Michael J. Marcangelo, MD

With nearly 30,000 organ transplants being performed in the United States each year (Box 1),¹ demand is growing for psychiatrists to provide presurgical and ongoing care.

How you might collaborate with a transplant team depends on each medical center’s protocols and individual patients’ mental health needs. A transplant candidate with depressive or anxiety symptoms may be referred to you for presurgical stabilization, for example, particularly if the patient lives far from a highly specialized transplant center.

Transplant assessments differ from usual psychiatric evaluations. Your findings will be used to help the transplant team evaluate the patient’s demographics, disease severity, and resources to give the patient the best chance for medical recovery. Inform patients at the beginning of the pretransplant evaluation that the results:

• will be shared with the transplant team
• may be used to help make decisions about transplant
• will not be the only factor determining if a transplant center will place a patient on an organ wait list.²

Pretransplant evaluation

Presurgical assessment helps determine the patient’s understanding of the transplant process and ability to provide consent (Table 1).³ Patients do not need a high level of medical sophistication to discuss transplantation, but they must understand the basics of the procedure and be able to rationally discuss their options. If a patient has severe cognitive impairment, dementia, or hepatic encephalopathy and cannot participate in the consent process, a surrogate is necessary.

Explore the patient’s attitudes and beliefs about transplant. If other team members have educated the patient about the procedure, your assessment can help determine how much the patient understood and if the patient has the capacity to make treatment decisions. Some patients believe the operation will “cure” them, despite education about the rigorous posttransplant routine. Alert the transplant team to these views, and begin aligning the patient’s views with reality.

Box 1

Table 1

Psychiatric assessment of the pretransplant patient

Assessing psychiatric comorbidity. Like other patients with life-threatening medical illnesses, many transplant patients present with major depression and anxiety. Screen for symptoms of mood and anxiety disorders and past episodes of depression or mania. Explore the patient’s response to psychiatric treatment, current therapies, and history of treatment adherence.

Depression. Patients listed for transplant are seriously ill and coping with the difficulties of the sick role. Organ failure symptoms and resultant disability—such as insomnia, anorexia, fatigue, and impaired concentration—overlap with depression’s neurovegetative signs. Suspect depression if a patient presents with anhedonia, tearfulness, apathy, or guilt.

Among heart, lung, and liver transplant candidates, the reported lifetime prevalence of depression averages approximately 20%.^4-6

Anxiety disorders. An estimated 40% of transplant patients have anxiety disorders,⁷ which may be caused by:

• stress of chronic illness
• uncertainty of the transplant process
• medical conditions such as hypothyroidism or pulmonary embolism.

Chronic mental illness. Patients with major mental illnesses such as schizophrenia might be appropriate candidates for organ transplant if they have adequate social support and history of treatment compliance.

Pharmacotherapy. Because of the variety of medical problems seen in transplant candidates, carefully consider medication side effects and drug-drug interactions when prescribing psychotropics.

Antidepressants. Among the selective serotonin reuptake inhibitors (SSRIs), citalopram, escitalopram, and sertraline are least likely to affect hepatic metabolism of other medications (Table 2).⁸ If a patient presents with liver failure, reduce the dosages of medications with hepatic metabolism.

Benzodiazepines. Use caution when treating anxiety with benzodiazepines because of the risk of tolerance, withdrawal, and dependence. Avoid benzodiazepines when treating transplant candidates with a substance abuse history. Also, these drugs might worsen hepatic encephalopathy and increase confusion.

Patients awaiting lung transplantation, especially those with high levels of CO₂ retention, require special care because benzodiazepines might decrease respiratory drive. Try other agents such as buspirone, gabapentin, SSRIs, or second-generation antipsychotics to treat their anxiety.

Psychotherapy. Supportive psychotherapy can help patients navigate the often-lengthy process of waiting for a donor organ. Support groups for organ transplant candidates may help ease patients’ depressive symptoms.

Table 2

Antidepressants’ half-life and effect on hepatic metabolism

Assessing substance abuse

Up to 50% of liver transplant candidates have a history of alcohol and/or drug abuse,⁹ the highest rate among transplant populations. Alcohol-induced cirrhosis and hepatitis C contracted from IV drug use are common indications for liver transplant. Effective treatment of substance abuse is essential because 30% to 50% of these patients relapse after the procedure.¹⁰ Assess:

• each substance abused, including onset, peak, and current use
• family history of substance abuse disorders
• past efforts at rehabilitation
• tobacco use (smoking before and after transplant is related to an increased incidence of new cancer diagnoses).¹¹

Some transplant centers require patients with substance
use disorders to participate in 12-step programs or
rehabilitation. Regardless of the institutions’
requirements, encourage patients to participate in
rehabilitation to prevent relapse and mitigate the
negative impact of substance abuse on physical
and mental well-being.

Mental status examination includes the usual elements such as appearance, behavior, speech, affect, and thought process. Assess for suicidal thinking or hopelessness, which have been linked to serious medical illness.¹² Question patients about hallucinations and give special attention to visual aberrations, which may occur in medically ill patients.

Cognitive testing. Use tools such as the Mini-Mental State Examination, clock drawing test, and Trail Making A and B tests to assess cognitive ability. If patients show signs of cognitive impairment, arrange for follow-up examinations and refer for neuropsychological testing.

Some cognitive impairment—such as that caused by hepatic encephalopathy—will likely improve after transplant, but other types—such as that caused by vascular disease—will not. If confusion is caused by hepatic encephalopathy, treatment with lactulose might rapidly improve symptoms. Remember that patients with hepatic encephalopathy might not exhibit elevated ammonia levels. Underlying causes of worsening hepatic encephalopathy—such as infections or bleeding—might require treatment.

Assessing adherence. Medication adherence after transplant is essential to prevent organ rejection and other complications. Posttransplant regimens are complex, and the frequency of follow-up assessments can be intense—particularly in the first year after transplant.

Your pretransplant assessment can identify where patients have struggled with adherence in the past. Before the transplant, your team can work to correct barriers such as inability to pay for medications, child care problems, or transportation needs.

Personality disorders have been identified as predictors of posttransplant nonadherence, and 50% to 60% of transplant programs consider personality disorders a relative contraindication to organ transplant.¹³ Address other contributors to poor adherence—such as substance abuse or depression—with ongoing psychiatric care.

Box 2

Social support is essential to help with the normal difficulties such as frequent clinic visits and initial physical disability patients face after successful transplant (Box 2). Ask about the candidate’s family, friends, spirituality, and finances during your pretransplant assessment. Poor social support is related to the development of posttransplant psychiatric disorders¹⁴ and adherence difficulties.¹⁵

Assessment instruments—such as the Psychosocial Assessment of Candidates for Transplantation and the Transplant Evaluation Rating Scale³—include social support items and can be useful in identifying weak areas.

Data collected by other team members can be invaluable. A nurse or social worker, for example, may observe that a patient is unwilling to take medications, contrary to the patient’s report. Other sources of information include the patient’s family and friends, a primary care physician, or other mental health providers such as a therapist or case manager.

Posttransplant psychiatric care

Depression. The incidence of depression is higher in the year following transplant than before transplant or in the immediate posttransplant period.⁵ Predictors of posttransplant depression include:

• history of depression
• poor social support
• passive coping strategies
• poor physical status after transplantation.^16,17

Carefully monitor patients who present with these factors after transplant. Treat depression with supportive measures designed to improve the patient’s social network and coping skills and pharmacotherapy. Select antidepressant medications based on side effect profiles and impact on the patient’s transplanted organs.

