Proper sleep hygiene can help your patients fall and stay asleep consistently. Patients with insomnia are at a higher risk of developing or experiencing a recurrence of a mood disorder, and poor sleep can worsen psychiatric symptoms such as depression or mania.¹ Data about combining behavioral approaches and hypnotic medications to treat insomnia are inconclusive;² however, using the 2 together may help patients who do not respond to a single approach.

First rule out other causes of insomnia, such as sleep apnea, other medical conditions, or medications. Patients may improve after these factors are addressed.

Teaching sleep hygiene principles (Box) does not mean patients will adopt these habits, but employing the following suggestions could improve adherence:

Obtain a detailed sleep history to identify specific behaviors to be changed. For example, a patient might only have to stop watching television in bed to get a good night’s sleep, although some may find a brief exposure to television or radio facilitates relaxation.

Explain the rationale for changing a behavior. For example, when telling patients to limit caffeine or alcohol at night, list these substances’ negative effects on sleep. Similarly, when instructing patients to avoid watching television in bed, tell them that using the bedroom only for sleep or sex will help condition them for sleep at bedtime.

Box

Discuss sleep regularly. A patient might not disclose poor sleeping habits during the first session.

Give your patient handouts on sleep hygiene principles and highlight the most pertinent information. Ask the patient to place the handout where he or she will see it regularly.

Involve the family to help identify a patient’s poor sleep habits and find ways to implement sleep hygiene principles.

Encourage patients to keep a sleep diary. Ask the patient to note how many hours and at what time he or she slept for at least 2 weeks, then bring this information to the next appointment. This record allows you to examine patients’ sleep patterns and recommend appropriate changes.

Ask patients for creative ideas to improve their sleep. This dialogue will facilitate the therapeutic alliance and encourage positive changes in patients’ lives.

Proper sleep hygiene can help your patients fall and stay asleep consistently. Patients with insomnia are at a higher risk of developing or experiencing a recurrence of a mood disorder, and poor sleep can worsen psychiatric symptoms such as depression or mania.¹ Data about combining behavioral approaches and hypnotic medications to treat insomnia are inconclusive;² however, using the 2 together may help patients who do not respond to a single approach.

First rule out other causes of insomnia, such as sleep apnea, other medical conditions, or medications. Patients may improve after these factors are addressed.

Teaching sleep hygiene principles (Box) does not mean patients will adopt these habits, but employing the following suggestions could improve adherence:

Obtain a detailed sleep history to identify specific behaviors to be changed. For example, a patient might only have to stop watching television in bed to get a good night’s sleep, although some may find a brief exposure to television or radio facilitates relaxation.

Explain the rationale for changing a behavior. For example, when telling patients to limit caffeine or alcohol at night, list these substances’ negative effects on sleep. Similarly, when instructing patients to avoid watching television in bed, tell them that using the bedroom only for sleep or sex will help condition them for sleep at bedtime.

Box

Discuss sleep regularly. A patient might not disclose poor sleeping habits during the first session.

Give your patient handouts on sleep hygiene principles and highlight the most pertinent information. Ask the patient to place the handout where he or she will see it regularly.

Involve the family to help identify a patient’s poor sleep habits and find ways to implement sleep hygiene principles.

Encourage patients to keep a sleep diary. Ask the patient to note how many hours and at what time he or she slept for at least 2 weeks, then bring this information to the next appointment. This record allows you to examine patients’ sleep patterns and recommend appropriate changes.

Ask patients for creative ideas to improve their sleep. This dialogue will facilitate the therapeutic alliance and encourage positive changes in patients’ lives.

Proper sleep hygiene can help your patients fall and stay asleep consistently. Patients with insomnia are at a higher risk of developing or experiencing a recurrence of a mood disorder, and poor sleep can worsen psychiatric symptoms such as depression or mania.¹ Data about combining behavioral approaches and hypnotic medications to treat insomnia are inconclusive;² however, using the 2 together may help patients who do not respond to a single approach.

First rule out other causes of insomnia, such as sleep apnea, other medical conditions, or medications. Patients may improve after these factors are addressed.

Teaching sleep hygiene principles (Box) does not mean patients will adopt these habits, but employing the following suggestions could improve adherence:

Obtain a detailed sleep history to identify specific behaviors to be changed. For example, a patient might only have to stop watching television in bed to get a good night’s sleep, although some may find a brief exposure to television or radio facilitates relaxation.

Explain the rationale for changing a behavior. For example, when telling patients to limit caffeine or alcohol at night, list these substances’ negative effects on sleep. Similarly, when instructing patients to avoid watching television in bed, tell them that using the bedroom only for sleep or sex will help condition them for sleep at bedtime.

Box

Discuss sleep regularly. A patient might not disclose poor sleeping habits during the first session.

Give your patient handouts on sleep hygiene principles and highlight the most pertinent information. Ask the patient to place the handout where he or she will see it regularly.

Involve the family to help identify a patient’s poor sleep habits and find ways to implement sleep hygiene principles.

Encourage patients to keep a sleep diary. Ask the patient to note how many hours and at what time he or she slept for at least 2 weeks, then bring this information to the next appointment. This record allows you to examine patients’ sleep patterns and recommend appropriate changes.

Ask patients for creative ideas to improve their sleep. This dialogue will facilitate the therapeutic alliance and encourage positive changes in patients’ lives.

Posttraumatic stress disorder (PTSD) is a preventable mental illness—without trauma, the illness does not occur. Primary prevention (such as eliminating war, rape, physical assaults, child abuse, or motor vehicle accidents) would be effective but is an unrealistic goal. Secondary prevention (such as preventing PTSD after individuals have been exposed to trauma) may be attainable.

No medication is FDA-approved to prevent PTSD, but patients recently exposed to trauma might benefit from drugs approved for other indications. Possibilities include noradrenergics such as propranolol, corticosteroids that affect the hypothalamic-pituitary-adrenal (HPA) axis, opioids, benzodiazepines, and antidepressants. Some investigational agents also might block the process that turns a traumatic experience into PTSD.

This article discusses these intriguing ideas and suggests which trauma victims might benefit now from acute pharmacologic PTSD prevention.

Who might be treated?

An estimated 8% to 10% of the U.S. population experiences PTSD at some point in life (Box 1).^1,2 A person’s risk of developing PTSD after a traumatic event depends on the type of trauma. For example, 10% of motor vehicle accident survivors develop PTSD, compared with 60% of rape survivors.¹

Targeting anyone who has experienced trauma for secondary PTSD prevention would expose large groups of people to medications they do not need. Targeting selected persons who are at the highest risk would be more efficient and cost-effective. In a group of acute trauma-exposed persons, 2 selection criteria could be considered simultaneously:

• Which patients may be most predisposed to PTSD?
• Which patients are showing early symptoms that may predict PTSD?

Box 1

Risk factors and resiliency. Certain factors have been shown to increase a person’s vulnerability for PTSD (Table 1).³ Other proposed risk factors include:

• personality types⁴
• psychophysiologic factors such as reactivity, conditionability, and resistance to extinction/habituation.⁵

Strong evidence also indicates that acute trauma-related symptoms—including excessive arousal and fear,⁶ peritraumatic dissociation, and depression—predict the later development of PTSD.

Once identified, individuals predisposed to developing PTSD could be given treatment to increase their resiliency after they have been exposed to trauma. Early evidence suggests that you also could consider giving these patients medications as secondary prevention (Table 2).

Table 1

Who develops PTSD? Risk and resiliency factors

Table 2

Medications being studied for PTSD prevention

Targeting noradrenergic activity

Increased noradrenergic activity has been associated with persistent memories and PTSD. Therefore, medications that reduce noradrenergic tone by blocking receptors or reduce norepinephrine release are being explored for PTSD prevention.

Propranolol. Three small studies have examined whether the beta-noradrenergic receptor blocker propranolol can prevent PTSD.

In a randomized, double-blind, placebo-controlled trial,⁷ 41 emergency department patients who had a heart rate of ≥ 80 bpm within 6 hours of a traumatic accident received propranolol, 40 mg qid, or placebo for 10 days. After 1 month, the 11 patients who completed propranolol treatment showed a nonsignificant trend toward lower scores on the Clinician-Administered PTSD Scale (CAPS), compared with 20 patients taking placebo. At 3 months, the propranolol group had less physiologic reactivity (as measured by heart rate and skin conductance) to trauma-related cues than the placebo group.

In a nonrandomized study,⁸ PTSD developed within 2 months in 1 of 11 trauma victims who agreed to take propranolol, 40 mg tid, immediately after the trauma, compared with 3 of 8 victims who refused the medication.

In an unpublished randomized, double-blind trial,⁹ 48 patients admitted to a level I trauma center received propranolol, 40 mg tid; gabapentin, 400 mg tid; or placebo for PTSD prevention. Gabapentin was chosen because it has few side effects or metabolic interactions and preliminary evidence of anxiolytic efficacy.

Neither propranolol nor gabapentin showed statistically significant benefit in preventing PTSD compared with placebo. Effect sizes with the 2 treatments were too small to suggest that larger samples would produce a statistically significant result.

