Current Psychiatry

“Bupropion: Off-label treatment for cocaine and methamphetamine addiction” (Pearls, Current Psychiatry, July 2010, p. 52) was a well-written, succinct article addressing a pharmacologic treatment in a difficult population. Bupropion has been utilized to target cravings associated with cocaine and methamphetamine addiction with mixed success.¹ Hopefully the cocaine vaccine mentioned in the article will be approved, which will provide clinicians with another agent for treating dual diagnosis patients.

Timothy R. Berigan, DDS, MD
Contract Psychiatrist
Behavioral Health Services
Fort Huachuca, AZ

“Bupropion: Off-label treatment for cocaine and methamphetamine addiction” (Pearls, Current Psychiatry, July 2010, p. 52) was a well-written, succinct article addressing a pharmacologic treatment in a difficult population. Bupropion has been utilized to target cravings associated with cocaine and methamphetamine addiction with mixed success.¹ Hopefully the cocaine vaccine mentioned in the article will be approved, which will provide clinicians with another agent for treating dual diagnosis patients.

Timothy R. Berigan, DDS, MD
Contract Psychiatrist
Behavioral Health Services
Fort Huachuca, AZ

“Bupropion: Off-label treatment for cocaine and methamphetamine addiction” (Pearls, Current Psychiatry, July 2010, p. 52) was a well-written, succinct article addressing a pharmacologic treatment in a difficult population. Bupropion has been utilized to target cravings associated with cocaine and methamphetamine addiction with mixed success.¹ Hopefully the cocaine vaccine mentioned in the article will be approved, which will provide clinicians with another agent for treating dual diagnosis patients.

Timothy R. Berigan, DDS, MD
Contract Psychiatrist
Behavioral Health Services
Fort Huachuca, AZ

In Dr. Henry A. Nasrallah’s “Psychiatric futurology” (From the Editor, Current Psychiatry, July 2010, p. 9-10) he seems to suggest that the best hope for the future of psychiatry is continued advances in neuroscience. I contend that clinical outcomes for patients with schizophrenia and bipolar disorder have remained static despite high-profile advances. Perhaps psychiatry’s orientation has moved too far in favor of biologic approaches and our patients would be better served by improving psychosocial approaches, such as assertive community treatment and supportive employment. These approaches, enacted in partnership with allied mental health providers, can act synergistically with biologic approaches, leading to wellness and recovery through community integration. Such an approach may provide the best hope for the future success of psychiatry.

Walter Rush, MD
South-Metro Human Services ACT
St. Paul, MN

In Dr. Henry A. Nasrallah’s “Psychiatric futurology” (From the Editor, Current Psychiatry, July 2010, p. 9-10) he seems to suggest that the best hope for the future of psychiatry is continued advances in neuroscience. I contend that clinical outcomes for patients with schizophrenia and bipolar disorder have remained static despite high-profile advances. Perhaps psychiatry’s orientation has moved too far in favor of biologic approaches and our patients would be better served by improving psychosocial approaches, such as assertive community treatment and supportive employment. These approaches, enacted in partnership with allied mental health providers, can act synergistically with biologic approaches, leading to wellness and recovery through community integration. Such an approach may provide the best hope for the future success of psychiatry.

Walter Rush, MD
South-Metro Human Services ACT
St. Paul, MN

In Dr. Henry A. Nasrallah’s “Psychiatric futurology” (From the Editor, Current Psychiatry, July 2010, p. 9-10) he seems to suggest that the best hope for the future of psychiatry is continued advances in neuroscience. I contend that clinical outcomes for patients with schizophrenia and bipolar disorder have remained static despite high-profile advances. Perhaps psychiatry’s orientation has moved too far in favor of biologic approaches and our patients would be better served by improving psychosocial approaches, such as assertive community treatment and supportive employment. These approaches, enacted in partnership with allied mental health providers, can act synergistically with biologic approaches, leading to wellness and recovery through community integration. Such an approach may provide the best hope for the future success of psychiatry.

Walter Rush, MD
South-Metro Human Services ACT
St. Paul, MN

“How to manage medical complications of the 5 most abused substances” (Current Psychiatry, November 2009, p. 35-47) contains several errors of fact, emphasis, and inappropriate citation of references that may mislead readers.

The article states “marijuana use can double or triple the risk of cancer of the respiratory tract and lungs” and cites a reference by Tashkin et al.¹ In fact, that review article states “…evidence that marijuana smoking may lead to…respiratory cancer is limited and inconsistent.” A subsequent case-control study by Tashkin and colleagues found no increased risk of lung or upper respiratory tract cancer among heavy marijuana smokers.² A smaller case-control study from New Zealand did find an 8% increased risk of lung cancer associated with each joint-year of marijuana smoking.³ However, the Current Psychiatry article grossly exaggerated the cancer risk from marijuana smoking and cited an inappropriate supporting reference.

The article states that “growing evidence shows that marijuana use could lead to cardiac arrhythmias, such as atrial fibrillation” and cites 1 supporting reference.⁴ That article reviewed the 6 published cases of atrial fibrillation (AF) associated with marijuana smoking and acknowledged “the exact incidence of AF related to marijuana smoking is difficult to be estimated.” Other reviews of the cardiovascular effects of marijuana smoking take a broader view, eg, “marijuana’s cardiovascular effects are not associated with serious health problems for most young, healthy users.”⁵ Given the ratio between 6 published case reports and the millions of people smoking marijuana daily, this may be a more appropriate perspective for a review article.

The article states “some studies show persistent cognitive impairments in longer term cannabis users, even after 2 years of abstinence” and cites 1 supporting reference by Pope et al⁶ (incorrectly cited as Harrison et al). In fact, that study did not test subjects beyond 28 days of abstinence; at the time, “the differences between users and controls had narrowed and were mostly nonsignificant.” Other studies have found no significant differences between marijuana smokers and non-users after 3 months of abstinence,⁷ nor are significant long-term cognitive deficits mentioned in recent reviews of the topic.⁸ Thus, we are not aware of any scientific basis for the statement in the article, which is not supported by the 1 study cited.

The paragraph on “cardiac complications” of cocaine use presents an incomplete picture of the risk of myocardial infarction (MI) and cites only 1 (2001) review article. What would have been useful to the reader was:

• cocaine-associated MI occurs in up to 6% of patients with cocaine-associated chest pain⁹
• cocaine-associated MI may have atypical symptomatic presentation, eg, without chest pain⁹
• in a large, population-based study, adults age 18 to 45 who used cocaine >10 times had a 3.5-fold increased risk of MI¹⁰
• two-thirds of MIs occur within 3 hours of cocaine ingestion, but MI may occur >18 hours after ingestion (possibly due to pharmacologically active cocaine metabolites).⁹ The recent review by McCord et al,⁹ which includes treatment recommendations from the American Heart Association, would have been useful to cite.

Most readers of Current Psychiatry are not specialists in the topics covered by its review articles. This places increased responsibility for ensuring accurate and balanced topic coverage with citation of appropriate, up-to-date review articles.

David A. Gorelick, MD, PhD
National Institute on Drug Abuse
Baltimore, MD

References

1. Tashkin DP. Smoked marijuana as a cause of lung injury. Monaldi Arch Chest Dis. 2005;63(2):93-100.

2. Hashibe M, Morgenstern H, Cui Y, et al. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1829-1834.

3. Aldington S, Harwood M, Cox B, et al. Cannabis use and risk of lung cancer: a case-control study. Eur Respir J. 2008;31(2):280-286.

4. Korantzopoulos P, Liu T, Papaioannides D, et al. Atrial fibrillation and marijuana smoking. Int J Clin Pract. 2008;62(2):308-313.

5. Jones RT. Cardiovascular system effects of marijuana. J Clin Pharmacol. 2002;42(11 suppl):58S-63S.

6. Pope HG, Jr, Gruber AJ, Hudson JI, et al. Cognitive measures in long-term cannabis users. J Clin Pharmacol. 2002;42(11 suppl):41S-47S.

7. Fried PA, Watkinson B, Gray R. Neurocognitive consequences of marihuana—a comparison with pre-drug performance. Neurotoxicol Teratol. 2005;27(2):231-239.

8. Schweinsburg AD, Brown SA, Tapert SF. The influence of marijuana use on neurocognitive functioning in adolescents. Curr Drug Abuse Rev. 2008;1(1):99-111.

9. McCord J, Jneid H, Hollander JE, et al. Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation. 2008;117(14):1897-1907.

10. Aslibekyan S, Levitan EB, Mittleman MA. Prevalent cocaine use and myocardial infarction. Am J Cardiol. 2008;102(8):966-969.

The authors respond

Dr. Gorelick’s detailed comments brought up many points, which we address below.

Marijuana and cancer—Dr. Gorelick commented that the article “grossly exaggerated the cancer risk from marijuana smoking” due to the cited reference stating that the evidence is “limited and inconsistent.” We agree the article mentions the evidence is not clear. However, in further reading of their discussion of the risk of lung cancer the authors point to several epidemiologic studies, some of which showed increased risk of cancer. Specifically, a study from the United States showed “a history of daily or near-daily marijuana smoking was associated with a 2.6-fold greater risk for developing head and neck cancer.”

