Q. My patient delivered the first of her twins vaginally but is still carrying the second fetus. When we report our services, how should we code for both the first and (eventual) second delivery? I know that I will be billing 59409 (vaginal delivery only [with or without episiotomy and/or forceps]) for the first delivery and 59400 (Routine obstetric care including antepartum care, vaginal delivery [with or without episiotomy, and/or forceps] and postpartum care) for the second—assuming that a cesarean section is not required. But can I use the diagnosis code 761.5 (multiple pregnancy) with these codes, as well?

A. Here is one of those situations that ICD9 was not constructed to handle! You may not report 761.5 on the mother’s record because this is still one pregnancy for both events. Code 761.5 can only be reported on the baby’s record once he or she is receiving direct care. Therefore, report the twin diagnosis code 651.01 for both deliveries. However, consider waiting and billing the deliveries together, on the same claim, with the different delivery dates specified (as so: “4/21: 59409, 651.01”; then “5/xx: 59400, 651.01”), and include an explanation with the claim to ensure payment for both deliveries.

In-office lab test is not an occasion for a modifier

Q. We billed an office visit and a wet mount (87210 [smear, primary source with interpretation; wet mount for infectious agents (eg, saline, India ink, KOH preps)]). The lab service was determined to be global by the insurance company and was denied. What is the appropriate code for the wet mount?

A. The A modifier is usually unnecessary for a laboratory test with an office visit. The closest modifier that would apply is -25 (significant, separately identifiable evaluation and management service by the same physician on the same day of a procedure).

I suspect that your problem may not be a global issue, but one of coverage for a lab test performed by your practice under CLIA (Clinical Laboratory Improvement Amendments). [Editor’s note: Details about coding for office lab tests (eg, wet mounts and KOH preps) in relation to CLIA certificate requirements were discussed in Reimbursement Adviser in the August 2006 issue of OBG Management. Read this installment at obgmanagement.com by linking to “Past Issues” on the top navigation bar of the home page.]

To sort out this situation, you first need to contact the payer to find out whether it considers a lab test global to an office visit, which should never be the case. Perhaps your billing staff misinterpreted the denial message. Or maybe this payer does, in fact, require a modifier for any service billed at the same time as an office visit.

On the other hand, it could also be that you do not have the required CLIA certificate to bill for the wet mount using code 87210.

Payer may balk at modified biophysical profile

Q. We are performing a limited ultrasonography to evaluate amniotic fluid volume and a fetal non-stress test at the same time on our pregnant patient. How can we best code this evaluation to ensure proper reimbursement?

A. No single code describes this modified (so to speak) biophysical profile. Instead, you have 2 coding options, either of which may cause a headache with the payer:

• Code for the complete biophysical profile (76818) but add a modifier -52 for a reduced service. The problem? Not all payers permit use of this modifier with an imaging code.
  
• Itemize your services by reporting 59025 for the fetal non-stress test and 76815 (limited pelvic ultrasound) for evaluation of amniotic fluid volume. The problem here? Code 59025 is bundled into code 76815; although you are allowed to use the modifier -59 (distinct procedural service) to bypass the edit, you can only do so if you can meet the criteria for doing so (eg, care involves a different incision or excision, a different patient encounter, or a different injury or site). Some payers may not accept that you’ve met those requirements, although I would disagree with that decision: Each test is performed independently and measures different things. So, to bill this combination of tests, add modifier -59 to the bundled code: 76815, 59025-59.
  

Hysteroscopy before but not during thermoablation

Q. Please clarify: How do we correctly report a thermoablation procedure when hysteroscopy is performed before the procedure but not for guidance during the procedure? Are 58353 (endometrial ablation, thermal, without hysteroscopic guidance) and 58555-51 (Hysteroscopy, diagnostic [separate procedure]; multiple procedure) appropriate codes?

A. The problem is that code 58555 is bundled into 58353 under National Correct Coding Initiative (NCCI) rules. Because of this, the modifier -51 (multiple procedures) cannot be used. Although this bundled code allows the use of a modifier -59 (distinct procedure), meeting the criteria for using it is almost impossible.

Modifier -59 is defined as follows in CPT: “…used to identify procedures/services that are not normally reported together, but are appropriate under the circumstances. This may represent a different session or patient encounter, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same physician.”

In the situation that you describe, the hysteroscope was inserted in the same area as the ablation, not at a different site; no separate excision or incision was made when inserting the hysteroscope; this was not a different surgical session; and, last, although hysteroscopy might, technically, be a distinct procedure from the ablation, it was directly related to the performance of the ablation in that it represented initial “exploration.”

I believe, therefore, that correct coding in this case is to report the all-inclusive 58563 (Hysteroscopy, surgical; with endometrial ablation [eg, endometrial resection, electrosurgical ablation, thermoablation]). Support for this opinion is found in ACOG’s Ob/GYN Coding Manual: Components of Correct Procedural Coding 2007. A comment included with code 58353 states: “If hysteroscopy is also performed, report code 58563 instead.”

Q. My patient delivered the first of her twins vaginally but is still carrying the second fetus. When we report our services, how should we code for both the first and (eventual) second delivery? I know that I will be billing 59409 (vaginal delivery only [with or without episiotomy and/or forceps]) for the first delivery and 59400 (Routine obstetric care including antepartum care, vaginal delivery [with or without episiotomy, and/or forceps] and postpartum care) for the second—assuming that a cesarean section is not required. But can I use the diagnosis code 761.5 (multiple pregnancy) with these codes, as well?

A. Here is one of those situations that ICD9 was not constructed to handle! You may not report 761.5 on the mother’s record because this is still one pregnancy for both events. Code 761.5 can only be reported on the baby’s record once he or she is receiving direct care. Therefore, report the twin diagnosis code 651.01 for both deliveries. However, consider waiting and billing the deliveries together, on the same claim, with the different delivery dates specified (as so: “4/21: 59409, 651.01”; then “5/xx: 59400, 651.01”), and include an explanation with the claim to ensure payment for both deliveries.

In-office lab test is not an occasion for a modifier

Q. We billed an office visit and a wet mount (87210 [smear, primary source with interpretation; wet mount for infectious agents (eg, saline, India ink, KOH preps)]). The lab service was determined to be global by the insurance company and was denied. What is the appropriate code for the wet mount?

