sheng-yu lee, md department of psychiatry nckuh. 躁鬱症 週期性的表現情緒高昂或低落...
Post on 26-Dec-2015
261 Views
Preview:
TRANSCRIPT
Sheng-Yu Lee, MDDepartment of Psychiatry
NCKUH
週期性的表現情緒高昂或低落 主要包括躁期與鬱期的臨床表現
情緒失調 特定的冒險行為 衝動表現 人際關係障礙 憂鬱症狀
可能造成個人痛苦、家庭社會與職業上的重大損害
Significant Public Health Impact Suicide rate ~ 12% Annual U.S. cost > $45.2 B 1
6th leading cause of disability worldwide 2
90% recurrence rate (median number of episodes = 9)
50% recurrence within one year after 1st episode
1Kleinman L, et al. Pharmacoeconomics 2003;21(9):601-22
2Woods SW. J Clin Psych 2000;61(suppl 13):38-41.
Affective Disorder
Unipolar
depression
Bipolar
Mixed mood
Rapid cycling
TOP
DOWN
DSM-IV至少 2 週,至少 5 項1.憂鬱心情2.失去興趣3.體重、食慾改變4.失眠或嗜睡5.精神性激動或呆滯6.失去活力7.無價值感、罪惡感8.注意力減退9.死亡或自殺意念、 計畫
DSM-IV至少一週,心情異常亢奮、開闊、易怒 至少 3 項1.自大狂2.睡眠需求減少3.較多話4.思考跳躍5.注意力分散6.增加目的取向活動7.過分參與活動
DSM-IV至少 4 天,心情異常亢奮、開闊、易怒 至少 3 項1.自大狂2.睡眠需求減少3.較多話4.思考跳躍5.注意力分散6.增加目的取向活動7.過分參與活動
症狀較躁期輕 時間較短 ( 定義為四天以內 ) 可能表現
突然間話多 活動量增加 性慾增加 計畫增加 社交活動增加 突然想交朋友 超出預算或需要的購物
因表現常不離譜 , 過去常被忽略
DSM-IV至少 2 週,至少 5 項1.憂鬱心情2.失去興趣3.體重、食慾改變4.失眠或嗜睡5.精神性激動或呆滯6.失去活力7.無價值感、罪惡感8.注意力減退9.死亡或自殺意念、 計畫
DSM-IV至少 2 年,憂鬱心情佔大部分未一次消失 2 個月以上心情憂鬱時,至少 2 項1.食慾改變2.失眠或嗜睡3.活力低或疲憊4.低自尊5.專注力減退6.無望感
•less severe •longer lasting•unremitting
Alterating between major depression
and dysthymia , but not remitting
DSM-IV
• Single manic episode
• Most recent episode hypomanic
• Most recent episode manic
• Most recent episode mixed
• Most recent episode depressed
• Most recent episode unspecified
1 2 3 4
Mania recurs at least 4 times a year
1
2
3
4
Rapid switches from mania to depression and back
One full depressive episode +at least one hypomanic episode
1. Mood swings above and below normal mood
2. Less severe than mania & depression
Former US National Epidemiological Catchment Area (ECA) study : 1.3%
Recent analysis of ECA (Subsyndromal manic symptoms included) : 6.4% (Kessler, et al., 2005)
Zurich study (soft BP II included) : 11% (Angst, 1998)
第一型躁鬱症 : 2.4% (Rhimer & Angst, 2004)
第二型雙極症 : 3.9-11% (Angst et al. 2003)
Often misdiagnosed or undiagnosed: 35-60% have depression first¹ May have several depressive episodes
prior to manic episode² Many will not report mania/hypomania Lag between symptom onset and first
treatment with mood stabilizer³
¹Goodwin FK, Jamison KR. Manic-Depressive Illness 1990:56-73;NY: Oxford Univ Press
²Lish JD, et al. J Affect Disord. 1994;31:281-294.
³Goldberg JF, Ernst CL. J Clin Psych. 2002 Nov;63(11):985-91.