In our article we focused more on the positive results than on the entire picture and would have served our readers better by not making such an equivocal statement about the increased risk of cancer.

Marijuana and AF—Dr. Gorelick questioned the tenacity of the association between marijuana and AF, stating “given the ratio between 6 published cases reports and the millions of people smoking marijuana daily, this may be a more appropriate perspective for a review article.”

Our comments were based on the following statements from the cited study: “During the past few years an increasing number of case reports indicate an association between marijuana smoking and the development of AF.” Also, “despite the small number of these reports, the observed close temporal relationship between marijuana smoking and AF occurrence, especially in young people without structural heart disease or other precipitating factors for AF, strongly supports an association between the two conditions.”

We mentioned AF because this is not something most people consider as a side effect of marijuana and we felt it was useful to call attention to it as a potential complication. However, we do agree that the sentence could have been worded differently because the number of cases remains low and the risk of developing AF in young healthy adults is low.

Marijuana and cognitive effects—Dr. Gorelick commented that there is “no scientific basis for the statement in the article” and that the article cited looked only at 28 days post-cannabis use. The following comments were made in the article we cited: “However, one electroencephalographic study suggested greater abnormalities in longer term cannabis users, and another found a strong correlation between performance on a selective attention task and duration of cannabis use, even in users abstinent for a mean of 2 years.”

Also, that article concluded “…an opposite impression emerges from a recent large, carefully controlled study by Solowij et al, who found that longer term cannabis users showed significantly greater deficits on several neuropsychological measures than shorter term users, and that these measures were often negatively correlated with lifetime duration of use.”

Again, we agree that our comment was likely too broad because the evidence is limited and not clear, which is why we wrote, “However, most studies suggest that marijuana-associated cognitive deficits are reversible and related to recent exposure.”

Cocaine and cardiac complications—We thank Dr. Gorelick for providing additional information and resources about the very important association between cocaine use and the MI risk. We certainly agree that the inclusion of his suggested references would have been appropriate.

Raheel Khan, DO
Assistant Clinical Professor
Psychosomatic Medicine
Department of Psychiatry and Behavioral Sciences

Robert M. McCarron, DO
Training Director, Internal Medicine/Psychiatry Residency
Department of Psychiatry and Behavioral Sciences
Department of Internal Medicine
University of California, Davis
Sacramento, CA

“How to manage medical complications of the 5 most abused substances” (Current Psychiatry, November 2009, p. 35-47) contains several errors of fact, emphasis, and inappropriate citation of references that may mislead readers.

The article states “marijuana use can double or triple the risk of cancer of the respiratory tract and lungs” and cites a reference by Tashkin et al.¹ In fact, that review article states “…evidence that marijuana smoking may lead to…respiratory cancer is limited and inconsistent.” A subsequent case-control study by Tashkin and colleagues found no increased risk of lung or upper respiratory tract cancer among heavy marijuana smokers.² A smaller case-control study from New Zealand did find an 8% increased risk of lung cancer associated with each joint-year of marijuana smoking.³ However, the Current Psychiatry article grossly exaggerated the cancer risk from marijuana smoking and cited an inappropriate supporting reference.

The article states that “growing evidence shows that marijuana use could lead to cardiac arrhythmias, such as atrial fibrillation” and cites 1 supporting reference.⁴ That article reviewed the 6 published cases of atrial fibrillation (AF) associated with marijuana smoking and acknowledged “the exact incidence of AF related to marijuana smoking is difficult to be estimated.” Other reviews of the cardiovascular effects of marijuana smoking take a broader view, eg, “marijuana’s cardiovascular effects are not associated with serious health problems for most young, healthy users.”⁵ Given the ratio between 6 published case reports and the millions of people smoking marijuana daily, this may be a more appropriate perspective for a review article.

The article states “some studies show persistent cognitive impairments in longer term cannabis users, even after 2 years of abstinence” and cites 1 supporting reference by Pope et al⁶ (incorrectly cited as Harrison et al). In fact, that study did not test subjects beyond 28 days of abstinence; at the time, “the differences between users and controls had narrowed and were mostly nonsignificant.” Other studies have found no significant differences between marijuana smokers and non-users after 3 months of abstinence,⁷ nor are significant long-term cognitive deficits mentioned in recent reviews of the topic.⁸ Thus, we are not aware of any scientific basis for the statement in the article, which is not supported by the 1 study cited.

The paragraph on “cardiac complications” of cocaine use presents an incomplete picture of the risk of myocardial infarction (MI) and cites only 1 (2001) review article. What would have been useful to the reader was:

• cocaine-associated MI occurs in up to 6% of patients with cocaine-associated chest pain⁹
• cocaine-associated MI may have atypical symptomatic presentation, eg, without chest pain⁹
• in a large, population-based study, adults age 18 to 45 who used cocaine >10 times had a 3.5-fold increased risk of MI¹⁰
• two-thirds of MIs occur within 3 hours of cocaine ingestion, but MI may occur >18 hours after ingestion (possibly due to pharmacologically active cocaine metabolites).⁹ The recent review by McCord et al,⁹ which includes treatment recommendations from the American Heart Association, would have been useful to cite.

Most readers of Current Psychiatry are not specialists in the topics covered by its review articles. This places increased responsibility for ensuring accurate and balanced topic coverage with citation of appropriate, up-to-date review articles.

David A. Gorelick, MD, PhD
National Institute on Drug Abuse
Baltimore, MD

References

1. Tashkin DP. Smoked marijuana as a cause of lung injury. Monaldi Arch Chest Dis. 2005;63(2):93-100.

2. Hashibe M, Morgenstern H, Cui Y, et al. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1829-1834.

3. Aldington S, Harwood M, Cox B, et al. Cannabis use and risk of lung cancer: a case-control study. Eur Respir J. 2008;31(2):280-286.

4. Korantzopoulos P, Liu T, Papaioannides D, et al. Atrial fibrillation and marijuana smoking. Int J Clin Pract. 2008;62(2):308-313.

5. Jones RT. Cardiovascular system effects of marijuana. J Clin Pharmacol. 2002;42(11 suppl):58S-63S.

6. Pope HG, Jr, Gruber AJ, Hudson JI, et al. Cognitive measures in long-term cannabis users. J Clin Pharmacol. 2002;42(11 suppl):41S-47S.

7. Fried PA, Watkinson B, Gray R. Neurocognitive consequences of marihuana—a comparison with pre-drug performance. Neurotoxicol Teratol. 2005;27(2):231-239.

8. Schweinsburg AD, Brown SA, Tapert SF. The influence of marijuana use on neurocognitive functioning in adolescents. Curr Drug Abuse Rev. 2008;1(1):99-111.

9. McCord J, Jneid H, Hollander JE, et al. Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation. 2008;117(14):1897-1907.

10. Aslibekyan S, Levitan EB, Mittleman MA. Prevalent cocaine use and myocardial infarction. Am J Cardiol. 2008;102(8):966-969.

The authors respond

Dr. Gorelick’s detailed comments brought up many points, which we address below.

Marijuana and cancer—Dr. Gorelick commented that the article “grossly exaggerated the cancer risk from marijuana smoking” due to the cited reference stating that the evidence is “limited and inconsistent.” We agree the article mentions the evidence is not clear. However, in further reading of their discussion of the risk of lung cancer the authors point to several epidemiologic studies, some of which showed increased risk of cancer. Specifically, a study from the United States showed “a history of daily or near-daily marijuana smoking was associated with a 2.6-fold greater risk for developing head and neck cancer.”

In our article we focused more on the positive results than on the entire picture and would have served our readers better by not making such an equivocal statement about the increased risk of cancer.

Marijuana and AF—Dr. Gorelick questioned the tenacity of the association between marijuana and AF, stating “given the ratio between 6 published cases reports and the millions of people smoking marijuana daily, this may be a more appropriate perspective for a review article.”

Our comments were based on the following statements from the cited study: “During the past few years an increasing number of case reports indicate an association between marijuana smoking and the development of AF.” Also, “despite the small number of these reports, the observed close temporal relationship between marijuana smoking and AF occurrence, especially in young people without structural heart disease or other precipitating factors for AF, strongly supports an association between the two conditions.”

We mentioned AF because this is not something most people consider as a side effect of marijuana and we felt it was useful to call attention to it as a potential complication. However, we do agree that the sentence could have been worded differently because the number of cases remains low and the risk of developing AF in young healthy adults is low.

Marijuana and cognitive effects—Dr. Gorelick commented that there is “no scientific basis for the statement in the article” and that the article cited looked only at 28 days post-cannabis use. The following comments were made in the article we cited: “However, one electroencephalographic study suggested greater abnormalities in longer term cannabis users, and another found a strong correlation between performance on a selective attention task and duration of cannabis use, even in users abstinent for a mean of 2 years.”

Also, that article concluded “…an opposite impression emerges from a recent large, carefully controlled study by Solowij et al, who found that longer term cannabis users showed significantly greater deficits on several neuropsychological measures than shorter term users, and that these measures were often negatively correlated with lifetime duration of use.”