Substance abuse. Patients with a pretransplant history of substance abuse often relapse. Among transplant recipients with a history of alcoholic liver disease, drinking rates of 30% to 40% have been reported 5 years after transplant. Most of these data represent occasional use, not heavy or regular drinking.¹⁸ Relapse can occur despite careful assessment and follow-up.

Some evidence suggests that transplant patients who resume drinking have worse outcomes than those who abstain. Alcoholism relapse has other negative consequences, such as relationship problems and employment difficulties.

Predictors of relapse include:

• pretransplant history of alcohol dependence
• family history of alcoholism
• rehabilitation history, which could indicate a severe substance abuse disorder.³

Medications for alcoholism treatment have not been studied systematically in transplant patients, but low doses of acamprosate, ≤2 g/d, and naltrexone, ≤200 mg/d, are options for patients interested in pharmacotherapy. Support from 12-step programs also helps treat substance-abusing patients.

Altered mental status. Immunosuppressive medications—including cyclosporine, tacrolimus, and prednisone—can have neuropsychiatric effects and could cause a change in mental status (Table 3).¹⁹ Check cyclosporine and tacrolimus serum levels against reference ranges when delirium is present. If levels are toxic the dosage often can be lowered, which might lead to clinical improvement.

Quality of life. In general, patients’ quality of life improves after their transplant. After the first year—which patients might find difficult because of changes in physical and social status—quality of life typically improves.⁵

Table 3

Neuropsychiatric side effects of medications
commonly used in transplant patients

Psychiatric disorders such as depression can worsen quality of life. However, quality of life can improve after depression is diagnosed and treated. Other predictors of improved quality of life include older age, marriage, and the absence of a personality disorder.⁴

Other posttransplant concerns of patients include changes in employment, finances, and relationships. Patients often have been away from work before transplant, and returning after a long absence can be stressful. Patients may find that they cannot work as well as before becoming ill, which may lead to frustration, depression, and/or anxiety symptoms. Transplant surgery requires a large financial investment, and money concerns usually persist long after the transplant.

The transplant recipient’s role within the family may shift after surgery. Families might expect the patient to “return to normal” and resume old activities. Alternatively, family members might continue to treat the patient as a person with chronic illness despite physical improvement. If patients are struggling with these changes, supportive psychotherapy is indicated.

Related resource

• United Network for Organ Sharing. www.unos.org.
• Transplant living. www.transplantliving.org.
• Trzepacz PT, DiMartini AF, eds. The transplant patient. Cambridge, UK: Cambridge University Press; 2000.
• Klapheke MM. The role of the psychiatrist in organ transplantation. Bull Menninger Clin 1999;63(1):13-39.

Drug brand names

• Acamprosate • Campral
• Buspirone • BuSpar
• Bupropion SR • Wellbutrin SR
• Citalopram • Celexa
• Cyclosporine • Sandimmune
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Gabapentin • Neurontin
• Lactulose • Cephulac, Chronulac
• Mirtazapine • Remeron
• Naltrexone • ReVia
• Paroxetine • Paxil
• Prednisone • Deltasone
• Sertraline • Zoloft
• Tacrolimus • Prograf
• Trazodone • Desyrel

Disclosure

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

With nearly 30,000 organ transplants being performed in the United States each year (Box 1),¹ demand is growing for psychiatrists to provide presurgical and ongoing care.

How you might collaborate with a transplant team depends on each medical center’s protocols and individual patients’ mental health needs. A transplant candidate with depressive or anxiety symptoms may be referred to you for presurgical stabilization, for example, particularly if the patient lives far from a highly specialized transplant center.

Transplant assessments differ from usual psychiatric evaluations. Your findings will be used to help the transplant team evaluate the patient’s demographics, disease severity, and resources to give the patient the best chance for medical recovery. Inform patients at the beginning of the pretransplant evaluation that the results:

• will be shared with the transplant team
• may be used to help make decisions about transplant
• will not be the only factor determining if a transplant center will place a patient on an organ wait list.²

Pretransplant evaluation

Presurgical assessment helps determine the patient’s understanding of the transplant process and ability to provide consent (Table 1).³ Patients do not need a high level of medical sophistication to discuss transplantation, but they must understand the basics of the procedure and be able to rationally discuss their options. If a patient has severe cognitive impairment, dementia, or hepatic encephalopathy and cannot participate in the consent process, a surrogate is necessary.

Explore the patient’s attitudes and beliefs about transplant. If other team members have educated the patient about the procedure, your assessment can help determine how much the patient understood and if the patient has the capacity to make treatment decisions. Some patients believe the operation will “cure” them, despite education about the rigorous posttransplant routine. Alert the transplant team to these views, and begin aligning the patient’s views with reality.

Box 1

Table 1

Psychiatric assessment of the pretransplant patient

Assessing psychiatric comorbidity. Like other patients with life-threatening medical illnesses, many transplant patients present with major depression and anxiety. Screen for symptoms of mood and anxiety disorders and past episodes of depression or mania. Explore the patient’s response to psychiatric treatment, current therapies, and history of treatment adherence.

Depression. Patients listed for transplant are seriously ill and coping with the difficulties of the sick role. Organ failure symptoms and resultant disability—such as insomnia, anorexia, fatigue, and impaired concentration—overlap with depression’s neurovegetative signs. Suspect depression if a patient presents with anhedonia, tearfulness, apathy, or guilt.

Among heart, lung, and liver transplant candidates, the reported lifetime prevalence of depression averages approximately 20%.^4-6

Anxiety disorders. An estimated 40% of transplant patients have anxiety disorders,⁷ which may be caused by:

• stress of chronic illness
• uncertainty of the transplant process
• medical conditions such as hypothyroidism or pulmonary embolism.

Chronic mental illness. Patients with major mental illnesses such as schizophrenia might be appropriate candidates for organ transplant if they have adequate social support and history of treatment compliance.

Pharmacotherapy. Because of the variety of medical problems seen in transplant candidates, carefully consider medication side effects and drug-drug interactions when prescribing psychotropics.

Antidepressants. Among the selective serotonin reuptake inhibitors (SSRIs), citalopram, escitalopram, and sertraline are least likely to affect hepatic metabolism of other medications (Table 2).⁸ If a patient presents with liver failure, reduce the dosages of medications with hepatic metabolism.

Benzodiazepines. Use caution when treating anxiety with benzodiazepines because of the risk of tolerance, withdrawal, and dependence. Avoid benzodiazepines when treating transplant candidates with a substance abuse history. Also, these drugs might worsen hepatic encephalopathy and increase confusion.

Patients awaiting lung transplantation, especially those with high levels of CO₂ retention, require special care because benzodiazepines might decrease respiratory drive. Try other agents such as buspirone, gabapentin, SSRIs, or second-generation antipsychotics to treat their anxiety.

Psychotherapy. Supportive psychotherapy can help patients navigate the often-lengthy process of waiting for a donor organ. Support groups for organ transplant candidates may help ease patients’ depressive symptoms.

