as a safeguard against more serious transgressions.^20,21

Reports of online misconduct by medical trainees and practitioners are plentiful.^22,23 In response, several medical organizations, including the AMA and the American College of Physicians, have developed professional guidelines for appropriate behavior on social media by physicians.^24,25 These guidelines stress the importance of maintaining a professional presence when one’s online activity is publicly viewable.

How much self-disclosure is appropriate?
Traditionally, psychiatrists (including psychoanalysts) have felt that occasional, limited, well-considered references to oneself are acceptable and even helpful in treatment.²⁶ The majority of therapists report using therapy-relevant self-disclosure, but they are cautious about what they say. Conscientious therapists avoid self-disclosure to satisfy their own needs, and they avoid self-disclosure with patients for whom it would have detrimental effects.^18,27

Dating Web sites contain a lot of personal information that physicians don’t usually share with patients. Although physicians who use social media are advised to be careful about the information they make available to the public,²⁸ this is more difficult to do with dating applications, where revealing some information about yourself is necessary for making meaningful connections. Creating an online dating profile means that you are potentially letting patients or patients’ relatives know about your place of residence, income, sexual orientation, number of children, and interests. You will need to think about how you will respond if a patient unexpectedly comments on your dating profile during a session or asks you out.

Beyond creating awkward situations, self-disclosure can have treatment implications, and it’s impossible to know how a particular comment will affect a particular client in a particular situation.²⁹ Psychiatrists who engage in online dating may want to limit their posted personal information only to what they would feel reasonably comfortable with having patients know about them, and hope this will suffice to capture the attention of potential partners.

Sustaining professionalism while remaining human. The term “medical professionalism” originally referred to ethical conduct during the practice of medicine³⁰ and to sustaining one’s commitment to patients, fellow professionals, and the institutions within which health care is provided.³¹ More recently, however, discussions of medical professionalism have encompassed how physicians comport themselves away from work. Physicians’ actions outside the office or hospital—and especially what they say, do, or post online—have a powerful effect on perceptions of their institutions and the medical profession as a whole.^25,32

Photos and comments posted by physicians can be seen by millions and can have major repercussions for employment prospects and public perceptions.²⁵ Questionable postings by physicians on social media outlets have resulted in disciplinary actions by licensing authorities and have damaged physicians’ careers.²³

What seems appropriate for a dating Web site varies from person to person. A suggestive smile or flirtatious joke that most people would find harmless may strike others as provocative. Derogatory language, depictions of intoxication or substance abuse, and inappropriate patient-related comments are clear-cut mistakes.^32-34 But also keep in mind that what medical professionals find acceptable to post on social networking sites does not always match what the general public thinks.³⁵

In the Table,^6,36 we provide some suggestions that might help Dr. R decide what to put in her profile and how to behave if she decides to seek romantic partners online.

 

Bottom Line

Most adults want to have happy romantic relationships. But meeting eligible companions and finding the time to date can feel nearly impossible to many physicians, especially residents, whose 80-hour work weeks limit opportunities to meet potential partners.¹

So it’s no surprise that Dr. R’s friends have suggested that she try online dating. If she does, she would be far from alone: 15% of U.S. adults have sought relationships online, and one-fourth of people in their 20s have used a mobile dating app.^2,3 Online dating might work well for Dr. R, too. Between 2005 and 2012, more than one-third of U.S. marriages started online, and these marriages seemed happier and ended in separation or divorce less often than marriages that started in more traditional ways.⁴

Online dating is just one example of how “the permeation of online and social media into everyday life is placing doctors in new situations that they find difficult to navigate.”⁵ Many physicians—psychiatrists among them—date online. Yet, like Dr. R, physicians are cautious about using social media because of worries about public exposure and legal concerns.⁵ Moreover, medical associations haven’t developed guidelines that would help physicians reconcile their professional and personal lives if they seek companionship online.⁶

Although we don’t have complete answers to Dr. R’s questions, we have gathered some ideas and information that she might find helpful. Read on as we explore:

• potential benefits for psychiatrists who try online dating
• problems when physicians use social media
• how to minimize mishaps if you seek companionship online.

Advantages and benefits

Online dating is most popular among young adults. But singles and divorcees of all ages, sexual orientations, and backgrounds are increasingly seeking long-term relationships with internet-based dating tools rather than hoping to meet people through family, friends, church, and the workplace. It has become common—and no longer stigmatizing—for couples to say they met online.^2,7

A dating Web site or app is a simple, fast, low-investment way to increase your opportunities to meet other singles and to make contact with more potential partners than you would meet otherwise. This is particularly helpful for people in thinner dating markets (eg, gays, lesbians, middle-age heterosexuals, and rural dwellers) or people seeking a companion of a particular type or lifestyle.^7,8 Many internet dating tools claim that their matching algorithms can increase your chances of meeting someone you will find compatible (although research questions whether the algorithms really work⁸). Dating sites and apps also let users engage in brief, computer-mediated communications that can foster greater attraction and comfort before meeting for a first date.⁸

Appeal to psychiatrists

Online dating may have special appeal to young psychiatrists such as Dr. R. Oddly enough, being a mental health professional can leave you socially isolated. Many people react cautiously when they learn you are a psychiatrist—they think you are evaluating them (and let’s face it: often, this is true).⁹ Psychiatrists should be cordial but circumspect in conducting work relationships, which limits the type and amount of social life they might generate in the setting where many people meet their future spouses.¹⁰

Online dating can help single psychiatrists overcome these barriers. Scientifically minded physicians can find plenty of research-grounded advice for improving online dating chances.^11-14 Two medical researchers even published a meta-analysis of evidence-based methods that can improve the chances of converting online contacts to a first date.¹⁵

Caution: Hazards ahead

When seeking romance online, psychiatrists shouldn’t forget their professional obligations, including the duty to maintain clear boundaries between their social and work lives.¹⁶ If Dr. R decides to try online dating, she will be making it possible for curious patients to gain access to some of her personal information. She will have to figure out how to avoid jeopardizing her professional reputation or inadvertently opening the door to sexual misconduct.¹⁷

Boundaries online. Psychiatrists use the term “boundaries” to refer to how they structure appointments and monitor their behavior during therapy to keep the treatment relationship free of personal, sexual, and romantic influences. Keeping one’s emotional life out of treatment helps prevent exploitation of patients and fosters a sense of safety and assurance that the physician is acting solely with the patient’s interest in mind. Breaching boundaries in ways that exploit patients or serve the doctor’s needs can undermine treatment, harm patients, and result in serious professional consequences.¹⁸

 

Maintaining appropriate boundaries can be challenging for psychiatrists who want to date online because the outside-the-office context can muddy the distinction between one’s professional and personal identity. Online dating environments make it easier for physicians to inadvertently initiate social or romantic interactions with people they have treated but don’t recognize (something the authors know has happened to colleagues). Additionally, the internet’s anonymity leaves users vulnerable to being lured into interactions with someone who is using a fictional online persona—an activity colloquially called “catfishing.”¹⁹

Although patients may play an active role in boundary breaches, the physician bears sole responsibility for maintaining proper limits within the therapeutic relationship.¹⁸ For many psychiatrists, innocuous but non-professional interactions with patients have been the first steps down a “slippery slope” toward serious boundary violations, including sexual contact—an activity that both the American Medical Association (AMA) and the American Psychiatric Association deem categorically unethical and that can lead to malpractice lawsuits, sanctions by medical license boards, and (in some jurisdictions) criminal prosecution.²⁰ When using social media and online dating tools, psychiatrists should avoid even seemingly minor boundary violations as a safeguard against more serious transgressions.^20,21

Reports of online misconduct by medical trainees and practitioners are plentiful.^22,23 In response, several medical organizations, including the AMA and the American College of Physicians, have developed professional guidelines for appropriate behavior on social media by physicians.^24,25 These guidelines stress the importance of maintaining a professional presence when one’s online activity is publicly viewable.

How much self-disclosure is appropriate?
Traditionally, psychiatrists (including psychoanalysts) have felt that occasional, limited, well-considered references to oneself are acceptable and even helpful in treatment.²⁶ The majority of therapists report using therapy-relevant self-disclosure, but they are cautious about what they say. Conscientious therapists avoid self-disclosure to satisfy their own needs, and they avoid self-disclosure with patients for whom it would have detrimental effects.^18,27

Dating Web sites contain a lot of personal information that physicians don’t usually share with patients. Although physicians who use social media are advised to be careful about the information they make available to the public,²⁸ this is more difficult to do with dating applications, where revealing some information about yourself is necessary for making meaningful connections. Creating an online dating profile means that you are potentially letting patients or patients’ relatives know about your place of residence, income, sexual orientation, number of children, and interests. You will need to think about how you will respond if a patient unexpectedly comments on your dating profile during a session or asks you out.

Beyond creating awkward situations, self-disclosure can have treatment implications, and it’s impossible to know how a particular comment will affect a particular client in a particular situation.²⁹ Psychiatrists who engage in online dating may want to limit their posted personal information only to what they would feel reasonably comfortable with having patients know about them, and hope this will suffice to capture the attention of potential partners.

Sustaining professionalism while remaining human. The term “medical professionalism” originally referred to ethical conduct during the practice of medicine³⁰ and to sustaining one’s commitment to patients, fellow professionals, and the institutions within which health care is provided.³¹ More recently, however, discussions of medical professionalism have encompassed how physicians comport themselves away from work. Physicians’ actions outside the office or hospital—and especially what they say, do, or post online—have a powerful effect on perceptions of their institutions and the medical profession as a whole.^25,32

Photos and comments posted by physicians can be seen by millions and can have major repercussions for employment prospects and public perceptions.²⁵ Questionable postings by physicians on social media outlets have resulted in disciplinary actions by licensing authorities and have damaged physicians’ careers.²³

What seems appropriate for a dating Web site varies from person to person. A suggestive smile or flirtatious joke that most people would find harmless may strike others as provocative. Derogatory language, depictions of intoxication or substance abuse, and inappropriate patient-related comments are clear-cut mistakes.^32-34 But also keep in mind that what medical professionals find acceptable to post on social networking sites does not always match what the general public thinks.³⁵

In the Table,^6,36 we provide some suggestions that might help Dr. R decide what to put in her profile and how to behave if she decides to seek romantic partners online.

 

Bottom Line

Most adults want to have happy romantic relationships. But meeting eligible companions and finding the time to date can feel nearly impossible to many physicians, especially residents, whose 80-hour work weeks limit opportunities to meet potential partners.¹

So it’s no surprise that Dr. R’s friends have suggested that she try online dating. If she does, she would be far from alone: 15% of U.S. adults have sought relationships online, and one-fourth of people in their 20s have used a mobile dating app.^2,3 Online dating might work well for Dr. R, too. Between 2005 and 2012, more than one-third of U.S. marriages started online, and these marriages seemed happier and ended in separation or divorce less often than marriages that started in more traditional ways.⁴

Online dating is just one example of how “the permeation of online and social media into everyday life is placing doctors in new situations that they find difficult to navigate.”⁵ Many physicians—psychiatrists among them—date online. Yet, like Dr. R, physicians are cautious about using social media because of worries about public exposure and legal concerns.⁵ Moreover, medical associations haven’t developed guidelines that would help physicians reconcile their professional and personal lives if they seek companionship online.⁶

Although we don’t have complete answers to Dr. R’s questions, we have gathered some ideas and information that she might find helpful. Read on as we explore:

• potential benefits for psychiatrists who try online dating
• problems when physicians use social media
• how to minimize mishaps if you seek companionship online.