Again, we agree that our comment was likely too broad because the evidence is limited and not clear, which is why we wrote, “However, most studies suggest that marijuana-associated cognitive deficits are reversible and related to recent exposure.”

Cocaine and cardiac complications—We thank Dr. Gorelick for providing additional information and resources about the very important association between cocaine use and the MI risk. We certainly agree that the inclusion of his suggested references would have been appropriate.

Raheel Khan, DO
Assistant Clinical Professor
Psychosomatic Medicine
Department of Psychiatry and Behavioral Sciences

Robert M. McCarron, DO
Training Director, Internal Medicine/Psychiatry Residency
Department of Psychiatry and Behavioral Sciences
Department of Internal Medicine
University of California, Davis
Sacramento, CA

“How to manage medical complications of the 5 most abused substances” (Current Psychiatry, November 2009, p. 35-47) contains several errors of fact, emphasis, and inappropriate citation of references that may mislead readers.

The article states “marijuana use can double or triple the risk of cancer of the respiratory tract and lungs” and cites a reference by Tashkin et al.¹ In fact, that review article states “…evidence that marijuana smoking may lead to…respiratory cancer is limited and inconsistent.” A subsequent case-control study by Tashkin and colleagues found no increased risk of lung or upper respiratory tract cancer among heavy marijuana smokers.² A smaller case-control study from New Zealand did find an 8% increased risk of lung cancer associated with each joint-year of marijuana smoking.³ However, the Current Psychiatry article grossly exaggerated the cancer risk from marijuana smoking and cited an inappropriate supporting reference.

The article states that “growing evidence shows that marijuana use could lead to cardiac arrhythmias, such as atrial fibrillation” and cites 1 supporting reference.⁴ That article reviewed the 6 published cases of atrial fibrillation (AF) associated with marijuana smoking and acknowledged “the exact incidence of AF related to marijuana smoking is difficult to be estimated.” Other reviews of the cardiovascular effects of marijuana smoking take a broader view, eg, “marijuana’s cardiovascular effects are not associated with serious health problems for most young, healthy users.”⁵ Given the ratio between 6 published case reports and the millions of people smoking marijuana daily, this may be a more appropriate perspective for a review article.

The article states “some studies show persistent cognitive impairments in longer term cannabis users, even after 2 years of abstinence” and cites 1 supporting reference by Pope et al⁶ (incorrectly cited as Harrison et al). In fact, that study did not test subjects beyond 28 days of abstinence; at the time, “the differences between users and controls had narrowed and were mostly nonsignificant.” Other studies have found no significant differences between marijuana smokers and non-users after 3 months of abstinence,⁷ nor are significant long-term cognitive deficits mentioned in recent reviews of the topic.⁸ Thus, we are not aware of any scientific basis for the statement in the article, which is not supported by the 1 study cited.

The paragraph on “cardiac complications” of cocaine use presents an incomplete picture of the risk of myocardial infarction (MI) and cites only 1 (2001) review article. What would have been useful to the reader was:

• cocaine-associated MI occurs in up to 6% of patients with cocaine-associated chest pain⁹
• cocaine-associated MI may have atypical symptomatic presentation, eg, without chest pain⁹
• in a large, population-based study, adults age 18 to 45 who used cocaine >10 times had a 3.5-fold increased risk of MI¹⁰
• two-thirds of MIs occur within 3 hours of cocaine ingestion, but MI may occur >18 hours after ingestion (possibly due to pharmacologically active cocaine metabolites).⁹ The recent review by McCord et al,⁹ which includes treatment recommendations from the American Heart Association, would have been useful to cite.

Most readers of Current Psychiatry are not specialists in the topics covered by its review articles. This places increased responsibility for ensuring accurate and balanced topic coverage with citation of appropriate, up-to-date review articles.

David A. Gorelick, MD, PhD
National Institute on Drug Abuse
Baltimore, MD

References

1. Tashkin DP. Smoked marijuana as a cause of lung injury. Monaldi Arch Chest Dis. 2005;63(2):93-100.

2. Hashibe M, Morgenstern H, Cui Y, et al. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1829-1834.

3. Aldington S, Harwood M, Cox B, et al. Cannabis use and risk of lung cancer: a case-control study. Eur Respir J. 2008;31(2):280-286.

4. Korantzopoulos P, Liu T, Papaioannides D, et al. Atrial fibrillation and marijuana smoking. Int J Clin Pract. 2008;62(2):308-313.

5. Jones RT. Cardiovascular system effects of marijuana. J Clin Pharmacol. 2002;42(11 suppl):58S-63S.

6. Pope HG, Jr, Gruber AJ, Hudson JI, et al. Cognitive measures in long-term cannabis users. J Clin Pharmacol. 2002;42(11 suppl):41S-47S.

7. Fried PA, Watkinson B, Gray R. Neurocognitive consequences of marihuana—a comparison with pre-drug performance. Neurotoxicol Teratol. 2005;27(2):231-239.

8. Schweinsburg AD, Brown SA, Tapert SF. The influence of marijuana use on neurocognitive functioning in adolescents. Curr Drug Abuse Rev. 2008;1(1):99-111.

9. McCord J, Jneid H, Hollander JE, et al. Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation. 2008;117(14):1897-1907.

10. Aslibekyan S, Levitan EB, Mittleman MA. Prevalent cocaine use and myocardial infarction. Am J Cardiol. 2008;102(8):966-969.

The authors respond

Dr. Gorelick’s detailed comments brought up many points, which we address below.

Marijuana and cancer—Dr. Gorelick commented that the article “grossly exaggerated the cancer risk from marijuana smoking” due to the cited reference stating that the evidence is “limited and inconsistent.” We agree the article mentions the evidence is not clear. However, in further reading of their discussion of the risk of lung cancer the authors point to several epidemiologic studies, some of which showed increased risk of cancer. Specifically, a study from the United States showed “a history of daily or near-daily marijuana smoking was associated with a 2.6-fold greater risk for developing head and neck cancer.”

In our article we focused more on the positive results than on the entire picture and would have served our readers better by not making such an equivocal statement about the increased risk of cancer.

Marijuana and AF—Dr. Gorelick questioned the tenacity of the association between marijuana and AF, stating “given the ratio between 6 published cases reports and the millions of people smoking marijuana daily, this may be a more appropriate perspective for a review article.”

Our comments were based on the following statements from the cited study: “During the past few years an increasing number of case reports indicate an association between marijuana smoking and the development of AF.” Also, “despite the small number of these reports, the observed close temporal relationship between marijuana smoking and AF occurrence, especially in young people without structural heart disease or other precipitating factors for AF, strongly supports an association between the two conditions.”

We mentioned AF because this is not something most people consider as a side effect of marijuana and we felt it was useful to call attention to it as a potential complication. However, we do agree that the sentence could have been worded differently because the number of cases remains low and the risk of developing AF in young healthy adults is low.

Marijuana and cognitive effects—Dr. Gorelick commented that there is “no scientific basis for the statement in the article” and that the article cited looked only at 28 days post-cannabis use. The following comments were made in the article we cited: “However, one electroencephalographic study suggested greater abnormalities in longer term cannabis users, and another found a strong correlation between performance on a selective attention task and duration of cannabis use, even in users abstinent for a mean of 2 years.”

Also, that article concluded “…an opposite impression emerges from a recent large, carefully controlled study by Solowij et al, who found that longer term cannabis users showed significantly greater deficits on several neuropsychological measures than shorter term users, and that these measures were often negatively correlated with lifetime duration of use.”

Again, we agree that our comment was likely too broad because the evidence is limited and not clear, which is why we wrote, “However, most studies suggest that marijuana-associated cognitive deficits are reversible and related to recent exposure.”

Cocaine and cardiac complications—We thank Dr. Gorelick for providing additional information and resources about the very important association between cocaine use and the MI risk. We certainly agree that the inclusion of his suggested references would have been appropriate.

Raheel Khan, DO
Assistant Clinical Professor
Psychosomatic Medicine
Department of Psychiatry and Behavioral Sciences

Robert M. McCarron, DO
Training Director, Internal Medicine/Psychiatry Residency
Department of Psychiatry and Behavioral Sciences
Department of Internal Medicine
University of California, Davis
Sacramento, CA

I appreciated “The psychotic pot smoker” (Cases that Test Your Skills, Current Psychiatry, September 2010, p. 42-47). There were few pointers that suggested looking for benzodiazepine or alcohol withdrawal, especially because the authors lacked a reliable history from the patient. They mentioned that the patient had mild tachycardia (101 bpm), elevated blood pressure (149/57 mm Hg), orientation to name (and I assume disoriented to place and time), and hyperreflexia (due to GABA effect).

One differential diagnosis was missing: delirium. I did not read about cognitive testing in this patient with a differential diagnosis of delirium; maybe a clock test would have done some good.

I would have approached this case as delirium and then proceeded with lab and imaging tests. Elevated white blood cell count and creatine phosphokinase test were distractors (lumbar puncture and electroencephalography can be justified). How would you justify giving diphenhydramine to a patient with delirium, considering that it might worsen confusion or agitation?

I agree, however, that this case was complex and can’t help but emphasize that benzodiazepine or alcohol withdrawal is a simple condition that can be life-threatening if missed.