Table 2

Antidepressants’ half-life and effect on hepatic metabolism

Assessing substance abuse

Up to 50% of liver transplant candidates have a history of alcohol and/or drug abuse,⁹ the highest rate among transplant populations. Alcohol-induced cirrhosis and hepatitis C contracted from IV drug use are common indications for liver transplant. Effective treatment of substance abuse is essential because 30% to 50% of these patients relapse after the procedure.¹⁰ Assess:

• each substance abused, including onset, peak, and current use
• family history of substance abuse disorders
• past efforts at rehabilitation
• tobacco use (smoking before and after transplant is related to an increased incidence of new cancer diagnoses).¹¹

Some transplant centers require patients with substance
use disorders to participate in 12-step programs or
rehabilitation. Regardless of the institutions’
requirements, encourage patients to participate in
rehabilitation to prevent relapse and mitigate the
negative impact of substance abuse on physical
and mental well-being.

Mental status examination includes the usual elements such as appearance, behavior, speech, affect, and thought process. Assess for suicidal thinking or hopelessness, which have been linked to serious medical illness.¹² Question patients about hallucinations and give special attention to visual aberrations, which may occur in medically ill patients.

Cognitive testing. Use tools such as the Mini-Mental State Examination, clock drawing test, and Trail Making A and B tests to assess cognitive ability. If patients show signs of cognitive impairment, arrange for follow-up examinations and refer for neuropsychological testing.

Some cognitive impairment—such as that caused by hepatic encephalopathy—will likely improve after transplant, but other types—such as that caused by vascular disease—will not. If confusion is caused by hepatic encephalopathy, treatment with lactulose might rapidly improve symptoms. Remember that patients with hepatic encephalopathy might not exhibit elevated ammonia levels. Underlying causes of worsening hepatic encephalopathy—such as infections or bleeding—might require treatment.

Assessing adherence. Medication adherence after transplant is essential to prevent organ rejection and other complications. Posttransplant regimens are complex, and the frequency of follow-up assessments can be intense—particularly in the first year after transplant.

Your pretransplant assessment can identify where patients have struggled with adherence in the past. Before the transplant, your team can work to correct barriers such as inability to pay for medications, child care problems, or transportation needs.

Personality disorders have been identified as predictors of posttransplant nonadherence, and 50% to 60% of transplant programs consider personality disorders a relative contraindication to organ transplant.¹³ Address other contributors to poor adherence—such as substance abuse or depression—with ongoing psychiatric care.

Box 2

Social support is essential to help with the normal difficulties such as frequent clinic visits and initial physical disability patients face after successful transplant (Box 2). Ask about the candidate’s family, friends, spirituality, and finances during your pretransplant assessment. Poor social support is related to the development of posttransplant psychiatric disorders¹⁴ and adherence difficulties.¹⁵

Assessment instruments—such as the Psychosocial Assessment of Candidates for Transplantation and the Transplant Evaluation Rating Scale³—include social support items and can be useful in identifying weak areas.

Data collected by other team members can be invaluable. A nurse or social worker, for example, may observe that a patient is unwilling to take medications, contrary to the patient’s report. Other sources of information include the patient’s family and friends, a primary care physician, or other mental health providers such as a therapist or case manager.

Posttransplant psychiatric care

Depression. The incidence of depression is higher in the year following transplant than before transplant or in the immediate posttransplant period.⁵ Predictors of posttransplant depression include:

• history of depression
• poor social support
• passive coping strategies
• poor physical status after transplantation.^16,17

Carefully monitor patients who present with these factors after transplant. Treat depression with supportive measures designed to improve the patient’s social network and coping skills and pharmacotherapy. Select antidepressant medications based on side effect profiles and impact on the patient’s transplanted organs.

Substance abuse. Patients with a pretransplant history of substance abuse often relapse. Among transplant recipients with a history of alcoholic liver disease, drinking rates of 30% to 40% have been reported 5 years after transplant. Most of these data represent occasional use, not heavy or regular drinking.¹⁸ Relapse can occur despite careful assessment and follow-up.

Some evidence suggests that transplant patients who resume drinking have worse outcomes than those who abstain. Alcoholism relapse has other negative consequences, such as relationship problems and employment difficulties.

Predictors of relapse include:

• pretransplant history of alcohol dependence
• family history of alcoholism
• rehabilitation history, which could indicate a severe substance abuse disorder.³

Medications for alcoholism treatment have not been studied systematically in transplant patients, but low doses of acamprosate, ≤2 g/d, and naltrexone, ≤200 mg/d, are options for patients interested in pharmacotherapy. Support from 12-step programs also helps treat substance-abusing patients.

Altered mental status. Immunosuppressive medications—including cyclosporine, tacrolimus, and prednisone—can have neuropsychiatric effects and could cause a change in mental status (Table 3).¹⁹ Check cyclosporine and tacrolimus serum levels against reference ranges when delirium is present. If levels are toxic the dosage often can be lowered, which might lead to clinical improvement.

Quality of life. In general, patients’ quality of life improves after their transplant. After the first year—which patients might find difficult because of changes in physical and social status—quality of life typically improves.⁵

Table 3

Neuropsychiatric side effects of medications
commonly used in transplant patients

Psychiatric disorders such as depression can worsen quality of life. However, quality of life can improve after depression is diagnosed and treated. Other predictors of improved quality of life include older age, marriage, and the absence of a personality disorder.⁴

Other posttransplant concerns of patients include changes in employment, finances, and relationships. Patients often have been away from work before transplant, and returning after a long absence can be stressful. Patients may find that they cannot work as well as before becoming ill, which may lead to frustration, depression, and/or anxiety symptoms. Transplant surgery requires a large financial investment, and money concerns usually persist long after the transplant.

The transplant recipient’s role within the family may shift after surgery. Families might expect the patient to “return to normal” and resume old activities. Alternatively, family members might continue to treat the patient as a person with chronic illness despite physical improvement. If patients are struggling with these changes, supportive psychotherapy is indicated.

Related resource

• United Network for Organ Sharing. www.unos.org.
• Transplant living. www.transplantliving.org.
• Trzepacz PT, DiMartini AF, eds. The transplant patient. Cambridge, UK: Cambridge University Press; 2000.
• Klapheke MM. The role of the psychiatrist in organ transplantation. Bull Menninger Clin 1999;63(1):13-39.

Drug brand names

• Acamprosate • Campral
• Buspirone • BuSpar
• Bupropion SR • Wellbutrin SR
• Citalopram • Celexa
• Cyclosporine • Sandimmune
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Gabapentin • Neurontin
• Lactulose • Cephulac, Chronulac
• Mirtazapine • Remeron
• Naltrexone • ReVia
• Paroxetine • Paxil
• Prednisone • Deltasone
• Sertraline • Zoloft
• Tacrolimus • Prograf
• Trazodone • Desyrel

Disclosure

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

With nearly 30,000 organ transplants being performed in the United States each year (Box 1),¹ demand is growing for psychiatrists to provide presurgical and ongoing care.

How you might collaborate with a transplant team depends on each medical center’s protocols and individual patients’ mental health needs. A transplant candidate with depressive or anxiety symptoms may be referred to you for presurgical stabilization, for example, particularly if the patient lives far from a highly specialized transplant center.

Transplant assessments differ from usual psychiatric evaluations. Your findings will be used to help the transplant team evaluate the patient’s demographics, disease severity, and resources to give the patient the best chance for medical recovery. Inform patients at the beginning of the pretransplant evaluation that the results:

• will be shared with the transplant team
• may be used to help make decisions about transplant
• will not be the only factor determining if a transplant center will place a patient on an organ wait list.²

Pretransplant evaluation

Presurgical assessment helps determine the patient’s understanding of the transplant process and ability to provide consent (Table 1).³ Patients do not need a high level of medical sophistication to discuss transplantation, but they must understand the basics of the procedure and be able to rationally discuss their options. If a patient has severe cognitive impairment, dementia, or hepatic encephalopathy and cannot participate in the consent process, a surrogate is necessary.