Advantages and benefits

Online dating is most popular among young adults. But singles and divorcees of all ages, sexual orientations, and backgrounds are increasingly seeking long-term relationships with internet-based dating tools rather than hoping to meet people through family, friends, church, and the workplace. It has become common—and no longer stigmatizing—for couples to say they met online.^2,7

A dating Web site or app is a simple, fast, low-investment way to increase your opportunities to meet other singles and to make contact with more potential partners than you would meet otherwise. This is particularly helpful for people in thinner dating markets (eg, gays, lesbians, middle-age heterosexuals, and rural dwellers) or people seeking a companion of a particular type or lifestyle.^7,8 Many internet dating tools claim that their matching algorithms can increase your chances of meeting someone you will find compatible (although research questions whether the algorithms really work⁸). Dating sites and apps also let users engage in brief, computer-mediated communications that can foster greater attraction and comfort before meeting for a first date.⁸

Appeal to psychiatrists

Online dating may have special appeal to young psychiatrists such as Dr. R. Oddly enough, being a mental health professional can leave you socially isolated. Many people react cautiously when they learn you are a psychiatrist—they think you are evaluating them (and let’s face it: often, this is true).⁹ Psychiatrists should be cordial but circumspect in conducting work relationships, which limits the type and amount of social life they might generate in the setting where many people meet their future spouses.¹⁰

Online dating can help single psychiatrists overcome these barriers. Scientifically minded physicians can find plenty of research-grounded advice for improving online dating chances.^11-14 Two medical researchers even published a meta-analysis of evidence-based methods that can improve the chances of converting online contacts to a first date.¹⁵

Caution: Hazards ahead

When seeking romance online, psychiatrists shouldn’t forget their professional obligations, including the duty to maintain clear boundaries between their social and work lives.¹⁶ If Dr. R decides to try online dating, she will be making it possible for curious patients to gain access to some of her personal information. She will have to figure out how to avoid jeopardizing her professional reputation or inadvertently opening the door to sexual misconduct.¹⁷

Boundaries online. Psychiatrists use the term “boundaries” to refer to how they structure appointments and monitor their behavior during therapy to keep the treatment relationship free of personal, sexual, and romantic influences. Keeping one’s emotional life out of treatment helps prevent exploitation of patients and fosters a sense of safety and assurance that the physician is acting solely with the patient’s interest in mind. Breaching boundaries in ways that exploit patients or serve the doctor’s needs can undermine treatment, harm patients, and result in serious professional consequences.¹⁸

 

Maintaining appropriate boundaries can be challenging for psychiatrists who want to date online because the outside-the-office context can muddy the distinction between one’s professional and personal identity. Online dating environments make it easier for physicians to inadvertently initiate social or romantic interactions with people they have treated but don’t recognize (something the authors know has happened to colleagues). Additionally, the internet’s anonymity leaves users vulnerable to being lured into interactions with someone who is using a fictional online persona—an activity colloquially called “catfishing.”¹⁹

Although patients may play an active role in boundary breaches, the physician bears sole responsibility for maintaining proper limits within the therapeutic relationship.¹⁸ For many psychiatrists, innocuous but non-professional interactions with patients have been the first steps down a “slippery slope” toward serious boundary violations, including sexual contact—an activity that both the American Medical Association (AMA) and the American Psychiatric Association deem categorically unethical and that can lead to malpractice lawsuits, sanctions by medical license boards, and (in some jurisdictions) criminal prosecution.²⁰ When using social media and online dating tools, psychiatrists should avoid even seemingly minor boundary violations as a safeguard against more serious transgressions.^20,21

Reports of online misconduct by medical trainees and practitioners are plentiful.^22,23 In response, several medical organizations, including the AMA and the American College of Physicians, have developed professional guidelines for appropriate behavior on social media by physicians.^24,25 These guidelines stress the importance of maintaining a professional presence when one’s online activity is publicly viewable.

How much self-disclosure is appropriate?
Traditionally, psychiatrists (including psychoanalysts) have felt that occasional, limited, well-considered references to oneself are acceptable and even helpful in treatment.²⁶ The majority of therapists report using therapy-relevant self-disclosure, but they are cautious about what they say. Conscientious therapists avoid self-disclosure to satisfy their own needs, and they avoid self-disclosure with patients for whom it would have detrimental effects.^18,27

Dating Web sites contain a lot of personal information that physicians don’t usually share with patients. Although physicians who use social media are advised to be careful about the information they make available to the public,²⁸ this is more difficult to do with dating applications, where revealing some information about yourself is necessary for making meaningful connections. Creating an online dating profile means that you are potentially letting patients or patients’ relatives know about your place of residence, income, sexual orientation, number of children, and interests. You will need to think about how you will respond if a patient unexpectedly comments on your dating profile during a session or asks you out.

Beyond creating awkward situations, self-disclosure can have treatment implications, and it’s impossible to know how a particular comment will affect a particular client in a particular situation.²⁹ Psychiatrists who engage in online dating may want to limit their posted personal information only to what they would feel reasonably comfortable with having patients know about them, and hope this will suffice to capture the attention of potential partners.

Sustaining professionalism while remaining human. The term “medical professionalism” originally referred to ethical conduct during the practice of medicine³⁰ and to sustaining one’s commitment to patients, fellow professionals, and the institutions within which health care is provided.³¹ More recently, however, discussions of medical professionalism have encompassed how physicians comport themselves away from work. Physicians’ actions outside the office or hospital—and especially what they say, do, or post online—have a powerful effect on perceptions of their institutions and the medical profession as a whole.^25,32

Photos and comments posted by physicians can be seen by millions and can have major repercussions for employment prospects and public perceptions.²⁵ Questionable postings by physicians on social media outlets have resulted in disciplinary actions by licensing authorities and have damaged physicians’ careers.²³

What seems appropriate for a dating Web site varies from person to person. A suggestive smile or flirtatious joke that most people would find harmless may strike others as provocative. Derogatory language, depictions of intoxication or substance abuse, and inappropriate patient-related comments are clear-cut mistakes.^32-34 But also keep in mind that what medical professionals find acceptable to post on social networking sites does not always match what the general public thinks.³⁵

In the Table,^6,36 we provide some suggestions that might help Dr. R decide what to put in her profile and how to behave if she decides to seek romantic partners online.

 

Bottom Line

Pharmacogenomics—the study of how genetic variability influences drug response—is increasingly being used to personalize pharmacotherapy. Used in the context of other clinical variables, genetic-based drug selection and dosing could help clinicians choose the right therapy for a patient, thus minimizing the incidence of treatment failure and intolerable side effects. Pharmacogenomics could be particularly useful in psychiatric pharmacotherapy, where response rates are low and the risk of adverse effects and nonadherence is high.

Despite the potential benefits of pharmacogenetic testing, many barriers prevent its routine use in practice, including a lack of knowledge about how to (1) order gene tests, (2) interpret results for an individual patient, and (3) apply those results to care. To help bridge this knowledge gap, we list practical, freely available pharmacogenomics resources that a psychiatric practitioner can use.

CPIC guidelines

The Clinical Pharmacogenetics Implement­ation Consortium (CPIC) is an international collaboration of pharmacogenomics experts that publishes clinical practice guidelines on using pharmacogenetic test results to optimize drug therapy.¹ Note: These guidelines do not address when tests should be ordered, but rather how results should be used to guide prescribing.

Each CPIC guideline includes a summary of the gene, the drug, and their pharmacogenetic relationship, as well as clear guidance on interpreting pharmacogenetic test results, including:

• how to convert genotype to phenotype
• how to modify drug selection or dosing based on these results
• the level of evidence for each recommendation.

CPIC guidelines and supplementary information are available on the CPIC Web site (https://www.cpicpgx.org) and are updated regularly. Table 1 provides current CPIC guidelines for neuropsychiatric drugs.

 

PharmGKB

Providing searchable annotations of pharmacogenetic variants, PharmGKB summarizes the clinical implications of important pharmacogenes, and includes FDA drug labels containing pharmacogenomics information (https://www.pharmgkb.org).² The Web site also provides users with evidence-based figures illustrating the pharmacokinetic and pharmacodynamic pathways of drugs that have pharmacogenetic implications.

PharmGKB is an excellent resource to consult for a summary of available evidence when a CPIC guideline does not exist for a given gene or drug.

Other resources

Table 2^3-8 lists other online resources for practitioners to aid in advancing pharmacogenomics knowledge as it relates to practice.

Putting guidance to best use

Familiarity with resources such as CPIC guidelines and PharmGKB can help ensure that patients with pharmacogenetic test results receive genetically tailored therapy that is more likely to be effective and less likely to cause adverse effects.^9,10

Pharmacogenomics—the study of how genetic variability influences drug response—is increasingly being used to personalize pharmacotherapy. Used in the context of other clinical variables, genetic-based drug selection and dosing could help clinicians choose the right therapy for a patient, thus minimizing the incidence of treatment failure and intolerable side effects. Pharmacogenomics could be particularly useful in psychiatric pharmacotherapy, where response rates are low and the risk of adverse effects and nonadherence is high.

Despite the potential benefits of pharmacogenetic testing, many barriers prevent its routine use in practice, including a lack of knowledge about how to (1) order gene tests, (2) interpret results for an individual patient, and (3) apply those results to care. To help bridge this knowledge gap, we list practical, freely available pharmacogenomics resources that a psychiatric practitioner can use.

CPIC guidelines

The Clinical Pharmacogenetics Implement­ation Consortium (CPIC) is an international collaboration of pharmacogenomics experts that publishes clinical practice guidelines on using pharmacogenetic test results to optimize drug therapy.¹ Note: These guidelines do not address when tests should be ordered, but rather how results should be used to guide prescribing.

Each CPIC guideline includes a summary of the gene, the drug, and their pharmacogenetic relationship, as well as clear guidance on interpreting pharmacogenetic test results, including:

• how to convert genotype to phenotype
• how to modify drug selection or dosing based on these results
• the level of evidence for each recommendation.

CPIC guidelines and supplementary information are available on the CPIC Web site (https://www.cpicpgx.org) and are updated regularly. Table 1 provides current CPIC guidelines for neuropsychiatric drugs.

 

PharmGKB

Providing searchable annotations of pharmacogenetic variants, PharmGKB summarizes the clinical implications of important pharmacogenes, and includes FDA drug labels containing pharmacogenomics information (https://www.pharmgkb.org).² The Web site also provides users with evidence-based figures illustrating the pharmacokinetic and pharmacodynamic pathways of drugs that have pharmacogenetic implications.

PharmGKB is an excellent resource to consult for a summary of available evidence when a CPIC guideline does not exist for a given gene or drug.

