Your SlideShare is downloading. ×
Bipolar disorder
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Bipolar disorder

179
views

Published on


0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
179
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
6
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Bipolar Disorder All questions, unless otherwise indicated, are from “PracticeGuideline for the Treatment of Patients with Bipolar Disorder, Second Edition, AJP, April 2003 Supplement. Or fromGoodwin and Jamison’s MANIC-DEPRESSIVE ILLNESS, 2ND Edition, 2007As of 30Mar2007. Next update of this PowerPoint is due onMay 31, 2007.
  • 2. Bipolar - DSM• Q. What are the four major DSM-IV-TR types of bipolar disorders? [Don’t spend time on this one, it is just to get us started.]
  • 3. Bipolar disorder, types• Ans.• -- Bipolar I disorder [with subtypes of most recent episode: hypomanic, manic, mixed, depressed, or unspecified]• -- Bipolar II disorder [with subtypes of most recent episode hypomanic or depressed]• -- Cyclothymic disorder• -- Bipolar, NOS• DSM-IV-TR, p 20.
  • 4. Bipolar – DSM criteria for manic episode• Q. What are the symptoms of a manic episode? List the required one, then list the seven of which 3 or 4 are required.
  • 5. Manic episode criteria• Criteria:• A. At least one week of abnormally elevated, expansive, or irritable mood.• B. In addition to “A” during that week or more: 3 of the those listed on the next slide [4 if “irritability” is all of “A”]• C. Not part of another disorder or illness.• Continued on next slide
  • 6. Manic episode criteria - 2• Elements of “B”:• -- grandiose• -- decrease need for sleep• -- talkative• -- flight of ideas• -- distractibility• -- increase in goal-directed activity or psychomotor agitation• -- excessive involvement in activity is likely to have untoward results [e.g., buying sprees]DSM-IV-TR, 362
  • 7. Criteria for depressive episode• Q. What are nine symptoms that form the criteria for depressive episode?
  • 8. Depressive episode criteria - 1• Criteria, two weeks or more of five or more of the following -- and not part of another disorder:• 1. sad [irritable counts in children]• 2. diminished interest in activities.• 3. weight loss or gain• 4. insomnia or hypersomnia• continued
  • 9. Depressive episode criteria - 2• 5. psychomotor agitation or retardation.• 6. anergy• 7. feelings of worthlessness or guilt• 8. difficulty concentration• 9. recurrent thoughts of death or suicidalDSM-IV-TR, P 356
  • 10. Dx criteria for hypomania• Q. What is the criteria for hypomania?
  • 11. Criteria for hypomania• Ans.• Same as manic episode except – Only has to be for 4 days – Is not severe enough to cause social or occupational/educational impairment. – Others have observed the symptoms, i.e., can’t be based on pt’s word alone [often a forgotten point by Board candidates]. DSM-IV-TR, P 368
  • 12. Criteria for mixed episode• Q. What is criteria for mixed episode?
  • 13. Criteria for mixed episode• Ans. At least one week of meeting both the signs of depressive episode and manic episode.DSM-IV-TR, 365
  • 14. Criteria for cyclothymic disorder• Q. What is the criteria for cyclothymic disorder?
  • 15. Criteria for cyclothymia• Ans.• 1. At least two years of numerous hypomanic episodes and numerous depressive episodes not severe enough to meet criteria of depressive episode [one year for kids].• 2. Not part of another disorder.DSM-IV-TR, 400
  • 16. Criteria for catatonic specifier• Q. What are the criteria for the catatonic specifier?
  • 17. Criteria for catatonic specifier• At least two of the following:• 1. motoric immobility• 2. excessive motor activity• 3. negativism• 4. stereotyped behaviors• 5. echolalia or echopraxia[same as when “catatonia” is applied to schizophrenia]DSM-IV-TR, 418
  • 18. Criteria for Melancholia• Q. What are criteria for melancholia?
