Transcript Bipolar Disorder - Steven Banderx

Bipolar Disorder:
Lessons for Rural Physicians:
Adjunctive Interventions for
Maintaining Remission
Steven Bander, DO, FACOFP
Bander Family Medical Center
Wylie, Texas
Disclosure
• Nothing to disclose
Objectives
• Recognize the importance of utilizing guideline
recommendations during maintenance treatment of patients
with bipolar disorder
• Develop a maintenance treatment plan for patients with
bipolar disorder based on guidelines
• Systematically monitor effectiveness and safety of
maintenance treatment
Epidemiology of Bipolar Disorder
• Lifetime prevalence rate is 0.7 to 1.6%
• Gender prevalence is equal for Bipolar I disorder
• Bipolar II and rapid cycling more common in women
• First degree relatives 24 times more likely to develop bipolar
disorder
• Concordance rate 79% in MZ twins and 19% in DZ twins
• Average onset age 21
Bill J
• Bill J. is sent by his employer for a fitness-for-duty
exam. He has been talking almost continuously for
days, sexually propositioning his supervisees, and
bursting into his boss’ office repeatedly with a “plan
to save the company.” He has worked there for 12
years and generally been a good employee. There
is no history of psychiatric illness. He talks non-stop
during his interview with you and seems grandiose
but not psychotic. States he really does not need
sleep. His physical exam is essentially normal.
Patients With Bipolar Disorder Are
Symptomatic for Almost Half of Their Lives
Weeks asymptomatic
Weeks manic/hypomanic
9%
32%
Weeks depressed
Weeks cycling/mixed
6%
53%
N = 146
12.8 years follow-up
Judd LL, et al. Arch Gen Psychiatry. 2002;59:530-537.
Bipolar I Disorder:
Diagnosis
• Single manic episode
• One manic or mixed episode (in patient’s history)
• Recurrent
• Current Manic, Major Depressive, Mixed, or Hypomanic episode
• Previous Manic, Major Depressive, or Mixed episode
• Relapsing and remitting course
• Major Depressive Episodes have usually occurred but are not required
for the diagnosis
• The mood symptoms are not better accounted for by a Psychotic
Disorder including Schizoaffective Disorder
• Clear distinction between episodes and inter-episodic functioning
• Often well or at least much better between episodes
Clinical Features of Mania
Mania
• Behavioral Symptoms
• Grandiosity, Diminished need for sleep,
Pressured Speech, Excessive Libido,
Recklessness, Impulsivity, Hostility,
Violence
• Affective Symptoms
Hypomania
•
Euthymia
• Depression, Anxiety, Euphoria, Irritability
Psychotic Symptoms (Psychosis occurs in
over 50% of manic episodes)
• Hallucinations, Delusions, Sensory
Hyperactivity
• Cognitive Symptoms
Dysthymia
•
Depression
• Racing Thoughts, Distractibility, Poor
Insight, Disorganization, Confusion,
Inattentiveness, Suicidal Thoughts
Suicide and Bipolar disorder (More likely
in depressive or mixed episode)
• 10-15% will complete suicide
Manic Episode
• Elevated, expansive, or irritable mood for 1 week
• 3 or more of the following, 4 if irritable mood: (DTRHIGH)
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Distractible
Talkative or pressured speech
Racing thoughts or flight of ideas
Hyper-alert = decreased need for sleep
Increased activity or psychomotor agitation
Grandiose
Hypersexual = risky acts
• Severe enough to cause:
• Marked impairment in functioning or Hospitalization (any duration of symptoms)
or Psychotic features
• Symptoms are not due to:
• Substance or General medical condition
Differential Diagnosis:
Mania
• General medical conditions
• Head trauma, Mass lesions, Post-CVA, MS, Hyperthyroidism, Cushing’s,
Huntington’s disease, complex partial seizures
• Substance induced
• Corticosteroids, levodopa, Stimulants: amphetamine, cocaine, ephedrine, Drug
or Alcohol withdrawal syndromes, Antidepressants, ECT, light therapy
• Schizophrenia, schizoaffective disorder
• Psychotic symptoms occur in absence of mood symptoms
• Borderline Personality Disorder
• Similarities: impulsivity, suicidal behavior, irritability, paranoid ideation
• Differences: enduring pattern, fear of abandonment, idealization/devaluation,
identity disturbance, emptiness
Bipolar I and II:
Frequency of Depressive Symptoms
Mixed 13%
Depressed
67%
Manic/
hypomanic
20%
 Bipolar I
Patients with bipolar I disorder (n =
146) experienced mood symptoms
47.3% of the time during a 12.8-year
follow-up period
 Depression 3.4-fold more frequent
than mania
Mixed 4.5%
Manic/
hypomanic
2.5%
Depressed
93%
Bipolar II
Patients with bipolar II disorder (n =
86) experienced mood symptoms
54% of the time during a 13.4-year
follow-up period
 Depression 37-fold more
frequent than mania
Judd LL, et al. Arch Gen Psychiatry. 2002;59:530-537.