Ghazanfar Khan, MD
PGY-IV, Psychiatry
University of Mississippi Medical Center
Jackson, MS

I appreciated “The psychotic pot smoker” (Cases that Test Your Skills, Current Psychiatry, September 2010, p. 42-47). There were few pointers that suggested looking for benzodiazepine or alcohol withdrawal, especially because the authors lacked a reliable history from the patient. They mentioned that the patient had mild tachycardia (101 bpm), elevated blood pressure (149/57 mm Hg), orientation to name (and I assume disoriented to place and time), and hyperreflexia (due to GABA effect).

One differential diagnosis was missing: delirium. I did not read about cognitive testing in this patient with a differential diagnosis of delirium; maybe a clock test would have done some good.

I would have approached this case as delirium and then proceeded with lab and imaging tests. Elevated white blood cell count and creatine phosphokinase test were distractors (lumbar puncture and electroencephalography can be justified). How would you justify giving diphenhydramine to a patient with delirium, considering that it might worsen confusion or agitation?

I agree, however, that this case was complex and can’t help but emphasize that benzodiazepine or alcohol withdrawal is a simple condition that can be life-threatening if missed.

Ghazanfar Khan, MD
PGY-IV, Psychiatry
University of Mississippi Medical Center
Jackson, MS

I appreciated “The psychotic pot smoker” (Cases that Test Your Skills, Current Psychiatry, September 2010, p. 42-47). There were few pointers that suggested looking for benzodiazepine or alcohol withdrawal, especially because the authors lacked a reliable history from the patient. They mentioned that the patient had mild tachycardia (101 bpm), elevated blood pressure (149/57 mm Hg), orientation to name (and I assume disoriented to place and time), and hyperreflexia (due to GABA effect).

One differential diagnosis was missing: delirium. I did not read about cognitive testing in this patient with a differential diagnosis of delirium; maybe a clock test would have done some good.

I would have approached this case as delirium and then proceeded with lab and imaging tests. Elevated white blood cell count and creatine phosphokinase test were distractors (lumbar puncture and electroencephalography can be justified). How would you justify giving diphenhydramine to a patient with delirium, considering that it might worsen confusion or agitation?

I agree, however, that this case was complex and can’t help but emphasize that benzodiazepine or alcohol withdrawal is a simple condition that can be life-threatening if missed.

Ghazanfar Khan, MD
PGY-IV, Psychiatry
University of Mississippi Medical Center
Jackson, MS

I couldn’t agree more with Dr. Henry A. Nasrallah’s editorial, “Integrating psychiatry with other medical specialties” (From the Editor, Current Psychiatry, September 2010, p. 14-15). We cannot expect our colleagues to take us seriously if we don’t afford ourselves self-respect. I came from family practice to psychiatry and have found it a convoluted place with identity issues. We want to be taken seriously but separate ourselves. I am also taken aback by blurry boundaries, starting with the term “client.” When did “patient” become a dirty word? We are doctors, not “friends” or “coaches.” In no other field of medicine is being a doctor or patient treated as a contagion to be avoided. Patient is a sacred term that implies trust and accountability. If I strive to maintain this boundary and sacred trust by wearing my lab coat and referring to my patients as “Mr.” or “Mrs.” rather than by their first name, am I somehow being elitist? Our patients have enough hurdles and gray areas in their lives; the patient-doctor relationship shouldn’t be 1 of them. We have a duty to walk a fine line with utmost care because our treatment is founded on that patient-doctor relationship. As a mentor once said, “In surgery they use scalpels. In psychiatry, we are the scalpels.”

Elizabeth Faust, MD
Psychiatrist
Iowa City, IA

I couldn’t agree more with Dr. Henry A. Nasrallah’s editorial, “Integrating psychiatry with other medical specialties” (From the Editor, Current Psychiatry, September 2010, p. 14-15). We cannot expect our colleagues to take us seriously if we don’t afford ourselves self-respect. I came from family practice to psychiatry and have found it a convoluted place with identity issues. We want to be taken seriously but separate ourselves. I am also taken aback by blurry boundaries, starting with the term “client.” When did “patient” become a dirty word? We are doctors, not “friends” or “coaches.” In no other field of medicine is being a doctor or patient treated as a contagion to be avoided. Patient is a sacred term that implies trust and accountability. If I strive to maintain this boundary and sacred trust by wearing my lab coat and referring to my patients as “Mr.” or “Mrs.” rather than by their first name, am I somehow being elitist? Our patients have enough hurdles and gray areas in their lives; the patient-doctor relationship shouldn’t be 1 of them. We have a duty to walk a fine line with utmost care because our treatment is founded on that patient-doctor relationship. As a mentor once said, “In surgery they use scalpels. In psychiatry, we are the scalpels.”

Elizabeth Faust, MD
Psychiatrist
Iowa City, IA

I couldn’t agree more with Dr. Henry A. Nasrallah’s editorial, “Integrating psychiatry with other medical specialties” (From the Editor, Current Psychiatry, September 2010, p. 14-15). We cannot expect our colleagues to take us seriously if we don’t afford ourselves self-respect. I came from family practice to psychiatry and have found it a convoluted place with identity issues. We want to be taken seriously but separate ourselves. I am also taken aback by blurry boundaries, starting with the term “client.” When did “patient” become a dirty word? We are doctors, not “friends” or “coaches.” In no other field of medicine is being a doctor or patient treated as a contagion to be avoided. Patient is a sacred term that implies trust and accountability. If I strive to maintain this boundary and sacred trust by wearing my lab coat and referring to my patients as “Mr.” or “Mrs.” rather than by their first name, am I somehow being elitist? Our patients have enough hurdles and gray areas in their lives; the patient-doctor relationship shouldn’t be 1 of them. We have a duty to walk a fine line with utmost care because our treatment is founded on that patient-doctor relationship. As a mentor once said, “In surgery they use scalpels. In psychiatry, we are the scalpels.”

Elizabeth Faust, MD
Psychiatrist
Iowa City, IA

I read with interest Dr. Henry A. Nasrallah’s perspective on the difficulties psychiatry has had in “Integrating psychiatry with other medical specialties” (From the Editor, Current Psychiatry, September 2010, p. 14-15). Dr. Nasrallah highlighted the “geographic separation” of psychiatric practice locations as a main barrier to integration. I strongly agree, but the geographic separation applies not only to practicing psychiatrists but also to trainees. I recently attended a lecture for psychiatrists on how to better collaborate and communicate with other physicians. I left the lecture contemplating why psychiatrists needed this lecture when communication with other physicians is an inherent part of medical practice for most physicians.

Changing the culture of poor communication must start with psychiatry training from the first day of residency. Trainees in other medical specialties work side by side, forming relationships that lend themselves to increased communication, referrals, and curbside consultation. Because psychiatry residents often train in separate locations, they might not work with physicians from other specialties. They might meet very few physicians of other specialties during training, and as a result fewer collaborative relationships are formed. This may contribute to psychiatrists’ decreased willingness to call other physicians to discuss patients or ask clinical questions. In contrast, most primary care physicians know clinicians in subspecialties who they refer to or call with a question. It seems that many of these physicians do not have that same familiarity with psychiatrists, which may further contribute to the perception that our specialty is “different.” Collaborative care models have been effective in mental health treatment in primary care settings,^1,2 but implementation outside of research settings has been limited.³ Any attempt at integration is more likely to be sustainable if it also involves implementing changes during training that encourage career-long patterns of communication with our colleagues across specialties.

Rachel Weir, MD
Clinical Assistant Professor of Psychiatry
University of Utah
Salt Lake City, UT

I read with interest Dr. Henry A. Nasrallah’s perspective on the difficulties psychiatry has had in “Integrating psychiatry with other medical specialties” (From the Editor, Current Psychiatry, September 2010, p. 14-15). Dr. Nasrallah highlighted the “geographic separation” of psychiatric practice locations as a main barrier to integration. I strongly agree, but the geographic separation applies not only to practicing psychiatrists but also to trainees. I recently attended a lecture for psychiatrists on how to better collaborate and communicate with other physicians. I left the lecture contemplating why psychiatrists needed this lecture when communication with other physicians is an inherent part of medical practice for most physicians.

Changing the culture of poor communication must start with psychiatry training from the first day of residency. Trainees in other medical specialties work side by side, forming relationships that lend themselves to increased communication, referrals, and curbside consultation. Because psychiatry residents often train in separate locations, they might not work with physicians from other specialties. They might meet very few physicians of other specialties during training, and as a result fewer collaborative relationships are formed. This may contribute to psychiatrists’ decreased willingness to call other physicians to discuss patients or ask clinical questions. In contrast, most primary care physicians know clinicians in subspecialties who they refer to or call with a question. It seems that many of these physicians do not have that same familiarity with psychiatrists, which may further contribute to the perception that our specialty is “different.” Collaborative care models have been effective in mental health treatment in primary care settings,^1,2 but implementation outside of research settings has been limited.³ Any attempt at integration is more likely to be sustainable if it also involves implementing changes during training that encourage career-long patterns of communication with our colleagues across specialties.