  • 19. Criteria for melancholia - 1• Ans. Two sets of signs:• 1. Either loss of please in almost all activities or does not feel pleasure even when something good happens• 2. Three or more of the six signs on the next slide
  • 20. Criteria for melancholia - 2• Continued, 3 or more of 6:• 1. Sadness is distinctly different than sadness associated with tragic events of the past.• 2. Sadness worse in the morning• 3. Early morning awaking• 4. Psychomotor retardation or agitation• 5. Anorexia or weight loss• 6. Excessive guiltDSM-IV-TR, 420
  • 21. Criteria for Atypical• Q. What is the criteria for the Atypical specifier?
  • 22. Criteria for atypical• Ans.• 1. Mood brightens with positive events.• 2. At least two of the following: – Weight gain – Hypersomnia – Laden paralysis – Hyper rejection sensitivity DSM-IV-TR, 422
  • 23. Criteria for postpartum specifier• Q. What is the criteria for the postpartum specifier?
  • 24. Criteria for postpartum specifier• Ans. Onset of episode within 4 weeks of delivery.DSM-IV-TR, 423
  • 25. Criteria for seasonal pattern• Q. What is criteria for seasonal pattern specifier?
  • 26. Criteria for seasonal pattern specifier• Ans. For at least two years:• 1. onset of mood episode has a temporal relationship, e.g., each October.• 2. no episodes other than those with a temporal episode.DSN-IV-TR, 427
  • 27. “Chronic”• Q. With mood disorders, “chronic” means?
  • 28. “Chronic”• Ans. Criteria have been met continuously for at least two years.• [Two years is also the way “chronic” is used in schizophrenia, although not part of DSM-IV-TR, “chronic” is part of the current ICD-9-CM for schizophrenia. For adjustment disorders, “chronic” is for 6 months. For PTSD, “chronic” is for 3 months.}DSM-IV-TR, 417
  • 29. Prevalence• Q. Prevalence of Bipolar I and II in the general population?
  • 30. Prevalence• Ans. 3.8%• [DSM-IV-TR: Bipolar I: 1%, Bipolar II: 0.5%]Ref: Hirschfield RMA: Guideline Watch: Practice Guideline for the Treatment of Patients with Bipolar Disorder. Arlington, VA: American Psychiatric Association. Hereafter: “Watch.”
  • 31. Co-morbidityQ. Most common co-morbid psychiatric disorder?
  • 32. Co-morbidityAns. Alcohol abuse.G&R [=Goodwin and Jamison], p 225
  • 33. gender• Q. Gender breakdown of bipolar disorder?• Give general breakdown, then which episode do men tend to have first? Which do women? Which has more rapid cycling?
  • 34. Gender• Ans.-- about equal generally, but some differences.-- men more likely to have a first episode of mania.-- women more likely have a first episode be depression.-- women more likely to rapid cycle.DSM-IV-TR, p 385
  • 35. Quality of life• Q. Does manic episodes or depressive episodes have the greatest impact on quality of life and duration of symptoms?
  • 36. Quality of life• Ans. Depressive episodes have the greatest negative impact on quality of life and have the longer duration.• Source: APA Watch on bipolar.
  • 37. Suicide• Q. Suicide rate among bipolar I disordered?
  • 38. Suicide• Ans. 10-15%
  • 39. Suicide• Q. What two phases of bipolar disorder have the high suicide rates -- manic, depressed or mixed?
  • 40. Suicide• Ans.• 1] depressive episodes• 2] mixed episodes
  • 41. Suicide risk factors• Q. List symptoms/signs that are associated with increased risk of suicide in bipolar I pts?
  • 42. Suicide risks• Ans. Practice Guideline lists:• -- agitation• -- pervasive insomnia• -- impulsiveness• -- psychosis [especially command hallucinations]*[Despite research that questions the lethality of command hallucinations, this wording is in the Guideline.]
  • 43. Suicide risks• Q. What co-morbid psychiatric disorders increase the risk of suicide in bipolars?
  • 44. Suicide risks• Ans. Practice Guideline lists:• -- Substance-related disorders• -- Personality disorders
  • 45. Med associated with suicide reduction• Q. What med has the clearest evidence of reducing suicides?
  • 46. Med associated with suicide reduction• Ans. Li.
  • 47. Secondary mania neurological disorders• Q. What neurological disorders are associated with secondary mania?