Other resources

Table 2^3-8 lists other online resources for practitioners to aid in advancing pharmacogenomics knowledge as it relates to practice.

Putting guidance to best use

Familiarity with resources such as CPIC guidelines and PharmGKB can help ensure that patients with pharmacogenetic test results receive genetically tailored therapy that is more likely to be effective and less likely to cause adverse effects.^9,10

Pharmacogenomics—the study of how genetic variability influences drug response—is increasingly being used to personalize pharmacotherapy. Used in the context of other clinical variables, genetic-based drug selection and dosing could help clinicians choose the right therapy for a patient, thus minimizing the incidence of treatment failure and intolerable side effects. Pharmacogenomics could be particularly useful in psychiatric pharmacotherapy, where response rates are low and the risk of adverse effects and nonadherence is high.

Despite the potential benefits of pharmacogenetic testing, many barriers prevent its routine use in practice, including a lack of knowledge about how to (1) order gene tests, (2) interpret results for an individual patient, and (3) apply those results to care. To help bridge this knowledge gap, we list practical, freely available pharmacogenomics resources that a psychiatric practitioner can use.

CPIC guidelines

The Clinical Pharmacogenetics Implement­ation Consortium (CPIC) is an international collaboration of pharmacogenomics experts that publishes clinical practice guidelines on using pharmacogenetic test results to optimize drug therapy.¹ Note: These guidelines do not address when tests should be ordered, but rather how results should be used to guide prescribing.

Each CPIC guideline includes a summary of the gene, the drug, and their pharmacogenetic relationship, as well as clear guidance on interpreting pharmacogenetic test results, including:

• how to convert genotype to phenotype
• how to modify drug selection or dosing based on these results
• the level of evidence for each recommendation.

CPIC guidelines and supplementary information are available on the CPIC Web site (https://www.cpicpgx.org) and are updated regularly. Table 1 provides current CPIC guidelines for neuropsychiatric drugs.

 

PharmGKB

Providing searchable annotations of pharmacogenetic variants, PharmGKB summarizes the clinical implications of important pharmacogenes, and includes FDA drug labels containing pharmacogenomics information (https://www.pharmgkb.org).² The Web site also provides users with evidence-based figures illustrating the pharmacokinetic and pharmacodynamic pathways of drugs that have pharmacogenetic implications.

PharmGKB is an excellent resource to consult for a summary of available evidence when a CPIC guideline does not exist for a given gene or drug.

Other resources

Table 2^3-8 lists other online resources for practitioners to aid in advancing pharmacogenomics knowledge as it relates to practice.

Putting guidance to best use

Familiarity with resources such as CPIC guidelines and PharmGKB can help ensure that patients with pharmacogenetic test results receive genetically tailored therapy that is more likely to be effective and less likely to cause adverse effects.^9,10

Ivy Sports Medicine (http://www.ivysportsmed.com/en)

Collagen Meniscus Implant

The number of patients undergoing arthroscopic partial meniscectomy has continued to increase. However, this is potentially not a benign procedure, as there are increased contact pressures on the articular cartilage even with the removal of only a segment of the meniscus.

The Collagen Meniscus Implant (CMI, Ivy Sports Medicine) is a resorbable and biocompatible Type I collagen matrix that was developed to restore the segmental loss of meniscal tissue in the knee. It consists of a porous cross-linked matrix scaffold that allows for the ingrowth of the body’s own cells. The CMI is the only meniscal implant composed of purely biological materials and is available in an off-the-shelf supply.

The CMI is available in the United States for use in the restoration of segmental loss of the medial meniscus. The CMI can be utilized in either an acute or chronic situation. In the acute case, it would be indicated when the medial meniscus is irreparable, and that segment must be removed. In the chronic case, the patient would have had a previous partial meniscectomy and/or failed meniscus repair and had developed either pain or signs of early articular cartilage wear in the compartment. The procedure can be done arthroscopically and as an outpatient. The CMI can be kept on the shelf to be available as needed; it has a 2-year shelf life. There are specialized instruments for measuring the length of implant needed and for delivery of the implant.

The CMI has been utilized clinically for 18 years with excellent clinical results. Patients treated with CMI have benefited in over 80% of cases. Studies have demonstrated improved knee function, activity levels, and pain values from the pre- to postoperative periods.^1,2 In addition, functional improvements have been maintained for over 10 years. The reoperation rate has been demonstrated to be 10% to 20%, which is comparable to the reoperation rate after meniscal repair.

Surgical pearl: The surgical technique for insertion of the CMI is relatively uncomplicated (Figures A, B).

The first step is the resection of all dysfunctional meniscus and then creating 90° walls to attach to posteriorly and anteriorly, and a firm peripheral rim to attach the CMI into.

The second step is to measure the length of your meniscus defect with the measuring rod.

Once measured, you want to oversize the implant 10% to 15% (ie, if you measure 30 mm, you will cut at least 34 mm). Use the measuring rod to measure the length of the CMI and mark your length. Use a new scalpel blade to cut the CMI.

 

Place the measured CMI into the delivery clamp and insert through a mini-arthrotomy into the meniscal defect. The fixation technique of the CMI is entirely up to the implanting surgeon. Most surgeons have used a combination of all-inside and inside-out meniscus repair techniques. It is recommended to start fixing the CMI first posteriorly. The posterior stitch is usually an all-inside horizontal mattress stitch. Coming 1 cm anteriorly, place a vertical mattress stitch. Continue this method sequentially while moving anteriorly. The anterior suture is the surgeon’s choice for device, but it should be a horizontal mattress like the most posterior stitch. It is important while tightening your suture tension to apply the concept of “approximated and not strangulated.” Once completed, close wounds in typical fashion.

Ivy Sports Medicine (http://www.ivysportsmed.com/en)

Collagen Meniscus Implant

The number of patients undergoing arthroscopic partial meniscectomy has continued to increase. However, this is potentially not a benign procedure, as there are increased contact pressures on the articular cartilage even with the removal of only a segment of the meniscus.

The Collagen Meniscus Implant (CMI, Ivy Sports Medicine) is a resorbable and biocompatible Type I collagen matrix that was developed to restore the segmental loss of meniscal tissue in the knee. It consists of a porous cross-linked matrix scaffold that allows for the ingrowth of the body’s own cells. The CMI is the only meniscal implant composed of purely biological materials and is available in an off-the-shelf supply.

The CMI is available in the United States for use in the restoration of segmental loss of the medial meniscus. The CMI can be utilized in either an acute or chronic situation. In the acute case, it would be indicated when the medial meniscus is irreparable, and that segment must be removed. In the chronic case, the patient would have had a previous partial meniscectomy and/or failed meniscus repair and had developed either pain or signs of early articular cartilage wear in the compartment. The procedure can be done arthroscopically and as an outpatient. The CMI can be kept on the shelf to be available as needed; it has a 2-year shelf life. There are specialized instruments for measuring the length of implant needed and for delivery of the implant.

The CMI has been utilized clinically for 18 years with excellent clinical results. Patients treated with CMI have benefited in over 80% of cases. Studies have demonstrated improved knee function, activity levels, and pain values from the pre- to postoperative periods.^1,2 In addition, functional improvements have been maintained for over 10 years. The reoperation rate has been demonstrated to be 10% to 20%, which is comparable to the reoperation rate after meniscal repair.

Surgical pearl: The surgical technique for insertion of the CMI is relatively uncomplicated (Figures A, B).

The first step is the resection of all dysfunctional meniscus and then creating 90° walls to attach to posteriorly and anteriorly, and a firm peripheral rim to attach the CMI into.

The second step is to measure the length of your meniscus defect with the measuring rod.

Once measured, you want to oversize the implant 10% to 15% (ie, if you measure 30 mm, you will cut at least 34 mm). Use the measuring rod to measure the length of the CMI and mark your length. Use a new scalpel blade to cut the CMI.

 

Place the measured CMI into the delivery clamp and insert through a mini-arthrotomy into the meniscal defect. The fixation technique of the CMI is entirely up to the implanting surgeon. Most surgeons have used a combination of all-inside and inside-out meniscus repair techniques. It is recommended to start fixing the CMI first posteriorly. The posterior stitch is usually an all-inside horizontal mattress stitch. Coming 1 cm anteriorly, place a vertical mattress stitch. Continue this method sequentially while moving anteriorly. The anterior suture is the surgeon’s choice for device, but it should be a horizontal mattress like the most posterior stitch. It is important while tightening your suture tension to apply the concept of “approximated and not strangulated.” Once completed, close wounds in typical fashion.

Ivy Sports Medicine (http://www.ivysportsmed.com/en)

Collagen Meniscus Implant

The number of patients undergoing arthroscopic partial meniscectomy has continued to increase. However, this is potentially not a benign procedure, as there are increased contact pressures on the articular cartilage even with the removal of only a segment of the meniscus.

The Collagen Meniscus Implant (CMI, Ivy Sports Medicine) is a resorbable and biocompatible Type I collagen matrix that was developed to restore the segmental loss of meniscal tissue in the knee. It consists of a porous cross-linked matrix scaffold that allows for the ingrowth of the body’s own cells. The CMI is the only meniscal implant composed of purely biological materials and is available in an off-the-shelf supply.

The CMI is available in the United States for use in the restoration of segmental loss of the medial meniscus. The CMI can be utilized in either an acute or chronic situation. In the acute case, it would be indicated when the medial meniscus is irreparable, and that segment must be removed. In the chronic case, the patient would have had a previous partial meniscectomy and/or failed meniscus repair and had developed either pain or signs of early articular cartilage wear in the compartment. The procedure can be done arthroscopically and as an outpatient. The CMI can be kept on the shelf to be available as needed; it has a 2-year shelf life. There are specialized instruments for measuring the length of implant needed and for delivery of the implant.

The CMI has been utilized clinically for 18 years with excellent clinical results. Patients treated with CMI have benefited in over 80% of cases. Studies have demonstrated improved knee function, activity levels, and pain values from the pre- to postoperative periods.^1,2 In addition, functional improvements have been maintained for over 10 years. The reoperation rate has been demonstrated to be 10% to 20%, which is comparable to the reoperation rate after meniscal repair.

Surgical pearl: The surgical technique for insertion of the CMI is relatively uncomplicated (Figures A, B).

The first step is the resection of all dysfunctional meniscus and then creating 90° walls to attach to posteriorly and anteriorly, and a firm peripheral rim to attach the CMI into.

The second step is to measure the length of your meniscus defect with the measuring rod.

Once measured, you want to oversize the implant 10% to 15% (ie, if you measure 30 mm, you will cut at least 34 mm). Use the measuring rod to measure the length of the CMI and mark your length. Use a new scalpel blade to cut the CMI.