Rachel Weir, MD
Clinical Assistant Professor of Psychiatry
University of Utah
Salt Lake City, UT

I read with interest Dr. Henry A. Nasrallah’s perspective on the difficulties psychiatry has had in “Integrating psychiatry with other medical specialties” (From the Editor, Current Psychiatry, September 2010, p. 14-15). Dr. Nasrallah highlighted the “geographic separation” of psychiatric practice locations as a main barrier to integration. I strongly agree, but the geographic separation applies not only to practicing psychiatrists but also to trainees. I recently attended a lecture for psychiatrists on how to better collaborate and communicate with other physicians. I left the lecture contemplating why psychiatrists needed this lecture when communication with other physicians is an inherent part of medical practice for most physicians.

Changing the culture of poor communication must start with psychiatry training from the first day of residency. Trainees in other medical specialties work side by side, forming relationships that lend themselves to increased communication, referrals, and curbside consultation. Because psychiatry residents often train in separate locations, they might not work with physicians from other specialties. They might meet very few physicians of other specialties during training, and as a result fewer collaborative relationships are formed. This may contribute to psychiatrists’ decreased willingness to call other physicians to discuss patients or ask clinical questions. In contrast, most primary care physicians know clinicians in subspecialties who they refer to or call with a question. It seems that many of these physicians do not have that same familiarity with psychiatrists, which may further contribute to the perception that our specialty is “different.” Collaborative care models have been effective in mental health treatment in primary care settings,^1,2 but implementation outside of research settings has been limited.³ Any attempt at integration is more likely to be sustainable if it also involves implementing changes during training that encourage career-long patterns of communication with our colleagues across specialties.

Rachel Weir, MD
Clinical Assistant Professor of Psychiatry
University of Utah
Salt Lake City, UT

Mr. M, age 70, presents to the emergency department (ED) complaining of new-onset fatigue, dizziness, and black, tarry stools. He is anemic (hemoglobin 8.9 g/dL) and his stool is positive for occult blood. Mr. M denies having any symptoms until 1 week ago and reports taking his medications as prescribed. An upper endoscopy reveals a gastrointestinal (GI) bleed and his physician stops his antiplatelet medications. Mr. M’s medical history includes hypertension, hyperlipidemia, and placement of a drug-eluding coronary artery stent 9 months ago. Before presenting to the ED, he had been maintained on lisinopril, 20 mg/d, simvastatin, 40 mg/d, aspirin, 325 mg/d, clopidogrel, 75 mg/d, and a daily multivitamin. Three weeks ago, Mr. M was started on citalopram, 20 mg/d, for depressed mood that he has had since his wife died a year ago.

The psychiatry service is consulted after Mr. M admits he has had thoughts of suicide and a few weeks ago was planning to take an overdose of his medications. He denies taking any extra medications and reports feeling more positive since starting citalopram. The psychiatrist discontinues citalopram, however, because of a possible drug interaction with antiplatelet medications, starts Mr. M on bupropion, 150 mg/d, and recommends he follow up with his primary care physician for management of his depressive symptoms.

Older patients frequently take multiple medications for various disease states, which increases their risk of drug-drug interactions. In addition, physiologic changes associated with aging alter how patients respond to medications. Drugs may interact pharmacokinetically and pharmacodynamically. Pharmacokinetic interactions are well understood and represent changes in absorption, distribution, metabolism, and elimination of specific medications. Pharmacodynamic drug-drug interactions, on the other hand, are less recognized and represent changes in medications’ mechanism of action. A clinician who understands pharmacodynamic interactions will be able to better identify potential drug-drug interactions and could avoid adverse events.¹

Antidepressants and bleeding

In Mr. M’s case, a pharmacodynamic drug-drug interaction among citalopram, aspirin, and clopidogrel caused a GI bleed. This type of interaction may be overlooked because of the relatively safe drug-drug interaction profile of selective serotonin reuptake inhibitors (SSRIs). However, any antidepressant that increases serotonin concentration, including serotonin-norepinephrine reuptake inhibitors, may cause this pharmacodynamic interaction.¹

Platelets release serotonin to promote aggregation, but do not produce it themselves and are dependent on the serotonin transporter system (reuptake pump) to acquire serotonin. Because SSRIs act on serotonin transporters found on platelet cell membranes, these drugs deplete platelets’ supply of serotonin, leading to diminished platelet aggregation. This effect may propagate the action of other medications that inhibit platelet aggregation, which may increase a patient’s risk of bruising and/or bleeding. This increased risk of bleeding is not associated with non-serotonergic antidepressants such as bupropion, and seems to decrease when SSRIs are discontinued.²

A modest increase in bleeding risk with SSRIs when used alone and with other platelet-inhibiting therapies has been described in case reports, case controlled studies, and chart reviews.^2-4 The agents studied include aspirin and clopidogrel, which Mr. M was receiving, but also other, often-overlooked medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, calcium channel blockers, and systemic corticosteroids. Patient factors and diseases—including a history of peptic ulcer disease, previous bleeding, heavy alcohol use, and older age—also may increase bleeding risk (Table).^2-5

Serotonin reuptake inhibitor medications have been associated with various bleeding events.⁵ Most case-control and cohort analyses have examined the risk of GI bleeding with SSRIs; however, serotonergic antidepressants also have been associated with an increased risk of uterine bleeding and perioperative blood loss and transfusions in various surgical procedures.⁶ Some reports have suggested that there may be a small increase in the incidence of hemorrhagic and fatal stroke with SSRI use^5,7; however, many studies have not found an association between SSRI use and increased risk of intracranial hemorrhage stroke.⁸ The Women’s Health Initiative Study, which reviewed cardiovascular morbidity and mortality data, showed that antidepressant use in postmenopausal women was associated with an increased risk of all-cause mortality, but not coronary heart disease.⁷ SSRI use was associated with an increased risk of stroke, specifically hemorrhagic stroke, although the absolute event risks were low and cannot be used to predict risk.

Table

Risk factors for gastrointestinal bleeding

Reducing bleeding risk

In a case-control study, de Abajo et al⁴ found that patients taking acid-suppressing drugs—proton pump inhibitors and histamine H2 receptor antagonists—had a lower risk of upper GI tract bleeding associated with serotonergic antidepressants compared with those not taking acid-suppressing medications. These drugs further reduced the risk of bleeding in patients taking NSAIDs or antiplatelet medications concomitantly with SSRIs. We suggest initiating prophylactic acid suppression therapy for any patient who is considered at high risk for a GI bleed and is taking an SSRI with or without other medications that inhibit platelet aggregation. Specifically, start with an H2 antagonist because of these medications’ faster onset of action and lower cost vs proton pump inhibitors.

Although the association between SSRIs and bleeding have been described in observational studies, it is impossible to rule out alternate causes and potential confounders that may have contributed to these events. Due diligence and therapeutic drug monitoring of all known and predicted drug-drug interactions is warranted for all patients taking serotonergic antidepressants in combination with medications known to increase bleeding risk.

Related Resources

• Indiana University School of Medicine. P450 drug interaction table. http://medicine.iupui.edu/clinpharm/ddis/table.asp.
• Hansten PD, Horn JR. The top 100 drug interactions: a guide to patient management. Edmonds, WA: H&H Publications; 2010.

Drug Brand Names

• Bupropion • Wellbutrin
• Citalopram • Celexa
• Clopidogrel • Plavix
• Lisinopril • Zestril, Prinivil
• Simvastatin • Zocor
• Warfarin • Coumadin

Disclosure

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

Mr. M, age 70, presents to the emergency department (ED) complaining of new-onset fatigue, dizziness, and black, tarry stools. He is anemic (hemoglobin 8.9 g/dL) and his stool is positive for occult blood. Mr. M denies having any symptoms until 1 week ago and reports taking his medications as prescribed. An upper endoscopy reveals a gastrointestinal (GI) bleed and his physician stops his antiplatelet medications. Mr. M’s medical history includes hypertension, hyperlipidemia, and placement of a drug-eluding coronary artery stent 9 months ago. Before presenting to the ED, he had been maintained on lisinopril, 20 mg/d, simvastatin, 40 mg/d, aspirin, 325 mg/d, clopidogrel, 75 mg/d, and a daily multivitamin. Three weeks ago, Mr. M was started on citalopram, 20 mg/d, for depressed mood that he has had since his wife died a year ago.

The psychiatry service is consulted after Mr. M admits he has had thoughts of suicide and a few weeks ago was planning to take an overdose of his medications. He denies taking any extra medications and reports feeling more positive since starting citalopram. The psychiatrist discontinues citalopram, however, because of a possible drug interaction with antiplatelet medications, starts Mr. M on bupropion, 150 mg/d, and recommends he follow up with his primary care physician for management of his depressive symptoms.