  • 48. Secondary mania neurological disorders• Ans. Practice guidelines mentions:• -- MS• -- lesions involving right-side subcortical areas.• -- lesions close to limbic system,
  • 49. Secondary mania substances• Q. What meds are associated with secondary mania [not asking about antidepressants]?
  • 50. Secondary mania substances• Ans. Practice guideline lists:• -- L-Dopa• -- corticosteroids
  • 51. Hospitalization• Q. Under what conditions should a person with bipolar disorder be hospitalized?
  • 52. Hospitalization• Ans.• 1. A threat to harm self or others• 2. Severely ill and lack social support• 3. Severely ill and significantly impaired judgment.• 4. Has another complicating medical [including psychiatric] illness.• 5. Has not responded to outpt treatment.
  • 53. Daily activities• Q. As to daily activities, what should be advised to pt and family?
  • 54. Daily activities• Ans. Regular patterns for eating, physical activities, social stimulation, and sleep are important.
  • 55. Meds for severe mania or mixed type• Q. What meds are recommended for first episode of severe mania or mixed episode?
  • 56. Meds• Ans. Two correct answers• Li and an antipsychotic• Valproate and an antipsychotic
  • 57. Meds• Q. First break mania, mild or moderately ill, list medication options. List FDA approved.
  • 58. Meds• Ans. Practice guidelines uses a lot of “may” as to mild or moderate manic episodes:• -- Li• -- valproate• -- atypical antipsychotic• -- carbamazepine or oxcarbazepine[FDA’s list: aripiprazole, chlorpromazine, Li, olanzapine, quetiapine, risperidone, valproate, and ziprasidone]
  • 59. Li and antipsychoticQ. You’ve placed your pt with mania on Li and she is no better, after two week. You add ziprasidone and still not better five days later. What to do?
  • 60. Li and antipsychoticAns. Add an anticonvulsant mood stabilizer.G & J, p 729
  • 61. Benzodiazepines• Q. Role of benzodiazepines in manic or mixed episodes?
  • 62. Benzodiazepines• Ans. As an adjunct and for only a short time. G & J use for insomnia to get the pt’s sleep pattern normal.
  • 63. Antidepressants• Q. What should be the approach to a pt on antidepressants and treating that pt’s first- break manic episode?
  • 64. Antidepressants• Ans. The antidepressant should be tapered and discontinued if practical.
  • 65. “breakthrough”• Q. How to manage breakthrough manic or mixed episode? By “breakthrough,” we mean that the pt was on a maintenance med or meds and now has a manic episode.
  • 66. breakthrough• Ans.• 1. Check serum levels to see if the pt is in therapeutic levels and consider higher levels that are still with acceptable levels, e.g. valproate at 90, consider pushing to 120..• 2. Consider adding an antipsychotic• 3. Consider short-term use of a benzodiazepine, especially if very agitated.
  • 67. Inadequate Response• Q. If first choice med fails to develop an adequate in a manic or mixed pt in two weeks, what to do? [Ans. has five general categories.]
  • 68. Inadequate response• Ans. Consider: – Another first line med – Adding an antipsychotic if not already using. If using, consider switching to another antipsychotic. – Adding carbamazepine/oxcarbazepine – Clozapine [Practice Guideline wording not clear, but apparently as an addition] – ECT
  • 69. ECT• Q. When is ECT an especially attractive option in the manic or mixed pt?
  • 70. ECT• A. Attractive when:• 1] Mania very severe and not responding to meds.• 2] Pt prefers ECT• 3] Pregnant• 4] Psychotic signs prominent.• [not listed, but catatonic or suicidal are probably correct answers too]
  • 71. Acute depression• Q. First line management of acute depression in bipolar?
  • 72. Acute depression• Ans. Three: Li, lamotrigine or olanzapine- fluoxetine combination.[Ref: Watch]
  • 73. SSRIs• Q. What about SSRIs for depressive episode?
  • 74. SSRIs• Ans. Not recommended as monotherapy. May be useful as an adjunct to a mood stabilizer, but mood stabilizers are first choice.• [Tertiary centers for bipolar disorders find they have to use an antidepressant with about a fifth of their pts.]
  • 75. Acute depression• Q. What about ECT?