Judd LL, et al. Arch Gen Psychiatry. 2003;60:261-269.
Major Depressive Disorder
• Relapsing and remitting course
• May eventually become chronic
• Minimum duration ≥ two weeks
• Clear distinction between episodes and interepisodic function
• Often well or at least much better between episodes
Clinical Features of Depression
Mania
• Affective Symptoms
• Depressed mood (sad, down, blue)
• Reduced interest or pleasure
• Cognitive Symptoms
Hypomania
Euthymia
• Poor concentration/easy distraction
• Inappropriate guilt/self reproach
• Thoughts of death, dying, suicide
• Behavioral Symptoms
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Change in appetite
Change in sleep pattern
Reduced energy level
Psychomotor agitation/retardation
• Suicide and Bipolar disorder (More
likely in depressive or mixed episode)
• 10-15% will complete suicide
Dysthymia
Depression
Clinical Features: Major Depression
• 5 or more of these for 2 weeks: (SIGECAPS)
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Depressed mood most of the day
Sleep decreased or increased
Interests decreased
Guilt (excessive) or worthlessness
Energy decreased
Concentration decreased or indecisive
Appetite change or weight change
Psychomotor retardation or agitation
Suicidal ideation or attempt
Differential Diagnosis:
Depression
• Psychiatric
• Adjustment D/O
• Bereavement
• General Medical
• Hypothyroidism, Anemia
• Post-CVA, Post-MI
• Ca of head of pancreas
• Substance-Related
• Rx meds: steroids, b-blockers, a-methyldopa
• Alcohol or Benzodiazepine abuse
• Cocaine/amphetamine withdrawal
Clinical Features of Mixed Episode
Mania
Hypomania
Euthymia
• Full symptoms of manic
and major depressive
episodes for 1 week
• Severe enough to cause:
• Marked impairment in
functioning
• Or
• Hospitalization
• Or
• Psychosis
Dysthymia
• Symptoms are not due to:
Depression
• Substance
• General medical condition
Clinical Features of Rapid Cycling
Mania
Hypomania
Euthymia
Dysthymia
Depression
• 4 or more mood
episodes in 12 months
• Major depressive,
manic, mixed, or
hypomanic episodes
• Separated by:
• Remission for 2
months
or
• Switch to opposite
polarity
Clinical Features of Bipolar II
Mania
Hypomania
Euthymia
Dysthymia
Depression
• Current or past Major
Depressive episode
• Current or past
Hypomanic episode
• Never a Manic or
Mixed episode
• Not a primary
psychotic disorder
• Clinically significant
distress or impairment
in functioning
Clinical Features of Hypomania
Mania
Hypomania
Euthymia
• Different from usual mood
• Clear change in
functioning
• Observable by others
• Does not cause:
• Marked impairment in
functioning
• Hospitalization
• Psychotic features
Dysthymia
• Symptoms are not due to:
Depression
• Substance
• General medical condition
Hypomanic Episode
• Elevated or irritable mood for 4 days
• 3 or more of the following: (DTRHIGH)
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Distractible
Talkative or pressured speech
Racing thoughts or flight of ideas
Hyper alert = decreased need for sleep
Increased activity or psychomotor agitation
Grandiose
Hypersexual = risky acts
Co-morbid Psychiatric Conditions
• Alcohol and drug abuse/dependence
• Most common co morbid condition
• Worse prognosis
• Must treat concurrently
• Personality disorders
• Anxiety disorders
• ADHD
Always ask about mania
before treating depression
Goals of Treatment
• Symptomatic Remission
• Full return of psychosocial functioning
• Prevention of relapses and recurrences
J Clin Psychiatry 66:7 July 2005
Setting the Stage for Treatment
• Engage the patient in the Treatment Plan
– Discuss the Diagnosis
– Discuss the treatment options
• Engage appropriate significant others in the Treatment Plan
– With the consent of the patient
• Encourage the patient to keep a daily mood log
• Encourage the patient to engage in therapy
– Psychoeducational
– Cognitive Therapy
J Clin Psychiatry 66:7 July
Evidence Based Treatment
• These recommendations for treating Bipolar Disorder are
based on:
• TIMA Algorithm for Bipolar
• Texas Implementation of Medication Algorithms (TIMA)