Explore the patient’s attitudes and beliefs about transplant. If other team members have educated the patient about the procedure, your assessment can help determine how much the patient understood and if the patient has the capacity to make treatment decisions. Some patients believe the operation will “cure” them, despite education about the rigorous posttransplant routine. Alert the transplant team to these views, and begin aligning the patient’s views with reality.

Box 1

Table 1

Psychiatric assessment of the pretransplant patient

Assessing psychiatric comorbidity. Like other patients with life-threatening medical illnesses, many transplant patients present with major depression and anxiety. Screen for symptoms of mood and anxiety disorders and past episodes of depression or mania. Explore the patient’s response to psychiatric treatment, current therapies, and history of treatment adherence.

Depression. Patients listed for transplant are seriously ill and coping with the difficulties of the sick role. Organ failure symptoms and resultant disability—such as insomnia, anorexia, fatigue, and impaired concentration—overlap with depression’s neurovegetative signs. Suspect depression if a patient presents with anhedonia, tearfulness, apathy, or guilt.

Among heart, lung, and liver transplant candidates, the reported lifetime prevalence of depression averages approximately 20%.^4-6

Anxiety disorders. An estimated 40% of transplant patients have anxiety disorders,⁷ which may be caused by:

• stress of chronic illness
• uncertainty of the transplant process
• medical conditions such as hypothyroidism or pulmonary embolism.

Chronic mental illness. Patients with major mental illnesses such as schizophrenia might be appropriate candidates for organ transplant if they have adequate social support and history of treatment compliance.

Pharmacotherapy. Because of the variety of medical problems seen in transplant candidates, carefully consider medication side effects and drug-drug interactions when prescribing psychotropics.

Antidepressants. Among the selective serotonin reuptake inhibitors (SSRIs), citalopram, escitalopram, and sertraline are least likely to affect hepatic metabolism of other medications (Table 2).⁸ If a patient presents with liver failure, reduce the dosages of medications with hepatic metabolism.

Benzodiazepines. Use caution when treating anxiety with benzodiazepines because of the risk of tolerance, withdrawal, and dependence. Avoid benzodiazepines when treating transplant candidates with a substance abuse history. Also, these drugs might worsen hepatic encephalopathy and increase confusion.

Patients awaiting lung transplantation, especially those with high levels of CO₂ retention, require special care because benzodiazepines might decrease respiratory drive. Try other agents such as buspirone, gabapentin, SSRIs, or second-generation antipsychotics to treat their anxiety.

Psychotherapy. Supportive psychotherapy can help patients navigate the often-lengthy process of waiting for a donor organ. Support groups for organ transplant candidates may help ease patients’ depressive symptoms.

Table 2

Antidepressants’ half-life and effect on hepatic metabolism

Assessing substance abuse

Up to 50% of liver transplant candidates have a history of alcohol and/or drug abuse,⁹ the highest rate among transplant populations. Alcohol-induced cirrhosis and hepatitis C contracted from IV drug use are common indications for liver transplant. Effective treatment of substance abuse is essential because 30% to 50% of these patients relapse after the procedure.¹⁰ Assess:

• each substance abused, including onset, peak, and current use
• family history of substance abuse disorders
• past efforts at rehabilitation
• tobacco use (smoking before and after transplant is related to an increased incidence of new cancer diagnoses).¹¹

Some transplant centers require patients with substance
use disorders to participate in 12-step programs or
rehabilitation. Regardless of the institutions’
requirements, encourage patients to participate in
rehabilitation to prevent relapse and mitigate the
negative impact of substance abuse on physical
and mental well-being.

Mental status examination includes the usual elements such as appearance, behavior, speech, affect, and thought process. Assess for suicidal thinking or hopelessness, which have been linked to serious medical illness.¹² Question patients about hallucinations and give special attention to visual aberrations, which may occur in medically ill patients.

Cognitive testing. Use tools such as the Mini-Mental State Examination, clock drawing test, and Trail Making A and B tests to assess cognitive ability. If patients show signs of cognitive impairment, arrange for follow-up examinations and refer for neuropsychological testing.

Some cognitive impairment—such as that caused by hepatic encephalopathy—will likely improve after transplant, but other types—such as that caused by vascular disease—will not. If confusion is caused by hepatic encephalopathy, treatment with lactulose might rapidly improve symptoms. Remember that patients with hepatic encephalopathy might not exhibit elevated ammonia levels. Underlying causes of worsening hepatic encephalopathy—such as infections or bleeding—might require treatment.

Assessing adherence. Medication adherence after transplant is essential to prevent organ rejection and other complications. Posttransplant regimens are complex, and the frequency of follow-up assessments can be intense—particularly in the first year after transplant.

Your pretransplant assessment can identify where patients have struggled with adherence in the past. Before the transplant, your team can work to correct barriers such as inability to pay for medications, child care problems, or transportation needs.

Personality disorders have been identified as predictors of posttransplant nonadherence, and 50% to 60% of transplant programs consider personality disorders a relative contraindication to organ transplant.¹³ Address other contributors to poor adherence—such as substance abuse or depression—with ongoing psychiatric care.

Box 2

Social support is essential to help with the normal difficulties such as frequent clinic visits and initial physical disability patients face after successful transplant (Box 2). Ask about the candidate’s family, friends, spirituality, and finances during your pretransplant assessment. Poor social support is related to the development of posttransplant psychiatric disorders¹⁴ and adherence difficulties.¹⁵

Assessment instruments—such as the Psychosocial Assessment of Candidates for Transplantation and the Transplant Evaluation Rating Scale³—include social support items and can be useful in identifying weak areas.

Data collected by other team members can be invaluable. A nurse or social worker, for example, may observe that a patient is unwilling to take medications, contrary to the patient’s report. Other sources of information include the patient’s family and friends, a primary care physician, or other mental health providers such as a therapist or case manager.

Posttransplant psychiatric care

Depression. The incidence of depression is higher in the year following transplant than before transplant or in the immediate posttransplant period.⁵ Predictors of posttransplant depression include:

• history of depression
• poor social support
• passive coping strategies
• poor physical status after transplantation.^16,17

Carefully monitor patients who present with these factors after transplant. Treat depression with supportive measures designed to improve the patient’s social network and coping skills and pharmacotherapy. Select antidepressant medications based on side effect profiles and impact on the patient’s transplanted organs.

Substance abuse. Patients with a pretransplant history of substance abuse often relapse. Among transplant recipients with a history of alcoholic liver disease, drinking rates of 30% to 40% have been reported 5 years after transplant. Most of these data represent occasional use, not heavy or regular drinking.¹⁸ Relapse can occur despite careful assessment and follow-up.

Some evidence suggests that transplant patients who resume drinking have worse outcomes than those who abstain. Alcoholism relapse has other negative consequences, such as relationship problems and employment difficulties.

Predictors of relapse include:

• pretransplant history of alcohol dependence
• family history of alcoholism
• rehabilitation history, which could indicate a severe substance abuse disorder.³

Medications for alcoholism treatment have not been studied systematically in transplant patients, but low doses of acamprosate, ≤2 g/d, and naltrexone, ≤200 mg/d, are options for patients interested in pharmacotherapy. Support from 12-step programs also helps treat substance-abusing patients.