Older patients frequently take multiple medications for various disease states, which increases their risk of drug-drug interactions. In addition, physiologic changes associated with aging alter how patients respond to medications. Drugs may interact pharmacokinetically and pharmacodynamically. Pharmacokinetic interactions are well understood and represent changes in absorption, distribution, metabolism, and elimination of specific medications. Pharmacodynamic drug-drug interactions, on the other hand, are less recognized and represent changes in medications’ mechanism of action. A clinician who understands pharmacodynamic interactions will be able to better identify potential drug-drug interactions and could avoid adverse events.¹

Antidepressants and bleeding

In Mr. M’s case, a pharmacodynamic drug-drug interaction among citalopram, aspirin, and clopidogrel caused a GI bleed. This type of interaction may be overlooked because of the relatively safe drug-drug interaction profile of selective serotonin reuptake inhibitors (SSRIs). However, any antidepressant that increases serotonin concentration, including serotonin-norepinephrine reuptake inhibitors, may cause this pharmacodynamic interaction.¹

Platelets release serotonin to promote aggregation, but do not produce it themselves and are dependent on the serotonin transporter system (reuptake pump) to acquire serotonin. Because SSRIs act on serotonin transporters found on platelet cell membranes, these drugs deplete platelets’ supply of serotonin, leading to diminished platelet aggregation. This effect may propagate the action of other medications that inhibit platelet aggregation, which may increase a patient’s risk of bruising and/or bleeding. This increased risk of bleeding is not associated with non-serotonergic antidepressants such as bupropion, and seems to decrease when SSRIs are discontinued.²

A modest increase in bleeding risk with SSRIs when used alone and with other platelet-inhibiting therapies has been described in case reports, case controlled studies, and chart reviews.^2-4 The agents studied include aspirin and clopidogrel, which Mr. M was receiving, but also other, often-overlooked medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, calcium channel blockers, and systemic corticosteroids. Patient factors and diseases—including a history of peptic ulcer disease, previous bleeding, heavy alcohol use, and older age—also may increase bleeding risk (Table).^2-5

Serotonin reuptake inhibitor medications have been associated with various bleeding events.⁵ Most case-control and cohort analyses have examined the risk of GI bleeding with SSRIs; however, serotonergic antidepressants also have been associated with an increased risk of uterine bleeding and perioperative blood loss and transfusions in various surgical procedures.⁶ Some reports have suggested that there may be a small increase in the incidence of hemorrhagic and fatal stroke with SSRI use^5,7; however, many studies have not found an association between SSRI use and increased risk of intracranial hemorrhage stroke.⁸ The Women’s Health Initiative Study, which reviewed cardiovascular morbidity and mortality data, showed that antidepressant use in postmenopausal women was associated with an increased risk of all-cause mortality, but not coronary heart disease.⁷ SSRI use was associated with an increased risk of stroke, specifically hemorrhagic stroke, although the absolute event risks were low and cannot be used to predict risk.

Table

Risk factors for gastrointestinal bleeding

Reducing bleeding risk

In a case-control study, de Abajo et al⁴ found that patients taking acid-suppressing drugs—proton pump inhibitors and histamine H2 receptor antagonists—had a lower risk of upper GI tract bleeding associated with serotonergic antidepressants compared with those not taking acid-suppressing medications. These drugs further reduced the risk of bleeding in patients taking NSAIDs or antiplatelet medications concomitantly with SSRIs. We suggest initiating prophylactic acid suppression therapy for any patient who is considered at high risk for a GI bleed and is taking an SSRI with or without other medications that inhibit platelet aggregation. Specifically, start with an H2 antagonist because of these medications’ faster onset of action and lower cost vs proton pump inhibitors.

Although the association between SSRIs and bleeding have been described in observational studies, it is impossible to rule out alternate causes and potential confounders that may have contributed to these events. Due diligence and therapeutic drug monitoring of all known and predicted drug-drug interactions is warranted for all patients taking serotonergic antidepressants in combination with medications known to increase bleeding risk.

Related Resources

• Indiana University School of Medicine. P450 drug interaction table. http://medicine.iupui.edu/clinpharm/ddis/table.asp.
• Hansten PD, Horn JR. The top 100 drug interactions: a guide to patient management. Edmonds, WA: H&H Publications; 2010.

Drug Brand Names

• Bupropion • Wellbutrin
• Citalopram • Celexa
• Clopidogrel • Plavix
• Lisinopril • Zestril, Prinivil
• Simvastatin • Zocor
• Warfarin • Coumadin

Disclosure

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

Mr. M, age 70, presents to the emergency department (ED) complaining of new-onset fatigue, dizziness, and black, tarry stools. He is anemic (hemoglobin 8.9 g/dL) and his stool is positive for occult blood. Mr. M denies having any symptoms until 1 week ago and reports taking his medications as prescribed. An upper endoscopy reveals a gastrointestinal (GI) bleed and his physician stops his antiplatelet medications. Mr. M’s medical history includes hypertension, hyperlipidemia, and placement of a drug-eluding coronary artery stent 9 months ago. Before presenting to the ED, he had been maintained on lisinopril, 20 mg/d, simvastatin, 40 mg/d, aspirin, 325 mg/d, clopidogrel, 75 mg/d, and a daily multivitamin. Three weeks ago, Mr. M was started on citalopram, 20 mg/d, for depressed mood that he has had since his wife died a year ago.

The psychiatry service is consulted after Mr. M admits he has had thoughts of suicide and a few weeks ago was planning to take an overdose of his medications. He denies taking any extra medications and reports feeling more positive since starting citalopram. The psychiatrist discontinues citalopram, however, because of a possible drug interaction with antiplatelet medications, starts Mr. M on bupropion, 150 mg/d, and recommends he follow up with his primary care physician for management of his depressive symptoms.

Older patients frequently take multiple medications for various disease states, which increases their risk of drug-drug interactions. In addition, physiologic changes associated with aging alter how patients respond to medications. Drugs may interact pharmacokinetically and pharmacodynamically. Pharmacokinetic interactions are well understood and represent changes in absorption, distribution, metabolism, and elimination of specific medications. Pharmacodynamic drug-drug interactions, on the other hand, are less recognized and represent changes in medications’ mechanism of action. A clinician who understands pharmacodynamic interactions will be able to better identify potential drug-drug interactions and could avoid adverse events.¹

Antidepressants and bleeding

In Mr. M’s case, a pharmacodynamic drug-drug interaction among citalopram, aspirin, and clopidogrel caused a GI bleed. This type of interaction may be overlooked because of the relatively safe drug-drug interaction profile of selective serotonin reuptake inhibitors (SSRIs). However, any antidepressant that increases serotonin concentration, including serotonin-norepinephrine reuptake inhibitors, may cause this pharmacodynamic interaction.¹

Platelets release serotonin to promote aggregation, but do not produce it themselves and are dependent on the serotonin transporter system (reuptake pump) to acquire serotonin. Because SSRIs act on serotonin transporters found on platelet cell membranes, these drugs deplete platelets’ supply of serotonin, leading to diminished platelet aggregation. This effect may propagate the action of other medications that inhibit platelet aggregation, which may increase a patient’s risk of bruising and/or bleeding. This increased risk of bleeding is not associated with non-serotonergic antidepressants such as bupropion, and seems to decrease when SSRIs are discontinued.²

A modest increase in bleeding risk with SSRIs when used alone and with other platelet-inhibiting therapies has been described in case reports, case controlled studies, and chart reviews.^2-4 The agents studied include aspirin and clopidogrel, which Mr. M was receiving, but also other, often-overlooked medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, calcium channel blockers, and systemic corticosteroids. Patient factors and diseases—including a history of peptic ulcer disease, previous bleeding, heavy alcohol use, and older age—also may increase bleeding risk (Table).^2-5

Serotonin reuptake inhibitor medications have been associated with various bleeding events.⁵ Most case-control and cohort analyses have examined the risk of GI bleeding with SSRIs; however, serotonergic antidepressants also have been associated with an increased risk of uterine bleeding and perioperative blood loss and transfusions in various surgical procedures.⁶ Some reports have suggested that there may be a small increase in the incidence of hemorrhagic and fatal stroke with SSRI use^5,7; however, many studies have not found an association between SSRI use and increased risk of intracranial hemorrhage stroke.⁸ The Women’s Health Initiative Study, which reviewed cardiovascular morbidity and mortality data, showed that antidepressant use in postmenopausal women was associated with an increased risk of all-cause mortality, but not coronary heart disease.⁷ SSRI use was associated with an increased risk of stroke, specifically hemorrhagic stroke, although the absolute event risks were low and cannot be used to predict risk.

Table

Risk factors for gastrointestinal bleeding

Reducing bleeding risk

In a case-control study, de Abajo et al⁴ found that patients taking acid-suppressing drugs—proton pump inhibitors and histamine H2 receptor antagonists—had a lower risk of upper GI tract bleeding associated with serotonergic antidepressants compared with those not taking acid-suppressing medications. These drugs further reduced the risk of bleeding in patients taking NSAIDs or antiplatelet medications concomitantly with SSRIs. We suggest initiating prophylactic acid suppression therapy for any patient who is considered at high risk for a GI bleed and is taking an SSRI with or without other medications that inhibit platelet aggregation. Specifically, start with an H2 antagonist because of these medications’ faster onset of action and lower cost vs proton pump inhibitors.