A. The A modifier is usually unnecessary for a laboratory test with an office visit. The closest modifier that would apply is -25 (significant, separately identifiable evaluation and management service by the same physician on the same day of a procedure).

I suspect that your problem may not be a global issue, but one of coverage for a lab test performed by your practice under CLIA (Clinical Laboratory Improvement Amendments). [Editor’s note: Details about coding for office lab tests (eg, wet mounts and KOH preps) in relation to CLIA certificate requirements were discussed in Reimbursement Adviser in the August 2006 issue of OBG Management. Read this installment at obgmanagement.com by linking to “Past Issues” on the top navigation bar of the home page.]

To sort out this situation, you first need to contact the payer to find out whether it considers a lab test global to an office visit, which should never be the case. Perhaps your billing staff misinterpreted the denial message. Or maybe this payer does, in fact, require a modifier for any service billed at the same time as an office visit.

On the other hand, it could also be that you do not have the required CLIA certificate to bill for the wet mount using code 87210.

Payer may balk at modified biophysical profile

Q. We are performing a limited ultrasonography to evaluate amniotic fluid volume and a fetal non-stress test at the same time on our pregnant patient. How can we best code this evaluation to ensure proper reimbursement?

A. No single code describes this modified (so to speak) biophysical profile. Instead, you have 2 coding options, either of which may cause a headache with the payer:

• Code for the complete biophysical profile (76818) but add a modifier -52 for a reduced service. The problem? Not all payers permit use of this modifier with an imaging code.
  
• Itemize your services by reporting 59025 for the fetal non-stress test and 76815 (limited pelvic ultrasound) for evaluation of amniotic fluid volume. The problem here? Code 59025 is bundled into code 76815; although you are allowed to use the modifier -59 (distinct procedural service) to bypass the edit, you can only do so if you can meet the criteria for doing so (eg, care involves a different incision or excision, a different patient encounter, or a different injury or site). Some payers may not accept that you’ve met those requirements, although I would disagree with that decision: Each test is performed independently and measures different things. So, to bill this combination of tests, add modifier -59 to the bundled code: 76815, 59025-59.
  

Hysteroscopy before but not during thermoablation

Q. Please clarify: How do we correctly report a thermoablation procedure when hysteroscopy is performed before the procedure but not for guidance during the procedure? Are 58353 (endometrial ablation, thermal, without hysteroscopic guidance) and 58555-51 (Hysteroscopy, diagnostic [separate procedure]; multiple procedure) appropriate codes?

A. The problem is that code 58555 is bundled into 58353 under National Correct Coding Initiative (NCCI) rules. Because of this, the modifier -51 (multiple procedures) cannot be used. Although this bundled code allows the use of a modifier -59 (distinct procedure), meeting the criteria for using it is almost impossible.

Modifier -59 is defined as follows in CPT: “…used to identify procedures/services that are not normally reported together, but are appropriate under the circumstances. This may represent a different session or patient encounter, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same physician.”

In the situation that you describe, the hysteroscope was inserted in the same area as the ablation, not at a different site; no separate excision or incision was made when inserting the hysteroscope; this was not a different surgical session; and, last, although hysteroscopy might, technically, be a distinct procedure from the ablation, it was directly related to the performance of the ablation in that it represented initial “exploration.”

I believe, therefore, that correct coding in this case is to report the all-inclusive 58563 (Hysteroscopy, surgical; with endometrial ablation [eg, endometrial resection, electrosurgical ablation, thermoablation]). Support for this opinion is found in ACOG’s Ob/GYN Coding Manual: Components of Correct Procedural Coding 2007. A comment included with code 58353 states: “If hysteroscopy is also performed, report code 58563 instead.”

Q. My patient delivered the first of her twins vaginally but is still carrying the second fetus. When we report our services, how should we code for both the first and (eventual) second delivery? I know that I will be billing 59409 (vaginal delivery only [with or without episiotomy and/or forceps]) for the first delivery and 59400 (Routine obstetric care including antepartum care, vaginal delivery [with or without episiotomy, and/or forceps] and postpartum care) for the second—assuming that a cesarean section is not required. But can I use the diagnosis code 761.5 (multiple pregnancy) with these codes, as well?

A. Here is one of those situations that ICD9 was not constructed to handle! You may not report 761.5 on the mother’s record because this is still one pregnancy for both events. Code 761.5 can only be reported on the baby’s record once he or she is receiving direct care. Therefore, report the twin diagnosis code 651.01 for both deliveries. However, consider waiting and billing the deliveries together, on the same claim, with the different delivery dates specified (as so: “4/21: 59409, 651.01”; then “5/xx: 59400, 651.01”), and include an explanation with the claim to ensure payment for both deliveries.

In-office lab test is not an occasion for a modifier

Q. We billed an office visit and a wet mount (87210 [smear, primary source with interpretation; wet mount for infectious agents (eg, saline, India ink, KOH preps)]). The lab service was determined to be global by the insurance company and was denied. What is the appropriate code for the wet mount?

A. The A modifier is usually unnecessary for a laboratory test with an office visit. The closest modifier that would apply is -25 (significant, separately identifiable evaluation and management service by the same physician on the same day of a procedure).

I suspect that your problem may not be a global issue, but one of coverage for a lab test performed by your practice under CLIA (Clinical Laboratory Improvement Amendments). [Editor’s note: Details about coding for office lab tests (eg, wet mounts and KOH preps) in relation to CLIA certificate requirements were discussed in Reimbursement Adviser in the August 2006 issue of OBG Management. Read this installment at obgmanagement.com by linking to “Past Issues” on the top navigation bar of the home page.]

To sort out this situation, you first need to contact the payer to find out whether it considers a lab test global to an office visit, which should never be the case. Perhaps your billing staff misinterpreted the denial message. Or maybe this payer does, in fact, require a modifier for any service billed at the same time as an office visit.

On the other hand, it could also be that you do not have the required CLIA certificate to bill for the wet mount using code 87210.

Payer may balk at modified biophysical profile

Q. We are performing a limited ultrasonography to evaluate amniotic fluid volume and a fetal non-stress test at the same time on our pregnant patient. How can we best code this evaluation to ensure proper reimbursement?