  • 76. Acute depression• Ans. ECT is useful for:• 1] life-threatening inanition• 2] suicidal• 3] psychotic• 4] pregnant
  • 77. Acute depression• Q. What about psychotherapy?
  • 78. Acute depression• Ans.• In addition to meds – not as solo, interpersonal or CBT has empirical basis.• Psychodynamic is frequently used but lacks controlled studies.
  • 79. Breakthrough depression• Q. Bipolar pt on maintenance meds and has breakthrough depression. What to do?
  • 80. Breakthrough depression• Ans. First, ensure serum levels of meds are at high therapeutic range.
  • 81. Breakthrough depression• Q. If serum levels of the mood stabilizers are at a high therapeutic level and still depressed? [“Breakthrough depression” = bipolar pt who was on maintenance mood stabilizer as adequate levels. List three general choices.]
  • 82. breakthrough depression• Ans. Three general choices.• 1] Add antidepressant: SSRI/venlafaxine/bupropion or MAOI or• 2] If psychotic, add antipsychotic [probably an acceptable choice even if not psychotic], or• 3] ECT
  • 83. Still depressed• Q. When to consider ECT?
  • 84. Still depressed, ECT• Ans. ECT when:• -- medication resistant• -- psychotic signs• -- catatonic features
  • 85. Rapid cycling• Q. What is definition of rapid cycling?
  • 86. Rapid cycling• Ans. 4 or more episodes/year and there has been two months of remission or partial between episodes. Hypomanic episodes count. Rapid cycling also can mean switching from one polarity to the opposite without the two months of remission or partial remission.
  • 87. Rapid cycling• Q. Identify two conditions that can lead to rapid cycling.
  • 88. Rapid cycling• Ans. There are lots, and the Practice Guideline lists two that may be among the examination’s choices• -- substances, including alcohol• -- hypothyroidism
  • 89. Rapid cycling• Q. Meds for rapid cycling?
  • 90. Rapid cycling - medsMeds for rapid cycling:• Li• Valproate or• Lamotrigine
  • 91. Rapid cycling• Q. Rapid cycling pt doesn’t respond to your initial med selection, so what next?
  • 92. Rapid cycling• Ans. Two choices?• -- Add another mood stabilizer• Or• -- Add an antipsychotic• [While not mentioned by Guideline, ECT is also an acceptable answer]
  • 93. Catatonic signs• Q. Which phase has catatonic signs and of what signs do they commonly consist?
  • 94. Catatonic signs• Ans. More common in manic episodes and consist of motor excitement, mutism, and stereotypic movements.
  • 95. Catatonic• Q. Treatment choice for bipolar with catatonia?
  • 96. Catatonia• Ans. While ECT is most efficacious, Practice Guideline seems to imply trying a benzodiazepine first.
  • 97. Maintenance• Q. Preferred meds for the maintenance [stable] phase?
  • 98. Maintenance• Ans.• Treatments with the most empirical support are Li and valproate.• Possible alternatives are lamotrigine, olanzapine, carbamazepine of oxcarbazepine.Watch provides additional support for lamotrigine and olanzapine.
  • 99. Maintenance - ECT• Q. ECT?
  • 100. Maintenance - ECT• Ans. Maintenance ECT should be consider for those pts whose stabilization was achieved with ECT. [In discussing this, keep in mind that outpt ECT, like meds, has high non-compliance.]
  • 101. Maintenance - Antipsychotics• Q. Role of antipsychotics for maintenance?
  • 102. Maintenance - antipsychotics• Ans. Not easy to answer. Practice Guidelines says they should be discontinued unless they have been shown with a pt to be needed to prevent relapse or to prevent psychotic features.• APA Watch on bipolar suggests that olanzapine is OK for maintenance, and is clear in saying that typical antipsychotics are not desirable. Other atypicals are listed for maintenance [e.g., Stephen Stahl’s Prescription Guide].
  • 103. Maintenance - psychotherapies• Q. Role of psychotherapies. If a role, which are used?
  • 104. Maintenance - psychotherapies• A. Supportive and psychodynamic therapies are commonly used in addition to the meds. CBT has been shown to reduce number of exacerbations.
  • 105. Maintenance – group therapies• Q. During maintenance, is group therapies used and, if so, for what purpose?