Altered mental status. Immunosuppressive medications—including cyclosporine, tacrolimus, and prednisone—can have neuropsychiatric effects and could cause a change in mental status (Table 3).¹⁹ Check cyclosporine and tacrolimus serum levels against reference ranges when delirium is present. If levels are toxic the dosage often can be lowered, which might lead to clinical improvement.

Quality of life. In general, patients’ quality of life improves after their transplant. After the first year—which patients might find difficult because of changes in physical and social status—quality of life typically improves.⁵

Table 3

Neuropsychiatric side effects of medications
commonly used in transplant patients

Psychiatric disorders such as depression can worsen quality of life. However, quality of life can improve after depression is diagnosed and treated. Other predictors of improved quality of life include older age, marriage, and the absence of a personality disorder.⁴

Other posttransplant concerns of patients include changes in employment, finances, and relationships. Patients often have been away from work before transplant, and returning after a long absence can be stressful. Patients may find that they cannot work as well as before becoming ill, which may lead to frustration, depression, and/or anxiety symptoms. Transplant surgery requires a large financial investment, and money concerns usually persist long after the transplant.

The transplant recipient’s role within the family may shift after surgery. Families might expect the patient to “return to normal” and resume old activities. Alternatively, family members might continue to treat the patient as a person with chronic illness despite physical improvement. If patients are struggling with these changes, supportive psychotherapy is indicated.

Related resource

• United Network for Organ Sharing. www.unos.org.
• Transplant living. www.transplantliving.org.
• Trzepacz PT, DiMartini AF, eds. The transplant patient. Cambridge, UK: Cambridge University Press; 2000.
• Klapheke MM. The role of the psychiatrist in organ transplantation. Bull Menninger Clin 1999;63(1):13-39.

Drug brand names

• Acamprosate • Campral
• Buspirone • BuSpar
• Bupropion SR • Wellbutrin SR
• Citalopram • Celexa
• Cyclosporine • Sandimmune
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Gabapentin • Neurontin
• Lactulose • Cephulac, Chronulac
• Mirtazapine • Remeron
• Naltrexone • ReVia
• Paroxetine • Paxil
• Prednisone • Deltasone
• Sertraline • Zoloft
• Tacrolimus • Prograf
• Trazodone • Desyrel

Disclosure

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

Treatment-resistant somatoform disorders are chronic (duration >1 year), can cause significant functional impairment, and respond poorly to routine care.

In the somatoform category, DSM-IV-TR includes diverse diagnoses such as conversion disorder, hypochondriasis, pain disorder, and body dysmorphic disorder. But like mismatched shoes, these disorders do not fit together well—one reason they are often misdiagnosed and ineffectively treated. This article describes:

• debate about how to categorize somatoform disorders—as psychological or physiologic
  
• evidence supporting psychotherapy and antidepressants to help patients with treatment-resistant somatoform disorders.
  

Box 1

Which category?

Somatoform disorders are common in primary care. A medical utilization survey of 1,500 primary care patients found somatization symptoms in >20%.³ Controlling for comorbid psychiatric or medical illness did not change the study’s findings, which suggests that somatization is a distinct entity and not a symptom of another underlying disorder.

Little is known about somatoform disorders’ pathophysiology (Box 1),¹ but their unifying theme is that psychological factors contribute to, amplify, or alter the presentation of physical illness. Not only do these disorders not form a coherent DSM category, but—as described by Mayou et al²—the lack of clearly defined thresholds between normal and pathologic behaviors is one of numerous problems that complicate diagnosis and treatment (Box 2).

Psychosomatic diad. Despite DSM-IV’s claims to etiologic neutrality, the origin of somatoform disorders’ physical symptoms clearly is meant to be psychological. As Lipowski⁴ said, somatization is “a tendency to experience and express somatic distress and symptoms unaccounted for by pathological findings, to attribute them to physical illness, and to seek medical help for them. It is often assumed that somatization becomes manifest in response to psychosocial stress brought about by life events that are personally stressful to the individual.”

Kroenke and others,^5,6 however, have pointed out 2 shortcomings of this definition:

• the difficulty in knowing when a physical symptom truly is unexplained, especially in patients with comorbid medical illness⁵
  
• the instability of somatoform diagnoses (in a cohort examined with the same questionnaire 12 months apart, 43% of “lifetime somatic symptoms” patients reported at the first screening were not reported at the second).⁶
  

Similarly, Mayou et al² contend that because most patients with somatoform disorders are treated by primary care physicians, having their disorders understood as psychiatric does not serve them well.

Psychiatric component. Conversely, patients with somatization disorder often have psychological symptoms, and many have personality disorders. The number of somatic symptoms with unexplained cause may be a normally distributed trait, with somatization disorders at the extreme end of the spectrum. Thus:

• Hypochondriasis could be reconsidered as health anxiety disorder because it features anxiety about potential illness.²
  
• Conversion disorders might be regrouped with other disorders focused on dissociation.²
  
• Body dysmorphic disorder might be regrouped with obsessive-compulsive disorder.⁷
  

Pain disorder could be removed from DSM because of persistent concerns about the validity of this diagnostic category. Tyrer⁸ reviewed his clinical experience and reported shifting from a view that people with excessive pain had a psychiatric disorder to the view that living with chronic pain produces a profile similar to that of a person with a psychiatric disorder.

Box 2

Box 3

New treatment approaches

As the categorization debate continues, a treatment approach is developing that includes cognitive-behavioral therapy (CBT) and antidepressants to address the psychological and physiologic effects of resistant somatoform disorders (Box 3).

Consultation letters. Sending a consultation letter to the patient’s primary care physician is considered the standard of care (Box 4).¹¹ In the study that introduced the consultation letter,¹² patients with somatization disorder were randomly assigned to treatment (a consultation letter) or control (treatment as usual). Health care utilization costs declined approximately 50%—largely because of decreased hospitalization—when patients’ physicians received consultation letters, compared with no change for usual treatment.

Consultation letters may reduce health care spending but are less effective in improving symptoms. Evidence is changing treatment as psychotherapies have been found to help patients with somatoform disorders.

Group psychotherapy. In a controlled trial, primary care patients with somatization disorder received short-term group CBT or treatment as usual, with follow-up 6 months later. Those in the CBT group—who had received patient education and relaxation training—showed moderate but significant improvement in physical illness and somatic preoccupation, hypochondriasis, and medication use. Usual-care patients did not improve.¹³

CBT vs relaxation. A group of 191 inpatients described as “highly impaired” by somatization syndrome—≥8 DSM-IV somatoform symptoms—was evaluated for psychopathology, subjective health status, and life satisfaction. They then were randomly assigned to somatization-focused CBT (“soma”) or relaxation training and compared with 34 control patients. At 1-year follow-up, doctor visits had declined significantly in patients who received CBT (“soma”), and their somatoform symptoms were reduced compared with controls’.¹¹

Psychotherapy vs listening. In a randomized, controlled trial, 102 patients with chronic refractory irritable bowel syndrome were assigned to receive exploratory psychotherapy or supportive listening. After 12 weeks, psychotherapy was more effective in improving physical and psychological symptoms, although the difference was statistically significant only in women. After 1 year, patients who received psychotherapy remained well and control patients who declined psychotherapy had relapsed.¹⁴

CBT vs usual treatment. In a randomized controlled trial, 84 patients with somatization disorder received 10 CBT sessions or treatment as usual. CBT’s goals were to:

• reduce physiologic arousal though relaxation techniques
  
• enhance activity regulation through increasing exercise and meaningful pleasurable activities and pacing activities
  
• increase awareness of emotions
  
• modify dysfunctional beliefs
  
• enhance communication of thoughts and emotions
  
• reduce spousal reinforcement of illness behavior.
  