A. No single code describes this modified (so to speak) biophysical profile. Instead, you have 2 coding options, either of which may cause a headache with the payer:

• Code for the complete biophysical profile (76818) but add a modifier -52 for a reduced service. The problem? Not all payers permit use of this modifier with an imaging code.
  
• Itemize your services by reporting 59025 for the fetal non-stress test and 76815 (limited pelvic ultrasound) for evaluation of amniotic fluid volume. The problem here? Code 59025 is bundled into code 76815; although you are allowed to use the modifier -59 (distinct procedural service) to bypass the edit, you can only do so if you can meet the criteria for doing so (eg, care involves a different incision or excision, a different patient encounter, or a different injury or site). Some payers may not accept that you’ve met those requirements, although I would disagree with that decision: Each test is performed independently and measures different things. So, to bill this combination of tests, add modifier -59 to the bundled code: 76815, 59025-59.
  

Hysteroscopy before but not during thermoablation

Q. Please clarify: How do we correctly report a thermoablation procedure when hysteroscopy is performed before the procedure but not for guidance during the procedure? Are 58353 (endometrial ablation, thermal, without hysteroscopic guidance) and 58555-51 (Hysteroscopy, diagnostic [separate procedure]; multiple procedure) appropriate codes?

A. The problem is that code 58555 is bundled into 58353 under National Correct Coding Initiative (NCCI) rules. Because of this, the modifier -51 (multiple procedures) cannot be used. Although this bundled code allows the use of a modifier -59 (distinct procedure), meeting the criteria for using it is almost impossible.

Modifier -59 is defined as follows in CPT: “…used to identify procedures/services that are not normally reported together, but are appropriate under the circumstances. This may represent a different session or patient encounter, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same physician.”

In the situation that you describe, the hysteroscope was inserted in the same area as the ablation, not at a different site; no separate excision or incision was made when inserting the hysteroscope; this was not a different surgical session; and, last, although hysteroscopy might, technically, be a distinct procedure from the ablation, it was directly related to the performance of the ablation in that it represented initial “exploration.”

I believe, therefore, that correct coding in this case is to report the all-inclusive 58563 (Hysteroscopy, surgical; with endometrial ablation [eg, endometrial resection, electrosurgical ablation, thermoablation]). Support for this opinion is found in ACOG’s Ob/GYN Coding Manual: Components of Correct Procedural Coding 2007. A comment included with code 58353 states: “If hysteroscopy is also performed, report code 58563 instead.”

Q. Recently, we were denied a claim for hospital care related to a patient’s premature labor. She was admitted to stop labor at 30 weeks but delivered 5 days after admission. The reason for denial? “Invalid ICD9 code.” But the code we used, 644.03 (threatened premature labor), appears to be correct. We also reported 644.21 (early onset of delivery) with the delivery code. Should we appeal, given that care prior to delivery is well documented?

A. I believe that your denial is based on incorrect use of the fifth digit on the reported diagnosis codes, not on refusal to reimburse separately for additional care before delivery. ICD9 guidelines related to fifth-digit coding for obstetric cases state:

“The fifth-digits, which are appropriate for each code number, are listed in brackets under each code. The fifth digits on each code should all be consistent with each other. That is, should a delivery occur all of the fifth digits should indicate the delivery.”

In this case, although the patient was still in the antepartum period during initial care, she did deliver during that hospitalization. That means a fifth digit of “3” (antepartum condition or complication) is incompatible with a fifth digit of “1” (delivered, with or without mention of antepartum condition), which is probably what generated the denial message. You have 2 choices:

• Resubmit a corrected claim, indicating a fifth digit of “1” for both diagnostic codes
  
• Appeal the denial, indicating the diagnostic correction and supplying information regarding the additional care for this patient.
  

Bundle codes for repair of a pelvic floor defect?

Q. To treat a patient who has a pelvic floor defect, we performed an anterior repair, a posterior repair, and an enterocele repair, using mesh—plus cystoscopy. Does one code capture all these procedures?

A. I assume that you used mesh to augment the anterior and posterior repairs. A single CPT code, 57265 (combined anteroposterior colporrhaphy; with enterocele repair) captures the first 3 procedures, and CPT allows the addon mesh code 57267 (insertion of mesh or other prosthesis for repair of pelvic floor defect, each site [anterior, posterior compartment], vaginal approach) to be reported with 57265.

Based on the definition of the addon mesh code, it is appropriate for you to bill for a quantity of 2: 1 for the anterior compartment repair and 1 for the posterior compartment repair, which includes the rectocele and enterocele.

As for reporting the cystoscopy (with 52000 [cystourethroscopy (separate procedure)]), the reason that you provide for the procedure will determine whether you are reimbursed. There must be a medical indication for cystoscopy beyond your simply checking your work, which is considered a standard of surgical care by most payers.

Q. Recently, we were denied a claim for hospital care related to a patient’s premature labor. She was admitted to stop labor at 30 weeks but delivered 5 days after admission. The reason for denial? “Invalid ICD9 code.” But the code we used, 644.03 (threatened premature labor), appears to be correct. We also reported 644.21 (early onset of delivery) with the delivery code. Should we appeal, given that care prior to delivery is well documented?

A. I believe that your denial is based on incorrect use of the fifth digit on the reported diagnosis codes, not on refusal to reimburse separately for additional care before delivery. ICD9 guidelines related to fifth-digit coding for obstetric cases state:

“The fifth-digits, which are appropriate for each code number, are listed in brackets under each code. The fifth digits on each code should all be consistent with each other. That is, should a delivery occur all of the fifth digits should indicate the delivery.”

In this case, although the patient was still in the antepartum period during initial care, she did deliver during that hospitalization. That means a fifth digit of “3” (antepartum condition or complication) is incompatible with a fifth digit of “1” (delivered, with or without mention of antepartum condition), which is probably what generated the denial message. You have 2 choices:

• Resubmit a corrected claim, indicating a fifth digit of “1” for both diagnostic codes
  
• Appeal the denial, indicating the diagnostic correction and supplying information regarding the additional care for this patient.
  

Bundle codes for repair of a pelvic floor defect?

Q. To treat a patient who has a pelvic floor defect, we performed an anterior repair, a posterior repair, and an enterocele repair, using mesh—plus cystoscopy. Does one code capture all these procedures?