Prazosin—an alpha-1 adrenergic receptor antagonist—has been evaluated in 3 controlled studies and found to reduce intrusive nightmares typical of chronic PTSD.

Ten combat veterans with chronic PTSD showed significantly improved sleep, fewer severe nightmares, and improved global clinical status after receiving prazosin (mean dose 9.5 mg at bedtime) in a 20-week, placebo-controlled, double-blind, crossover study.¹⁰

In a larger randomized, parallel group trial,¹¹ the same authors compared prazosin with placebo in 40 combat veterans (mean age 56) with chronic PTSD. After 8 weeks, veterans taking prazosin (mean 13.3 ± 3 mg) had significantly fewer trauma nightmares, improved sleep (including return of normal dreams), and improved global clinical status vs placebo. Overall CAP scores did not decline significantly, however.

In a third placebo-controlled study,¹² a midmorning dose of prazosin was added to the regimens of 11 civilian trauma patients already taking the drug at bedtime to suppress trauma-related nightmares. Their daytime PTSD symptoms improved, as shown by reduced psychological distress in response to verbal trauma cues.

Prazosin can reduce chronic PTSD manifestations of nightmares and disturbed sleep, but it has not been shown to ameliorate the full PTSD syndrome. Prazosin has not been studied as an early PTSD intervention.

Other antiadrenergics that reduce the release of norepinephrine—including clonidine and guanfacine—have been studied in open trials as treatment for PTSD. The only controlled study¹³ showed no benefit from guanfacine for PTSD prevention.

De-stressing the HPA axis

Hydrocortisone has been proposed to prevent PTSD by reducing HPA axis activation, acting as a countermeasure to elevated corticotropin-releasing factor found in patients with chronic PTSD.

IV hydrocortisone’s effect on the development of PTSD was compared with placebo in 20 septic shock survivors after discharge from intensive care.¹⁴ One of 9 patients (11%) in the hydrocortisone group was diagnosed with PTSD at follow-up (mean 31 months), compared with 7 of 11 (64%) in the placebo group.

In a similar study, the same researchers gave patients hydrocortisone before, during, and after cardiac surgery. Follow-up interviews revealed significantly lower PTSD and chronic stress symptom scores in the treatment group vs the placebo group.¹⁵

These studies—although provocative—are limited by the narrow range of trauma related to severe medical illness or extensive medical procedures.

Norepinephrine-blocking opioids

When the noradrenergic system is activated, one physiologic response is the activation of endogenous opioid systems, which may promote recovery by inhibiting the HPA axis. Opioid systems might be involved in PTSD, as suggested by:

• preclinical evidence that opioids modulate memory¹⁶
• studies showing low pain thresholds¹⁷ and abnormal beta-endorphin (an opioid peptide neurotransmitter)¹⁸ and methionine enkephalin (an opioid peptide)¹⁹ levels in PTSD patients.

In theory, opioid administration immediately after trauma may attenuate norepinephrine release, thus thwarting arousal-charged memory consolidation, hyperarousal, and re-experiencing.

One uncontrolled report of pediatric burn victims found a significant association between the morphine dose given for pain during hospitalization and reduced PTSD symptoms 6 months later.²⁰ Decreased pain did not explain the reduction in PTSD, as no significant correlation was seen between pain symptoms and PTSD outcome measures. Similarly, a longitudinal study of substance use among Vietnam War veterans with PTSD found decreased hyperarousal symptoms in heroin users.²¹

Using opioids to prevent PTSD would be feasible and efficient in acute care settings because 80% to 90% of traumatically-injured patients are discharged on opioid analgesics (compared with <10% on beta blockers or corticosteroids).²² However, 20% to 40% of physically injured inpatients are diagnosed with a substance use disorder at some point in life, making the use of opioid analgesics a practical concern.²³

GABA-benzodiazepine paradox

The GABA-benzodiazepine system plays an important role in mediating anxiety, which is consistent with the potent anxiolytic effects of benzodiazepines. Even so, trials of benzodiazepines have found these drugs surprisingly unhelpful—and perhaps harmful—in patients with acute trauma.

Alprazolam did not reduce PTSD symptoms in a small randomized, double-blind study.²⁴ Another trial found that receiving benzodiazepines shortly after trauma exposure was associated with increased PTSD risk in trauma survivors. Nine of 13 patients (69%) who received alprazolam or clonazepam met PTSD diagnostic criteria 6 months after the trauma, compared with 3 of 13 controls (15%).²⁵

Similarly, in a randomized controlled trial, 22 patients were given temazepam for 7 nights, starting approximately 14 days after exposure to a traumatic event. Six weeks later, 55% of those receiving temazepam and 27% of those receiving placebo met criteria for PTSD.²⁶

In summary, benzodiazepines might be helpful when given for a few days after traumatization to control overwhelming anxiety but could be harmful over a longer term.

Other agents for PTSD

Antidepressants. Early trauma-related symptoms of depression predict later development of PTSD.²⁷ Thus, antidepressants have been proposed for early intervention in addition to their well-established role as first-line treatment of PTSD.²⁸

One study supports this idea: a 7-day randomized double-blind trial that compared the tricyclic antidepressant imipramine with chloral hydrate in pediatric burn patients with acute stress disorder (ASD). Imipramine was more effective (83% response) than chloral hydrate (38% response) in reducing ASD symptoms.²⁹

Drugs in development. Three new medications being explored for treating anxiety and depression also might be useful for PTSD prevention. Neuropeptide Y (NPY) agonists,³⁰ substance P antagonists,³¹ and CRH-antagonists³² are thought to hold promise because of their more proximate roles—compared with monoamine neurotransmitters such as dopamine, norepinephrine and serotonin—in mediating the stress response.

Box 2

Analyzing the evidence

Insufficient evidence exists to determine which strategies might be most effective to prevent PTSD, what optimal dosing might be, and which traumatized individuals might be best targeted with these approaches.

• Beta-blockers and corticosteroids—the most theoretically compelling strategies—are the most difficult agents to use for PTSD prevention because they have the most medical contraindications. In addition, evidence supporting their ability to prevent PTSD is meager at best.
• Prazosin is intriguing but has contra-indications similar to those of beta blockers, no studies of secondary prevention, and no clear indication that it works for the overall PTSD syndrome.
• Opioids are restricted agents with substantial contraindications.
• Evidence is limited but points most strongly toward earlier use of antidepressants. Early trauma-related symptoms of depression predict later development of PTSD,²⁷ and a number of selective serotonin reuptake inhibitors—such as citalopram, fluoxetine, paroxetine, and sertraline—are FDA-approved or used off-label for treating PTSD.³³

Prescribing recommendations. Consider practicality, ease of use, and safety of the proposed medication when choosing a drug for PTSD prevention (Table 3).²² Based on the evidence, the most reasonable posttrauma approach (Box 2) might be to consider starting an approved antidepressant for individuals thought to be particularly vulnerable to PTSD because of:

• past history of PTSD, depression, or anxiety disorder
• severity of the trauma (such as in cases of sexual assault or torture)
• pain (antidepressants with analgesic properties—such as venlafaxine or duloxetine—might be useful in patients whose trauma is associated with physical injury, although neither is FDA-approved to treat PTSD).

Table 3

4 considerations when choosing a drug for PTSD prevention

Related resources

• Mental health and mass violence: Evidence-based early psychological intervention for victims/survivors of mass violence. A workshop to reach consensus on best practices. Rockland, MD: National Institute of Mental Health; 2002. www.nimh.nih.gov.
• Post-traumatic stress disorder: the management of PTSD in adults and children in primary and secondary care (clinical guideline 26). London, UK: National Institute for Clinical Excellence; 2005. www.nice.org.uk.
• Ursano RJ, Bell C, Eth S, et al. Practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 2004;161(suppl 11):3-31.

Drug brand names

• Alprazolam • Xanax
• Amitriptyline • Elavil
• Citalopram • Celexa
• Clonazepam • Klonopin
• Clonidine • Catapres
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Guanfacine • Tenex
• Imipramine • Tofranil
• Lamotrigine • Lamictal
• Paroxetine • Paxil
• Prazosin • Minipress
• Propranolol • Inderal
• Sertraline • Zoloft
• Temazepam • Restoril
• Venlafaxine • Effexor

Disclosure

Dr. Bennett and Dr. Zatzick report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Roy-Byrne is a consultant to Jazz Pharmaceuticals and Solvay and has received speaker honoraria from Wyeth and Forrest Pharmaceuticals.

Posttraumatic stress disorder (PTSD) is a preventable mental illness—without trauma, the illness does not occur. Primary prevention (such as eliminating war, rape, physical assaults, child abuse, or motor vehicle accidents) would be effective but is an unrealistic goal. Secondary prevention (such as preventing PTSD after individuals have been exposed to trauma) may be attainable.

No medication is FDA-approved to prevent PTSD, but patients recently exposed to trauma might benefit from drugs approved for other indications. Possibilities include noradrenergics such as propranolol, corticosteroids that affect the hypothalamic-pituitary-adrenal (HPA) axis, opioids, benzodiazepines, and antidepressants. Some investigational agents also might block the process that turns a traumatic experience into PTSD.

This article discusses these intriguing ideas and suggests which trauma victims might benefit now from acute pharmacologic PTSD prevention.