Patients without perceived and report to clinicians (Dunner and Tay,
1993)
Clinicians without asking directly (hypo)mania (Angst and Gamma, 2002)
40% of patients initially misdiagnosed and inappropriate
treatment (Ghaemi et al., 2002)
Overdiagnosis of major depression and schizo-affective
schizophrenia Missed treatment : increased suicide risk, psychosocial suffering
and social resources utilization (McCombs et al., 2006)
Accurate diagnosis and appropriate treatment: BPII ≥ 12yrs BPI ≥
5yrs (Hirschfeld et al., 2003)
Highly awareness of BPII is necessary
complete suicide and psychiatric disorder
(~90%)
major depressive episode in particular (Zheng et al.,
1997)
suicide risk in UP v.s. BP: inconsistent findings
higher lethality, more aggression and impulsivity
in BP attempters (Rhimer and Kiss, 2002)
suicide attempt in BP: 25-50%, 15-20% die of
suicide
(Michaelis et al., 2003)
History of mania Family history of bipolar disorder Earlier age of onset¹ Multiple episodes Abrupt onset and termination of
depressive episodes Worsening with antidepressant
treatment²
¹Lish JD, et al. J Affect Disord. 1994 Aug;31(4):281-94.
²Ghaemi SN, et al. J Clin Psychiatry. 2000;61:804-808.
More depressive recurrences
Higher rates of substance use disorders
Greater degree of social disruption (marital, occupational)
Minor antisocial behavior (Angst et al., 2003)
Atypical features ? (Angst et al., 2002; Benazzi, 2003; Posternak and
Zimmerman, 2002)
BP family history (Merikangas et al., 2002)
Frequent “ups and downs” (Benazzi, 2004)
more likely to have a family history of bipolar disorder and to have earlier age of onset
Have you experienced sustained periods of feeling uncharacteristically energetic?
Have you had periods of not sleeping but not feeling tired?
Have you felt that your thoughts were racing and couldn't be slowed down?
Have you had periods where you were excessive in sexual interest, spending money, or taking unusual risks?
Onset: 15-25 years old, rare after 65y/o relapses and remissions. Manic episode: duration: 3-6months, 90% of individuals with one manic
episode have another within five years 90% of individuals with bipolar disorder
have at least one psychiatric hospitalization and 2/3 have two or more hospitalizations in their lifetime
Mixed Mania Simultaneous mania and depression May be > 40% prevalence of episodes*
Rapid Cycling > 4 episodes/year
Bipolar II Hypomania (< 4 days duration) alternating with
depression Secondary Mania
e.g., drugs, tumor, CVA, lupus, endocrine, infectious, Huntington’s, Wilson’s
*Akiskal HS, et al. J Affect Disord 2000 Sep;59 Suppl 1:S5-S30
All subtypes less responsive to Lithium
Impulse control disorder
Conduct disorder
migraine bulimiaThyroid disorders
Acute mania/mixed mania: 1st line: lithium or valproate or antipsychotic* 1st line severe: lithium or valproate + antipsychotic*
Acute depression: 1st line: lithium or lamotrigine 1st line severe: lithium + antidepressant
Maintenance lithium or valproate: Alternatives: lamotrigine, carbamazepine,
oxycarbazepine Atypical antipsychotics “may be considered”
*APA recommends atypical antipsychotics > typical antipsychotics
Lithium*Valproic AcidLamictal* (lamotrigine)Tegretol (carbamazepine)Trileptal (oxcarbazepine)Neurontin (gabapentin)Topamax (topiramate)Gabitril (tiagibine)Keppra (levetiracetam)
*FDA-approved
Advantages: 50+ years worldwide experience (FDA-approved 1970) effective in euphoric mania and hypomania inexpensive reduces suicide rate¹‚²
Disadvantages: slow onset ~ 14 days narrow therapeutic index non-response in > 50% (usually bipolar subtypes) frequent side effects (polyuria, tremor, GI symptoms)
and non-compliance discontinuation associated with high relapse rate³
¹Baldessarini RJ, et al. J Clin Psychiatry. 2003;64 Suppl 5:44-52.
²Goodwin FK, et al. JAMA. 2003 Sep 17;290(11):1467-73.
³Cavanagh J, et al. Acta Psychiatr Scand. 2004 Feb;109(2):91-5.
Predictors of response to Lithium: euphoric mania good inter-episode functioning family history of Bipolar Disorder (and of
Lithium response¹) mania/depression/euthymia sequence
vs. depression/mania/euthymia²
¹Duffy A, et al. J Clin Psych. 2002 Dec;63(12):1171-8.