A. I assume that you used mesh to augment the anterior and posterior repairs. A single CPT code, 57265 (combined anteroposterior colporrhaphy; with enterocele repair) captures the first 3 procedures, and CPT allows the addon mesh code 57267 (insertion of mesh or other prosthesis for repair of pelvic floor defect, each site [anterior, posterior compartment], vaginal approach) to be reported with 57265.

Based on the definition of the addon mesh code, it is appropriate for you to bill for a quantity of 2: 1 for the anterior compartment repair and 1 for the posterior compartment repair, which includes the rectocele and enterocele.

As for reporting the cystoscopy (with 52000 [cystourethroscopy (separate procedure)]), the reason that you provide for the procedure will determine whether you are reimbursed. There must be a medical indication for cystoscopy beyond your simply checking your work, which is considered a standard of surgical care by most payers.

Q. Recently, we were denied a claim for hospital care related to a patient’s premature labor. She was admitted to stop labor at 30 weeks but delivered 5 days after admission. The reason for denial? “Invalid ICD9 code.” But the code we used, 644.03 (threatened premature labor), appears to be correct. We also reported 644.21 (early onset of delivery) with the delivery code. Should we appeal, given that care prior to delivery is well documented?

A. I believe that your denial is based on incorrect use of the fifth digit on the reported diagnosis codes, not on refusal to reimburse separately for additional care before delivery. ICD9 guidelines related to fifth-digit coding for obstetric cases state:

“The fifth-digits, which are appropriate for each code number, are listed in brackets under each code. The fifth digits on each code should all be consistent with each other. That is, should a delivery occur all of the fifth digits should indicate the delivery.”

In this case, although the patient was still in the antepartum period during initial care, she did deliver during that hospitalization. That means a fifth digit of “3” (antepartum condition or complication) is incompatible with a fifth digit of “1” (delivered, with or without mention of antepartum condition), which is probably what generated the denial message. You have 2 choices:

• Resubmit a corrected claim, indicating a fifth digit of “1” for both diagnostic codes
  
• Appeal the denial, indicating the diagnostic correction and supplying information regarding the additional care for this patient.
  

Bundle codes for repair of a pelvic floor defect?

Q. To treat a patient who has a pelvic floor defect, we performed an anterior repair, a posterior repair, and an enterocele repair, using mesh—plus cystoscopy. Does one code capture all these procedures?

A. I assume that you used mesh to augment the anterior and posterior repairs. A single CPT code, 57265 (combined anteroposterior colporrhaphy; with enterocele repair) captures the first 3 procedures, and CPT allows the addon mesh code 57267 (insertion of mesh or other prosthesis for repair of pelvic floor defect, each site [anterior, posterior compartment], vaginal approach) to be reported with 57265.

Based on the definition of the addon mesh code, it is appropriate for you to bill for a quantity of 2: 1 for the anterior compartment repair and 1 for the posterior compartment repair, which includes the rectocele and enterocele.

As for reporting the cystoscopy (with 52000 [cystourethroscopy (separate procedure)]), the reason that you provide for the procedure will determine whether you are reimbursed. There must be a medical indication for cystoscopy beyond your simply checking your work, which is considered a standard of surgical care by most payers.

Lisdexamfetamine—FDA-approved to treat attention-deficit/hyperactivity disorder (ADHD) in children ages 6 to 12 (Table 1)—reduces ADHD symptoms during and after school and may be less likely to be abused than other psychostimulants, particularly immediate-release preparations, clinical data suggest.

Table 1

Lisdexamfetamine: Fast facts

Clinical implications

Because it is effective for about 12 hours, lisdexamfetamine might improve the child’s ability to complete homework and participate in extracurricular activities, which in turn might enhance academic performance and/or socialization skills.

Lisdexamfetamine could help the child with ADHD who shows no contraindications to the drug —particularly if he or she needs daylong coverage.

How it works

Lisdexamfetamine—a dextroamphetamine derivative—is rapidly absorbed and converted to dextroamphetamine, which is believed to exert therapeutic effect by:

• blocking norepinephrine and dopamine reuptake into presynaptic neurons
• increasing the neurotransmitters’ release into the extraneuronal space.

The medication’s amphetamine release is highly predictable, which contributes to its therapeutic benefit in ADHD. Amphetamine is released through GI metabolism of lisdexamfetamine, which produces the active d-amphetamine moiety that reaches the bloodstream. The medication is derived from d-amphetamine, with negligible amounts of lysine cleaved.

Lisdexamfetamine requires in vivo metabolism (in the GI tract) to its active constituent d-amphetamine. As a result, the medication will not produce high d-amphetamine blood levels—and should not cause euphoria or other reinforcing effects—if injected or snorted. Its abuse potential is lower overall compared with immediate-release psychostimulant formulations.

Pharmacokinetics

Dextroamphetamine’s plasma elimination half-life is approximately 9½ hours—which accounts for lisdexamfetamine’s extended action. The drug reaches steady-state concentrations in 2 to 3 days.

Food does not affect absorption and delays maximum concentration by 1 hour or less, so taking lisdexamfetamine during breakfast should not slow its therapeutic effect. Because dextroamphetamine reaches maximum concentration in approximately 3½ hours, the medication should take effect by the time the child gets to school. In one randomized, phase-2 trial, children with ADHD who received lisdexamfetamine, 30 to 70 mg/d, showed overall improvement within 2 hours after dosing.¹

Efficacy

Lisdexamfetamine reduced ADHD symptoms in 2 double-blind studies: a phase-2 crossover study and a phase-3 random-dose trial.

Phase-2 crossover study.² Fifty-two children ages 6 to 12 with combined or hyperactive-impulsive type ADHD received extended-release mixed amphetamine salts (MAS) for 3 weeks. Subjects received 10 mg/d or dosages titrated to 20 or 30 mg/d based on response to medication.

The youths then were divided into 3 groups based on optimal MAS dosage and received 3 treatments for 1 week each:

• group 1: placebo; MAS, 10 mg/d; lisdexamfetamine, 30 mg/d
• group 2: placebo; MAS, 20 mg/d; lisdexamfetamine, 50 mg/d
• group 3: placebo; MAS, 30 mg/d; lisdexamfetamine, 70 mg/d.