Who might be treated?

An estimated 8% to 10% of the U.S. population experiences PTSD at some point in life (Box 1).^1,2 A person’s risk of developing PTSD after a traumatic event depends on the type of trauma. For example, 10% of motor vehicle accident survivors develop PTSD, compared with 60% of rape survivors.¹

Targeting anyone who has experienced trauma for secondary PTSD prevention would expose large groups of people to medications they do not need. Targeting selected persons who are at the highest risk would be more efficient and cost-effective. In a group of acute trauma-exposed persons, 2 selection criteria could be considered simultaneously:

• Which patients may be most predisposed to PTSD?
• Which patients are showing early symptoms that may predict PTSD?

Box 1

Risk factors and resiliency. Certain factors have been shown to increase a person’s vulnerability for PTSD (Table 1).³ Other proposed risk factors include:

• personality types⁴
• psychophysiologic factors such as reactivity, conditionability, and resistance to extinction/habituation.⁵

Strong evidence also indicates that acute trauma-related symptoms—including excessive arousal and fear,⁶ peritraumatic dissociation, and depression—predict the later development of PTSD.

Once identified, individuals predisposed to developing PTSD could be given treatment to increase their resiliency after they have been exposed to trauma. Early evidence suggests that you also could consider giving these patients medications as secondary prevention (Table 2).

Table 1

Who develops PTSD? Risk and resiliency factors

Table 2

Medications being studied for PTSD prevention

Targeting noradrenergic activity

Increased noradrenergic activity has been associated with persistent memories and PTSD. Therefore, medications that reduce noradrenergic tone by blocking receptors or reduce norepinephrine release are being explored for PTSD prevention.

Propranolol. Three small studies have examined whether the beta-noradrenergic receptor blocker propranolol can prevent PTSD.

In a randomized, double-blind, placebo-controlled trial,⁷ 41 emergency department patients who had a heart rate of ≥ 80 bpm within 6 hours of a traumatic accident received propranolol, 40 mg qid, or placebo for 10 days. After 1 month, the 11 patients who completed propranolol treatment showed a nonsignificant trend toward lower scores on the Clinician-Administered PTSD Scale (CAPS), compared with 20 patients taking placebo. At 3 months, the propranolol group had less physiologic reactivity (as measured by heart rate and skin conductance) to trauma-related cues than the placebo group.

In a nonrandomized study,⁸ PTSD developed within 2 months in 1 of 11 trauma victims who agreed to take propranolol, 40 mg tid, immediately after the trauma, compared with 3 of 8 victims who refused the medication.

In an unpublished randomized, double-blind trial,⁹ 48 patients admitted to a level I trauma center received propranolol, 40 mg tid; gabapentin, 400 mg tid; or placebo for PTSD prevention. Gabapentin was chosen because it has few side effects or metabolic interactions and preliminary evidence of anxiolytic efficacy.

Neither propranolol nor gabapentin showed statistically significant benefit in preventing PTSD compared with placebo. Effect sizes with the 2 treatments were too small to suggest that larger samples would produce a statistically significant result.

Prazosin—an alpha-1 adrenergic receptor antagonist—has been evaluated in 3 controlled studies and found to reduce intrusive nightmares typical of chronic PTSD.

Ten combat veterans with chronic PTSD showed significantly improved sleep, fewer severe nightmares, and improved global clinical status after receiving prazosin (mean dose 9.5 mg at bedtime) in a 20-week, placebo-controlled, double-blind, crossover study.¹⁰

In a larger randomized, parallel group trial,¹¹ the same authors compared prazosin with placebo in 40 combat veterans (mean age 56) with chronic PTSD. After 8 weeks, veterans taking prazosin (mean 13.3 ± 3 mg) had significantly fewer trauma nightmares, improved sleep (including return of normal dreams), and improved global clinical status vs placebo. Overall CAP scores did not decline significantly, however.

In a third placebo-controlled study,¹² a midmorning dose of prazosin was added to the regimens of 11 civilian trauma patients already taking the drug at bedtime to suppress trauma-related nightmares. Their daytime PTSD symptoms improved, as shown by reduced psychological distress in response to verbal trauma cues.

Prazosin can reduce chronic PTSD manifestations of nightmares and disturbed sleep, but it has not been shown to ameliorate the full PTSD syndrome. Prazosin has not been studied as an early PTSD intervention.

Other antiadrenergics that reduce the release of norepinephrine—including clonidine and guanfacine—have been studied in open trials as treatment for PTSD. The only controlled study¹³ showed no benefit from guanfacine for PTSD prevention.

De-stressing the HPA axis

Hydrocortisone has been proposed to prevent PTSD by reducing HPA axis activation, acting as a countermeasure to elevated corticotropin-releasing factor found in patients with chronic PTSD.

IV hydrocortisone’s effect on the development of PTSD was compared with placebo in 20 septic shock survivors after discharge from intensive care.¹⁴ One of 9 patients (11%) in the hydrocortisone group was diagnosed with PTSD at follow-up (mean 31 months), compared with 7 of 11 (64%) in the placebo group.

In a similar study, the same researchers gave patients hydrocortisone before, during, and after cardiac surgery. Follow-up interviews revealed significantly lower PTSD and chronic stress symptom scores in the treatment group vs the placebo group.¹⁵

These studies—although provocative—are limited by the narrow range of trauma related to severe medical illness or extensive medical procedures.

Norepinephrine-blocking opioids

When the noradrenergic system is activated, one physiologic response is the activation of endogenous opioid systems, which may promote recovery by inhibiting the HPA axis. Opioid systems might be involved in PTSD, as suggested by:

• preclinical evidence that opioids modulate memory¹⁶
• studies showing low pain thresholds¹⁷ and abnormal beta-endorphin (an opioid peptide neurotransmitter)¹⁸ and methionine enkephalin (an opioid peptide)¹⁹ levels in PTSD patients.

In theory, opioid administration immediately after trauma may attenuate norepinephrine release, thus thwarting arousal-charged memory consolidation, hyperarousal, and re-experiencing.

One uncontrolled report of pediatric burn victims found a significant association between the morphine dose given for pain during hospitalization and reduced PTSD symptoms 6 months later.²⁰ Decreased pain did not explain the reduction in PTSD, as no significant correlation was seen between pain symptoms and PTSD outcome measures. Similarly, a longitudinal study of substance use among Vietnam War veterans with PTSD found decreased hyperarousal symptoms in heroin users.²¹

Using opioids to prevent PTSD would be feasible and efficient in acute care settings because 80% to 90% of traumatically-injured patients are discharged on opioid analgesics (compared with <10% on beta blockers or corticosteroids).²² However, 20% to 40% of physically injured inpatients are diagnosed with a substance use disorder at some point in life, making the use of opioid analgesics a practical concern.²³

GABA-benzodiazepine paradox

The GABA-benzodiazepine system plays an important role in mediating anxiety, which is consistent with the potent anxiolytic effects of benzodiazepines. Even so, trials of benzodiazepines have found these drugs surprisingly unhelpful—and perhaps harmful—in patients with acute trauma.

Alprazolam did not reduce PTSD symptoms in a small randomized, double-blind study.²⁴ Another trial found that receiving benzodiazepines shortly after trauma exposure was associated with increased PTSD risk in trauma survivors. Nine of 13 patients (69%) who received alprazolam or clonazepam met PTSD diagnostic criteria 6 months after the trauma, compared with 3 of 13 controls (15%).²⁵

Similarly, in a randomized controlled trial, 22 patients were given temazepam for 7 nights, starting approximately 14 days after exposure to a traumatic event. Six weeks later, 55% of those receiving temazepam and 27% of those receiving placebo met criteria for PTSD.²⁶

In summary, benzodiazepines might be helpful when given for a few days after traumatization to control overwhelming anxiety but could be harmful over a longer term.

Other agents for PTSD

Antidepressants. Early trauma-related symptoms of depression predict later development of PTSD.²⁷ Thus, antidepressants have been proposed for early intervention in addition to their well-established role as first-line treatment of PTSD.²⁸

One study supports this idea: a 7-day randomized double-blind trial that compared the tricyclic antidepressant imipramine with chloral hydrate in pediatric burn patients with acute stress disorder (ASD). Imipramine was more effective (83% response) than chloral hydrate (38% response) in reducing ASD symptoms.²⁹

Drugs in development. Three new medications being explored for treating anxiety and depression also might be useful for PTSD prevention. Neuropeptide Y (NPY) agonists,³⁰ substance P antagonists,³¹ and CRH-antagonists³² are thought to hold promise because of their more proximate roles—compared with monoamine neurotransmitters such as dopamine, norepinephrine and serotonin—in mediating the stress response.

Box 2

Analyzing the evidence

Insufficient evidence exists to determine which strategies might be most effective to prevent PTSD, what optimal dosing might be, and which traumatized individuals might be best targeted with these approaches.