• APA Treatment Guidelines for Bipolar
• American Psychiatric Association
Algorithm – Mania Symptoms
• Treating Acute Hypomanic/Manic/Mixed Episodes of Bipolar
I Disorder
• Monotherapy (Euphoric)
• Lithium, valproate, aripiprazole, quetiapine, risperdone,
ziprazidone
• No response: olanzapine, carbamazepine
• Monotherapy (mixed)
• valproate, aripiprazole, risperdal, ziprazidone
• No response: olanzapine, carbamazepine
Algorithm
• If monotherapy fails (two drug combinations)
• lithium, valproate, or atypical antipsychotic
• Note: not two atypical antipsychotics and not aripiprazole or
clozapine
• If partial or no response
• lithium, valproate, atypical antipsychotic, carbamazepine,
oxcarbazepine, typical antipsychotic
• Note: not two atypical antipsychotics and not clozapine
Algorithm – Depressive Symptoms
• Treating Acute Depressive Episodes in Patients with Bipolar
I Disorder
• To begin this algorithm we must establish some key facts:
• A patient taking lithium (increase to 0.8 mEq/L), or
• A patient is taking another antimanic medication, or
• Patient is not taking any antimanic medication and has a history of
severe and/or recent mania
• The treatment step would be to provide the patient with an
antimanic medication and lamotrigine
Algorithm – Depressive Symptoms
• You may have a patient without a history of severe and/or
recent mania and is not taking any antimanic medication
• The treatment step would be to provide the patient with
lamotrigine
Algorithm – Depressive Symptoms
• The previous 2 slides outlined Stage 1 of the TIMA algorithm
for Treating Acute Depressive Episodes in Patients with
Bipolar I Disorder
• If there was only partial or non-response to stage 1
interventions taper off any medications that need tapering
and start a monotherapy of
• quetiapine or an olanzapine-fluoxetine combination
Algorithm – Depressive Symptoms
• If there was only partial or non-response to stage 2
interventions and start a combination therapy of any two of
the following medications
• lithium, lamotragine, quetiapine or an olanzapine-fluoxetine
combination
• Consider consultation if this fails
FDA Approved Drugs
• FDA Approved Drugs for Mania
• Aripiprazole
• Carbamazepine
• Chlorpromazine
• Divalproex
• Lithium
• Olanzapine
• Quetiapine
• Risperidone
• Ziprasidone
• FDA Approved Drugs for Bipolar
Depression
• Olanzapine-Fluoxetine
Combination
• Quetiapine
Definition of a Mood Stabilizer
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Treats acute depression and/or mania
Reduces risk of relapse of mania and/or depression
Does not increase risk of mania
Does not increase risk of depression
Rationale for lithium salts as the Mood
Stabilizer of First Choice
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Track record (dating to 1960s)
Evidence of efficacy
Well-characterized tolerability and safety profiles
Low cost
Evidence of reduction of suicidal behavior
Lithium Carbonate
• FDA approved for acute mania and maintenance
• Workup
• Beta-HCG, BUN, creatinine, thyroid profile, EKG
• Serum levels
• Acute mania=1.0-1.5 meq/L
• Maintenance=0.6-1.2 meq/L
• Toxicity at above 1.5 meq/L
Lithium Carbonate
• Pregnancy
• First trimester: cardiac defects
• Toxicity
• Narrow therapeutic index
• Nausea, vomiting, blurred vision, vertigo, confusion, seizures,
coma
• Lithium level increased by:
• Low serum sodium, Diuretics, ACE inhibitors, NSAID’s
• Excreted by kidneys
Lithium: Adverse Effects
• Diuretics (e.g., thiazides) can reduce lithium clearance by as much as 25% -Preferentially
eliminate Na+
• NSAIDs can reduce lithium clearance.
• Worsens extrapyramidal syndromes produced by older antipsychotic drugs.
• Side Effects and their management
• Begin with dose decrease
• Tremor - propranolol
• Polyuria - amiloride
• Hypothyroidism – levothyroxine -TSH every 6-12 months
• G.I. Distress - take with food, change to lithium citrate
• Cardiac: T-wave & conduction changes
• Mild cognitive impairment
• Transient acneiform eruptions
• Leukocytosis
Efficacy of Lithium: All Relapse
Geddes JR, et al. Am J Psychiatry. 2004;161(2):217-222.