²Kleindienst N, Greil W. Neuropsychobiology. 2002;42 Suppl 1:2-10.
Advantages: extensive experience (FDA-approved for epilepsy
1983; for bipolar mania 1995) rapid onset (1-4 days) loading dose strategy¹ well-tolerated:
20 mgs/kg 77% moderate to marked response
effective in Bipolar subtypes effective for psychotic symptoms² plasma levels (50-125 mcg/ml) less cognitive impairment than lithium³
¹McElroy SL, Keck PE. Neuropsychobiol. 1993;27(3):146-9.
²McElroy SL, et al. J Clin Psych. 1996 Apr;57(4):142-6.
³Zajecka J, et al. J Clin Psych. 1996 Aug;57(8):356-9.
Disadvantages: sedation transient hair loss weight gain tremor GI upset dose-related thrombocytopenia rare hepatotoxicity, pancreatitis possible Polycystic Ovarian Syndrome plasma level monitoring
FDA-approved for maintenance treatment of Bipolar I Disorder
Black box warning for serious rash (includes Stevens-Johnson Syndrome and toxic epidermal necrolysis)
Slow titration necessary Interaction with other AEDs
(especially valproic acid and carbamazepine)
Stevens-Johnson syndrome 死亡率達 3~15% 在台灣地區,預估每年每百萬人會有八人發生 SJS ,相較
於歐美地區每年每百萬人的二至三人,往往淪為無法解決的醫療糾紛。
在長庚醫院治療的 SJS 患者中,有 26% 的病例是由Tegretol 所引起,這個情形也不同於歐美各國主要是由磺胺劑所造成。
鐘文宏說:「這可能與種族體質有關,也可能是台灣在藥物的使用上較不謹慎。」
長庚醫院便與中研院生醫所合作,於基因型鑑定核心設施實驗室展開了尋找基因標記的研究。
Utilization Effective in bipolar mania, in
maintenance treatment for preventing manic recurrence
Less study in bipolar depression Second-line mood stabilizer
Side effects Bone marrow suppression Notable induction of CYP450 3A4 Sedation Fetal toxicity, such as neural tube
defects
Monitoring Blood counts
Clozaril (clozapine) Risperdal* (risperidone) Zyprexa* (olanzapine) Seroquel* (quetiapine) Geodon* (ziprasidone) Abilify* (aripiprazole)
*FDA-approved
Comparable efficacy on positive symptom Better efficacy for improving cognitive and
affective (“negative”) symptoms Less risk of extrapyramidal symptoms
D1 D2
5HT2A
5HT1A
A1
A2
H1
M
ClozapineClozapineOlanzapineOlanzapine
RisperidoneRisperidone
D1 D2
5HT2A
5HT1A
A1
A2
H1
QuetiapineQuetiapine
ZiprasidoneZiprasidoneD2
D1
5HT2A
5HT1A
A1
HaloperidolHaloperidol
Receptor:Receptor:
AA1, 2 1, 2 = a= a11, a, a22 adrenergicadrenergic
DD1,21,2 = dopamine = dopamine
HH11 = histamine = histamine
5HT5HT1A, 2A1A, 2A = serotonin = serotonin
M = muscarinicM = muscarinicGoldstein 1999Goldstein 1999
D2 antagonist/partial agonist 1. Block dopamine hyperactivity2. reduce psychotic symptoms in mania
5HT2A antagonist
1. Reduce glutamate hyperactivity2. Reduce non-psychotic manic and depressed symptoms
High 5HT2:DA blockade (aripiprazole: unique mechanism)
5HT-2a antagonism: Mesolimbic: does not reverse
antipsychotic action at D2 receptors Nigrostriatal: reverses enough D2
blockade to EPS Mesocortical: DA enough to improve
cognition
Receptor actions that improve mood and cognition: 5HT2a antagonism (CLZ/RIS/OLZ/QTP/ZIP/ARI)
5HT2c antagonism (RIS/OLZ/ZIP)
5HT1a agonism (CLZ/QTP/ZIP/ARI)
5HT/NE reuptake blockade (ZIP)
Proper dosing:
Drug Initial launch Current
Risperidone 16 mgs 4-8 mgs
Olanzapine 10 mgs 15-20 mgs
Quetiapine 200-300 mgs 600-800 mgs
Ziprasidone 40-80 mgs 120-160 mgs
Aripiprazole 20-30 mgs 5-10 mgs
Young Mania Rating Scale items*: Elevated mood Increased motor activity Sexual interest Sleep Irritability Speech Language Content Disruptive/aggressive behavior Appearance Insight
*Possible Score = 0-60
FDA-approved for acute mania (2000) and bipolar maintenance (2004)
First-line treatment for mania per APA 2002 Practice Guidelines (along with lithium & divalproex)
Superior to placebo¹ Equivalent to lithium² Superior efficacy (vs. placebo) as add-on