• Beta-blockers and corticosteroids—the most theoretically compelling strategies—are the most difficult agents to use for PTSD prevention because they have the most medical contraindications. In addition, evidence supporting their ability to prevent PTSD is meager at best.
• Prazosin is intriguing but has contra-indications similar to those of beta blockers, no studies of secondary prevention, and no clear indication that it works for the overall PTSD syndrome.
• Opioids are restricted agents with substantial contraindications.
• Evidence is limited but points most strongly toward earlier use of antidepressants. Early trauma-related symptoms of depression predict later development of PTSD,²⁷ and a number of selective serotonin reuptake inhibitors—such as citalopram, fluoxetine, paroxetine, and sertraline—are FDA-approved or used off-label for treating PTSD.³³

Prescribing recommendations. Consider practicality, ease of use, and safety of the proposed medication when choosing a drug for PTSD prevention (Table 3).²² Based on the evidence, the most reasonable posttrauma approach (Box 2) might be to consider starting an approved antidepressant for individuals thought to be particularly vulnerable to PTSD because of:

• past history of PTSD, depression, or anxiety disorder
• severity of the trauma (such as in cases of sexual assault or torture)
• pain (antidepressants with analgesic properties—such as venlafaxine or duloxetine—might be useful in patients whose trauma is associated with physical injury, although neither is FDA-approved to treat PTSD).

Table 3

4 considerations when choosing a drug for PTSD prevention

Related resources

• Mental health and mass violence: Evidence-based early psychological intervention for victims/survivors of mass violence. A workshop to reach consensus on best practices. Rockland, MD: National Institute of Mental Health; 2002. www.nimh.nih.gov.
• Post-traumatic stress disorder: the management of PTSD in adults and children in primary and secondary care (clinical guideline 26). London, UK: National Institute for Clinical Excellence; 2005. www.nice.org.uk.
• Ursano RJ, Bell C, Eth S, et al. Practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 2004;161(suppl 11):3-31.

Drug brand names

• Alprazolam • Xanax
• Amitriptyline • Elavil
• Citalopram • Celexa
• Clonazepam • Klonopin
• Clonidine • Catapres
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Guanfacine • Tenex
• Imipramine • Tofranil
• Lamotrigine • Lamictal
• Paroxetine • Paxil
• Prazosin • Minipress
• Propranolol • Inderal
• Sertraline • Zoloft
• Temazepam • Restoril
• Venlafaxine • Effexor

Disclosure

Dr. Bennett and Dr. Zatzick report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Roy-Byrne is a consultant to Jazz Pharmaceuticals and Solvay and has received speaker honoraria from Wyeth and Forrest Pharmaceuticals.

Posttraumatic stress disorder (PTSD) is a preventable mental illness—without trauma, the illness does not occur. Primary prevention (such as eliminating war, rape, physical assaults, child abuse, or motor vehicle accidents) would be effective but is an unrealistic goal. Secondary prevention (such as preventing PTSD after individuals have been exposed to trauma) may be attainable.

No medication is FDA-approved to prevent PTSD, but patients recently exposed to trauma might benefit from drugs approved for other indications. Possibilities include noradrenergics such as propranolol, corticosteroids that affect the hypothalamic-pituitary-adrenal (HPA) axis, opioids, benzodiazepines, and antidepressants. Some investigational agents also might block the process that turns a traumatic experience into PTSD.

This article discusses these intriguing ideas and suggests which trauma victims might benefit now from acute pharmacologic PTSD prevention.

Who might be treated?

An estimated 8% to 10% of the U.S. population experiences PTSD at some point in life (Box 1).^1,2 A person’s risk of developing PTSD after a traumatic event depends on the type of trauma. For example, 10% of motor vehicle accident survivors develop PTSD, compared with 60% of rape survivors.¹

Targeting anyone who has experienced trauma for secondary PTSD prevention would expose large groups of people to medications they do not need. Targeting selected persons who are at the highest risk would be more efficient and cost-effective. In a group of acute trauma-exposed persons, 2 selection criteria could be considered simultaneously:

• Which patients may be most predisposed to PTSD?
• Which patients are showing early symptoms that may predict PTSD?

Box 1

Risk factors and resiliency. Certain factors have been shown to increase a person’s vulnerability for PTSD (Table 1).³ Other proposed risk factors include:

• personality types⁴
• psychophysiologic factors such as reactivity, conditionability, and resistance to extinction/habituation.⁵

Strong evidence also indicates that acute trauma-related symptoms—including excessive arousal and fear,⁶ peritraumatic dissociation, and depression—predict the later development of PTSD.

Once identified, individuals predisposed to developing PTSD could be given treatment to increase their resiliency after they have been exposed to trauma. Early evidence suggests that you also could consider giving these patients medications as secondary prevention (Table 2).

Table 1

Who develops PTSD? Risk and resiliency factors

Table 2

Medications being studied for PTSD prevention

Targeting noradrenergic activity

Increased noradrenergic activity has been associated with persistent memories and PTSD. Therefore, medications that reduce noradrenergic tone by blocking receptors or reduce norepinephrine release are being explored for PTSD prevention.

Propranolol. Three small studies have examined whether the beta-noradrenergic receptor blocker propranolol can prevent PTSD.

In a randomized, double-blind, placebo-controlled trial,⁷ 41 emergency department patients who had a heart rate of ≥ 80 bpm within 6 hours of a traumatic accident received propranolol, 40 mg qid, or placebo for 10 days. After 1 month, the 11 patients who completed propranolol treatment showed a nonsignificant trend toward lower scores on the Clinician-Administered PTSD Scale (CAPS), compared with 20 patients taking placebo. At 3 months, the propranolol group had less physiologic reactivity (as measured by heart rate and skin conductance) to trauma-related cues than the placebo group.

In a nonrandomized study,⁸ PTSD developed within 2 months in 1 of 11 trauma victims who agreed to take propranolol, 40 mg tid, immediately after the trauma, compared with 3 of 8 victims who refused the medication.

In an unpublished randomized, double-blind trial,⁹ 48 patients admitted to a level I trauma center received propranolol, 40 mg tid; gabapentin, 400 mg tid; or placebo for PTSD prevention. Gabapentin was chosen because it has few side effects or metabolic interactions and preliminary evidence of anxiolytic efficacy.

Neither propranolol nor gabapentin showed statistically significant benefit in preventing PTSD compared with placebo. Effect sizes with the 2 treatments were too small to suggest that larger samples would produce a statistically significant result.

Prazosin—an alpha-1 adrenergic receptor antagonist—has been evaluated in 3 controlled studies and found to reduce intrusive nightmares typical of chronic PTSD.

Ten combat veterans with chronic PTSD showed significantly improved sleep, fewer severe nightmares, and improved global clinical status after receiving prazosin (mean dose 9.5 mg at bedtime) in a 20-week, placebo-controlled, double-blind, crossover study.¹⁰

In a larger randomized, parallel group trial,¹¹ the same authors compared prazosin with placebo in 40 combat veterans (mean age 56) with chronic PTSD. After 8 weeks, veterans taking prazosin (mean 13.3 ± 3 mg) had significantly fewer trauma nightmares, improved sleep (including return of normal dreams), and improved global clinical status vs placebo. Overall CAP scores did not decline significantly, however.

In a third placebo-controlled study,¹² a midmorning dose of prazosin was added to the regimens of 11 civilian trauma patients already taking the drug at bedtime to suppress trauma-related nightmares. Their daytime PTSD symptoms improved, as shown by reduced psychological distress in response to verbal trauma cues.

Prazosin can reduce chronic PTSD manifestations of nightmares and disturbed sleep, but it has not been shown to ameliorate the full PTSD syndrome. Prazosin has not been studied as an early PTSD intervention.

Other antiadrenergics that reduce the release of norepinephrine—including clonidine and guanfacine—have been studied in open trials as treatment for PTSD. The only controlled study¹³ showed no benefit from guanfacine for PTSD prevention.

De-stressing the HPA axis

Hydrocortisone has been proposed to prevent PTSD by reducing HPA axis activation, acting as a countermeasure to elevated corticotropin-releasing factor found in patients with chronic PTSD.

IV hydrocortisone’s effect on the development of PTSD was compared with placebo in 20 septic shock survivors after discharge from intensive care.¹⁴ One of 9 patients (11%) in the hydrocortisone group was diagnosed with PTSD at follow-up (mean 31 months), compared with 7 of 11 (64%) in the placebo group.

In a similar study, the same researchers gave patients hydrocortisone before, during, and after cardiac surgery. Follow-up interviews revealed significantly lower PTSD and chronic stress symptom scores in the treatment group vs the placebo group.¹⁵

These studies—although provocative—are limited by the narrow range of trauma related to severe medical illness or extensive medical procedures.

Norepinephrine-blocking opioids

When the noradrenergic system is activated, one physiologic response is the activation of endogenous opioid systems, which may promote recovery by inhibiting the HPA axis. Opioid systems might be involved in PTSD, as suggested by:

• preclinical evidence that opioids modulate memory¹⁶
• studies showing low pain thresholds¹⁷ and abnormal beta-endorphin (an opioid peptide neurotransmitter)¹⁸ and methionine enkephalin (an opioid peptide)¹⁹ levels in PTSD patients.

In theory, opioid administration immediately after trauma may attenuate norepinephrine release, thus thwarting arousal-charged memory consolidation, hyperarousal, and re-experiencing.