Valproic Acid
• Formulations
• Valproic acid
• Sodium valproate
• Divalproex sodium=combination of both
• Compared to lithium
• Faster onset of anti-manic effects
• Better for mixed episodes & rapid cycling
• Wide therapeutic window
Valproic Acid
• Side Effects and their management
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Elevated hepatic transaminases - monitor LFT’s
Rare hepatotoxicity
Leukopenia - monitor WBC
G.I. Distress - decrease dose, try divalproex
Sedation - give more at bedtime
Weight gain - diet & exercise
Hair loss - zinc, selenium
Valproic Acid
• Pregnancy
• First trimester - neural tube defects, craniofacial abnormalities
• Therapeutic serum level
• 50-125 mcg/mL
• Workup
• Beta-HCG, CBC + differential, liver function tests (LFT’s)
Rationale for status of Divalproex
• Efficacy comparable to lithium
• Useful in patients who do not respond to or don’t
tolerate lithium
• More useful than lithium for patients with mixed
affective states and significant substance abuse
histories
• Vigorously marketed, without opposition, from 19942002
Market Share
Shifts in Prescription
of Lithium and Divalproex
Total N: 20,638
Goodwin, et al. JAMA 2003;290:1467-1473
Carbamazepine
• Side Effects
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Sedation, weight gain
Dermatitis, rashes
G.I. Distress
Dizziness, ataxia, diplopia
Leukopenia, LFT elevations
• Rare, but serious
• Agranulocytosis, aplastic anemia
• Exfoliative dermatitis (Stevens-Johnson syndrome)
• Hepatic failure
Carbamazepine
• Pregnancy
• First trimester - neural tube defects
• Drug-drug interactions
• Induces metabolism and decreases levels of:
• Carbamazepine (auto-induction), valproic acid, lamotrigine, oral contraceptives
• Therapeutic serum level
• 4-12 mcg/mL
• Workup
• CBC + differential, platelets, liver function tests
Lithium, Divalproex or Carbamazepine,
Risk of Suicidal Behaviors
Advantage for Lithium
vs. DVPX
vs. CARB
Suicide attempts: ER
1.8 (1.4–2.2)*
1.4 (1.0-2.0)
Suicide attempts:
Admission
1.7 (1.2-2.3)*
2.9 (1.9-4.4)*
Suicide attempts: Death
2.7 (1.1-6.3)*
1.5 (0.3-7.0)
Goodwin, et al. JAMA 2003;290:1467-1473
Lamotrigine
• Not effective in acute mania
• Lamotrigine is especially effective against depression (Bowden et al 2003)
• Effective for bipolar depression
• Serious side effect
• Stevens-Johnson syndrome
• Discontinue if rash occurs
• Use slow titration
• Drug-drug interactions
• Valproic acid inhibits metabolism & doubles serum concentration
• Carbamazepine induces metabolism and halves serum concentration
Second Generation Antipsychotic Safety and
Tolerability Concerns
• Weight gain
• ± Akathisia
• Sedation
• ± Hyperprolactinemia
• Diabetes
• Cerebrovascular
(elders)
• Cardiac
Olanzapine
• FDA approved for acute mania
• Side effects
• Sedation
• Weight gain
• Elevated hepatic transaminases
Quetiapine
• FDA approved for acute mania
• Side effects
• Sedation
• Orthostasis (during titration)
Risperidone
• FDA approved for acute mania
• Side effects: at higher doses
• Extrapyramidal symptoms
• Elevated serum prolactin
Antidepressants
• Use in bipolar depression
• Concurrent with mood stabilizer
• Some cause switch to mania
• Tricyclic antidepressants & venlafaxine
• Bupropion and paroxetine have low rate of switch to
mania
Adjunctive medications
• Antipsychotics
• Use when psychosis is present
• Taper and discontinue when psychosis resolves
• Benzodiazepines
• Lorazepam, clonazepam
• Use in severe mania as a short term sedative
Electroconvulsive therapy
• Highly effective treatment
• Acute illness and maintenance treatment
• Indications
• Severe or refractory mania or depression
• Psychosis with depression or mania
• Patient cannot tolerate medication
Other Mood Stabilizers:
Antipsychotics or Benzodiazepines
• Antipsychotics
• Including: olanzapine, haloperidol, risperidone,
quetiapine, ziprasidone, and aripiprazole
• Primarily used for controlling acute mania.