 

Place the measured CMI into the delivery clamp and insert through a mini-arthrotomy into the meniscal defect. The fixation technique of the CMI is entirely up to the implanting surgeon. Most surgeons have used a combination of all-inside and inside-out meniscus repair techniques. It is recommended to start fixing the CMI first posteriorly. The posterior stitch is usually an all-inside horizontal mattress stitch. Coming 1 cm anteriorly, place a vertical mattress stitch. Continue this method sequentially while moving anteriorly. The anterior suture is the surgeon’s choice for device, but it should be a horizontal mattress like the most posterior stitch. It is important while tightening your suture tension to apply the concept of “approximated and not strangulated.” Once completed, close wounds in typical fashion.

Practices and hospitals invest significant time and money in recruiting a new physician. From phone interviews to site visits to contract negotiations, it’s a long and involved process.

Beyond setting up a new physician’s office and appointment schedule, completing human resources paperwork, and ordering business cards, what does your practice do to support new physicians to ensure they are successful? Although a new colleague may arrive with excellent clinical skills, even the most promising surgeon can fall short if not provided with the right expectations, training, and collegial support. Here’s how to fast track your new physician to professional heights.

Credentialing Is Key

At the crux of a new physician’s success is credentialing him or her with hospitals and insurance plans before the official start date to see patients.

“A state medical license is the first domino,” says orthopedic surgeon Michael R. Marks, MD, MBA, consultant and coding educator with KarenZupko & Associates, Inc. Marks has led or participated in physician recruitment in orthopedic and multispecialty groups. The firm has developed a comprehensive New Physician Onboarding Checklist, available at https://www.karenzupko.com/new-physician-onboarding-checklist/.

“Without a medical license,” Marks continues, “you can’t get the new physician hospital privileges and you can’t get him or her credentialed with plans. Without being credentialed, the physician can’t bill for patients treated.” Because commercial carriers won’t allow retrospective billing for services already rendered, “even a 3-month delay in credentialing could cost an orthopedic practice $60,000 to $180,000 in lost revenue.”(These figures are based on typical revenue generated by several specialties, as well as professional experience with multiple practices.)

And if you think you can bill the new physician’s services under another partner’s name, you are incorrect. “The billing physician will have signed the note, but not have treated the patient,” warns Marks. “This is improper billing. Don’t do it.”

The remedy for ensuring that the new physician is credentialed is simple: get organized and plan ahead.

“When I first started participating in recruitment, I remember telling physicians, ‘I need you tomorrow!’” admits Amon T. Ferry, MD, a practicing orthopedist who leads recruitment efforts at IMS Orthopedics, a division of Integrated Medical Specialists in Phoenix, Arizona. “So they’d get hired before the practice was prepared and before credentialing was completed. Now, I set more realistic expectations,” he says, noting that in Arizona it takes 3 months to get a medical license, 6 months to contract with the hospital, and 9 months to get on insurance plans. And even after a plan has credentialed a new physician, “sometimes it still takes 4 to 6 weeks before the physician’s data is loaded into the plan’s computer systems.”

“The way to do credentialing right is to get all departments communicating,” Marks says. “If you keep everyone siloed, staff don’t understand that a lack of timeliness on their part impacts other areas of the practice.”

Ferry agrees, and says his group learned to organize its multiple departments after making mistakes and missing deadlines. “We now have an 8-page pre-employment application for new physicians,” he explains. “In addition to asking for contact information and everything we need to know in order to get the physician credentialed, we ask questions about malpractice suit history and whether there are issues with the medical board. We also ask about gaps in employment and details about where the physician has practiced in the past.” All of this is done to identify early whether credentialing will require more time and effort. Ferry says that the application has solved a number of processing problems the practice had in the past.

And whether credentialing is done within the practice or outsourced, Ferry says that it pays to be persistent. “Don’t sit back and assume it will get done. Even if you have outsourced credentialing to a company, someone must check with payers and hospitals weekly and provide the practice a status update.”

In one case, when getting a new physician contracted at a hospital was taking forever, Ferry directed the staff to call. “Turns out, they had been trying to reach us and had the wrong phone number,” he says. “When people are processing thousands of physician renewals, things get lost. You have to be proactive and be your own advocate. Don’t be afraid to be the squeaky wheel.”

 

Staff Relationships and Operational Wisdom

Marks points out that in many practices, the new physician is shown the examination rooms and his or her office, gets electronic health record (EHR) training, and that’s it. To be successful, Marks insists that the new physician must build relationships with personnel and understand operational basics. “In other business industries, successful leaders understand at least the basics of what everyone does. Part of how they do this is by getting to know the employees.”

Ideally, Marks advises that new physicians spend time with each staff member. “The best time to do this is in the first few weeks of employment,” he suggests. “Odds are, the new orthopedist doesn’t have 40 patients a day on the schedule. So schedule conversations within the first few weeks or month, and schedule observation time as well. When a patient complains about check-in, the physician will have an understanding of how things work up there if he or she knows the basic processes.” The new doctor should also spend time in the billing office getting to know the challenges faced by staff, and sit with the surgery coordinator to understand the process of getting cases booked and scheduled.

Plan for an initial and then periodic meetings with the practice administrator and other supervisors. Transparency about business operations, data, and strategy will help the new physician get up to speed faster.

“The executive director of our group was an absolutely invaluable information resource,” says Kathryn J. McCarthy, MD, an orthopedic spine surgeon with Arkansas Specialty Orthopaedics in Little Rock, Arkansas. McCarthy has been with the group for 3 years.

The practice’s executive director developed and presented a PowerPoint (Microsoft) explaining general business procedures, expectations for the coding and billing process, and pertinent compliance and risk issues. She had also developed an interactive model of the compensation formula and buy-in program, using Excel (Microsoft). McCarthy met with the executive director at 3 months, 6 months, and 9 months to review her patient and case volumes and how they were trending against the estimates made about her income, bonus, and buy-in status.

From the new physician’s perspective, McCarthy says having the new physician understand the complexities of certain business systems helps them understand things better. “If you sit in the business meetings long enough, you figure it out,” she says, “but it would have made some of the growing pains less painful if I understood what my overhead charge was going to, or more about the workflow of the clinic.” She adds that an overview of hospital relationships and any overlapping ownership interests will benefit new physicians as well.

“I think it’s useful to provide new physicians with a history of the practice and the vision of where things are going,” McCarthy says. “It’s important to outline the business vision, especially for subspecialties. If you explain to the new physician where you want to grow and when the practice plans on bringing on the next physician, it could really drive someone to grow their practice.”

Don’t Underestimate the Need for Coding Training

“When fellows come out of training, they are comfortable with clinical activity but uncomfortable with business administration,” Marks says. “And we know they don’t get training on coding and billing.”

Marks cites a recent conversation at an American Academy of Orthopaedic Surgeons (AAOS) coding workshop. “A surgeon new in practice told me, ‘I’ve been in practice for 4 months. I understand the clinical side but nobody educated me about coding and billing before this course.’” Practices must provide new physicians with coding and documentation training, and coach them to make sure they feel up to speed and comfortable. “The practice’s future revenue depends on it,” Marks says.

McCarthy agrees. “Having an administrative mentorship for coding is incredibly valuable. They don’t teach it in school.”

So from a practical standpoint, purchase AAOS’ Orthopaedic Code-X, a software tool that will help the new physician navigate and integrate Current Procedural Terminology (CPT), ICD-10 (International Classification of Diseases, Tenth Revision), and other coding data easily and accurately. Send him or her to one of the Academy’s regional coding and reimbursement workshops as well. “It will behoove the practice to send them even before they start seeing patients,” Marks says.

And don’t just stop there. High-performing groups conduct peer reviews of evaluation and management (E/M) and operative notes, blinding the codes billed and discussing which CPT and ICD-10 codes are appropriate for the visit or case. “It will take time for the new physician to completely integrate coding with their clinical care,” says Marks. “Peer review sessions, as well as having a partner review codes before they go to the billing office, can help speed learning.”

 

Collegial Coaching Counts

The week before her official start day, Mc-Carthy scrubbed in as a first assist with each of her new partners. “It was a great way to start ramping up,” she says. “I could see what kind of equipment was present in the hospitals, and got a touch point for hospital logistics. Plus, as a young surgeon it’s great to see how your skill sets match up with your new partners, and which best practices are being deployed by the group.”

This kind of “collegial coaching” is a vital part of the clinical and cultural integration to the practice. Beyond providing clinical support, it builds relationships and trust among the group, and fosters collaboration.

Arkansas Specialty Orthopaedics organized McCarthy’s clinic and operating room (OR) schedules so that a partner was always present. “There was also someone I could bounce ideas off of,” McCarthy explains. “Every day in the OR, there was a partner there at the same time. If I got into a sticky situation, one of my colleagues was willing to come in and scrub in the OR.”

McCarthy says that patients responded favorably when she told them her plan was developed in conjunction with her partners. “Patients find comfort in knowing that several people’s opinions were considered,” she says. “And as a young surgeon, knowing that you have backup, even if you don’t use it, when caring for high-risk and complex cases really means a lot,” she says.

And although her group didn’t offer a formal mentoring program, McCarthy found that an informal mentorship grew organically when a friendship developed with one of her new partners. “In the first 6 months, every single weekend we sat by the pool and rolled through a ton of cases,” she says. “That was fabulous and it alleviated so much stress for me.” And when it was time for McCarthy to move into board case selection, this colleague and another were instrumental in her board preparation because, “they knew my style and where I would need to focus.”

IMS Orthopedics’ approach is to provide the staff and systems that allow new physicians to step up and take responsibility. “If they want to scrub in with me, that’s great. If they’d like to visit additional facilities and get the lay of the land, we encourage it. But we don’t do a lot of handholding. We set them up for success and make sure people are in place to help them,” says Ferry.

A Marketing Plan Is a Must

“The vast majority of practices do very little when it comes to thinking about how to market and build the practice of their new physician,” Marks says. “Practice-building is more of a challenge for surgical specialists today than it was in the old days when new surgeons could easily meet internists as they were rounding at the hospital. Now, a new physician and the practice must come up with a game plan.”

That game plan starts with the easy things: order business cards, schedule a photo shoot, and update the practice’s Web site pages with the physician’s biography and an introductory video. But with social media, online reviews, and subspecialty competition, Marks says practices must think beyond the basics. Think through each element of marketing, from online to outreach to developing referral relationships.

“I tell practices to draft a written marketing plan,” he says. “Not only does it provide a roadmap for the new physician, but also indicates that the practice has put some thought into how he or she can build a practice. It can make the new physician feel less overwhelmed knowing that he or she doesn’t have to do the marketing alone.” Once you’ve developed a list of actions, Marks suggests creating a spreadsheet with deadlines, and ensuring each action is completed.

McCarthy was scheduled to visit family practice clinics, and joined by the administrator who “handed out cookies and cards while I talked,” she says. Arkansas Specialty Orthopaedics also hired an external marketing firm to develop promotional opportunities for her. For example, “I was scheduled to appear on news channels, where I discussed new and interesting procedures,” she says. “It got my name out into the community.”

If your practice is too small to hire an outside firm, Marks suggests reaching out to agencies such as nursing homes, fitness centers, or the YMCA, which frequently offers educational programs for members. “Contact the administrators or medical directors in these organizations. A few minutes on the phone or a short visit can go a long way to building these relationships and getting your new physician on the map.”