to lithium or valproate ³ Superior to depakine4
1. Tohen M, et al. Am J Psych. 1999 May;156(5):702-9.
2. Berk M, et al. Int Clin Psychopharmacol. 1999 Nov;14(6):339-43.
3. Tohen M, et al. Arch Gen Psych. 2002 Jan;59(1):62-9.
4. Tohen M, et al. Am J Psych. 2003 Jul;160(7):1263-71.
FDA-approved for acute mania (2003)
Superior to placebo (equivalent to haloperidol) as add-on to mood stabilizer (lithium or divalproex)¹
Equivalent to lithium or haloperidol monotherapy²
¹Sachs, et al. Am J Psych 2002 Jul;159(7):1146-54
²Segal J, et al. Clin Neuropharm 1998 May-Jun;21(3):176-80
FDA-approved for acute mania up to 12 weeks (2004)
2 monotherapy and 2 adjunct therapy studies completed*
Superior efficacy on YMRS, PANSS, CGI (including Response and Remission rates on YMRS) for 3 of 4 studies
*Data on file, AstraZeneca Pharmaceuticals LP, Wilmington, DEPresented at 16th Annual U.S. Psychiatric & Mental Health Congress. Nov 6-9, 2003. Orlando, FL
No clinically significant changes observed on ECG parameters (including QTc)
No clinically significant changes in glucose levels (random test) from baseline to endpoint
No other laboratory abnormalities occurred
No clinically significant change observed in blood pressure (including orthostatic)
No difference from placebo in EPS or prolactin levels
No difference from placebo in withdrawal due to adverse events
FDA-approved for mania August 2004 3-week, double-blind, randomized trial
(DSM-IV mania/mixed mania) N = 210 Ziprasidone 40-80 mgs B.I.D. vs. placebo Outcome: SADS (MRS), PANSS, CGI-I, CGI-
S, GAF Ziprasidone superior from day 2 on all
primary and most secondary efficacy measures
Keck PE, et al. Am J Psych. 2003 Apr; 160(4):741-8.
FDA-approved for mania October 2004 3-week, multi-center, double-blind,
randomized trial (acute mania/mixed mania) N=262 aripiprazole 30 mgs vs. placebo Outcome: YMRS change from baseline and
response rate ( > 50%) aripiprazole superior from day 4:
YMRS (-8.2 vs. –3.4) YMRS response (40% vs. 19%) Similar discontinuation rate, weight, prolactin,
QTc
Keck PE, et al. Am J Psych. 2003 Sep; 160(9):1651-8.
Quetiapine
Olanzapine
Aripiprazole
Olanzapine
DRUG WEIGHT GAIN DIABETES RISK
WORSENING LIPID PROFILE
CLOZAPINE +++ + +
OLANZAPINE +++ + +
RISPERIDONE ++ D D
QUETIAPINE ++ D D
ARIPIPRAZOLE +/– – –
ZIPRASIDONE +/– – –
(+) = increase; (–) = no effect; D = discrepant results
Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes.
Diabetes Care. 2004 Feb. 27(2):596-601.
New Onset DM DKA/Coma Deaths
Clozapine 242 80 25
Olanzapine 225 100 23
Risperidone 131 36 5
Quetiapine° 69 21 11
Ziprasidone 1 1 0
Aripiprazole ? ? ?
*Data from MedWatch and Koller et al. Am J Med. 2001;111:716-23/ Koller et al. Pharmaotherapy. 2002;22:841-52.
°J Clin Psychiatry 2004;65:857-863
Literature reports through July 2003 and post-marketing surveillance date through August 2002
Drug: EPS: Weight Gain:
Sedation: Prolactin:
Aripiprazole 0/+ 0 0 0Clozapine 0 +++++ +++++ 0
Olanzapine ++ ++++ ++ ++
Quetiapine 0 ++ +++ 0Risperidone +++ +++ + +++Ziprasidone ++ 0 + +
“Negative” symptom benefits Cognitive benefits Decreased dysphoria Improved compliance Lower risk for tardive dyskinesia
Tandon R, Jibson MD. Annals Clin Psychiatry 2002;14(2):123-9.