• Clonazepam or Lorazepam
• Benzodiazepines may be given to control acute mania
(often as an adjunct to treatment with an antipsychotic
drug or other mood stabilizing drug, be cautious of
disinhibition).
Combination Therapy
Average Number of Medications in 258 Bipolar Outpatients
Followed Up Prospectively for 1 Year
60
Number of Patients
20.9%
50
18.2%
17.1%
40
12.0%
30
20
12.0%
6.6%
6.6%
10
3.1%
1.9%
0.8%
0.8%
0
0
1
2
3
4
5
6
7
8
9
10
Total Number of Medications
Post RM, et al. J Clin Psychiatry. 2003;64(6):680-690.
Pros and Cons of Combination Therapy
FOR
•
40% of patients do not
respond to monotherapy
•
Lower doses
improved tolerability
AGAINST
•
Drug interactions
•
Suboptimal dosing of
both agents
•
More complex
treatment regimen
•
Decreased adherence
•
Increased side effects
•
Cost
Bowden 2004; Goodwin & Vieta 2005
Goal of Treatment: Mood Stabilization
Mania
Mood stabilizers
• Effective in the acute treatment
or stabilization of manic/mixed,
hypomanic, and depressive
episodes
Hypomania
Euthymia
• Do not induce alternate mood
symptoms
(ie, switch)
• Prevent against future relapse or
recurrence of manic/mixed,
hypomanic, or depressive
symptoms or episodes
Dysthymia
Depression
Visit Timelines
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First Week
Third Week
Monthly for at least 3 months
Then Every 2-3 months thereafter
When the patient has been stable for 4 to 6 months (engage
the patient via phone or contact with non-physician
clinicians)
Therapeutic Challenges
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No cure for bipolar disorder
Noncompliance rate is high
Symptom overlap among comorbid diagnoses
Longer Term Efficacy
• Across symptom domains
• Definition of a mood stablizer
• Safety and tolerability
Managing Complex
Medication Regimens
• Try to ensure that at least 1 medication is a mood
stabilizer
• Understand that side effect burden is additive
• Periodically review the need for all medications
Recommended Options for Acute Treatment
of “Breakthrough” Bipolar Depression
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Optimization of mood stabilizer (MS)
Addition of second MS or SGA
Addition of antidepressant to MS
Addition of focused Psychotherapy to MS
How long should antidepressants be
continued?
What do we do when there’s no consensus?
• Expert recommendations for duration of
antidepressant therapy range between “8–12
weeks” and “indefinite-lifetime”
Role of Psychotherapy
in Bipolar Disorder
• If effective for depression, avoids pharmacologic risk of TEAS
• Only 1 controlled study of acute phase therapy (conducted as part of
STEP-BD)
• Preferred option for many patients
• Relapse prevention and adherence-enhancing effects demonstrated
for CBT, FFT, and IPSRT
TEAS=treatment emergent affective switch.
CBT=cognitive behavioral therapy.
FFT= functional family therapy.
IPSRT= Interpersonal and Social Rhythm Therapy.
STEP-BD=Systematic Treatment Enhancement Program for Bipolar Disorder.
Miklowitz DJ, et al. Arch Gen Psychiatry. 2007;64(4):419-426.
Importance of Treatment
Adherence
• Most people with bipolar disorder will have periods
of non-adherence to therapy
• Abrupt discontinuation of medications hastens
relapse
• Ask about adherence at each visit!
• Keep track of prescription refills
Factors Frequently Associated With
Noncompliance in Bipolar Patients
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Young age
Male gender
Being unmarried
Multiple medication regimens
Fewer episodes
First year of lithium treatment
History of manic episodes
Comorbid psychiatric illness
Substance abuse
The Fundamental Factor in
Long-Term Outcome in Bipolar Disorder
• Being in a treatment relationship
• Inadequate treatment associated with adverse
outcomes (e.g., use of antidepressants alone)
• Treatment per se, even with placebo, improves
outcomes, including reduced suicidality
• Not being in treatment increases costs, principally by
higher rates of hospitalization, emergency care
Begley CE et al. (2001), Pharmacoeconomics 19(5 pt 1):483-495, Angst F et al. (2002), J Affect Disord 68(2-3):167-181; Yerevanian BI et al. (2003), J Affect Disord 73(3):223-228