  • 106. Maintenance – group therapy• Ans. Supportive groups are used to educate as to: – Information about the illness – Adherence strategies – Address enhancing self-esteem – Adaptation to having a chronic illness – Management of psychosocial issues, e.g. job related issues
  • 107. Maintenance – family therapy• Q. Family therapy in the maintenance phase is used to?
  • 108. Maintenance – family therapy• A. Same as the issues listed for group psychotherapy supra.
  • 109. Maintenance - problems• A. If the pt is still having subthreshold symptoms or breakthrough manic or depression, what to do?
  • 110. Maintenance - problems• A. Consider:• -- adding another mood stabilizer• -- adding an atypical antipsychotic• -- adding an antidepressant if the mood breakthrough is depressive signs.• -- adding maintenance ECT
  • 111. Li - workup• Q. What is the workup for Li?
  • 112. Li - workup• A.• 1] general medical hx and physical exam.• 2] BUN and creatinine level• 3] Thyroid function• 4] > 40 years old, EKG• 5] Women in child bearing age, pregnancy test
  • 113. Li - dosing• Q. What is typical Li dosing?
  • 114. Li - dosing• A. Usually start at 300 mg tid or even lower and gradually increase until control of signs is reached of blood level gets to about 1.0
  • 115. Li – blood levels• Q. When to check blood levels?
  • 116. Li – blood levels• A. Check with each increase in dosing, but keep in mind that it takes 5 days before the new level plateaus.• B. After desired level is reached, check every 6 months.• C. Check when there is a significant change in signs or symptoms.
  • 117. Li – renal function• Q. How often to check renal function?
  • 118. Li – renal function• A. Every 6 to 12 months.
  • 119. Li – thyroid function• Q. How often should one check thyroid function?
  • 120. Li – thyroid function• Ans. Every 6 to 12 months.
  • 121. Alcohol and Li• Q. Alcohol dehydration does what to the Li blood level?
  • 122. Alcohol and Li• Ans. Alcohol dehydration can raise Li to toxic levels
  • 123. Valproate – work up• Q. Work up for valproate?
  • 124. Valproate – work up• Ans.• 1. general medical hx with attention to hepatic, hematological and bleeding abnormalities• 2. Obtain liver function tests• 3. Obtain hematological measures
  • 125. Valproate - dosing• Q. What is typical dosing?
  • 126. Valproate - dosing• Ans.• For hospitalized inpts in manic phase, 20- 30 mg/kilo, aiming for blood level of 50 - 125.• B. For outpts, 250 mg tid and go up slowly aiming for blood level of 50 – 125.
  • 127. Valproate - ER• Q. How does Extended Release valproate compare to immediate release in terms of blood level of the med?
  • 128. Valproate - ER• A. ER tends to achieve blood level about 15% lower than immediate release.
  • 129. Valproate – lab tests• Q. If pt is stable on valproate, what lab tests are still indicated and how often?
  • 130. Valproate – lab tests• Ans. Test hematology and hepatic functions every 6 months.
  • 131. Valproate & lamotrigine• Q. Pt on valproate and you want to add lamotrigine. What dose of lamotrigine is advised?
  • 132. Valproate & lamotrigine• A. Since valproate inhibits lamotrigine metabolism, begin lamotrigine at half the usual doses.
  • 133. Lamotrigine – Stevens-Johnson• Q. Frequency of Stevens-Johnson, in children? In adults?
  • 134. Lamotrigine – Stevens-Johnson• Q. 1% in children. 0.3% in adults in the use in pts with epilepsy. Rate has been less in psychiatry with bipolar adults when used as monotherapy: 0.08%. When used as an adjunctive med: 0.13%.
  • 135. Lamotrigine – worrisome rash• Q. Signs that make the rash worrisome include?
  • 136. rash - worrisome• A. Worrisome if: – Fever – Sore throat – Rash is diffuse and wide-spread – Prominent facial and mucosal involvement
  • 137. Rash - worrisome• Q. What to do if worrisome? What if the pt is on both lamotrigine and valproate?
  • 138. Rash - worrisome• A. Discontinue lamotrigine. If on both, discontinue both.
  • 139. Lamotrigine dosing• Q. What is typical lamotrigine dosing?