As the old saying goes, an ounce of prevention is worth a pound of cure. Scheduling time for orientation, training, staff integration, and collegial coaching will speed up a new physician’s integration into the practice, and increase his or her opportunity for success.

Practices and hospitals invest significant time and money in recruiting a new physician. From phone interviews to site visits to contract negotiations, it’s a long and involved process.

Beyond setting up a new physician’s office and appointment schedule, completing human resources paperwork, and ordering business cards, what does your practice do to support new physicians to ensure they are successful? Although a new colleague may arrive with excellent clinical skills, even the most promising surgeon can fall short if not provided with the right expectations, training, and collegial support. Here’s how to fast track your new physician to professional heights.

Credentialing Is Key

At the crux of a new physician’s success is credentialing him or her with hospitals and insurance plans before the official start date to see patients.

“A state medical license is the first domino,” says orthopedic surgeon Michael R. Marks, MD, MBA, consultant and coding educator with KarenZupko & Associates, Inc. Marks has led or participated in physician recruitment in orthopedic and multispecialty groups. The firm has developed a comprehensive New Physician Onboarding Checklist, available at https://www.karenzupko.com/new-physician-onboarding-checklist/.

“Without a medical license,” Marks continues, “you can’t get the new physician hospital privileges and you can’t get him or her credentialed with plans. Without being credentialed, the physician can’t bill for patients treated.” Because commercial carriers won’t allow retrospective billing for services already rendered, “even a 3-month delay in credentialing could cost an orthopedic practice $60,000 to $180,000 in lost revenue.”(These figures are based on typical revenue generated by several specialties, as well as professional experience with multiple practices.)

And if you think you can bill the new physician’s services under another partner’s name, you are incorrect. “The billing physician will have signed the note, but not have treated the patient,” warns Marks. “This is improper billing. Don’t do it.”

The remedy for ensuring that the new physician is credentialed is simple: get organized and plan ahead.

“When I first started participating in recruitment, I remember telling physicians, ‘I need you tomorrow!’” admits Amon T. Ferry, MD, a practicing orthopedist who leads recruitment efforts at IMS Orthopedics, a division of Integrated Medical Specialists in Phoenix, Arizona. “So they’d get hired before the practice was prepared and before credentialing was completed. Now, I set more realistic expectations,” he says, noting that in Arizona it takes 3 months to get a medical license, 6 months to contract with the hospital, and 9 months to get on insurance plans. And even after a plan has credentialed a new physician, “sometimes it still takes 4 to 6 weeks before the physician’s data is loaded into the plan’s computer systems.”

“The way to do credentialing right is to get all departments communicating,” Marks says. “If you keep everyone siloed, staff don’t understand that a lack of timeliness on their part impacts other areas of the practice.”

Ferry agrees, and says his group learned to organize its multiple departments after making mistakes and missing deadlines. “We now have an 8-page pre-employment application for new physicians,” he explains. “In addition to asking for contact information and everything we need to know in order to get the physician credentialed, we ask questions about malpractice suit history and whether there are issues with the medical board. We also ask about gaps in employment and details about where the physician has practiced in the past.” All of this is done to identify early whether credentialing will require more time and effort. Ferry says that the application has solved a number of processing problems the practice had in the past.

And whether credentialing is done within the practice or outsourced, Ferry says that it pays to be persistent. “Don’t sit back and assume it will get done. Even if you have outsourced credentialing to a company, someone must check with payers and hospitals weekly and provide the practice a status update.”

In one case, when getting a new physician contracted at a hospital was taking forever, Ferry directed the staff to call. “Turns out, they had been trying to reach us and had the wrong phone number,” he says. “When people are processing thousands of physician renewals, things get lost. You have to be proactive and be your own advocate. Don’t be afraid to be the squeaky wheel.”

 

Staff Relationships and Operational Wisdom

Marks points out that in many practices, the new physician is shown the examination rooms and his or her office, gets electronic health record (EHR) training, and that’s it. To be successful, Marks insists that the new physician must build relationships with personnel and understand operational basics. “In other business industries, successful leaders understand at least the basics of what everyone does. Part of how they do this is by getting to know the employees.”

Ideally, Marks advises that new physicians spend time with each staff member. “The best time to do this is in the first few weeks of employment,” he suggests. “Odds are, the new orthopedist doesn’t have 40 patients a day on the schedule. So schedule conversations within the first few weeks or month, and schedule observation time as well. When a patient complains about check-in, the physician will have an understanding of how things work up there if he or she knows the basic processes.” The new doctor should also spend time in the billing office getting to know the challenges faced by staff, and sit with the surgery coordinator to understand the process of getting cases booked and scheduled.

Plan for an initial and then periodic meetings with the practice administrator and other supervisors. Transparency about business operations, data, and strategy will help the new physician get up to speed faster.

“The executive director of our group was an absolutely invaluable information resource,” says Kathryn J. McCarthy, MD, an orthopedic spine surgeon with Arkansas Specialty Orthopaedics in Little Rock, Arkansas. McCarthy has been with the group for 3 years.

The practice’s executive director developed and presented a PowerPoint (Microsoft) explaining general business procedures, expectations for the coding and billing process, and pertinent compliance and risk issues. She had also developed an interactive model of the compensation formula and buy-in program, using Excel (Microsoft). McCarthy met with the executive director at 3 months, 6 months, and 9 months to review her patient and case volumes and how they were trending against the estimates made about her income, bonus, and buy-in status.

From the new physician’s perspective, McCarthy says having the new physician understand the complexities of certain business systems helps them understand things better. “If you sit in the business meetings long enough, you figure it out,” she says, “but it would have made some of the growing pains less painful if I understood what my overhead charge was going to, or more about the workflow of the clinic.” She adds that an overview of hospital relationships and any overlapping ownership interests will benefit new physicians as well.

“I think it’s useful to provide new physicians with a history of the practice and the vision of where things are going,” McCarthy says. “It’s important to outline the business vision, especially for subspecialties. If you explain to the new physician where you want to grow and when the practice plans on bringing on the next physician, it could really drive someone to grow their practice.”

Don’t Underestimate the Need for Coding Training

“When fellows come out of training, they are comfortable with clinical activity but uncomfortable with business administration,” Marks says. “And we know they don’t get training on coding and billing.”

Marks cites a recent conversation at an American Academy of Orthopaedic Surgeons (AAOS) coding workshop. “A surgeon new in practice told me, ‘I’ve been in practice for 4 months. I understand the clinical side but nobody educated me about coding and billing before this course.’” Practices must provide new physicians with coding and documentation training, and coach them to make sure they feel up to speed and comfortable. “The practice’s future revenue depends on it,” Marks says.

McCarthy agrees. “Having an administrative mentorship for coding is incredibly valuable. They don’t teach it in school.”

So from a practical standpoint, purchase AAOS’ Orthopaedic Code-X, a software tool that will help the new physician navigate and integrate Current Procedural Terminology (CPT), ICD-10 (International Classification of Diseases, Tenth Revision), and other coding data easily and accurately. Send him or her to one of the Academy’s regional coding and reimbursement workshops as well. “It will behoove the practice to send them even before they start seeing patients,” Marks says.

And don’t just stop there. High-performing groups conduct peer reviews of evaluation and management (E/M) and operative notes, blinding the codes billed and discussing which CPT and ICD-10 codes are appropriate for the visit or case. “It will take time for the new physician to completely integrate coding with their clinical care,” says Marks. “Peer review sessions, as well as having a partner review codes before they go to the billing office, can help speed learning.”

 

Collegial Coaching Counts

The week before her official start day, Mc-Carthy scrubbed in as a first assist with each of her new partners. “It was a great way to start ramping up,” she says. “I could see what kind of equipment was present in the hospitals, and got a touch point for hospital logistics. Plus, as a young surgeon it’s great to see how your skill sets match up with your new partners, and which best practices are being deployed by the group.”

This kind of “collegial coaching” is a vital part of the clinical and cultural integration to the practice. Beyond providing clinical support, it builds relationships and trust among the group, and fosters collaboration.

Arkansas Specialty Orthopaedics organized McCarthy’s clinic and operating room (OR) schedules so that a partner was always present. “There was also someone I could bounce ideas off of,” McCarthy explains. “Every day in the OR, there was a partner there at the same time. If I got into a sticky situation, one of my colleagues was willing to come in and scrub in the OR.”

McCarthy says that patients responded favorably when she told them her plan was developed in conjunction with her partners. “Patients find comfort in knowing that several people’s opinions were considered,” she says. “And as a young surgeon, knowing that you have backup, even if you don’t use it, when caring for high-risk and complex cases really means a lot,” she says.

And although her group didn’t offer a formal mentoring program, McCarthy found that an informal mentorship grew organically when a friendship developed with one of her new partners. “In the first 6 months, every single weekend we sat by the pool and rolled through a ton of cases,” she says. “That was fabulous and it alleviated so much stress for me.” And when it was time for McCarthy to move into board case selection, this colleague and another were instrumental in her board preparation because, “they knew my style and where I would need to focus.”

IMS Orthopedics’ approach is to provide the staff and systems that allow new physicians to step up and take responsibility. “If they want to scrub in with me, that’s great. If they’d like to visit additional facilities and get the lay of the land, we encourage it. But we don’t do a lot of handholding. We set them up for success and make sure people are in place to help them,” says Ferry.

A Marketing Plan Is a Must

“The vast majority of practices do very little when it comes to thinking about how to market and build the practice of their new physician,” Marks says. “Practice-building is more of a challenge for surgical specialists today than it was in the old days when new surgeons could easily meet internists as they were rounding at the hospital. Now, a new physician and the practice must come up with a game plan.”

That game plan starts with the easy things: order business cards, schedule a photo shoot, and update the practice’s Web site pages with the physician’s biography and an introductory video. But with social media, online reviews, and subspecialty competition, Marks says practices must think beyond the basics. Think through each element of marketing, from online to outreach to developing referral relationships.

“I tell practices to draft a written marketing plan,” he says. “Not only does it provide a roadmap for the new physician, but also indicates that the practice has put some thought into how he or she can build a practice. It can make the new physician feel less overwhelmed knowing that he or she doesn’t have to do the marketing alone.” Once you’ve developed a list of actions, Marks suggests creating a spreadsheet with deadlines, and ensuring each action is completed.

McCarthy was scheduled to visit family practice clinics, and joined by the administrator who “handed out cookies and cards while I talked,” she says. Arkansas Specialty Orthopaedics also hired an external marketing firm to develop promotional opportunities for her. For example, “I was scheduled to appear on news channels, where I discussed new and interesting procedures,” she says. “It got my name out into the community.”

If your practice is too small to hire an outside firm, Marks suggests reaching out to agencies such as nursing homes, fitness centers, or the YMCA, which frequently offers educational programs for members. “Contact the administrators or medical directors in these organizations. A few minutes on the phone or a short visit can go a long way to building these relationships and getting your new physician on the map.”

As the old saying goes, an ounce of prevention is worth a pound of cure. Scheduling time for orientation, training, staff integration, and collegial coaching will speed up a new physician’s integration into the practice, and increase his or her opportunity for success.