Psychotherapy’s success in these and other studies supports the idea that somatoform spectrum disorders resemble other conditions—such as mood and anxiety disorders—that respond to psychological treatment.

Antidepressant therapy

Controlled trials also have shown that some antidepressants are more effective than placebo in improving somatoform symptoms.

St. John’s wort. In a randomized, placebo-controlled, double-blind trial, 184 patients with somatoform disorders but not major depression received St. John’s wort extract, 300 mg bid, or placebo. After 6 weeks, 45% of patients responded to St. John’s wort, compared with 21% for placebo (P=0.0006). Six measures determined response; St. John’s wort and placebo were equally well tolerated.¹⁶

Box 4

Primary outcome was change in the 15-item Patient Health Questionnaire (PHQ-15) somatic symptom severity score. After 12 weeks, PHQ-15 scores declined significantly (P P=0.097). Among secondary measures, venlafaxine ER was more effective than placebo in improving bodily pain (P=0.03), physical symptoms (P=0.02), and anxiety (P=0.02).¹⁷

Citalopram. In an 8-week trial, investigators compared the efficacy of a selective serotonin reuptake inhibitor (SSRI) and a selective noradrenaline reuptake inhibitor (SNRI) on pain symptoms in 35 patients with somatoform pain disorder. Patients were randomly assigned to double-blind treatment with the SSRI citalopram, 40 mg/d (n=17), or the SNRI reboxetine, 8 mg/d (n=18).

In patients receiving citalopram, scores decreased significantly from baseline on the Present Pain Intensity scale (3.5 vs 2.8, P=0.045) and Total Pain Rating Index of the McGill Pain Questionnaire (41.9 vs 30, P=0.004), but these scores did not change significantly in patients receiving reboxetine. Depression symptoms, as measured by the Zung Self-Rating Depression Scale, did not change significantly in either group.

The authors concluded that citalopram was moderately effective for somatoform pain disorder in this small trial. Although antidepressants’ efficacy for somatoform symptoms may be mediated through changes in comorbid mood and anxiety disorders, these authors observed that citalopram’s analgesic effect appeared to be independent of how patients rated their depressive symptoms.¹⁸

Treatment recommendations

Based on the evidence and our experience, we recommend offering CBT to patients with recent symptom onset and insight into their comorbid mood and anxiety disorders. If the patient does not improve after 8 to 12 sessions, consider adding an antidepressant such as:

• citalopram, 20 to 60 mg/d
  
• venlafaxine XR, 150 to 375 mg/d.
  

Side effects are a frequent concern in this patient population, so titrate dosages slowly. Aim for the target antidepressant dosages used to treat major depression, and avoid declaring a treatment failure without first completing adequate trials. Once the patient is stable on medication, continue for a least 1 somatization-free year.

Allow patients to discuss their physical concerns, and attempt to support them in their suffering. At the same time, help them focus on attaining realistic goals for occupational and social functioning.

Work closely with the primary care provider in treatment planning to avoid sending the patient mixed messages. Communicating in the spirit of respect and collaboration with primary care colleagues can help prevent “splitting,” in which the patient may come to idealize one practitioner and devalue the other.

Remember that patients with somatization can become medically ill. Remind their primary care providers to perform expected evaluations as dictated by objective findings.

Related resources

• VHA/DoD clinical practice guideline for the management of medically unexplained symptoms: chronic pain and fatigue (brief summary). www.guideline.gov/summary/summary.aspx?doc_id=3415.
  
• Abbey SE. Somatization and somatoform disorders. In: Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. Washington, DC: American Psychiatric Publishing; 2005:271-96.
  

• Citalopram • Celexa
  
• Venlafaxine extended-release • Effexor XR
  

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

Dr. Wise is a consultant to or speaker for Eli Lilly and Co., GlaxoSmithKline, and Pfizer.

Treatment-resistant somatoform disorders are chronic (duration >1 year), can cause significant functional impairment, and respond poorly to routine care.

In the somatoform category, DSM-IV-TR includes diverse diagnoses such as conversion disorder, hypochondriasis, pain disorder, and body dysmorphic disorder. But like mismatched shoes, these disorders do not fit together well—one reason they are often misdiagnosed and ineffectively treated. This article describes:

• debate about how to categorize somatoform disorders—as psychological or physiologic
  
• evidence supporting psychotherapy and antidepressants to help patients with treatment-resistant somatoform disorders.
  

Box 1

Which category?

Somatoform disorders are common in primary care. A medical utilization survey of 1,500 primary care patients found somatization symptoms in >20%.³ Controlling for comorbid psychiatric or medical illness did not change the study’s findings, which suggests that somatization is a distinct entity and not a symptom of another underlying disorder.

Little is known about somatoform disorders’ pathophysiology (Box 1),¹ but their unifying theme is that psychological factors contribute to, amplify, or alter the presentation of physical illness. Not only do these disorders not form a coherent DSM category, but—as described by Mayou et al²—the lack of clearly defined thresholds between normal and pathologic behaviors is one of numerous problems that complicate diagnosis and treatment (Box 2).

Psychosomatic diad. Despite DSM-IV’s claims to etiologic neutrality, the origin of somatoform disorders’ physical symptoms clearly is meant to be psychological. As Lipowski⁴ said, somatization is “a tendency to experience and express somatic distress and symptoms unaccounted for by pathological findings, to attribute them to physical illness, and to seek medical help for them. It is often assumed that somatization becomes manifest in response to psychosocial stress brought about by life events that are personally stressful to the individual.”

Kroenke and others,^5,6 however, have pointed out 2 shortcomings of this definition:

• the difficulty in knowing when a physical symptom truly is unexplained, especially in patients with comorbid medical illness⁵
  
• the instability of somatoform diagnoses (in a cohort examined with the same questionnaire 12 months apart, 43% of “lifetime somatic symptoms” patients reported at the first screening were not reported at the second).⁶
  

Similarly, Mayou et al² contend that because most patients with somatoform disorders are treated by primary care physicians, having their disorders understood as psychiatric does not serve them well.

Psychiatric component. Conversely, patients with somatization disorder often have psychological symptoms, and many have personality disorders. The number of somatic symptoms with unexplained cause may be a normally distributed trait, with somatization disorders at the extreme end of the spectrum. Thus:

• Hypochondriasis could be reconsidered as health anxiety disorder because it features anxiety about potential illness.²
  
• Conversion disorders might be regrouped with other disorders focused on dissociation.²
  
• Body dysmorphic disorder might be regrouped with obsessive-compulsive disorder.⁷
  

Pain disorder could be removed from DSM because of persistent concerns about the validity of this diagnostic category. Tyrer⁸ reviewed his clinical experience and reported shifting from a view that people with excessive pain had a psychiatric disorder to the view that living with chronic pain produces a profile similar to that of a person with a psychiatric disorder.

Box 2

Box 3

New treatment approaches

As the categorization debate continues, a treatment approach is developing that includes cognitive-behavioral therapy (CBT) and antidepressants to address the psychological and physiologic effects of resistant somatoform disorders (Box 3).

Consultation letters. Sending a consultation letter to the patient’s primary care physician is considered the standard of care (Box 4).¹¹ In the study that introduced the consultation letter,¹² patients with somatization disorder were randomly assigned to treatment (a consultation letter) or control (treatment as usual). Health care utilization costs declined approximately 50%—largely because of decreased hospitalization—when patients’ physicians received consultation letters, compared with no change for usual treatment.