Although the association between SSRIs and bleeding have been described in observational studies, it is impossible to rule out alternate causes and potential confounders that may have contributed to these events. Due diligence and therapeutic drug monitoring of all known and predicted drug-drug interactions is warranted for all patients taking serotonergic antidepressants in combination with medications known to increase bleeding risk.

Related Resources

• Indiana University School of Medicine. P450 drug interaction table. http://medicine.iupui.edu/clinpharm/ddis/table.asp.
• Hansten PD, Horn JR. The top 100 drug interactions: a guide to patient management. Edmonds, WA: H&H Publications; 2010.

Drug Brand Names

• Bupropion • Wellbutrin
• Citalopram • Celexa
• Clopidogrel • Plavix
• Lisinopril • Zestril, Prinivil
• Simvastatin • Zocor
• Warfarin • Coumadin

Disclosure

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

Mr. C, a 78-year-old nursing home resident, wants to discontinue psychotropics because he has difficulty swallowing pills. He receives cholinesterase inhibitors for dementia and an antipsychotic for occasional agitation.

A 45-year-old patient diagnosed with bipolar disorder says that she felt coerced and her personal space violated when she was administered an intramuscular antipsychotic while agitated a few days earlier.

A nurse expresses frustration to the staff psychiatrist about continued disruptive behavior of a patient who has a minimal blood level of a mood stabilizer after 5 days of pharmacotherapy. The nurse suspects the patient is hiding pills in his mouth and later discarding them.

A child psychiatrist worries about her 8-year-old patient’s lack of response to an atypical antipsychotic. The mother reveals that the child often does not take his medication because he does not like taking large pills and is afraid of choking.

Clinical scenarios such as these highlight the importance of liquid drug formulations in enhancing compliance and respecting patient autonomy. Liquid formulations of psychotropics are useful for patients who have difficulty swallowing tablets or capsules, such as children or older adults. These formulations also are helpful in acute care settings, especially for uncooperative patients. Monitoring medication ingestion to ensure compliance is another benefit of liquid formulations. Many clinicians administer intramuscular antipsychotics to relieve acute agitation¹; however, patients may consider this approach coercive, and it carries a risk of injury, especially when patients are agitated and uncooperative. Agitated patients may be amenable to ingesting liquid medication instead of oral tablets. Some liquid medications can be mixed with juice, which might help improve medication compliance in children.

The Table^2,3 lists some psychotropics that are available in a liquid formulation and their dosage strengths. Be aware of the exact strength of liquid formulations. Educate patients about how to use calibrated dosing spoons to enhance compliance and ensure patients ingest an appropriate dosage.⁴ We hope that using liquid formulations when indicated will enhance patient satisfaction and compliance, leading to improved prognosis.

Disclosure: The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Balon played no role in the peer review of this article.

Table

Psychotropic medications available in liquid formulation

Mr. C, a 78-year-old nursing home resident, wants to discontinue psychotropics because he has difficulty swallowing pills. He receives cholinesterase inhibitors for dementia and an antipsychotic for occasional agitation.

A 45-year-old patient diagnosed with bipolar disorder says that she felt coerced and her personal space violated when she was administered an intramuscular antipsychotic while agitated a few days earlier.

A nurse expresses frustration to the staff psychiatrist about continued disruptive behavior of a patient who has a minimal blood level of a mood stabilizer after 5 days of pharmacotherapy. The nurse suspects the patient is hiding pills in his mouth and later discarding them.

A child psychiatrist worries about her 8-year-old patient’s lack of response to an atypical antipsychotic. The mother reveals that the child often does not take his medication because he does not like taking large pills and is afraid of choking.

Clinical scenarios such as these highlight the importance of liquid drug formulations in enhancing compliance and respecting patient autonomy. Liquid formulations of psychotropics are useful for patients who have difficulty swallowing tablets or capsules, such as children or older adults. These formulations also are helpful in acute care settings, especially for uncooperative patients. Monitoring medication ingestion to ensure compliance is another benefit of liquid formulations. Many clinicians administer intramuscular antipsychotics to relieve acute agitation¹; however, patients may consider this approach coercive, and it carries a risk of injury, especially when patients are agitated and uncooperative. Agitated patients may be amenable to ingesting liquid medication instead of oral tablets. Some liquid medications can be mixed with juice, which might help improve medication compliance in children.

The Table^2,3 lists some psychotropics that are available in a liquid formulation and their dosage strengths. Be aware of the exact strength of liquid formulations. Educate patients about how to use calibrated dosing spoons to enhance compliance and ensure patients ingest an appropriate dosage.⁴ We hope that using liquid formulations when indicated will enhance patient satisfaction and compliance, leading to improved prognosis.

Disclosure: The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Balon played no role in the peer review of this article.

Table

Psychotropic medications available in liquid formulation

Mr. C, a 78-year-old nursing home resident, wants to discontinue psychotropics because he has difficulty swallowing pills. He receives cholinesterase inhibitors for dementia and an antipsychotic for occasional agitation.

A 45-year-old patient diagnosed with bipolar disorder says that she felt coerced and her personal space violated when she was administered an intramuscular antipsychotic while agitated a few days earlier.

A nurse expresses frustration to the staff psychiatrist about continued disruptive behavior of a patient who has a minimal blood level of a mood stabilizer after 5 days of pharmacotherapy. The nurse suspects the patient is hiding pills in his mouth and later discarding them.

A child psychiatrist worries about her 8-year-old patient’s lack of response to an atypical antipsychotic. The mother reveals that the child often does not take his medication because he does not like taking large pills and is afraid of choking.

Clinical scenarios such as these highlight the importance of liquid drug formulations in enhancing compliance and respecting patient autonomy. Liquid formulations of psychotropics are useful for patients who have difficulty swallowing tablets or capsules, such as children or older adults. These formulations also are helpful in acute care settings, especially for uncooperative patients. Monitoring medication ingestion to ensure compliance is another benefit of liquid formulations. Many clinicians administer intramuscular antipsychotics to relieve acute agitation¹; however, patients may consider this approach coercive, and it carries a risk of injury, especially when patients are agitated and uncooperative. Agitated patients may be amenable to ingesting liquid medication instead of oral tablets. Some liquid medications can be mixed with juice, which might help improve medication compliance in children.

The Table^2,3 lists some psychotropics that are available in a liquid formulation and their dosage strengths. Be aware of the exact strength of liquid formulations. Educate patients about how to use calibrated dosing spoons to enhance compliance and ensure patients ingest an appropriate dosage.⁴ We hope that using liquid formulations when indicated will enhance patient satisfaction and compliance, leading to improved prognosis.

Disclosure: The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Balon played no role in the peer review of this article.

Table

Psychotropic medications available in liquid formulation

One of the basic psychiatric principles accepted by all practicing psychiatrists is that a delusion is a fundamental symptom of psychosis.

A delusion is defined as “a fixed false belief not commensurate with the person’s educational and cultural background” and is almost universally associated with schizophrenia and other psychotic disorders. But if we apply the notion that a fixed false belief is delusional, then several “nonpsychotic” psychiatric disorders would qualify as psychoses based on their core clinical symptoms. Consider the following:

Major depressive disorder (MDD). The most prominent symptoms of MDD are feelings of “worthlessness” and “hopelessness.” Patients with clinical depression almost always believe—even if they are successful people—that they are failures, awful people, or a burden on their families. They also often believe that there is no hope for them, no way out of their rut and misery, and that death by suicide is the only option. Yet such patients—who clearly have reality distortion and who harbor a completely false view of themselves, the world, and the future—are not regarded as having a psychosis, but a standard depressive episode and are generally treated with antidepressants. Only when depressed patients express a paranoid idea or that their body is full of excrement or that God is punishing them for their evil acts are they given the diagnosis of “psychotic depression,” and an antipsychotic is considered a necessary adjunct to their antidepressant regimen.

But isn’t there just a dimensional difference in the severity of the delusion between MDD and psychotic depression? Shouldn’t worthlessness and hopelessness be regarded as psychotic symptoms congruent with the mood disorder? Interestingly, 2 atypical antipsychotics—aripiprazole and quetiapine—have been FDA-approved as add-on therapy for patients who do not respond to 1 or 2 antidepressants. Could the D2 dopamine antagonism exerted by antipsychotics be the reason for the stronger antidepressant response?

Obsessive-compulsive disorder (OCD). Is it not a fixed false belief when a person suffering from OCD washes his hands 50 to 100 times a day until his skin is raw because of the erroneous belief that his hands are dirty? Is it not psychosis when an OCD patient performs hours of daily rituals that render her dysfunctional because she falsely believes that unless she performs the rituals “something terrible will happen” to her or her loved ones?

Anxiety disorder. How about the reality distortion of anxiety disorder patients who would never board a plane because they falsely believe it will crash or will not drive over a bridge or in a tunnel because they believe it will collapse? Even when such false beliefs impair patients’ functioning, clinicians do not regard it as a psychosis but as “anxiety fear.” Is fear not the essence of paranoia?

Anorexia nervosa (AN). Is a severely emaciated AN patient’s fixed false belief that he or she is fat—which can be life-threatening—not a form of psychosis?