Practices and hospitals invest significant time and money in recruiting a new physician. From phone interviews to site visits to contract negotiations, it’s a long and involved process.

Beyond setting up a new physician’s office and appointment schedule, completing human resources paperwork, and ordering business cards, what does your practice do to support new physicians to ensure they are successful? Although a new colleague may arrive with excellent clinical skills, even the most promising surgeon can fall short if not provided with the right expectations, training, and collegial support. Here’s how to fast track your new physician to professional heights.

Credentialing Is Key

At the crux of a new physician’s success is credentialing him or her with hospitals and insurance plans before the official start date to see patients.

“A state medical license is the first domino,” says orthopedic surgeon Michael R. Marks, MD, MBA, consultant and coding educator with KarenZupko & Associates, Inc. Marks has led or participated in physician recruitment in orthopedic and multispecialty groups. The firm has developed a comprehensive New Physician Onboarding Checklist, available at https://www.karenzupko.com/new-physician-onboarding-checklist/.

“Without a medical license,” Marks continues, “you can’t get the new physician hospital privileges and you can’t get him or her credentialed with plans. Without being credentialed, the physician can’t bill for patients treated.” Because commercial carriers won’t allow retrospective billing for services already rendered, “even a 3-month delay in credentialing could cost an orthopedic practice $60,000 to $180,000 in lost revenue.”(These figures are based on typical revenue generated by several specialties, as well as professional experience with multiple practices.)

And if you think you can bill the new physician’s services under another partner’s name, you are incorrect. “The billing physician will have signed the note, but not have treated the patient,” warns Marks. “This is improper billing. Don’t do it.”

The remedy for ensuring that the new physician is credentialed is simple: get organized and plan ahead.

“When I first started participating in recruitment, I remember telling physicians, ‘I need you tomorrow!’” admits Amon T. Ferry, MD, a practicing orthopedist who leads recruitment efforts at IMS Orthopedics, a division of Integrated Medical Specialists in Phoenix, Arizona. “So they’d get hired before the practice was prepared and before credentialing was completed. Now, I set more realistic expectations,” he says, noting that in Arizona it takes 3 months to get a medical license, 6 months to contract with the hospital, and 9 months to get on insurance plans. And even after a plan has credentialed a new physician, “sometimes it still takes 4 to 6 weeks before the physician’s data is loaded into the plan’s computer systems.”

“The way to do credentialing right is to get all departments communicating,” Marks says. “If you keep everyone siloed, staff don’t understand that a lack of timeliness on their part impacts other areas of the practice.”

Ferry agrees, and says his group learned to organize its multiple departments after making mistakes and missing deadlines. “We now have an 8-page pre-employment application for new physicians,” he explains. “In addition to asking for contact information and everything we need to know in order to get the physician credentialed, we ask questions about malpractice suit history and whether there are issues with the medical board. We also ask about gaps in employment and details about where the physician has practiced in the past.” All of this is done to identify early whether credentialing will require more time and effort. Ferry says that the application has solved a number of processing problems the practice had in the past.

And whether credentialing is done within the practice or outsourced, Ferry says that it pays to be persistent. “Don’t sit back and assume it will get done. Even if you have outsourced credentialing to a company, someone must check with payers and hospitals weekly and provide the practice a status update.”

In one case, when getting a new physician contracted at a hospital was taking forever, Ferry directed the staff to call. “Turns out, they had been trying to reach us and had the wrong phone number,” he says. “When people are processing thousands of physician renewals, things get lost. You have to be proactive and be your own advocate. Don’t be afraid to be the squeaky wheel.”

 

Staff Relationships and Operational Wisdom

Marks points out that in many practices, the new physician is shown the examination rooms and his or her office, gets electronic health record (EHR) training, and that’s it. To be successful, Marks insists that the new physician must build relationships with personnel and understand operational basics. “In other business industries, successful leaders understand at least the basics of what everyone does. Part of how they do this is by getting to know the employees.”

Ideally, Marks advises that new physicians spend time with each staff member. “The best time to do this is in the first few weeks of employment,” he suggests. “Odds are, the new orthopedist doesn’t have 40 patients a day on the schedule. So schedule conversations within the first few weeks or month, and schedule observation time as well. When a patient complains about check-in, the physician will have an understanding of how things work up there if he or she knows the basic processes.” The new doctor should also spend time in the billing office getting to know the challenges faced by staff, and sit with the surgery coordinator to understand the process of getting cases booked and scheduled.

Plan for an initial and then periodic meetings with the practice administrator and other supervisors. Transparency about business operations, data, and strategy will help the new physician get up to speed faster.

“The executive director of our group was an absolutely invaluable information resource,” says Kathryn J. McCarthy, MD, an orthopedic spine surgeon with Arkansas Specialty Orthopaedics in Little Rock, Arkansas. McCarthy has been with the group for 3 years.

The practice’s executive director developed and presented a PowerPoint (Microsoft) explaining general business procedures, expectations for the coding and billing process, and pertinent compliance and risk issues. She had also developed an interactive model of the compensation formula and buy-in program, using Excel (Microsoft). McCarthy met with the executive director at 3 months, 6 months, and 9 months to review her patient and case volumes and how they were trending against the estimates made about her income, bonus, and buy-in status.

From the new physician’s perspective, McCarthy says having the new physician understand the complexities of certain business systems helps them understand things better. “If you sit in the business meetings long enough, you figure it out,” she says, “but it would have made some of the growing pains less painful if I understood what my overhead charge was going to, or more about the workflow of the clinic.” She adds that an overview of hospital relationships and any overlapping ownership interests will benefit new physicians as well.

“I think it’s useful to provide new physicians with a history of the practice and the vision of where things are going,” McCarthy says. “It’s important to outline the business vision, especially for subspecialties. If you explain to the new physician where you want to grow and when the practice plans on bringing on the next physician, it could really drive someone to grow their practice.”

Don’t Underestimate the Need for Coding Training

“When fellows come out of training, they are comfortable with clinical activity but uncomfortable with business administration,” Marks says. “And we know they don’t get training on coding and billing.”

Marks cites a recent conversation at an American Academy of Orthopaedic Surgeons (AAOS) coding workshop. “A surgeon new in practice told me, ‘I’ve been in practice for 4 months. I understand the clinical side but nobody educated me about coding and billing before this course.’” Practices must provide new physicians with coding and documentation training, and coach them to make sure they feel up to speed and comfortable. “The practice’s future revenue depends on it,” Marks says.

McCarthy agrees. “Having an administrative mentorship for coding is incredibly valuable. They don’t teach it in school.”

So from a practical standpoint, purchase AAOS’ Orthopaedic Code-X, a software tool that will help the new physician navigate and integrate Current Procedural Terminology (CPT), ICD-10 (International Classification of Diseases, Tenth Revision), and other coding data easily and accurately. Send him or her to one of the Academy’s regional coding and reimbursement workshops as well. “It will behoove the practice to send them even before they start seeing patients,” Marks says.

And don’t just stop there. High-performing groups conduct peer reviews of evaluation and management (E/M) and operative notes, blinding the codes billed and discussing which CPT and ICD-10 codes are appropriate for the visit or case. “It will take time for the new physician to completely integrate coding with their clinical care,” says Marks. “Peer review sessions, as well as having a partner review codes before they go to the billing office, can help speed learning.”

 

Collegial Coaching Counts

The week before her official start day, Mc-Carthy scrubbed in as a first assist with each of her new partners. “It was a great way to start ramping up,” she says. “I could see what kind of equipment was present in the hospitals, and got a touch point for hospital logistics. Plus, as a young surgeon it’s great to see how your skill sets match up with your new partners, and which best practices are being deployed by the group.”

This kind of “collegial coaching” is a vital part of the clinical and cultural integration to the practice. Beyond providing clinical support, it builds relationships and trust among the group, and fosters collaboration.

Arkansas Specialty Orthopaedics organized McCarthy’s clinic and operating room (OR) schedules so that a partner was always present. “There was also someone I could bounce ideas off of,” McCarthy explains. “Every day in the OR, there was a partner there at the same time. If I got into a sticky situation, one of my colleagues was willing to come in and scrub in the OR.”

McCarthy says that patients responded favorably when she told them her plan was developed in conjunction with her partners. “Patients find comfort in knowing that several people’s opinions were considered,” she says. “And as a young surgeon, knowing that you have backup, even if you don’t use it, when caring for high-risk and complex cases really means a lot,” she says.

And although her group didn’t offer a formal mentoring program, McCarthy found that an informal mentorship grew organically when a friendship developed with one of her new partners. “In the first 6 months, every single weekend we sat by the pool and rolled through a ton of cases,” she says. “That was fabulous and it alleviated so much stress for me.” And when it was time for McCarthy to move into board case selection, this colleague and another were instrumental in her board preparation because, “they knew my style and where I would need to focus.”

IMS Orthopedics’ approach is to provide the staff and systems that allow new physicians to step up and take responsibility. “If they want to scrub in with me, that’s great. If they’d like to visit additional facilities and get the lay of the land, we encourage it. But we don’t do a lot of handholding. We set them up for success and make sure people are in place to help them,” says Ferry.

A Marketing Plan Is a Must

“The vast majority of practices do very little when it comes to thinking about how to market and build the practice of their new physician,” Marks says. “Practice-building is more of a challenge for surgical specialists today than it was in the old days when new surgeons could easily meet internists as they were rounding at the hospital. Now, a new physician and the practice must come up with a game plan.”

That game plan starts with the easy things: order business cards, schedule a photo shoot, and update the practice’s Web site pages with the physician’s biography and an introductory video. But with social media, online reviews, and subspecialty competition, Marks says practices must think beyond the basics. Think through each element of marketing, from online to outreach to developing referral relationships.

“I tell practices to draft a written marketing plan,” he says. “Not only does it provide a roadmap for the new physician, but also indicates that the practice has put some thought into how he or she can build a practice. It can make the new physician feel less overwhelmed knowing that he or she doesn’t have to do the marketing alone.” Once you’ve developed a list of actions, Marks suggests creating a spreadsheet with deadlines, and ensuring each action is completed.

McCarthy was scheduled to visit family practice clinics, and joined by the administrator who “handed out cookies and cards while I talked,” she says. Arkansas Specialty Orthopaedics also hired an external marketing firm to develop promotional opportunities for her. For example, “I was scheduled to appear on news channels, where I discussed new and interesting procedures,” she says. “It got my name out into the community.”

If your practice is too small to hire an outside firm, Marks suggests reaching out to agencies such as nursing homes, fitness centers, or the YMCA, which frequently offers educational programs for members. “Contact the administrators or medical directors in these organizations. A few minutes on the phone or a short visit can go a long way to building these relationships and getting your new physician on the map.”

As the old saying goes, an ounce of prevention is worth a pound of cure. Scheduling time for orientation, training, staff integration, and collegial coaching will speed up a new physician’s integration into the practice, and increase his or her opportunity for success.