  • 140. Lamotrigine dosing• A. 25 mg/d for 2 weeks, then increase 25 mg every two weeks until desired clinical results or reach 200 mg/d. [With valproate, would be ½ that.]
  • 141. Lamotrigine & carbamazepine• Q. Lamotrigine doses when combined with carbamazepine?
  • 142. Lamotrigine & carbamazepine• A. Carbamazepine increases metabolism of lamotrigine, so will need to use increased doses of lamotrigine.
  • 143. Carbamazepine – work up• Q. What is the expected work up for carbamazepine?
  • 144. Carbamazepine – work up• Ans. – Hematological – Liver function – Renal function – Electrolytes
  • 145. ElectrolytesQ. What is the worry as to electrolytes?
  • 146. Carbamazepine - electrolytes• Ans. hyponatremia
  • 147. Oral contraceptives• Q. What does carbamazepine, oxcarbazepine and topiramate do the metabolism of oral contraceptives?
  • 148. Oral contraceptives• Ans. Increases the metabolism and reduces their effectiveness.
  • 149. Pregnancy - Li• Q. Your pt on Li becomes pregnant. Your advice should include?
  • 150. Pregnancy - Li• Ans. While wording, obviously varies from pt to pt, the facts are that Ebstein’s anomaly is 10-20 times more common if on Li during first trimester. Discontinuing Li, especially rapidly, however, increases chance of return of bipolar episodes.
  • 151. Ebstein’s anomaly• Q. What is Ebstein’s anomaly?
  • 152. Ebstein’s anomaly• Ans. Congenital downward displacement of the tricuspid valve into the right ventricle.[PDR Medical Dictionary, 1995, p 94]
  • 153. Pregnancy - valproate• Q. What abnormalities are associated with valproate during first trimester?
  • 154. Pregnancy - valproate• Ans.• neural tube defects*• craniofacial abnormalities• limb abnormalities• cardiac defects* Probable the focus of an examiner’s question.
  • 155. Pregnancy - carbamazepine• Q. Associated with carbamazepine exposure?
  • 156. Pregnancy - carbamazepine• Ans.• -- neural tube defects, first trimester• -- craniofacial abnormalities
  • 157. Antidepressant meds – teratogenic• Q. Which antidepressant meds have been shown to be teratogenic?
  • 158. Antidepressant meds – teratogenic• Ans. None, including tricyclics, have been shown to be teratogenic.
  • 159. Pregnancy – antipsychotics• Q. What, if any, antipsychotics are recommended during pregnancy?
  • 160. Pregnancy - antipsychotics• Ans. If an antipsychotic is needed, a typical high potency one is recommended, e.g., haloperidol. Neonates may show EPS after birth, but usually short-lived.
  • 161. Prenatal monitoring• Q. Your pt has decided to remain on Li, on valproate or on carbamazepine during first trimester. What test do you want to perform before 20th week?
  • 162. Prenatal monitoring• Ans.• Amniocentesis checking for elevated alpha-fetoprotein.• Ultrasound examination to detect cardiac abnormalities.
  • 163. Alpha-fetoproteinQ. What is the significance of alpha- fetoprotein?
  • 164. Alpha-fetoproteinAns. If found in amniocentesis, an indicator of neural tube defect.
  • 165. Postpartum issues• Q. Your bipolar pt is pregnant and psychiatrically stable. Will the postpartum period be problematic?
  • 166. Postpartum issues• Ans. Marked increase chance of manic, depressed or mixed episodes.
  • 167. Breast feeding• Q. Which meds, routinely used in treating bipolar pts, are secreted in breast milk?
  • 168. Breast feeding• Ans. All are secreted.
  • 169. Breast feeding – med especially not recommended• Q. Of the meds routinely used in bipolar disorder, which does the practice guideline specially suggest not be used if breastfeeding?
  • 170. Breast feeding –med specifically not recommended• Ans. Li
  • 171. Dosing Chinese pts• Q. When dosing Chinese pts, what cytochrome fact needs to be kept in mind as to dosing?
  • 172. Dosing Chinese pts.• Ans. Lower cytochrome P-450 isoenzyme levels mean using lower does of meds metabolized by that enzyme.