While taking lisdexamfetamine or MAS, subjects showed similar improvement in behavior, based on Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scores, and inattention, based on SKAMP and Permanent Product Measure of Performance scores.

Both psychostimulants outperformed placebo in both measures, and both improved behavior more decisively than inattention. Based on post-hoc analysis, improvement 12 hours after dosing was more substantial with lisdexamfetamine than with MAS.

Phase-3 random-dose trial.³ A total of 290 children ages 6 to 12 with combined or hyperactive-impulsive type ADHD were “washed out” from prior medications over 1 week, then received lisdexamfetamine or placebo for 4 weeks. Treatment-group children were started at 30 mg/d; some received dosages titrated at random to 50 or 70 mg/d in weekly 20-mg increments.

Over 4 weeks, ADHD Rating Scale Version IV (ADHD-RS-IV) scores fell 50% to 59% among the 3 lisdexamfetamine dosage groups, compared with a 15% reduction in the placebo group. Substantial ADHD-RS-IV score improvements after 1 week of lisdexamfetamine were maintained throughout the trial, suggesting the medication sustains ADHD symptom improvement. Controlled trials have not addressed lisdexamfetamine use >4 weeks, however.

Based on parents’ and guardians’ reports, treatment-group patients’ ADHD symptoms were notably less severe at 10 AM, 2 PM, and 6 PM compared with placebo-group children.³ This suggests that lisdexamfetamine offers a daylong therapeutic effect.

Tolerability

In the phase-3 study,³ 162 of 218 (74%) children receiving any dosage of lisdexamfetamine reported an adverse event, compared with 34 of 72 (47%) children in the placebo group. Overall, 39% of lisdexamfetamine-group patients reported decreased appetite. Also common were insomnia, headaches, irritability, upper abdominal pain, vomiting, and weight loss (Table 2).

Although most adverse events were mild to moderate, 9.2% of treatment-group children dropped out because of intolerability, compared with 1.4% of the placebo group. The investigators increased dosages quickly, regardless of efficacy or tolerability,³ which might have increased side-effect incidence among the treatment groups.

In the phase-2 crossover trial,² adverse event rates were similar among the lisdexamfetamine, extended-release MAS, and placebo groups (15% to 18%). Among youths receiving lisdexamfetamine, 8% reported insomnia and 6% reported appetite loss, compared with 2% and 4% of the MAS group, respectively.

Table 2

Rates of commonly reported adverse effects
during phase-3 lisdexamfetamine (LDX) study

Safety

Findling et al⁴ found a larger change in corrected QT interval with lisdexamfetamine (7 to 14 msec) than with extended-release MAS (5 to 10 msec) 5 and 10½ hours after dosing. The authors reasoned that these findings are atypical, and no children suffered serious adverse events during the trial. Nonetheless, more research on whether lisdexamfetamine increases cardiac risk is needed.

In a lethal-dose study in rats,⁵ oral lisdexamfetamine doses up to 1,000 mg/kg did not result in death, suggesting the medication might undergo saturation kinetics in the GI tract that may protect against overdose or abuse at higher dosages. By comparison, the median lethal oral dosage of d-amphetamine in rats was 96.8 mg/kg.⁵

Abuse potential

As with other psychostimulants indicated for ADHD, the Drug Enforcement Administration has classified lisdexamfetamine as a schedule II drug, which applies to addictive prescription-only medications with an accepted medical use.

Clinical data suggest, however, that lisdexamfetamine might be less “enjoyable”—and less likely to be abused intravenously, orally, or intranasally—than equipotent d-amphetamine. In an abuse liability study,⁶ 12 adults with histories of stimulant abuse received intravenous immediate-release (IR) d-amphetamine, 10 or 20 mg. Two days later, they received a comparable dose of IV lisdexamfetamine, 25 or 50 mg. The researchers found that:

• Plasma d-amphetamine peaked within 5 minutes after injection, compared with 2 to 3 hours after lisdexamfetamine dosing.
• Subjects who received IR d-amphetamine said they felt euphoria within 15 minutes of injection. By contrast, no one reported euphoria or amphetamine-like subjective effects after receiving lisdexamfetamine.

When asked which medication they would try again, 9 of 12 subjects chose IR d-amphetamine and 1 chose lisdexamfetamine.

In a double-blind, randomized, placebo-controlled study,⁷ oral lisdexamfetamine, 50 or 100 mg, was not more “likeable” than placebo. Subjects reported “liking” effects with 150 mg of lisdexamfetamine, however, suggesting the medication could be misused or abused at higher-than-therapeutic dosages.

Contraindications

As with other psychostimulants, do not give lisdexamfetamine to youths with preexisting serious structural cardiac abnormalities or other heart problems. Assess patient and family history of heart disease before prescribing this medication.

Do not prescribe lisdexamfetamine to patients taking a monoamine oxidase inhibitor (MAOI). By slowing amphetamine metabolism, these antidepressants intensify amphetamines’ effect on monoamine release, which can cause headaches and lead to hypertensive crisis. Before starting lisdexamfetamine, ask if the patient is taking an MAOI or has taken one within 2 weeks of presentation.

Use caution when prescribing lisdexamfetamine to patients with:

• a comorbid eating disorder or sleep disturbance. Determine whether to address the comorbidity before treating ADHD symptoms, and make sure lisdexamfetamine is not worsening the comorbid symptoms.
• untreated hypertension or other cardiovascular conditions, as stimulant medications can increase blood pressure and heart rate. Watch for significant heart rate and blood pressure changes in patients taking lisdexamfetamine, which probably would not cause sustained blood pressure increase in patients taking antihypertensives.⁸

Related resources

• Lisdexamfetamine Web site. www.vyvanse.com.

Drug brand names

• Extended-release mixed amphetamine salts • Adderall XR
• Lisdexamfetamine • Vyvanse

Disclosure

Dr. Wilens receives research/grant support from Abbott Laboratories, Eli Lilly and Company, National Institute on Drug Abuse, NeuroSearch, Ortho-McNeil, and Shire; is a speaker for Novartis Pharmaceuticals Corp., Ortho-McNeil, and Shire; and is a consultant to Abbott Laboratories, Eli Lilly and Company, GlaxoSmithKline, National Institute on Drug Abuse, Novartis Pharmaceuticals Corp., Ortho-McNeil, Pfizer, and Shire.