One uncontrolled report of pediatric burn victims found a significant association between the morphine dose given for pain during hospitalization and reduced PTSD symptoms 6 months later.²⁰ Decreased pain did not explain the reduction in PTSD, as no significant correlation was seen between pain symptoms and PTSD outcome measures. Similarly, a longitudinal study of substance use among Vietnam War veterans with PTSD found decreased hyperarousal symptoms in heroin users.²¹

Using opioids to prevent PTSD would be feasible and efficient in acute care settings because 80% to 90% of traumatically-injured patients are discharged on opioid analgesics (compared with <10% on beta blockers or corticosteroids).²² However, 20% to 40% of physically injured inpatients are diagnosed with a substance use disorder at some point in life, making the use of opioid analgesics a practical concern.²³

GABA-benzodiazepine paradox

The GABA-benzodiazepine system plays an important role in mediating anxiety, which is consistent with the potent anxiolytic effects of benzodiazepines. Even so, trials of benzodiazepines have found these drugs surprisingly unhelpful—and perhaps harmful—in patients with acute trauma.

Alprazolam did not reduce PTSD symptoms in a small randomized, double-blind study.²⁴ Another trial found that receiving benzodiazepines shortly after trauma exposure was associated with increased PTSD risk in trauma survivors. Nine of 13 patients (69%) who received alprazolam or clonazepam met PTSD diagnostic criteria 6 months after the trauma, compared with 3 of 13 controls (15%).²⁵

Similarly, in a randomized controlled trial, 22 patients were given temazepam for 7 nights, starting approximately 14 days after exposure to a traumatic event. Six weeks later, 55% of those receiving temazepam and 27% of those receiving placebo met criteria for PTSD.²⁶

In summary, benzodiazepines might be helpful when given for a few days after traumatization to control overwhelming anxiety but could be harmful over a longer term.

Other agents for PTSD

Antidepressants. Early trauma-related symptoms of depression predict later development of PTSD.²⁷ Thus, antidepressants have been proposed for early intervention in addition to their well-established role as first-line treatment of PTSD.²⁸

One study supports this idea: a 7-day randomized double-blind trial that compared the tricyclic antidepressant imipramine with chloral hydrate in pediatric burn patients with acute stress disorder (ASD). Imipramine was more effective (83% response) than chloral hydrate (38% response) in reducing ASD symptoms.²⁹

Drugs in development. Three new medications being explored for treating anxiety and depression also might be useful for PTSD prevention. Neuropeptide Y (NPY) agonists,³⁰ substance P antagonists,³¹ and CRH-antagonists³² are thought to hold promise because of their more proximate roles—compared with monoamine neurotransmitters such as dopamine, norepinephrine and serotonin—in mediating the stress response.

Box 2

Analyzing the evidence

Insufficient evidence exists to determine which strategies might be most effective to prevent PTSD, what optimal dosing might be, and which traumatized individuals might be best targeted with these approaches.

• Beta-blockers and corticosteroids—the most theoretically compelling strategies—are the most difficult agents to use for PTSD prevention because they have the most medical contraindications. In addition, evidence supporting their ability to prevent PTSD is meager at best.
• Prazosin is intriguing but has contra-indications similar to those of beta blockers, no studies of secondary prevention, and no clear indication that it works for the overall PTSD syndrome.
• Opioids are restricted agents with substantial contraindications.
• Evidence is limited but points most strongly toward earlier use of antidepressants. Early trauma-related symptoms of depression predict later development of PTSD,²⁷ and a number of selective serotonin reuptake inhibitors—such as citalopram, fluoxetine, paroxetine, and sertraline—are FDA-approved or used off-label for treating PTSD.³³

Prescribing recommendations. Consider practicality, ease of use, and safety of the proposed medication when choosing a drug for PTSD prevention (Table 3).²² Based on the evidence, the most reasonable posttrauma approach (Box 2) might be to consider starting an approved antidepressant for individuals thought to be particularly vulnerable to PTSD because of:

• past history of PTSD, depression, or anxiety disorder
• severity of the trauma (such as in cases of sexual assault or torture)
• pain (antidepressants with analgesic properties—such as venlafaxine or duloxetine—might be useful in patients whose trauma is associated with physical injury, although neither is FDA-approved to treat PTSD).

Table 3

4 considerations when choosing a drug for PTSD prevention

Related resources

• Mental health and mass violence: Evidence-based early psychological intervention for victims/survivors of mass violence. A workshop to reach consensus on best practices. Rockland, MD: National Institute of Mental Health; 2002. www.nimh.nih.gov.
• Post-traumatic stress disorder: the management of PTSD in adults and children in primary and secondary care (clinical guideline 26). London, UK: National Institute for Clinical Excellence; 2005. www.nice.org.uk.
• Ursano RJ, Bell C, Eth S, et al. Practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 2004;161(suppl 11):3-31.

Drug brand names

• Alprazolam • Xanax
• Amitriptyline • Elavil
• Citalopram • Celexa
• Clonazepam • Klonopin
• Clonidine • Catapres
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Guanfacine • Tenex
• Imipramine • Tofranil
• Lamotrigine • Lamictal
• Paroxetine • Paxil
• Prazosin • Minipress
• Propranolol • Inderal
• Sertraline • Zoloft
• Temazepam • Restoril
• Venlafaxine • Effexor

Disclosure

Dr. Bennett and Dr. Zatzick report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Roy-Byrne is a consultant to Jazz Pharmaceuticals and Solvay and has received speaker honoraria from Wyeth and Forrest Pharmaceuticals.

Vaginal, vulvar conditions: Simpler reporting

This year’s additions include codes for vaginal intraepithelial neoplasia (VAIN) and expansion of the vulvar intraepithelial neoplasia (VIN) category to match.

An “excludes” note has also been added to 622.1 [dysplasia of cervix (uteri)] to clarify that a diagnosis of carcinoma in situ I or II may not be reported unless this diagnosis is assigned based on a biopsy finding—not on an abnormal finding on a Pap smear.

New code for trauma during delivery

Anal sphincter tears can occur during delivery without an accompanying third-degree perineal laceration, so a new code [664.6X, anal sphincter tear complicating delivery, not associated with third-degree perineal laceration] has been added to capture this information. Keep in mind these important points:

• Report the new code when an anal tear is noted at or after delivery. The only acceptable fifth digits for this code are 0 [unspecified as to episode of care or not applicable], 1 [delivered, with or without mention of antepartum condition], or 4 [postpartum condition or complication].
  
• Report the established code, 664.2X [third-degree perineal laceration] if an anal tear is noted in addition to a third-degree perineal tear. The fifth digit will be 0, 1, or 4, as it is with the code for an anal sphincter tear.
  
• Report the established code 654.8X [congenital or acquired abnormality of vulva] if the patient had an anal tear from a prior pregnancy, before the current delivery.
  
• Last, report the new code 569.43 [anal sphincter tear (healed) (old)] if you observe that the patient has an old anal tear but isn’t pregnant. Report an additional code for any associated fecal incontinence (787.6).
  

Report dysplasia follow-up as “medical necessity”

Once a patient has been treated for cervical dysplasia, long-term follow-up care is required to test for recurrence. The only code available to report that history last year was V13.29, a general code that reported all types of genital systems and obstetric disorders. This year, you can specify and report V13.22 [personal history of cervical dysplasia].

The role of human papillomavirus (HPV) as the cause of cervical cancer is well known, and routine screening tests for this infection are generally as accurate as a routine Pap smear. Because of this, a new code, V73.81 [human papillomavirus (HPV)], has been added to document encounters for HPV screening. The new code can be reported in conjunction with the routine gyn exam code, V72.31, or V76.2 [special screening for malignant neoplasm of cervix] to signal that additional screening is planned.

Better documentation of malignant ascites

789.51  Malignant ascites

789.59  Other ascites

Malignant ascites is seen most often in ovarian, endometrial, breast, colon, gastric, and pancreatic cancer. Management of this condition may include systemic chemotherapy, instillation of radioisotopes or chemotherapy drugs into peritoneal fluid, and peritoneal–venous shunting procedures.

Before October 1, under ICD-9 rules, malignant ascites could be reported only using the code 197.6 [secondary malignant neoplasm of retroperitoneum and peritoneum].The problem is that this condition can also be caused by a primary ovarian malignancy, for which there has been no reporting mechanism. With expansion of the code 789.5 [ascites], you can specify the type of malignant ascites.

Note: Instructions in ICD-9 indicate that you should list a code for the site of the current malignancy first, such as 183.0 [malignant neoplasm of ovary] or 197.6 [secondary malignant neoplasm of retroperitoneum and peritoneum].

Assisted reproductive fertility procedure status

Every endocrinologist is aware that assisted reproductive fertility procedures are a multistage undertaking. A number of pretreatment diagnostic tests are independent of the procedure itself, and payers might cover such tests if there were a way to identify patients who were undergoing a procedure from those who were still undergoing pretreatment testing.

Before October 1, only one code, V26.8 [other specified procreative management], was available. Starting this month, to identify a patient undergoing treatment, use V26.81 [encounter for assisted reproductive fertility procedure cycle], with an additional code to identify the type of infertility. With this expansion, a second code was added to capture “other specified procreative management” [V26.89].