Body dysmorphic disorder (BDD). The completely unwarranted or fallacious perception of ugliness or blemishes in a BDD patient are a form of fixed false beliefs that may lead to functional disability or dozens of plastic surgeries. Regardless of whether a perceptual disturbance is involved, the phenotype qualifies as a psychotic disorder.

Hypochondriasis. When a person adamantly and falsely believes that he has a serious physical disease and expends time, effort, and money doctor-shopping to receive treatment for an illusory somatic ailment, why do we label it as a somatoform disorder instead of a somatic delusion? Interestingly, DSM-IV-TR criterion C of hypochondriasis specifies that the preoccupation of having a serious disease should not be of “delusional intensity (as in delusional disorder, somatic type).” What is the definition of delusional intensity? At what point does a false belief move from mild to intense status and becomes psychotic?

Personality disorders. Consider how various thematic false beliefs pervade several axis II disorders, such as paranoid, schizotypal, borderline, narcissistic, or avoidant personality disorders. They all have an enduring component of a fixed false belief that falls on the continuum of psychosis.

By now, some readers may have arrived at the conclusion that this editor has developed his own fixed false belief that practically all psychiatric disorders are psychotic! Well, not exactly, but I did intend to provoke you to reconsider what we take for granted in the DSM, where psychotic disorders are set aside as just one section of 17 types of disorders. At least I hope that I convinced you that a thread of psychotic thinking can be identified across many of the other 16 supposedly “nonpsychotic” groupings.

One of the basic psychiatric principles accepted by all practicing psychiatrists is that a delusion is a fundamental symptom of psychosis.

A delusion is defined as “a fixed false belief not commensurate with the person’s educational and cultural background” and is almost universally associated with schizophrenia and other psychotic disorders. But if we apply the notion that a fixed false belief is delusional, then several “nonpsychotic” psychiatric disorders would qualify as psychoses based on their core clinical symptoms. Consider the following:

Major depressive disorder (MDD). The most prominent symptoms of MDD are feelings of “worthlessness” and “hopelessness.” Patients with clinical depression almost always believe—even if they are successful people—that they are failures, awful people, or a burden on their families. They also often believe that there is no hope for them, no way out of their rut and misery, and that death by suicide is the only option. Yet such patients—who clearly have reality distortion and who harbor a completely false view of themselves, the world, and the future—are not regarded as having a psychosis, but a standard depressive episode and are generally treated with antidepressants. Only when depressed patients express a paranoid idea or that their body is full of excrement or that God is punishing them for their evil acts are they given the diagnosis of “psychotic depression,” and an antipsychotic is considered a necessary adjunct to their antidepressant regimen.

But isn’t there just a dimensional difference in the severity of the delusion between MDD and psychotic depression? Shouldn’t worthlessness and hopelessness be regarded as psychotic symptoms congruent with the mood disorder? Interestingly, 2 atypical antipsychotics—aripiprazole and quetiapine—have been FDA-approved as add-on therapy for patients who do not respond to 1 or 2 antidepressants. Could the D2 dopamine antagonism exerted by antipsychotics be the reason for the stronger antidepressant response?

Obsessive-compulsive disorder (OCD). Is it not a fixed false belief when a person suffering from OCD washes his hands 50 to 100 times a day until his skin is raw because of the erroneous belief that his hands are dirty? Is it not psychosis when an OCD patient performs hours of daily rituals that render her dysfunctional because she falsely believes that unless she performs the rituals “something terrible will happen” to her or her loved ones?

Anxiety disorder. How about the reality distortion of anxiety disorder patients who would never board a plane because they falsely believe it will crash or will not drive over a bridge or in a tunnel because they believe it will collapse? Even when such false beliefs impair patients’ functioning, clinicians do not regard it as a psychosis but as “anxiety fear.” Is fear not the essence of paranoia?

Anorexia nervosa (AN). Is a severely emaciated AN patient’s fixed false belief that he or she is fat—which can be life-threatening—not a form of psychosis?

Body dysmorphic disorder (BDD). The completely unwarranted or fallacious perception of ugliness or blemishes in a BDD patient are a form of fixed false beliefs that may lead to functional disability or dozens of plastic surgeries. Regardless of whether a perceptual disturbance is involved, the phenotype qualifies as a psychotic disorder.

Hypochondriasis. When a person adamantly and falsely believes that he has a serious physical disease and expends time, effort, and money doctor-shopping to receive treatment for an illusory somatic ailment, why do we label it as a somatoform disorder instead of a somatic delusion? Interestingly, DSM-IV-TR criterion C of hypochondriasis specifies that the preoccupation of having a serious disease should not be of “delusional intensity (as in delusional disorder, somatic type).” What is the definition of delusional intensity? At what point does a false belief move from mild to intense status and becomes psychotic?

Personality disorders. Consider how various thematic false beliefs pervade several axis II disorders, such as paranoid, schizotypal, borderline, narcissistic, or avoidant personality disorders. They all have an enduring component of a fixed false belief that falls on the continuum of psychosis.

By now, some readers may have arrived at the conclusion that this editor has developed his own fixed false belief that practically all psychiatric disorders are psychotic! Well, not exactly, but I did intend to provoke you to reconsider what we take for granted in the DSM, where psychotic disorders are set aside as just one section of 17 types of disorders. At least I hope that I convinced you that a thread of psychotic thinking can be identified across many of the other 16 supposedly “nonpsychotic” groupings.

One of the basic psychiatric principles accepted by all practicing psychiatrists is that a delusion is a fundamental symptom of psychosis.

A delusion is defined as “a fixed false belief not commensurate with the person’s educational and cultural background” and is almost universally associated with schizophrenia and other psychotic disorders. But if we apply the notion that a fixed false belief is delusional, then several “nonpsychotic” psychiatric disorders would qualify as psychoses based on their core clinical symptoms. Consider the following:

Major depressive disorder (MDD). The most prominent symptoms of MDD are feelings of “worthlessness” and “hopelessness.” Patients with clinical depression almost always believe—even if they are successful people—that they are failures, awful people, or a burden on their families. They also often believe that there is no hope for them, no way out of their rut and misery, and that death by suicide is the only option. Yet such patients—who clearly have reality distortion and who harbor a completely false view of themselves, the world, and the future—are not regarded as having a psychosis, but a standard depressive episode and are generally treated with antidepressants. Only when depressed patients express a paranoid idea or that their body is full of excrement or that God is punishing them for their evil acts are they given the diagnosis of “psychotic depression,” and an antipsychotic is considered a necessary adjunct to their antidepressant regimen.

But isn’t there just a dimensional difference in the severity of the delusion between MDD and psychotic depression? Shouldn’t worthlessness and hopelessness be regarded as psychotic symptoms congruent with the mood disorder? Interestingly, 2 atypical antipsychotics—aripiprazole and quetiapine—have been FDA-approved as add-on therapy for patients who do not respond to 1 or 2 antidepressants. Could the D2 dopamine antagonism exerted by antipsychotics be the reason for the stronger antidepressant response?

Obsessive-compulsive disorder (OCD). Is it not a fixed false belief when a person suffering from OCD washes his hands 50 to 100 times a day until his skin is raw because of the erroneous belief that his hands are dirty? Is it not psychosis when an OCD patient performs hours of daily rituals that render her dysfunctional because she falsely believes that unless she performs the rituals “something terrible will happen” to her or her loved ones?

Anxiety disorder. How about the reality distortion of anxiety disorder patients who would never board a plane because they falsely believe it will crash or will not drive over a bridge or in a tunnel because they believe it will collapse? Even when such false beliefs impair patients’ functioning, clinicians do not regard it as a psychosis but as “anxiety fear.” Is fear not the essence of paranoia?

Anorexia nervosa (AN). Is a severely emaciated AN patient’s fixed false belief that he or she is fat—which can be life-threatening—not a form of psychosis?

Body dysmorphic disorder (BDD). The completely unwarranted or fallacious perception of ugliness or blemishes in a BDD patient are a form of fixed false beliefs that may lead to functional disability or dozens of plastic surgeries. Regardless of whether a perceptual disturbance is involved, the phenotype qualifies as a psychotic disorder.

Hypochondriasis. When a person adamantly and falsely believes that he has a serious physical disease and expends time, effort, and money doctor-shopping to receive treatment for an illusory somatic ailment, why do we label it as a somatoform disorder instead of a somatic delusion? Interestingly, DSM-IV-TR criterion C of hypochondriasis specifies that the preoccupation of having a serious disease should not be of “delusional intensity (as in delusional disorder, somatic type).” What is the definition of delusional intensity? At what point does a false belief move from mild to intense status and becomes psychotic?

Personality disorders. Consider how various thematic false beliefs pervade several axis II disorders, such as paranoid, schizotypal, borderline, narcissistic, or avoidant personality disorders. They all have an enduring component of a fixed false belief that falls on the continuum of psychosis.

By now, some readers may have arrived at the conclusion that this editor has developed his own fixed false belief that practically all psychiatric disorders are psychotic! Well, not exactly, but I did intend to provoke you to reconsider what we take for granted in the DSM, where psychotic disorders are set aside as just one section of 17 types of disorders. At least I hope that I convinced you that a thread of psychotic thinking can be identified across many of the other 16 supposedly “nonpsychotic” groupings.