Consultation letters may reduce health care spending but are less effective in improving symptoms. Evidence is changing treatment as psychotherapies have been found to help patients with somatoform disorders.

Group psychotherapy. In a controlled trial, primary care patients with somatization disorder received short-term group CBT or treatment as usual, with follow-up 6 months later. Those in the CBT group—who had received patient education and relaxation training—showed moderate but significant improvement in physical illness and somatic preoccupation, hypochondriasis, and medication use. Usual-care patients did not improve.¹³

CBT vs relaxation. A group of 191 inpatients described as “highly impaired” by somatization syndrome—≥8 DSM-IV somatoform symptoms—was evaluated for psychopathology, subjective health status, and life satisfaction. They then were randomly assigned to somatization-focused CBT (“soma”) or relaxation training and compared with 34 control patients. At 1-year follow-up, doctor visits had declined significantly in patients who received CBT (“soma”), and their somatoform symptoms were reduced compared with controls’.¹¹

Psychotherapy vs listening. In a randomized, controlled trial, 102 patients with chronic refractory irritable bowel syndrome were assigned to receive exploratory psychotherapy or supportive listening. After 12 weeks, psychotherapy was more effective in improving physical and psychological symptoms, although the difference was statistically significant only in women. After 1 year, patients who received psychotherapy remained well and control patients who declined psychotherapy had relapsed.¹⁴

CBT vs usual treatment. In a randomized controlled trial, 84 patients with somatization disorder received 10 CBT sessions or treatment as usual. CBT’s goals were to:

• reduce physiologic arousal though relaxation techniques
  
• enhance activity regulation through increasing exercise and meaningful pleasurable activities and pacing activities
  
• increase awareness of emotions
  
• modify dysfunctional beliefs
  
• enhance communication of thoughts and emotions
  
• reduce spousal reinforcement of illness behavior.
  

Psychotherapy’s success in these and other studies supports the idea that somatoform spectrum disorders resemble other conditions—such as mood and anxiety disorders—that respond to psychological treatment.

Antidepressant therapy

Controlled trials also have shown that some antidepressants are more effective than placebo in improving somatoform symptoms.

St. John’s wort. In a randomized, placebo-controlled, double-blind trial, 184 patients with somatoform disorders but not major depression received St. John’s wort extract, 300 mg bid, or placebo. After 6 weeks, 45% of patients responded to St. John’s wort, compared with 21% for placebo (P=0.0006). Six measures determined response; St. John’s wort and placebo were equally well tolerated.¹⁶

Box 4

Primary outcome was change in the 15-item Patient Health Questionnaire (PHQ-15) somatic symptom severity score. After 12 weeks, PHQ-15 scores declined significantly (P P=0.097). Among secondary measures, venlafaxine ER was more effective than placebo in improving bodily pain (P=0.03), physical symptoms (P=0.02), and anxiety (P=0.02).¹⁷

Citalopram. In an 8-week trial, investigators compared the efficacy of a selective serotonin reuptake inhibitor (SSRI) and a selective noradrenaline reuptake inhibitor (SNRI) on pain symptoms in 35 patients with somatoform pain disorder. Patients were randomly assigned to double-blind treatment with the SSRI citalopram, 40 mg/d (n=17), or the SNRI reboxetine, 8 mg/d (n=18).

In patients receiving citalopram, scores decreased significantly from baseline on the Present Pain Intensity scale (3.5 vs 2.8, P=0.045) and Total Pain Rating Index of the McGill Pain Questionnaire (41.9 vs 30, P=0.004), but these scores did not change significantly in patients receiving reboxetine. Depression symptoms, as measured by the Zung Self-Rating Depression Scale, did not change significantly in either group.

The authors concluded that citalopram was moderately effective for somatoform pain disorder in this small trial. Although antidepressants’ efficacy for somatoform symptoms may be mediated through changes in comorbid mood and anxiety disorders, these authors observed that citalopram’s analgesic effect appeared to be independent of how patients rated their depressive symptoms.¹⁸

Treatment recommendations

Based on the evidence and our experience, we recommend offering CBT to patients with recent symptom onset and insight into their comorbid mood and anxiety disorders. If the patient does not improve after 8 to 12 sessions, consider adding an antidepressant such as:

• citalopram, 20 to 60 mg/d
  
• venlafaxine XR, 150 to 375 mg/d.
  

Side effects are a frequent concern in this patient population, so titrate dosages slowly. Aim for the target antidepressant dosages used to treat major depression, and avoid declaring a treatment failure without first completing adequate trials. Once the patient is stable on medication, continue for a least 1 somatization-free year.

Allow patients to discuss their physical concerns, and attempt to support them in their suffering. At the same time, help them focus on attaining realistic goals for occupational and social functioning.

Work closely with the primary care provider in treatment planning to avoid sending the patient mixed messages. Communicating in the spirit of respect and collaboration with primary care colleagues can help prevent “splitting,” in which the patient may come to idealize one practitioner and devalue the other.

Remember that patients with somatization can become medically ill. Remind their primary care providers to perform expected evaluations as dictated by objective findings.

Related resources

• VHA/DoD clinical practice guideline for the management of medically unexplained symptoms: chronic pain and fatigue (brief summary). www.guideline.gov/summary/summary.aspx?doc_id=3415.
  
• Abbey SE. Somatization and somatoform disorders. In: Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. Washington, DC: American Psychiatric Publishing; 2005:271-96.
  

• Citalopram • Celexa
  
• Venlafaxine extended-release • Effexor XR
  

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

Dr. Wise is a consultant to or speaker for Eli Lilly and Co., GlaxoSmithKline, and Pfizer.

Treatment-resistant somatoform disorders are chronic (duration >1 year), can cause significant functional impairment, and respond poorly to routine care.

In the somatoform category, DSM-IV-TR includes diverse diagnoses such as conversion disorder, hypochondriasis, pain disorder, and body dysmorphic disorder. But like mismatched shoes, these disorders do not fit together well—one reason they are often misdiagnosed and ineffectively treated. This article describes:

• debate about how to categorize somatoform disorders—as psychological or physiologic
  
• evidence supporting psychotherapy and antidepressants to help patients with treatment-resistant somatoform disorders.
  

Box 1

Which category?

Somatoform disorders are common in primary care. A medical utilization survey of 1,500 primary care patients found somatization symptoms in >20%.³ Controlling for comorbid psychiatric or medical illness did not change the study’s findings, which suggests that somatization is a distinct entity and not a symptom of another underlying disorder.

Little is known about somatoform disorders’ pathophysiology (Box 1),¹ but their unifying theme is that psychological factors contribute to, amplify, or alter the presentation of physical illness. Not only do these disorders not form a coherent DSM category, but—as described by Mayou et al²—the lack of clearly defined thresholds between normal and pathologic behaviors is one of numerous problems that complicate diagnosis and treatment (Box 2).

Psychosomatic diad. Despite DSM-IV’s claims to etiologic neutrality, the origin of somatoform disorders’ physical symptoms clearly is meant to be psychological. As Lipowski⁴ said, somatization is “a tendency to experience and express somatic distress and symptoms unaccounted for by pathological findings, to attribute them to physical illness, and to seek medical help for them. It is often assumed that somatization becomes manifest in response to psychosocial stress brought about by life events that are personally stressful to the individual.”