Natural family planning comes of age

Natural family planning helps a couple determine when sexual intercourse is likely to (and not likely to) result in pregnancy. It encompasses provider counseling and education on either of two acceptable methods: tracking ovulation by examining cervical mucus or temperature charting. ICD-9 has expanded the existing code, V26.4, to capture this means of family planning more accurately:

V26.41  Procreative counseling and advice using natural family planning

In addition, a code was added to the contraceptive counseling codes to capture this approach as well:

V25.04  Counseling and instruction in natural family planning to avoid pregnancy

Last, a new code also covers other types of procreative management counseling and advice:

V26.49  Other procreative management counseling and advice

Disability certificates, made easy(ier) to report

Do patients come to you to have medical forms and certificates completed? Now you can be more specific, when coding, about the type of document you’re asked to fill out.

V68.01  Disability examination

V68.09  Other issue of medical certificates

The old code, V68.0, was a catch-all of medical certificates, including cause of death, fitness, and disability. The new codes distinguish a certificate for a disability examination from the rest of the pack. That’s a useful change because insurers and state disability programs often reimburse for a disability exam.

Remember: You still need to identify the specific exam, screening, or testing performed by using a code from the series V72.0–V82.9 as a secondary diagnosis. Examples: V72.31 for a gyn exam and V81.6 [screening for other and unspecified genitourinary conditions].

Diversified codes for iatrogenic ID complications

Patients sometimes develop infection in the presence of a central venous catheter or after injection or vaccination. Previously, you used code 999.3 to report such a complication, but that code lumped into one all reasons for infection.

This year, a new code, 993.31, exclusively covers infection caused by a central venous catheter. The code lists several catheter types—Hickman, peripherally inserted central catheter (PICC), triplelumen catheter—and makes clear that it should not be used to report infection caused by a urinary (996.64), arterial (996.62), venous (996.62), or unspecified type of catheter (996.69).

An additional code, 999.39, has been added to report all infections after intravenous infusion, injection, transfusion, or vaccination.

Vaginal, vulvar conditions: Simpler reporting

This year’s additions include codes for vaginal intraepithelial neoplasia (VAIN) and expansion of the vulvar intraepithelial neoplasia (VIN) category to match.

An “excludes” note has also been added to 622.1 [dysplasia of cervix (uteri)] to clarify that a diagnosis of carcinoma in situ I or II may not be reported unless this diagnosis is assigned based on a biopsy finding—not on an abnormal finding on a Pap smear.

New code for trauma during delivery

Anal sphincter tears can occur during delivery without an accompanying third-degree perineal laceration, so a new code [664.6X, anal sphincter tear complicating delivery, not associated with third-degree perineal laceration] has been added to capture this information. Keep in mind these important points:

• Report the new code when an anal tear is noted at or after delivery. The only acceptable fifth digits for this code are 0 [unspecified as to episode of care or not applicable], 1 [delivered, with or without mention of antepartum condition], or 4 [postpartum condition or complication].
  
• Report the established code, 664.2X [third-degree perineal laceration] if an anal tear is noted in addition to a third-degree perineal tear. The fifth digit will be 0, 1, or 4, as it is with the code for an anal sphincter tear.
  
• Report the established code 654.8X [congenital or acquired abnormality of vulva] if the patient had an anal tear from a prior pregnancy, before the current delivery.
  
• Last, report the new code 569.43 [anal sphincter tear (healed) (old)] if you observe that the patient has an old anal tear but isn’t pregnant. Report an additional code for any associated fecal incontinence (787.6).
  

Report dysplasia follow-up as “medical necessity”

Once a patient has been treated for cervical dysplasia, long-term follow-up care is required to test for recurrence. The only code available to report that history last year was V13.29, a general code that reported all types of genital systems and obstetric disorders. This year, you can specify and report V13.22 [personal history of cervical dysplasia].

The role of human papillomavirus (HPV) as the cause of cervical cancer is well known, and routine screening tests for this infection are generally as accurate as a routine Pap smear. Because of this, a new code, V73.81 [human papillomavirus (HPV)], has been added to document encounters for HPV screening. The new code can be reported in conjunction with the routine gyn exam code, V72.31, or V76.2 [special screening for malignant neoplasm of cervix] to signal that additional screening is planned.

Better documentation of malignant ascites

789.51  Malignant ascites

789.59  Other ascites

Malignant ascites is seen most often in ovarian, endometrial, breast, colon, gastric, and pancreatic cancer. Management of this condition may include systemic chemotherapy, instillation of radioisotopes or chemotherapy drugs into peritoneal fluid, and peritoneal–venous shunting procedures.

Before October 1, under ICD-9 rules, malignant ascites could be reported only using the code 197.6 [secondary malignant neoplasm of retroperitoneum and peritoneum].The problem is that this condition can also be caused by a primary ovarian malignancy, for which there has been no reporting mechanism. With expansion of the code 789.5 [ascites], you can specify the type of malignant ascites.

Note: Instructions in ICD-9 indicate that you should list a code for the site of the current malignancy first, such as 183.0 [malignant neoplasm of ovary] or 197.6 [secondary malignant neoplasm of retroperitoneum and peritoneum].

Assisted reproductive fertility procedure status

Every endocrinologist is aware that assisted reproductive fertility procedures are a multistage undertaking. A number of pretreatment diagnostic tests are independent of the procedure itself, and payers might cover such tests if there were a way to identify patients who were undergoing a procedure from those who were still undergoing pretreatment testing.

Before October 1, only one code, V26.8 [other specified procreative management], was available. Starting this month, to identify a patient undergoing treatment, use V26.81 [encounter for assisted reproductive fertility procedure cycle], with an additional code to identify the type of infertility. With this expansion, a second code was added to capture “other specified procreative management” [V26.89].

Natural family planning comes of age

Natural family planning helps a couple determine when sexual intercourse is likely to (and not likely to) result in pregnancy. It encompasses provider counseling and education on either of two acceptable methods: tracking ovulation by examining cervical mucus or temperature charting. ICD-9 has expanded the existing code, V26.4, to capture this means of family planning more accurately:

V26.41  Procreative counseling and advice using natural family planning

In addition, a code was added to the contraceptive counseling codes to capture this approach as well:

V25.04  Counseling and instruction in natural family planning to avoid pregnancy

Last, a new code also covers other types of procreative management counseling and advice:

V26.49  Other procreative management counseling and advice

Disability certificates, made easy(ier) to report

Do patients come to you to have medical forms and certificates completed? Now you can be more specific, when coding, about the type of document you’re asked to fill out.

V68.01  Disability examination

V68.09  Other issue of medical certificates

The old code, V68.0, was a catch-all of medical certificates, including cause of death, fitness, and disability. The new codes distinguish a certificate for a disability examination from the rest of the pack. That’s a useful change because insurers and state disability programs often reimburse for a disability exam.

Remember: You still need to identify the specific exam, screening, or testing performed by using a code from the series V72.0–V82.9 as a secondary diagnosis. Examples: V72.31 for a gyn exam and V81.6 [screening for other and unspecified genitourinary conditions].

Diversified codes for iatrogenic ID complications

Patients sometimes develop infection in the presence of a central venous catheter or after injection or vaccination. Previously, you used code 999.3 to report such a complication, but that code lumped into one all reasons for infection.

This year, a new code, 993.31, exclusively covers infection caused by a central venous catheter. The code lists several catheter types—Hickman, peripherally inserted central catheter (PICC), triplelumen catheter—and makes clear that it should not be used to report infection caused by a urinary (996.64), arterial (996.62), venous (996.62), or unspecified type of catheter (996.69).

An additional code, 999.39, has been added to report all infections after intravenous infusion, injection, transfusion, or vaccination.

Vaginal, vulvar conditions: Simpler reporting

This year’s additions include codes for vaginal intraepithelial neoplasia (VAIN) and expansion of the vulvar intraepithelial neoplasia (VIN) category to match.

An “excludes” note has also been added to 622.1 [dysplasia of cervix (uteri)] to clarify that a diagnosis of carcinoma in situ I or II may not be reported unless this diagnosis is assigned based on a biopsy finding—not on an abnormal finding on a Pap smear.

New code for trauma during delivery

Anal sphincter tears can occur during delivery without an accompanying third-degree perineal laceration, so a new code [664.6X, anal sphincter tear complicating delivery, not associated with third-degree perineal laceration] has been added to capture this information. Keep in mind these important points:

• Report the new code when an anal tear is noted at or after delivery. The only acceptable fifth digits for this code are 0 [unspecified as to episode of care or not applicable], 1 [delivered, with or without mention of antepartum condition], or 4 [postpartum condition or complication].
  
• Report the established code, 664.2X [third-degree perineal laceration] if an anal tear is noted in addition to a third-degree perineal tear. The fifth digit will be 0, 1, or 4, as it is with the code for an anal sphincter tear.
  
• Report the established code 654.8X [congenital or acquired abnormality of vulva] if the patient had an anal tear from a prior pregnancy, before the current delivery.
  
• Last, report the new code 569.43 [anal sphincter tear (healed) (old)] if you observe that the patient has an old anal tear but isn’t pregnant. Report an additional code for any associated fecal incontinence (787.6).
  