Lisdexamfetamine—FDA-approved to treat attention-deficit/hyperactivity disorder (ADHD) in children ages 6 to 12 (Table 1)—reduces ADHD symptoms during and after school and may be less likely to be abused than other psychostimulants, particularly immediate-release preparations, clinical data suggest.

Table 1

Lisdexamfetamine: Fast facts

Clinical implications

Because it is effective for about 12 hours, lisdexamfetamine might improve the child’s ability to complete homework and participate in extracurricular activities, which in turn might enhance academic performance and/or socialization skills.

Lisdexamfetamine could help the child with ADHD who shows no contraindications to the drug —particularly if he or she needs daylong coverage.

How it works

Lisdexamfetamine—a dextroamphetamine derivative—is rapidly absorbed and converted to dextroamphetamine, which is believed to exert therapeutic effect by:

• blocking norepinephrine and dopamine reuptake into presynaptic neurons
• increasing the neurotransmitters’ release into the extraneuronal space.

The medication’s amphetamine release is highly predictable, which contributes to its therapeutic benefit in ADHD. Amphetamine is released through GI metabolism of lisdexamfetamine, which produces the active d-amphetamine moiety that reaches the bloodstream. The medication is derived from d-amphetamine, with negligible amounts of lysine cleaved.

Lisdexamfetamine requires in vivo metabolism (in the GI tract) to its active constituent d-amphetamine. As a result, the medication will not produce high d-amphetamine blood levels—and should not cause euphoria or other reinforcing effects—if injected or snorted. Its abuse potential is lower overall compared with immediate-release psychostimulant formulations.

Pharmacokinetics

Dextroamphetamine’s plasma elimination half-life is approximately 9½ hours—which accounts for lisdexamfetamine’s extended action. The drug reaches steady-state concentrations in 2 to 3 days.

Food does not affect absorption and delays maximum concentration by 1 hour or less, so taking lisdexamfetamine during breakfast should not slow its therapeutic effect. Because dextroamphetamine reaches maximum concentration in approximately 3½ hours, the medication should take effect by the time the child gets to school. In one randomized, phase-2 trial, children with ADHD who received lisdexamfetamine, 30 to 70 mg/d, showed overall improvement within 2 hours after dosing.¹

Efficacy

Lisdexamfetamine reduced ADHD symptoms in 2 double-blind studies: a phase-2 crossover study and a phase-3 random-dose trial.

Phase-2 crossover study.² Fifty-two children ages 6 to 12 with combined or hyperactive-impulsive type ADHD received extended-release mixed amphetamine salts (MAS) for 3 weeks. Subjects received 10 mg/d or dosages titrated to 20 or 30 mg/d based on response to medication.

The youths then were divided into 3 groups based on optimal MAS dosage and received 3 treatments for 1 week each:

• group 1: placebo; MAS, 10 mg/d; lisdexamfetamine, 30 mg/d
• group 2: placebo; MAS, 20 mg/d; lisdexamfetamine, 50 mg/d
• group 3: placebo; MAS, 30 mg/d; lisdexamfetamine, 70 mg/d.

While taking lisdexamfetamine or MAS, subjects showed similar improvement in behavior, based on Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scores, and inattention, based on SKAMP and Permanent Product Measure of Performance scores.

Both psychostimulants outperformed placebo in both measures, and both improved behavior more decisively than inattention. Based on post-hoc analysis, improvement 12 hours after dosing was more substantial with lisdexamfetamine than with MAS.

Phase-3 random-dose trial.³ A total of 290 children ages 6 to 12 with combined or hyperactive-impulsive type ADHD were “washed out” from prior medications over 1 week, then received lisdexamfetamine or placebo for 4 weeks. Treatment-group children were started at 30 mg/d; some received dosages titrated at random to 50 or 70 mg/d in weekly 20-mg increments.

Over 4 weeks, ADHD Rating Scale Version IV (ADHD-RS-IV) scores fell 50% to 59% among the 3 lisdexamfetamine dosage groups, compared with a 15% reduction in the placebo group. Substantial ADHD-RS-IV score improvements after 1 week of lisdexamfetamine were maintained throughout the trial, suggesting the medication sustains ADHD symptom improvement. Controlled trials have not addressed lisdexamfetamine use >4 weeks, however.

Based on parents’ and guardians’ reports, treatment-group patients’ ADHD symptoms were notably less severe at 10 AM, 2 PM, and 6 PM compared with placebo-group children.³ This suggests that lisdexamfetamine offers a daylong therapeutic effect.

Tolerability

In the phase-3 study,³ 162 of 218 (74%) children receiving any dosage of lisdexamfetamine reported an adverse event, compared with 34 of 72 (47%) children in the placebo group. Overall, 39% of lisdexamfetamine-group patients reported decreased appetite. Also common were insomnia, headaches, irritability, upper abdominal pain, vomiting, and weight loss (Table 2).

Although most adverse events were mild to moderate, 9.2% of treatment-group children dropped out because of intolerability, compared with 1.4% of the placebo group. The investigators increased dosages quickly, regardless of efficacy or tolerability,³ which might have increased side-effect incidence among the treatment groups.

In the phase-2 crossover trial,² adverse event rates were similar among the lisdexamfetamine, extended-release MAS, and placebo groups (15% to 18%). Among youths receiving lisdexamfetamine, 8% reported insomnia and 6% reported appetite loss, compared with 2% and 4% of the MAS group, respectively.

Table 2

Rates of commonly reported adverse effects
during phase-3 lisdexamfetamine (LDX) study

Safety

Findling et al⁴ found a larger change in corrected QT interval with lisdexamfetamine (7 to 14 msec) than with extended-release MAS (5 to 10 msec) 5 and 10½ hours after dosing. The authors reasoned that these findings are atypical, and no children suffered serious adverse events during the trial. Nonetheless, more research on whether lisdexamfetamine increases cardiac risk is needed.

In a lethal-dose study in rats,⁵ oral lisdexamfetamine doses up to 1,000 mg/kg did not result in death, suggesting the medication might undergo saturation kinetics in the GI tract that may protect against overdose or abuse at higher dosages. By comparison, the median lethal oral dosage of d-amphetamine in rats was 96.8 mg/kg.⁵

Abuse potential

As with other psychostimulants indicated for ADHD, the Drug Enforcement Administration has classified lisdexamfetamine as a schedule II drug, which applies to addictive prescription-only medications with an accepted medical use.