After over 4 decades of experience with total knee arthroplasty (TKA), I have learned many lessons regarding surgical technique. These include exposure issues, alignment methods, bone preparation, correction of deformity, and implantation techniques. Most of these lessons have been self-taught, but some have been suggested by or modified from colleague and student interaction. Attribution is given when possible.

The Incision

The skin incision should be marked in flexion rather than extension because the skin moves approximately 1 cm laterally from extension to flexion.¹ This occurs because the tibia internally rotates beneath the skin as the knee is flexed and externally rotates as full extension is achieved. This lateral movement of the skin could bring an incision marked in extension on top of the tibial tubercle when the knee is flexed and may result in pain and dysfunction when the patient attempts to kneel. A review of kneeling ability after TKA showed that most patients are hesitant to kneel initially after their arthroplasty, but gain confidence and improved comfort and ability as their scar matures.²

Exposure

Patellar eversion can be difficult in a markedly obese or ankylosed knee, especially when the patella is difficult to grasp. This is facilitated by the use of a standard patellar clamp that is normally used to compress the patella during component cementation (Figure 1).³

When using this technique, remember to protect the patellar tendon from avulsion by using the techniques described below.

Exposing the Ankylosed Knee and Protecting the Patellar Tendon From Avulsion

A tibial tubercle osteotomy is often recommended in the ankylosed knee but can be avoided by making a short inverted “V” incision in the proximal quadriceps tendon (Figure 2).⁴

This maneuver, along with a smooth 1/8-inchpin in the tibial tubercle, also protects the patellar tendon from avulsing (Figure 3).

The patella can be easily everted and access to the lateral parapatellar scar tissue allows a lateral release to be performed from inside out to further mobilize the knee and enhance exposure. The inverted “V” incision can be closed anatomically, and no modifications of the postoperative physical therapy program are necessary.

Protecting the Soft Tissues During Surgery

Moist wound towels sewn into the joint capsule protect the underlying soft tissues from debris and desiccation during the procedure and will intuitively lower the chance of wound infection from contamination and tissue injury (Figures 4A, 4B).

Since I have done this routinely in both hip and knee arthroplasty over the last 7000 consecutive primary arthroplasties, I have had no operative deep infections. This experience is without the use of antibiotics in the bone cement.

Locating and Coagulating the Lateral Inferior Genicular Vessels

The lateral inferior genicular artery and vein can be easily located and coagulated just outside the posterior rim of the lateral meniscus near the popliteus hiatus. This will minimize both intraoperative and postoperative blood loss.

Determining the Entry Point in the Distal Femur for Intramedullary Alignment Devices

Templating the femoral entry point for insertion of an intramedullary alignment device on a preoperative radiograph will help avoid inadvertent excessive distal femoral valgus resection. This is especially important in valgus knees that have a valgus metaphyseal bow (Figure 5).

In these cases, the entry point must be moved medially and/or the valgus angle chosen must be diminished.

Avoiding Notching of the Anterior Femoral Cortex

Notching the anterior femoral cortex when in-between femoral sizes or when there is a preexisting dysplastic or shallow trochlea (Figure 6)

can be avoided by making the distal femoral resection in an extra 3° of flexion. In most TKA systems, the prosthetic trochlear flange diverges 3° or 4° away from the posterior femoral condyles. If the distal femoral resection is made in an extra 3° of flexion, the femoral component utilized can be anatomically sized off the patient’s posterior femoral condyles and the diverging trochlear flange will avoid notching the anterior femoral cortex while providing increased surface contact with the trochlear bone, enhancing prosthetic fixation. The only potential adverse effects of increased femoral component flexion would occur in a system that does not allow hyperextension of the femoral/tibial articulation without loss of articular contact or in a posterior-stabilized articulation where there could be post impingement in hyperextension. Total knee systems vary in the amount of hyperextension that can be tolerated.

Obtaining a Medial Release by Removing Peripheral Medial Tibial Bone

Varus deformities can be corrected without performing a formal medial collateral ligament (MCL) release by a so-called reduction tibial osteotomy.^5,6 In mild varus deformity, sufficient medial release can be achieved by removing medial femoral and tibial peripheral osteophytes that tent up the MCL and medial capsule. When this is insufficient, removal of additional peripheral tibial bone further shortens the distance between the origin and insertion of the MCL, effectively lengthening the ligament (Figure 7).

 

An Inverted Cruciform Lateral Retinacular Release to Correct Severe Valgus Deformity

An inverted cruciform lateral retinacular release effectively corrects a severe valgus deformity and avoids the need for a lateral collateral ligament (LCL) release.⁷

The release is best done after bone resection but without trial components in place, because this facilitates exposure to the lateral retinaculum (Figure 8).

The lateral superior genicular vessels should be identified and preserved. The vertical part of the release begins distal to the vessels and ends at the tibial resection. The horizontal limbs extend posteriorly short of the LCL and anteriorly short of the patellar tendon. If the extent of this release does not sufficiently balance the knee, it can be propagated by placing trial components with an insert thickness that stabilizes the medial side. Under this circumstance, the tight lateral side will now prohibit full passive extension. With gentle manipulation of the knee into extension, the lateral release will be propagated to its appropriate length. Postoperative perineal nerve palsies are rare with this technique. Immediate postoperative assessment, however, should always be done and the patient’s dressing loosened and their knee placed in flexion if there is any concern. Almost all of these rare palsies make a complete recovery.

Relieving Posterior Femoral Impingement

Uncapped posterior condylar bone or retained posterior osteophytes can limit both flexion and extension and cause impingement. Trimming the posterior femoral condyles and removing posterior osteophytes is best accomplished using a trial femoral component as a template.⁴ A curved osteotome is passed tangential to the metallic condyles to define the bone requiring resection. After removal of the trial, the outlined bone can be easily and accurately resected.

Minimizing Postoperative Posterior Condylar Bone-Cement Radiolucencies

Zone 4 femoral bone-cement radiolucencies⁸ can be minimized using the “smear” technique.⁴ These radiolucencies are common because most prosthetic femoral components have posterior condyles that are parallel to the femoral fixation lugs and do not allow for compression of this interface during implantation. Most surgeons put no cement on the posterior condylar bone but place it on the inside of the prosthetic condyle instead. The lack of compression upon insertion leads to a poor interface and the resultant lucencies. In the long term, these lucencies could allow access of wear debris to the posterior condylar bone, with the potential for osteolysis and loosening. To improve this interface, cement can be smeared or packed into the posterior condyles and also placed on the posterior condyles of the prosthesis. This could lead to posterior extrusion of some cement during polymerization, so a removable trial insert should be utilized to allow access posteriorly after polymerization is complete.

Predicting Potential Postoperative Flexion

The best indicator of potential postoperative flexion for any individual patient is not preoperative flexion but is intraoperative flexion against gravity measured after capsular closure.⁹ Surgeons should measure and record this value for reference if a patient has difficulty regaining flexion during their recovery (Figure 9).

If a patient had 120° of flexion against gravity after capsular closure but achieves only 80° at 2 months, a knee manipulation is probably indicated. If their flexion after closure was only 80°, a manipulation is unlikely to lead to any improvement.

Summary

The short- and long-term success of TKA is highly dependent on surgical technique that allows proper and safe exposure under all circumstances, correction of deformity, and accurate component implantation while minimizing intraoperative and postoperative complications. The surgical pearls shared above will hopefully aid in achieving these goals.

 

Am J Orthop. 2016;45(6):384-388. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

After over 4 decades of experience with total knee arthroplasty (TKA), I have learned many lessons regarding surgical technique. These include exposure issues, alignment methods, bone preparation, correction of deformity, and implantation techniques. Most of these lessons have been self-taught, but some have been suggested by or modified from colleague and student interaction. Attribution is given when possible.

The Incision

The skin incision should be marked in flexion rather than extension because the skin moves approximately 1 cm laterally from extension to flexion.¹ This occurs because the tibia internally rotates beneath the skin as the knee is flexed and externally rotates as full extension is achieved. This lateral movement of the skin could bring an incision marked in extension on top of the tibial tubercle when the knee is flexed and may result in pain and dysfunction when the patient attempts to kneel. A review of kneeling ability after TKA showed that most patients are hesitant to kneel initially after their arthroplasty, but gain confidence and improved comfort and ability as their scar matures.²

Exposure

Patellar eversion can be difficult in a markedly obese or ankylosed knee, especially when the patella is difficult to grasp. This is facilitated by the use of a standard patellar clamp that is normally used to compress the patella during component cementation (Figure 1).³

When using this technique, remember to protect the patellar tendon from avulsion by using the techniques described below.

Exposing the Ankylosed Knee and Protecting the Patellar Tendon From Avulsion

A tibial tubercle osteotomy is often recommended in the ankylosed knee but can be avoided by making a short inverted “V” incision in the proximal quadriceps tendon (Figure 2).⁴

This maneuver, along with a smooth 1/8-inchpin in the tibial tubercle, also protects the patellar tendon from avulsing (Figure 3).

The patella can be easily everted and access to the lateral parapatellar scar tissue allows a lateral release to be performed from inside out to further mobilize the knee and enhance exposure. The inverted “V” incision can be closed anatomically, and no modifications of the postoperative physical therapy program are necessary.

Protecting the Soft Tissues During Surgery

Moist wound towels sewn into the joint capsule protect the underlying soft tissues from debris and desiccation during the procedure and will intuitively lower the chance of wound infection from contamination and tissue injury (Figures 4A, 4B).

Since I have done this routinely in both hip and knee arthroplasty over the last 7000 consecutive primary arthroplasties, I have had no operative deep infections. This experience is without the use of antibiotics in the bone cement.

Locating and Coagulating the Lateral Inferior Genicular Vessels

The lateral inferior genicular artery and vein can be easily located and coagulated just outside the posterior rim of the lateral meniscus near the popliteus hiatus. This will minimize both intraoperative and postoperative blood loss.

Determining the Entry Point in the Distal Femur for Intramedullary Alignment Devices

Templating the femoral entry point for insertion of an intramedullary alignment device on a preoperative radiograph will help avoid inadvertent excessive distal femoral valgus resection. This is especially important in valgus knees that have a valgus metaphyseal bow (Figure 5).

In these cases, the entry point must be moved medially and/or the valgus angle chosen must be diminished.

Avoiding Notching of the Anterior Femoral Cortex

Notching the anterior femoral cortex when in-between femoral sizes or when there is a preexisting dysplastic or shallow trochlea (Figure 6)

can be avoided by making the distal femoral resection in an extra 3° of flexion. In most TKA systems, the prosthetic trochlear flange diverges 3° or 4° away from the posterior femoral condyles. If the distal femoral resection is made in an extra 3° of flexion, the femoral component utilized can be anatomically sized off the patient’s posterior femoral condyles and the diverging trochlear flange will avoid notching the anterior femoral cortex while providing increased surface contact with the trochlear bone, enhancing prosthetic fixation. The only potential adverse effects of increased femoral component flexion would occur in a system that does not allow hyperextension of the femoral/tibial articulation without loss of articular contact or in a posterior-stabilized articulation where there could be post impingement in hyperextension. Total knee systems vary in the amount of hyperextension that can be tolerated.