Report dysplasia follow-up as “medical necessity”

Once a patient has been treated for cervical dysplasia, long-term follow-up care is required to test for recurrence. The only code available to report that history last year was V13.29, a general code that reported all types of genital systems and obstetric disorders. This year, you can specify and report V13.22 [personal history of cervical dysplasia].

The role of human papillomavirus (HPV) as the cause of cervical cancer is well known, and routine screening tests for this infection are generally as accurate as a routine Pap smear. Because of this, a new code, V73.81 [human papillomavirus (HPV)], has been added to document encounters for HPV screening. The new code can be reported in conjunction with the routine gyn exam code, V72.31, or V76.2 [special screening for malignant neoplasm of cervix] to signal that additional screening is planned.

Better documentation of malignant ascites

789.51  Malignant ascites

789.59  Other ascites

Malignant ascites is seen most often in ovarian, endometrial, breast, colon, gastric, and pancreatic cancer. Management of this condition may include systemic chemotherapy, instillation of radioisotopes or chemotherapy drugs into peritoneal fluid, and peritoneal–venous shunting procedures.

Before October 1, under ICD-9 rules, malignant ascites could be reported only using the code 197.6 [secondary malignant neoplasm of retroperitoneum and peritoneum].The problem is that this condition can also be caused by a primary ovarian malignancy, for which there has been no reporting mechanism. With expansion of the code 789.5 [ascites], you can specify the type of malignant ascites.

Note: Instructions in ICD-9 indicate that you should list a code for the site of the current malignancy first, such as 183.0 [malignant neoplasm of ovary] or 197.6 [secondary malignant neoplasm of retroperitoneum and peritoneum].

Assisted reproductive fertility procedure status

Every endocrinologist is aware that assisted reproductive fertility procedures are a multistage undertaking. A number of pretreatment diagnostic tests are independent of the procedure itself, and payers might cover such tests if there were a way to identify patients who were undergoing a procedure from those who were still undergoing pretreatment testing.

Before October 1, only one code, V26.8 [other specified procreative management], was available. Starting this month, to identify a patient undergoing treatment, use V26.81 [encounter for assisted reproductive fertility procedure cycle], with an additional code to identify the type of infertility. With this expansion, a second code was added to capture “other specified procreative management” [V26.89].

Natural family planning comes of age

Natural family planning helps a couple determine when sexual intercourse is likely to (and not likely to) result in pregnancy. It encompasses provider counseling and education on either of two acceptable methods: tracking ovulation by examining cervical mucus or temperature charting. ICD-9 has expanded the existing code, V26.4, to capture this means of family planning more accurately:

V26.41  Procreative counseling and advice using natural family planning

In addition, a code was added to the contraceptive counseling codes to capture this approach as well:

V25.04  Counseling and instruction in natural family planning to avoid pregnancy

Last, a new code also covers other types of procreative management counseling and advice:

V26.49  Other procreative management counseling and advice

Disability certificates, made easy(ier) to report

Do patients come to you to have medical forms and certificates completed? Now you can be more specific, when coding, about the type of document you’re asked to fill out.

V68.01  Disability examination

V68.09  Other issue of medical certificates

The old code, V68.0, was a catch-all of medical certificates, including cause of death, fitness, and disability. The new codes distinguish a certificate for a disability examination from the rest of the pack. That’s a useful change because insurers and state disability programs often reimburse for a disability exam.

Remember: You still need to identify the specific exam, screening, or testing performed by using a code from the series V72.0–V82.9 as a secondary diagnosis. Examples: V72.31 for a gyn exam and V81.6 [screening for other and unspecified genitourinary conditions].

Diversified codes for iatrogenic ID complications

Patients sometimes develop infection in the presence of a central venous catheter or after injection or vaccination. Previously, you used code 999.3 to report such a complication, but that code lumped into one all reasons for infection.

This year, a new code, 993.31, exclusively covers infection caused by a central venous catheter. The code lists several catheter types—Hickman, peripherally inserted central catheter (PICC), triplelumen catheter—and makes clear that it should not be used to report infection caused by a urinary (996.64), arterial (996.62), venous (996.62), or unspecified type of catheter (996.69).

An additional code, 999.39, has been added to report all infections after intravenous infusion, injection, transfusion, or vaccination.

Evidence summary

Although a number of studies have evaluated various appetite stimulants—megestrol, dronabinol (Marinol), cyproheptadine (Periactin), thalidomide (Thalomid), pentoxifylline (Pentoxil/Trental), nandrolone decanoate (DecaDurabolin), oxandrolone (Oxandrin), and corticosteroids—in patients with AIDS, anorexia cachexia syndrome, and advanced cancer, only megestrol has been studied in malnourished elderly patients.

Two studies, mixed results

One placebo-controlled randomized clinical trial studied 45 malnourished patients who were recently discharged from an acute care hospital to a nursing home. The patients (predominately female, with a mean age of 83) were randomized into 4 treatment arms (placebo or megestrol 200 mg, 400 mg, or 800 mg daily) and followed for 63 days.

Only those receiving megestrol (400 mg or 800 mg daily) demonstrated a statistically significant increase in patient appetite and a dose-responsive increase in prealbumin level at the 20 day interim analysis (7.5 and 9.0 mg/dL, respectfully). But at the final assessment (63 days), only the 400-mg dose maintained a statistically significant increase in prealbumin over placebo. However, there was no significant improvement in serum albumin or clinical endpoints (weight, functional status, or health-related quality of life).¹

In contrast, an earlier Veterans Administration (and predominantly male) study showed 13/21 of those treated with megestrol (800 mg daily for 12 weeks) noted weight gain (≥4 lb sustained at 3 months post-treatment), compared with 5/23 of those receiving placebo (number needed to treat [NNT]=2.5).² Of note, only 9/26 patients had sustained weight gain in the megestrol group at the 12-month endpoint post-treatment, comparable with 7/25 in the placebo group.

Some small, but statistically significant, score improvements were noted during the treatment period in appetite and enjoyment of life; however, no differences were noted in scores on the more widely accepted Geriatric Depression Scale.

Adverse effects

As in all therapeutic interventions, benefit must be balanced against risk. The Megace ES package insert notes the following potential adverse effects: diarrhea, cardiomyopathy, palpitation, hepatomegaly, leukopenia, edema, paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking, thrombophlebitis, pulmonary embolism, and glucose intolerance.³

To date, the prevalence rates of these potential adverse effects have only been studied in patients with AIDS. No data reflecting potential rates in elderly patients have been published.

Recommendations from others

The American Geriatric Society⁴ made 3 comments on appetite stimulation:

1. There are no FDA-approved drugs available for the promotion of weight gain in older adults.
2. A minority of patients receiving mirtazapine report appetite stimulation and weight gain.
3. All drugs used for appetite have substantial potential adverse events.

We found only 1 national guideline on this topic: Unintentional Weight Loss in the Elderly from the University of Texas School of Nursing.⁵ The guideline indicates that drugs should not be used as first-line intervention in the elderly, as there has been inadequate testing in this population. Benefits are restricted to small weight gains without indication of decreased morbidity or mortality, improved quality of life, or improved functional ability.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Although a number of studies have evaluated various appetite stimulants—megestrol, dronabinol (Marinol), cyproheptadine (Periactin), thalidomide (Thalomid), pentoxifylline (Pentoxil/Trental), nandrolone decanoate (DecaDurabolin), oxandrolone (Oxandrin), and corticosteroids—in patients with AIDS, anorexia cachexia syndrome, and advanced cancer, only megestrol has been studied in malnourished elderly patients.

Two studies, mixed results

One placebo-controlled randomized clinical trial studied 45 malnourished patients who were recently discharged from an acute care hospital to a nursing home. The patients (predominately female, with a mean age of 83) were randomized into 4 treatment arms (placebo or megestrol 200 mg, 400 mg, or 800 mg daily) and followed for 63 days.

Only those receiving megestrol (400 mg or 800 mg daily) demonstrated a statistically significant increase in patient appetite and a dose-responsive increase in prealbumin level at the 20 day interim analysis (7.5 and 9.0 mg/dL, respectfully). But at the final assessment (63 days), only the 400-mg dose maintained a statistically significant increase in prealbumin over placebo. However, there was no significant improvement in serum albumin or clinical endpoints (weight, functional status, or health-related quality of life).¹

In contrast, an earlier Veterans Administration (and predominantly male) study showed 13/21 of those treated with megestrol (800 mg daily for 12 weeks) noted weight gain (≥4 lb sustained at 3 months post-treatment), compared with 5/23 of those receiving placebo (number needed to treat [NNT]=2.5).² Of note, only 9/26 patients had sustained weight gain in the megestrol group at the 12-month endpoint post-treatment, comparable with 7/25 in the placebo group.

Some small, but statistically significant, score improvements were noted during the treatment period in appetite and enjoyment of life; however, no differences were noted in scores on the more widely accepted Geriatric Depression Scale.