Loss of libido Anorgasmia/Ejaculation difficulty Amenorrhea Gynecomastia Galactorrhea Osteoporosis
*DA blockade in tubero-infundibular tract
Appropriate use and effectiveness is controversial
Antidepressant-induced mania in 20-40% with all antidepressant classes (TCAs > others)¹‚²
Increased risk of switching³: Previous antidepressant-induced mania Bipolar family history Exposure to multiple antidepressant
trials¹Stoll AL, et al. Am J Psych 1994 Nov;151(1):1642-45
²Calabrese JR, et al. Eur Neuropsychopharm 1999 Aug;9 Suppl 4:S109-12
³Goldberg JF, et al. Bipolar Disord 2003 Dec;5(6):407-20
Conflicting evidence for efficacy against depressive relapse: Protective?:
Altshuler L, et al¹ (retrospective, 39 pts, 1 year): 35% relapse rate with antidepressant continuation 68% relapse rate with antidepressant discontinuation
Altshuler L, et al² (prospective, 84 pts, 1 year): 36% relapse rate with antidepressant continuation 70% relapse rate with antidepressant discontinuation
¹Altshuler L, et al. J Clin Psychiatry. 2001;62:612-16.
²Altshuler L, et al. Am J Psychiatry. 2003;160:1252-62.
No benefit?: Frankle WG, et al¹ (retrospective, 50 pts, 30
weeks): No difference in length of depressive episode
regardless of antidepressant status Ghaemi S, et al² (open, randomized 33 pts, 1
year): Relapse rate 50% within 20 weeks regardless of
antidepressant status
¹Frankle WG, et al. Psychol Med. 2002 Nov;32:1417-23.
²Ghaemi S, et al. San Juan, PR: American College of Neuropsychopharmacology annual meeting, 2003.
Antidepressants can be safe and effective* Review of 12 randomized, controlled
trials in Bipolar Depression (1,088 patients):
Antidepressants more effective than placebo Switch rate 3.8% for antidepressants and
4.7% for placebo Tricyclics had 10% switch rate vs. 3.2% for
all other antidepressants
*Gijsman HJ, et al. Am J Psychiatry 2004; 161:1537-1547.
Recommendations for Bipolar depression*: Augment mood stabilizer with
antidepressant, unless: “ultra-rapid” cycler (>4 episodes/week) History of antidepressant-induced cycle
acceleration History of multiple episodes antidepressant-
induced mania despite mood stabilizer treatment Continue maintenance antidepressant if
stable for 2 months
*Post RM. Current Psychiatry. 2004 July. 3(7):40-49.
Electroconvulsive treatment¹‚²: superior to pharmacotherapy bilateral ECT superior to unilateral ECT psychotic depression predicts better response effective in depressed and manic phases > 300 case reports of ECT during pregnancy
Phototherapy (bright light treatment) Benefit as monotherapy³ or augmentation4
especially if seasonal component Sleep deprivation5
improvement in 40-60% (may last weeks) some risk of hypo-mania
¹UK ECT Review Group. Lancet. 2003 Mar 8;361(9360):799-808; ²Kho KH, et al. J ECT. 2003 Sep;19(3):139-47; ³Levitt AJ, et al. J Affect Disord. 2002 Sep;71(1-3):243-8; 4Loving RT, et al. Depress Anxiety. 2002;16(1):1-3; 5Giedke H, Schwarzler F. Sleep Med Rev. 2002 Oct;6(5):361-77.
Psychotherapy issues: acceptance of illness effect of illness on relationships effect on employment enhance compliance (>50% non-
compliance: M>F, white>non-white, combination therapy>monotherapy, substance abusers)*
identify precipitants to mood episodes manage/reduce stress
*Keck PE, et al. Psychopharm Bull 1997;33(1):87-91
Bipolar disorder: Significant public health impact Highly recurrent Must look to find
Usually presents in depressed phase Subtypes exist and are less lithium-responsive First-line treatment:
Mood stabilizers Atypical antipsychotics
Thank you!!
top related