Obtaining a Medial Release by Removing Peripheral Medial Tibial Bone

Varus deformities can be corrected without performing a formal medial collateral ligament (MCL) release by a so-called reduction tibial osteotomy.^5,6 In mild varus deformity, sufficient medial release can be achieved by removing medial femoral and tibial peripheral osteophytes that tent up the MCL and medial capsule. When this is insufficient, removal of additional peripheral tibial bone further shortens the distance between the origin and insertion of the MCL, effectively lengthening the ligament (Figure 7).

 

An Inverted Cruciform Lateral Retinacular Release to Correct Severe Valgus Deformity

An inverted cruciform lateral retinacular release effectively corrects a severe valgus deformity and avoids the need for a lateral collateral ligament (LCL) release.⁷

The release is best done after bone resection but without trial components in place, because this facilitates exposure to the lateral retinaculum (Figure 8).

The lateral superior genicular vessels should be identified and preserved. The vertical part of the release begins distal to the vessels and ends at the tibial resection. The horizontal limbs extend posteriorly short of the LCL and anteriorly short of the patellar tendon. If the extent of this release does not sufficiently balance the knee, it can be propagated by placing trial components with an insert thickness that stabilizes the medial side. Under this circumstance, the tight lateral side will now prohibit full passive extension. With gentle manipulation of the knee into extension, the lateral release will be propagated to its appropriate length. Postoperative perineal nerve palsies are rare with this technique. Immediate postoperative assessment, however, should always be done and the patient’s dressing loosened and their knee placed in flexion if there is any concern. Almost all of these rare palsies make a complete recovery.

Relieving Posterior Femoral Impingement

Uncapped posterior condylar bone or retained posterior osteophytes can limit both flexion and extension and cause impingement. Trimming the posterior femoral condyles and removing posterior osteophytes is best accomplished using a trial femoral component as a template.⁴ A curved osteotome is passed tangential to the metallic condyles to define the bone requiring resection. After removal of the trial, the outlined bone can be easily and accurately resected.

Minimizing Postoperative Posterior Condylar Bone-Cement Radiolucencies

Zone 4 femoral bone-cement radiolucencies⁸ can be minimized using the “smear” technique.⁴ These radiolucencies are common because most prosthetic femoral components have posterior condyles that are parallel to the femoral fixation lugs and do not allow for compression of this interface during implantation. Most surgeons put no cement on the posterior condylar bone but place it on the inside of the prosthetic condyle instead. The lack of compression upon insertion leads to a poor interface and the resultant lucencies. In the long term, these lucencies could allow access of wear debris to the posterior condylar bone, with the potential for osteolysis and loosening. To improve this interface, cement can be smeared or packed into the posterior condyles and also placed on the posterior condyles of the prosthesis. This could lead to posterior extrusion of some cement during polymerization, so a removable trial insert should be utilized to allow access posteriorly after polymerization is complete.

Predicting Potential Postoperative Flexion

The best indicator of potential postoperative flexion for any individual patient is not preoperative flexion but is intraoperative flexion against gravity measured after capsular closure.⁹ Surgeons should measure and record this value for reference if a patient has difficulty regaining flexion during their recovery (Figure 9).

If a patient had 120° of flexion against gravity after capsular closure but achieves only 80° at 2 months, a knee manipulation is probably indicated. If their flexion after closure was only 80°, a manipulation is unlikely to lead to any improvement.

Summary

The short- and long-term success of TKA is highly dependent on surgical technique that allows proper and safe exposure under all circumstances, correction of deformity, and accurate component implantation while minimizing intraoperative and postoperative complications. The surgical pearls shared above will hopefully aid in achieving these goals.

 

Am J Orthop. 2016;45(6):384-388. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

After over 4 decades of experience with total knee arthroplasty (TKA), I have learned many lessons regarding surgical technique. These include exposure issues, alignment methods, bone preparation, correction of deformity, and implantation techniques. Most of these lessons have been self-taught, but some have been suggested by or modified from colleague and student interaction. Attribution is given when possible.

The Incision

The skin incision should be marked in flexion rather than extension because the skin moves approximately 1 cm laterally from extension to flexion.¹ This occurs because the tibia internally rotates beneath the skin as the knee is flexed and externally rotates as full extension is achieved. This lateral movement of the skin could bring an incision marked in extension on top of the tibial tubercle when the knee is flexed and may result in pain and dysfunction when the patient attempts to kneel. A review of kneeling ability after TKA showed that most patients are hesitant to kneel initially after their arthroplasty, but gain confidence and improved comfort and ability as their scar matures.²

Exposure

Patellar eversion can be difficult in a markedly obese or ankylosed knee, especially when the patella is difficult to grasp. This is facilitated by the use of a standard patellar clamp that is normally used to compress the patella during component cementation (Figure 1).³

When using this technique, remember to protect the patellar tendon from avulsion by using the techniques described below.

Exposing the Ankylosed Knee and Protecting the Patellar Tendon From Avulsion

A tibial tubercle osteotomy is often recommended in the ankylosed knee but can be avoided by making a short inverted “V” incision in the proximal quadriceps tendon (Figure 2).⁴

This maneuver, along with a smooth 1/8-inchpin in the tibial tubercle, also protects the patellar tendon from avulsing (Figure 3).

The patella can be easily everted and access to the lateral parapatellar scar tissue allows a lateral release to be performed from inside out to further mobilize the knee and enhance exposure. The inverted “V” incision can be closed anatomically, and no modifications of the postoperative physical therapy program are necessary.

Protecting the Soft Tissues During Surgery

Moist wound towels sewn into the joint capsule protect the underlying soft tissues from debris and desiccation during the procedure and will intuitively lower the chance of wound infection from contamination and tissue injury (Figures 4A, 4B).

Since I have done this routinely in both hip and knee arthroplasty over the last 7000 consecutive primary arthroplasties, I have had no operative deep infections. This experience is without the use of antibiotics in the bone cement.

Locating and Coagulating the Lateral Inferior Genicular Vessels

The lateral inferior genicular artery and vein can be easily located and coagulated just outside the posterior rim of the lateral meniscus near the popliteus hiatus. This will minimize both intraoperative and postoperative blood loss.

Determining the Entry Point in the Distal Femur for Intramedullary Alignment Devices

Templating the femoral entry point for insertion of an intramedullary alignment device on a preoperative radiograph will help avoid inadvertent excessive distal femoral valgus resection. This is especially important in valgus knees that have a valgus metaphyseal bow (Figure 5).

In these cases, the entry point must be moved medially and/or the valgus angle chosen must be diminished.

Avoiding Notching of the Anterior Femoral Cortex

Notching the anterior femoral cortex when in-between femoral sizes or when there is a preexisting dysplastic or shallow trochlea (Figure 6)

can be avoided by making the distal femoral resection in an extra 3° of flexion. In most TKA systems, the prosthetic trochlear flange diverges 3° or 4° away from the posterior femoral condyles. If the distal femoral resection is made in an extra 3° of flexion, the femoral component utilized can be anatomically sized off the patient’s posterior femoral condyles and the diverging trochlear flange will avoid notching the anterior femoral cortex while providing increased surface contact with the trochlear bone, enhancing prosthetic fixation. The only potential adverse effects of increased femoral component flexion would occur in a system that does not allow hyperextension of the femoral/tibial articulation without loss of articular contact or in a posterior-stabilized articulation where there could be post impingement in hyperextension. Total knee systems vary in the amount of hyperextension that can be tolerated.

Obtaining a Medial Release by Removing Peripheral Medial Tibial Bone

Varus deformities can be corrected without performing a formal medial collateral ligament (MCL) release by a so-called reduction tibial osteotomy.^5,6 In mild varus deformity, sufficient medial release can be achieved by removing medial femoral and tibial peripheral osteophytes that tent up the MCL and medial capsule. When this is insufficient, removal of additional peripheral tibial bone further shortens the distance between the origin and insertion of the MCL, effectively lengthening the ligament (Figure 7).

 

An Inverted Cruciform Lateral Retinacular Release to Correct Severe Valgus Deformity

An inverted cruciform lateral retinacular release effectively corrects a severe valgus deformity and avoids the need for a lateral collateral ligament (LCL) release.⁷

The release is best done after bone resection but without trial components in place, because this facilitates exposure to the lateral retinaculum (Figure 8).

The lateral superior genicular vessels should be identified and preserved. The vertical part of the release begins distal to the vessels and ends at the tibial resection. The horizontal limbs extend posteriorly short of the LCL and anteriorly short of the patellar tendon. If the extent of this release does not sufficiently balance the knee, it can be propagated by placing trial components with an insert thickness that stabilizes the medial side. Under this circumstance, the tight lateral side will now prohibit full passive extension. With gentle manipulation of the knee into extension, the lateral release will be propagated to its appropriate length. Postoperative perineal nerve palsies are rare with this technique. Immediate postoperative assessment, however, should always be done and the patient’s dressing loosened and their knee placed in flexion if there is any concern. Almost all of these rare palsies make a complete recovery.

Relieving Posterior Femoral Impingement

Uncapped posterior condylar bone or retained posterior osteophytes can limit both flexion and extension and cause impingement. Trimming the posterior femoral condyles and removing posterior osteophytes is best accomplished using a trial femoral component as a template.⁴ A curved osteotome is passed tangential to the metallic condyles to define the bone requiring resection. After removal of the trial, the outlined bone can be easily and accurately resected.

Minimizing Postoperative Posterior Condylar Bone-Cement Radiolucencies

Zone 4 femoral bone-cement radiolucencies⁸ can be minimized using the “smear” technique.⁴ These radiolucencies are common because most prosthetic femoral components have posterior condyles that are parallel to the femoral fixation lugs and do not allow for compression of this interface during implantation. Most surgeons put no cement on the posterior condylar bone but place it on the inside of the prosthetic condyle instead. The lack of compression upon insertion leads to a poor interface and the resultant lucencies. In the long term, these lucencies could allow access of wear debris to the posterior condylar bone, with the potential for osteolysis and loosening. To improve this interface, cement can be smeared or packed into the posterior condyles and also placed on the posterior condyles of the prosthesis. This could lead to posterior extrusion of some cement during polymerization, so a removable trial insert should be utilized to allow access posteriorly after polymerization is complete.

Predicting Potential Postoperative Flexion

The best indicator of potential postoperative flexion for any individual patient is not preoperative flexion but is intraoperative flexion against gravity measured after capsular closure.⁹ Surgeons should measure and record this value for reference if a patient has difficulty regaining flexion during their recovery (Figure 9).

If a patient had 120° of flexion against gravity after capsular closure but achieves only 80° at 2 months, a knee manipulation is probably indicated. If their flexion after closure was only 80°, a manipulation is unlikely to lead to any improvement.

Summary

The short- and long-term success of TKA is highly dependent on surgical technique that allows proper and safe exposure under all circumstances, correction of deformity, and accurate component implantation while minimizing intraoperative and postoperative complications. The surgical pearls shared above will hopefully aid in achieving these goals.

 

Am J Orthop. 2016;45(6):384-388. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.