Adverse effects

As in all therapeutic interventions, benefit must be balanced against risk. The Megace ES package insert notes the following potential adverse effects: diarrhea, cardiomyopathy, palpitation, hepatomegaly, leukopenia, edema, paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking, thrombophlebitis, pulmonary embolism, and glucose intolerance.³

To date, the prevalence rates of these potential adverse effects have only been studied in patients with AIDS. No data reflecting potential rates in elderly patients have been published.

Recommendations from others

The American Geriatric Society⁴ made 3 comments on appetite stimulation:

1. There are no FDA-approved drugs available for the promotion of weight gain in older adults.
2. A minority of patients receiving mirtazapine report appetite stimulation and weight gain.
3. All drugs used for appetite have substantial potential adverse events.

We found only 1 national guideline on this topic: Unintentional Weight Loss in the Elderly from the University of Texas School of Nursing.⁵ The guideline indicates that drugs should not be used as first-line intervention in the elderly, as there has been inadequate testing in this population. Benefits are restricted to small weight gains without indication of decreased morbidity or mortality, improved quality of life, or improved functional ability.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Although a number of studies have evaluated various appetite stimulants—megestrol, dronabinol (Marinol), cyproheptadine (Periactin), thalidomide (Thalomid), pentoxifylline (Pentoxil/Trental), nandrolone decanoate (DecaDurabolin), oxandrolone (Oxandrin), and corticosteroids—in patients with AIDS, anorexia cachexia syndrome, and advanced cancer, only megestrol has been studied in malnourished elderly patients.

Two studies, mixed results

One placebo-controlled randomized clinical trial studied 45 malnourished patients who were recently discharged from an acute care hospital to a nursing home. The patients (predominately female, with a mean age of 83) were randomized into 4 treatment arms (placebo or megestrol 200 mg, 400 mg, or 800 mg daily) and followed for 63 days.

Only those receiving megestrol (400 mg or 800 mg daily) demonstrated a statistically significant increase in patient appetite and a dose-responsive increase in prealbumin level at the 20 day interim analysis (7.5 and 9.0 mg/dL, respectfully). But at the final assessment (63 days), only the 400-mg dose maintained a statistically significant increase in prealbumin over placebo. However, there was no significant improvement in serum albumin or clinical endpoints (weight, functional status, or health-related quality of life).¹

In contrast, an earlier Veterans Administration (and predominantly male) study showed 13/21 of those treated with megestrol (800 mg daily for 12 weeks) noted weight gain (≥4 lb sustained at 3 months post-treatment), compared with 5/23 of those receiving placebo (number needed to treat [NNT]=2.5).² Of note, only 9/26 patients had sustained weight gain in the megestrol group at the 12-month endpoint post-treatment, comparable with 7/25 in the placebo group.

Some small, but statistically significant, score improvements were noted during the treatment period in appetite and enjoyment of life; however, no differences were noted in scores on the more widely accepted Geriatric Depression Scale.

Adverse effects

As in all therapeutic interventions, benefit must be balanced against risk. The Megace ES package insert notes the following potential adverse effects: diarrhea, cardiomyopathy, palpitation, hepatomegaly, leukopenia, edema, paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking, thrombophlebitis, pulmonary embolism, and glucose intolerance.³

To date, the prevalence rates of these potential adverse effects have only been studied in patients with AIDS. No data reflecting potential rates in elderly patients have been published.

Recommendations from others

The American Geriatric Society⁴ made 3 comments on appetite stimulation:

1. There are no FDA-approved drugs available for the promotion of weight gain in older adults.
2. A minority of patients receiving mirtazapine report appetite stimulation and weight gain.
3. All drugs used for appetite have substantial potential adverse events.

We found only 1 national guideline on this topic: Unintentional Weight Loss in the Elderly from the University of Texas School of Nursing.⁵ The guideline indicates that drugs should not be used as first-line intervention in the elderly, as there has been inadequate testing in this population. Benefits are restricted to small weight gains without indication of decreased morbidity or mortality, improved quality of life, or improved functional ability.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

AMSTERDAM — Diclofenac 3% gel was well tolerated and showed an excellent safety profile for treatment of multiple actinic keratoses in a postmarketing safety surveillance study.

The study, conducted in 140 primary care practices in the United Kingdom, showed no severe treatment-related adverse events in 450 treated patients. The most common adverse events were mild to moderate dry skin, itching, and redness, each occurring in 16%-20% of patients, Dr. Ron Higson reported at the 11th World Congress on Cancers of the Skin.

Severe versions of these side effects occurred in fewer than 4% of patients, added Dr. Higson of Clitheroe (U.K.) Health Centre.

Participants in this observational study were instructed to apply diclofenac 3% gel (Solaraze) twice daily for 12 weeks to areas of actinic keratoses (AKs). The topical nonsteroidal anti-inflammatory drug is licensed for treatment of AKs in the United States, United Kingdom, and some other European countries. Patients were assessed during office visits at baseline and at weeks 6, 12, and 16.

Although this was designed primarily as a safety study, there was a secondary efficacy end point consisting of change over time in the longest AK axis from each patient's three largest AKs. The mean reduction in the size of AKs located on the head, face, or neck was 2.8 mm at week 6 and 6.4 mm at the week 16 follow-up visit, Dr. Higson said at the congress, which was cosponsored by the Skin Cancer Foundation and Erasmus University, Rotterdam, the Netherlands.

The study was funded by Shire Pharmaceuticals.

Dr. Eggert Stockfleth, director of the skin cancer center at Charité University Hospital, Berlin, commented that diclofenac gel's two major advantages are its safety—the topical agent induces only very mild erythema and has no systemic effects—and the fact that it treats not only visible AK lesions but also what he calls the "field cancerization"—the underlying dysplasia that gives rise to new AKs and eventually to skin cancers.

AMSTERDAM — Diclofenac 3% gel was well tolerated and showed an excellent safety profile for treatment of multiple actinic keratoses in a postmarketing safety surveillance study.

The study, conducted in 140 primary care practices in the United Kingdom, showed no severe treatment-related adverse events in 450 treated patients. The most common adverse events were mild to moderate dry skin, itching, and redness, each occurring in 16%-20% of patients, Dr. Ron Higson reported at the 11th World Congress on Cancers of the Skin.

Severe versions of these side effects occurred in fewer than 4% of patients, added Dr. Higson of Clitheroe (U.K.) Health Centre.

Participants in this observational study were instructed to apply diclofenac 3% gel (Solaraze) twice daily for 12 weeks to areas of actinic keratoses (AKs). The topical nonsteroidal anti-inflammatory drug is licensed for treatment of AKs in the United States, United Kingdom, and some other European countries. Patients were assessed during office visits at baseline and at weeks 6, 12, and 16.

Although this was designed primarily as a safety study, there was a secondary efficacy end point consisting of change over time in the longest AK axis from each patient's three largest AKs. The mean reduction in the size of AKs located on the head, face, or neck was 2.8 mm at week 6 and 6.4 mm at the week 16 follow-up visit, Dr. Higson said at the congress, which was cosponsored by the Skin Cancer Foundation and Erasmus University, Rotterdam, the Netherlands.

The study was funded by Shire Pharmaceuticals.

Dr. Eggert Stockfleth, director of the skin cancer center at Charité University Hospital, Berlin, commented that diclofenac gel's two major advantages are its safety—the topical agent induces only very mild erythema and has no systemic effects—and the fact that it treats not only visible AK lesions but also what he calls the "field cancerization"—the underlying dysplasia that gives rise to new AKs and eventually to skin cancers.

AMSTERDAM — Diclofenac 3% gel was well tolerated and showed an excellent safety profile for treatment of multiple actinic keratoses in a postmarketing safety surveillance study.

The study, conducted in 140 primary care practices in the United Kingdom, showed no severe treatment-related adverse events in 450 treated patients. The most common adverse events were mild to moderate dry skin, itching, and redness, each occurring in 16%-20% of patients, Dr. Ron Higson reported at the 11th World Congress on Cancers of the Skin.

Severe versions of these side effects occurred in fewer than 4% of patients, added Dr. Higson of Clitheroe (U.K.) Health Centre.

Participants in this observational study were instructed to apply diclofenac 3% gel (Solaraze) twice daily for 12 weeks to areas of actinic keratoses (AKs). The topical nonsteroidal anti-inflammatory drug is licensed for treatment of AKs in the United States, United Kingdom, and some other European countries. Patients were assessed during office visits at baseline and at weeks 6, 12, and 16.

Although this was designed primarily as a safety study, there was a secondary efficacy end point consisting of change over time in the longest AK axis from each patient's three largest AKs. The mean reduction in the size of AKs located on the head, face, or neck was 2.8 mm at week 6 and 6.4 mm at the week 16 follow-up visit, Dr. Higson said at the congress, which was cosponsored by the Skin Cancer Foundation and Erasmus University, Rotterdam, the Netherlands.

The study was funded by Shire Pharmaceuticals.

Dr. Eggert Stockfleth, director of the skin cancer center at Charité University Hospital, Berlin, commented that diclofenac gel's two major advantages are its safety—the topical agent induces only very mild erythema and has no systemic effects—and the fact that it treats not only visible AK lesions but also what he calls the "field cancerization"—the underlying dysplasia that gives rise to new AKs and eventually to skin cancers.