Kroenke and others,^5,6 however, have pointed out 2 shortcomings of this definition:

• the difficulty in knowing when a physical symptom truly is unexplained, especially in patients with comorbid medical illness⁵
  
• the instability of somatoform diagnoses (in a cohort examined with the same questionnaire 12 months apart, 43% of “lifetime somatic symptoms” patients reported at the first screening were not reported at the second).⁶
  

Similarly, Mayou et al² contend that because most patients with somatoform disorders are treated by primary care physicians, having their disorders understood as psychiatric does not serve them well.

Psychiatric component. Conversely, patients with somatization disorder often have psychological symptoms, and many have personality disorders. The number of somatic symptoms with unexplained cause may be a normally distributed trait, with somatization disorders at the extreme end of the spectrum. Thus:

• Hypochondriasis could be reconsidered as health anxiety disorder because it features anxiety about potential illness.²
  
• Conversion disorders might be regrouped with other disorders focused on dissociation.²
  
• Body dysmorphic disorder might be regrouped with obsessive-compulsive disorder.⁷
  

Pain disorder could be removed from DSM because of persistent concerns about the validity of this diagnostic category. Tyrer⁸ reviewed his clinical experience and reported shifting from a view that people with excessive pain had a psychiatric disorder to the view that living with chronic pain produces a profile similar to that of a person with a psychiatric disorder.

Box 2

Box 3

New treatment approaches

As the categorization debate continues, a treatment approach is developing that includes cognitive-behavioral therapy (CBT) and antidepressants to address the psychological and physiologic effects of resistant somatoform disorders (Box 3).

Consultation letters. Sending a consultation letter to the patient’s primary care physician is considered the standard of care (Box 4).¹¹ In the study that introduced the consultation letter,¹² patients with somatization disorder were randomly assigned to treatment (a consultation letter) or control (treatment as usual). Health care utilization costs declined approximately 50%—largely because of decreased hospitalization—when patients’ physicians received consultation letters, compared with no change for usual treatment.

Consultation letters may reduce health care spending but are less effective in improving symptoms. Evidence is changing treatment as psychotherapies have been found to help patients with somatoform disorders.

Group psychotherapy. In a controlled trial, primary care patients with somatization disorder received short-term group CBT or treatment as usual, with follow-up 6 months later. Those in the CBT group—who had received patient education and relaxation training—showed moderate but significant improvement in physical illness and somatic preoccupation, hypochondriasis, and medication use. Usual-care patients did not improve.¹³

CBT vs relaxation. A group of 191 inpatients described as “highly impaired” by somatization syndrome—≥8 DSM-IV somatoform symptoms—was evaluated for psychopathology, subjective health status, and life satisfaction. They then were randomly assigned to somatization-focused CBT (“soma”) or relaxation training and compared with 34 control patients. At 1-year follow-up, doctor visits had declined significantly in patients who received CBT (“soma”), and their somatoform symptoms were reduced compared with controls’.¹¹

Psychotherapy vs listening. In a randomized, controlled trial, 102 patients with chronic refractory irritable bowel syndrome were assigned to receive exploratory psychotherapy or supportive listening. After 12 weeks, psychotherapy was more effective in improving physical and psychological symptoms, although the difference was statistically significant only in women. After 1 year, patients who received psychotherapy remained well and control patients who declined psychotherapy had relapsed.¹⁴

CBT vs usual treatment. In a randomized controlled trial, 84 patients with somatization disorder received 10 CBT sessions or treatment as usual. CBT’s goals were to:

• reduce physiologic arousal though relaxation techniques
  
• enhance activity regulation through increasing exercise and meaningful pleasurable activities and pacing activities
  
• increase awareness of emotions
  
• modify dysfunctional beliefs
  
• enhance communication of thoughts and emotions
  
• reduce spousal reinforcement of illness behavior.
  

Psychotherapy’s success in these and other studies supports the idea that somatoform spectrum disorders resemble other conditions—such as mood and anxiety disorders—that respond to psychological treatment.

Antidepressant therapy

Controlled trials also have shown that some antidepressants are more effective than placebo in improving somatoform symptoms.

St. John’s wort. In a randomized, placebo-controlled, double-blind trial, 184 patients with somatoform disorders but not major depression received St. John’s wort extract, 300 mg bid, or placebo. After 6 weeks, 45% of patients responded to St. John’s wort, compared with 21% for placebo (P=0.0006). Six measures determined response; St. John’s wort and placebo were equally well tolerated.¹⁶

Box 4

Primary outcome was change in the 15-item Patient Health Questionnaire (PHQ-15) somatic symptom severity score. After 12 weeks, PHQ-15 scores declined significantly (P P=0.097). Among secondary measures, venlafaxine ER was more effective than placebo in improving bodily pain (P=0.03), physical symptoms (P=0.02), and anxiety (P=0.02).¹⁷

Citalopram. In an 8-week trial, investigators compared the efficacy of a selective serotonin reuptake inhibitor (SSRI) and a selective noradrenaline reuptake inhibitor (SNRI) on pain symptoms in 35 patients with somatoform pain disorder. Patients were randomly assigned to double-blind treatment with the SSRI citalopram, 40 mg/d (n=17), or the SNRI reboxetine, 8 mg/d (n=18).

In patients receiving citalopram, scores decreased significantly from baseline on the Present Pain Intensity scale (3.5 vs 2.8, P=0.045) and Total Pain Rating Index of the McGill Pain Questionnaire (41.9 vs 30, P=0.004), but these scores did not change significantly in patients receiving reboxetine. Depression symptoms, as measured by the Zung Self-Rating Depression Scale, did not change significantly in either group.

The authors concluded that citalopram was moderately effective for somatoform pain disorder in this small trial. Although antidepressants’ efficacy for somatoform symptoms may be mediated through changes in comorbid mood and anxiety disorders, these authors observed that citalopram’s analgesic effect appeared to be independent of how patients rated their depressive symptoms.¹⁸

Treatment recommendations

Based on the evidence and our experience, we recommend offering CBT to patients with recent symptom onset and insight into their comorbid mood and anxiety disorders. If the patient does not improve after 8 to 12 sessions, consider adding an antidepressant such as:

• citalopram, 20 to 60 mg/d
  
• venlafaxine XR, 150 to 375 mg/d.
  

Side effects are a frequent concern in this patient population, so titrate dosages slowly. Aim for the target antidepressant dosages used to treat major depression, and avoid declaring a treatment failure without first completing adequate trials. Once the patient is stable on medication, continue for a least 1 somatization-free year.

Allow patients to discuss their physical concerns, and attempt to support them in their suffering. At the same time, help them focus on attaining realistic goals for occupational and social functioning.

Work closely with the primary care provider in treatment planning to avoid sending the patient mixed messages. Communicating in the spirit of respect and collaboration with primary care colleagues can help prevent “splitting,” in which the patient may come to idealize one practitioner and devalue the other.

Remember that patients with somatization can become medically ill. Remind their primary care providers to perform expected evaluations as dictated by objective findings.

Related resources

• VHA/DoD clinical practice guideline for the management of medically unexplained symptoms: chronic pain and fatigue (brief summary). www.guideline.gov/summary/summary.aspx?doc_id=3415.
  
• Abbey SE. Somatization and somatoform disorders. In: Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. Washington, DC: American Psychiatric Publishing; 2005:271-96.
  

• Citalopram • Celexa
  
• Venlafaxine extended-release • Effexor XR
  

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

Dr. Wise is a consultant to or speaker for Eli Lilly and Co., GlaxoSmithKline, and Pfizer.