Clinical data suggest, however, that lisdexamfetamine might be less “enjoyable”—and less likely to be abused intravenously, orally, or intranasally—than equipotent d-amphetamine. In an abuse liability study,⁶ 12 adults with histories of stimulant abuse received intravenous immediate-release (IR) d-amphetamine, 10 or 20 mg. Two days later, they received a comparable dose of IV lisdexamfetamine, 25 or 50 mg. The researchers found that:

• Plasma d-amphetamine peaked within 5 minutes after injection, compared with 2 to 3 hours after lisdexamfetamine dosing.
• Subjects who received IR d-amphetamine said they felt euphoria within 15 minutes of injection. By contrast, no one reported euphoria or amphetamine-like subjective effects after receiving lisdexamfetamine.

When asked which medication they would try again, 9 of 12 subjects chose IR d-amphetamine and 1 chose lisdexamfetamine.

In a double-blind, randomized, placebo-controlled study,⁷ oral lisdexamfetamine, 50 or 100 mg, was not more “likeable” than placebo. Subjects reported “liking” effects with 150 mg of lisdexamfetamine, however, suggesting the medication could be misused or abused at higher-than-therapeutic dosages.

Contraindications

As with other psychostimulants, do not give lisdexamfetamine to youths with preexisting serious structural cardiac abnormalities or other heart problems. Assess patient and family history of heart disease before prescribing this medication.

Do not prescribe lisdexamfetamine to patients taking a monoamine oxidase inhibitor (MAOI). By slowing amphetamine metabolism, these antidepressants intensify amphetamines’ effect on monoamine release, which can cause headaches and lead to hypertensive crisis. Before starting lisdexamfetamine, ask if the patient is taking an MAOI or has taken one within 2 weeks of presentation.

Use caution when prescribing lisdexamfetamine to patients with:

• a comorbid eating disorder or sleep disturbance. Determine whether to address the comorbidity before treating ADHD symptoms, and make sure lisdexamfetamine is not worsening the comorbid symptoms.
• untreated hypertension or other cardiovascular conditions, as stimulant medications can increase blood pressure and heart rate. Watch for significant heart rate and blood pressure changes in patients taking lisdexamfetamine, which probably would not cause sustained blood pressure increase in patients taking antihypertensives.⁸

Related resources

• Lisdexamfetamine Web site. www.vyvanse.com.

Drug brand names

• Extended-release mixed amphetamine salts • Adderall XR
• Lisdexamfetamine • Vyvanse

Disclosure

Dr. Wilens receives research/grant support from Abbott Laboratories, Eli Lilly and Company, National Institute on Drug Abuse, NeuroSearch, Ortho-McNeil, and Shire; is a speaker for Novartis Pharmaceuticals Corp., Ortho-McNeil, and Shire; and is a consultant to Abbott Laboratories, Eli Lilly and Company, GlaxoSmithKline, National Institute on Drug Abuse, Novartis Pharmaceuticals Corp., Ortho-McNeil, Pfizer, and Shire.

Lisdexamfetamine—FDA-approved to treat attention-deficit/hyperactivity disorder (ADHD) in children ages 6 to 12 (Table 1)—reduces ADHD symptoms during and after school and may be less likely to be abused than other psychostimulants, particularly immediate-release preparations, clinical data suggest.

Table 1

Lisdexamfetamine: Fast facts

Clinical implications

Because it is effective for about 12 hours, lisdexamfetamine might improve the child’s ability to complete homework and participate in extracurricular activities, which in turn might enhance academic performance and/or socialization skills.

Lisdexamfetamine could help the child with ADHD who shows no contraindications to the drug —particularly if he or she needs daylong coverage.

How it works

Lisdexamfetamine—a dextroamphetamine derivative—is rapidly absorbed and converted to dextroamphetamine, which is believed to exert therapeutic effect by:

• blocking norepinephrine and dopamine reuptake into presynaptic neurons
• increasing the neurotransmitters’ release into the extraneuronal space.

The medication’s amphetamine release is highly predictable, which contributes to its therapeutic benefit in ADHD. Amphetamine is released through GI metabolism of lisdexamfetamine, which produces the active d-amphetamine moiety that reaches the bloodstream. The medication is derived from d-amphetamine, with negligible amounts of lysine cleaved.

Lisdexamfetamine requires in vivo metabolism (in the GI tract) to its active constituent d-amphetamine. As a result, the medication will not produce high d-amphetamine blood levels—and should not cause euphoria or other reinforcing effects—if injected or snorted. Its abuse potential is lower overall compared with immediate-release psychostimulant formulations.

Pharmacokinetics

Dextroamphetamine’s plasma elimination half-life is approximately 9½ hours—which accounts for lisdexamfetamine’s extended action. The drug reaches steady-state concentrations in 2 to 3 days.

Food does not affect absorption and delays maximum concentration by 1 hour or less, so taking lisdexamfetamine during breakfast should not slow its therapeutic effect. Because dextroamphetamine reaches maximum concentration in approximately 3½ hours, the medication should take effect by the time the child gets to school. In one randomized, phase-2 trial, children with ADHD who received lisdexamfetamine, 30 to 70 mg/d, showed overall improvement within 2 hours after dosing.¹

Efficacy

Lisdexamfetamine reduced ADHD symptoms in 2 double-blind studies: a phase-2 crossover study and a phase-3 random-dose trial.

Phase-2 crossover study.² Fifty-two children ages 6 to 12 with combined or hyperactive-impulsive type ADHD received extended-release mixed amphetamine salts (MAS) for 3 weeks. Subjects received 10 mg/d or dosages titrated to 20 or 30 mg/d based on response to medication.

The youths then were divided into 3 groups based on optimal MAS dosage and received 3 treatments for 1 week each:

• group 1: placebo; MAS, 10 mg/d; lisdexamfetamine, 30 mg/d
• group 2: placebo; MAS, 20 mg/d; lisdexamfetamine, 50 mg/d
• group 3: placebo; MAS, 30 mg/d; lisdexamfetamine, 70 mg/d.

While taking lisdexamfetamine or MAS, subjects showed similar improvement in behavior, based on Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scores, and inattention, based on SKAMP and Permanent Product Measure of Performance scores.

Both psychostimulants outperformed placebo in both measures, and both improved behavior more decisively than inattention. Based on post-hoc analysis, improvement 12 hours after dosing was more substantial with lisdexamfetamine than with MAS.

Phase-3 random-dose trial.³ A total of 290 children ages 6 to 12 with combined or hyperactive-impulsive type ADHD were “washed out” from prior medications over 1 week, then received lisdexamfetamine or placebo for 4 weeks. Treatment-group children were started at 30 mg/d; some received dosages titrated at random to 50 or 70 mg/d in weekly 20-mg increments.

Over 4 weeks, ADHD Rating Scale Version IV (ADHD-RS-IV) scores fell 50% to 59% among the 3 lisdexamfetamine dosage groups, compared with a 15% reduction in the placebo group. Substantial ADHD-RS-IV score improvements after 1 week of lisdexamfetamine were maintained throughout the trial, suggesting the medication sustains ADHD symptom improvement. Controlled trials have not addressed lisdexamfetamine use >4 weeks, however.

Based on parents’ and guardians’ reports, treatment-group patients’ ADHD symptoms were notably less severe at 10 AM, 2 PM, and 6 PM compared with placebo-group children.³ This suggests that lisdexamfetamine offers a daylong therapeutic effect.

Tolerability

In the phase-3 study,³ 162 of 218 (74%) children receiving any dosage of lisdexamfetamine reported an adverse event, compared with 34 of 72 (47%) children in the placebo group. Overall, 39% of lisdexamfetamine-group patients reported decreased appetite. Also common were insomnia, headaches, irritability, upper abdominal pain, vomiting, and weight loss (Table 2).

Although most adverse events were mild to moderate, 9.2% of treatment-group children dropped out because of intolerability, compared with 1.4% of the placebo group. The investigators increased dosages quickly, regardless of efficacy or tolerability,³ which might have increased side-effect incidence among the treatment groups.

In the phase-2 crossover trial,² adverse event rates were similar among the lisdexamfetamine, extended-release MAS, and placebo groups (15% to 18%). Among youths receiving lisdexamfetamine, 8% reported insomnia and 6% reported appetite loss, compared with 2% and 4% of the MAS group, respectively.

Table 2

Rates of commonly reported adverse effects
during phase-3 lisdexamfetamine (LDX) study

Safety

Findling et al⁴ found a larger change in corrected QT interval with lisdexamfetamine (7 to 14 msec) than with extended-release MAS (5 to 10 msec) 5 and 10½ hours after dosing. The authors reasoned that these findings are atypical, and no children suffered serious adverse events during the trial. Nonetheless, more research on whether lisdexamfetamine increases cardiac risk is needed.

In a lethal-dose study in rats,⁵ oral lisdexamfetamine doses up to 1,000 mg/kg did not result in death, suggesting the medication might undergo saturation kinetics in the GI tract that may protect against overdose or abuse at higher dosages. By comparison, the median lethal oral dosage of d-amphetamine in rats was 96.8 mg/kg.⁵

Abuse potential

As with other psychostimulants indicated for ADHD, the Drug Enforcement Administration has classified lisdexamfetamine as a schedule II drug, which applies to addictive prescription-only medications with an accepted medical use.

Clinical data suggest, however, that lisdexamfetamine might be less “enjoyable”—and less likely to be abused intravenously, orally, or intranasally—than equipotent d-amphetamine. In an abuse liability study,⁶ 12 adults with histories of stimulant abuse received intravenous immediate-release (IR) d-amphetamine, 10 or 20 mg. Two days later, they received a comparable dose of IV lisdexamfetamine, 25 or 50 mg. The researchers found that:

• Plasma d-amphetamine peaked within 5 minutes after injection, compared with 2 to 3 hours after lisdexamfetamine dosing.
• Subjects who received IR d-amphetamine said they felt euphoria within 15 minutes of injection. By contrast, no one reported euphoria or amphetamine-like subjective effects after receiving lisdexamfetamine.

When asked which medication they would try again, 9 of 12 subjects chose IR d-amphetamine and 1 chose lisdexamfetamine.

In a double-blind, randomized, placebo-controlled study,⁷ oral lisdexamfetamine, 50 or 100 mg, was not more “likeable” than placebo. Subjects reported “liking” effects with 150 mg of lisdexamfetamine, however, suggesting the medication could be misused or abused at higher-than-therapeutic dosages.

Contraindications

As with other psychostimulants, do not give lisdexamfetamine to youths with preexisting serious structural cardiac abnormalities or other heart problems. Assess patient and family history of heart disease before prescribing this medication.

Do not prescribe lisdexamfetamine to patients taking a monoamine oxidase inhibitor (MAOI). By slowing amphetamine metabolism, these antidepressants intensify amphetamines’ effect on monoamine release, which can cause headaches and lead to hypertensive crisis. Before starting lisdexamfetamine, ask if the patient is taking an MAOI or has taken one within 2 weeks of presentation.

Use caution when prescribing lisdexamfetamine to patients with:

• a comorbid eating disorder or sleep disturbance. Determine whether to address the comorbidity before treating ADHD symptoms, and make sure lisdexamfetamine is not worsening the comorbid symptoms.
• untreated hypertension or other cardiovascular conditions, as stimulant medications can increase blood pressure and heart rate. Watch for significant heart rate and blood pressure changes in patients taking lisdexamfetamine, which probably would not cause sustained blood pressure increase in patients taking antihypertensives.⁸

Related resources

• Lisdexamfetamine Web site. www.vyvanse.com.

Drug brand names

• Extended-release mixed amphetamine salts • Adderall XR
• Lisdexamfetamine • Vyvanse

Disclosure

Dr. Wilens receives research/grant support from Abbott Laboratories, Eli Lilly and Company, National Institute on Drug Abuse, NeuroSearch, Ortho-McNeil, and Shire; is a speaker for Novartis Pharmaceuticals Corp., Ortho-McNeil, and Shire; and is a consultant to Abbott Laboratories, Eli Lilly and Company, GlaxoSmithKline, National Institute on Drug Abuse, Novartis Pharmaceuticals Corp., Ortho-McNeil, Pfizer, and Shire.