Approach to Bipolar Spectrum Disorders

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Approach to Bipolar Spectrum Disorders
M NAJIB M ALWI MD(USM), Dip IC(UK), MSc(UK),
MRCPsych(UK) Dept of Psychiatry School of
Medical Sciences Universiti Sains Malaysia
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Mania/Hypomania EpisodeDSM-IV Symptoms

• Persistently elevated, expansive, or irritable
  mood (at least 1 gt3 of below, 4)
• Inflated self-esteem or grandiosity
• Decreased need for sleep
• Talkativeness or pressured speech
• Flight of ideas or racing thoughts
• Distractibility
• Increase in goal-directed activity or psychomotor
  agitation
• Excessive involvement in pleasurable activities
  with high potential for negative consequences
• DURATION 1 week / need for hospitalisation
  (MANIA) 4 days (HYPOMANIA)

1. American Psychiatric Association Diagnostic
and Statistical Manual of Mental Disorders,
Fourth Edition, Text Revision Washington, DC.
American Psychiatric Association, 2000. 2.
Ghaemi SN. Bipolar Disorder and Antidepressants
An Ongoing Controversy. Primary Psychiatry.
2001(8)28-34.
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Major Depressive EpisodeDSM-IV Symptoms

• Depressed mood
• ? interest/pleasure
• Weight loss/gain
• ? or ? need for sleep
• Psychomotor agitation/retardation
• Fatigue/loss of energy
• Feelings of worthlessness
• ? ability to think or concentrate
• Suicidal thoughts or thoughts of death
• Either must be present for the diagnosis of a
  major depressive episode.

American Psychiatric Association Diagnostic and
Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision. Washington, DC. American
Psychiatric Association, 2000.
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Bipolar DisorderMixed Mania and Rapid Cycling

• Mixed mania
• Simultaneous symptoms of depression and mania
• Evident in up to 30-40 of all bipolar I patients
• Women gtmen
• Rapid cycling
• 4 mood episodes yearly
• 3 times women gtmen
• Ultrarapid cycling 4 episodes monthly

1. Evans DL. J Clin Psych 200061 (Suppl
13)26-31. 2. American Psychiatric Association
Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, Text Revision.
Washington, DC. American Psychiatric Association,
2000.
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BIPOLAR DISORDERS (DSM-IV)

• Bipolar I Disorder
• (manic depressive illness with or without
  psychosis)
• Bipolar II disorder
• (episodes of major depression alternating with
  episodes of hypomania which are not severe enough
  to result in impairment of function)
• Cyclothymic disorder
• (brief and attenuated episodes of depression and
  hypomania sometimes known as minor cyclic mood
  disorder)
• Lifetime prevalence 3 to 4 of general
  population

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Misdiagnosis
2000 National DMDA Bipolar Survey(n600)
Most frequent misdiagnosis Unipolar depression
NDMDA National Depressive and Manic-Depressive
Association. Hirschfeld RMA, et al. J Clin
Psychiatry. 200364161-174.
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Further Diagnostic Difficulty

• A much larger group of patients demonstrate
  milder and/or atypical forms of episodic mood
  disturbances
• Frequently resistant to standard antidepressants
• Some worsened by antidepressants
• Efforts at clinical subtyping the so-called soft
  bipolar spectrum are ongoing
• Currently DSM-IV Bipolar II Disorder, NOS (not
  otherwise specified).
• If included lifetime prevalence of Bipolar DO -
  5 to 8 of the general population

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The Mood-Psychotic Disorder Spectrum
Psychotic MDD
Chronic MDD
Bipolar NOS
Dysthymia
Bipolar I
SA
Atypical MDD
Single MDE
Cyclothymia
Bipolar II
Recurrent MDD
MDD major depressive disorder MDE major
depressive episode NOS not otherwise
specified SA schizoaffective disorder
1. Goodwin FK and Ghaemi SN, New Oxford Textbook
of Psychiatry, 2000677-682. 2. American
Psychiatric Association Diagnostic and
Statistical Manual of Mental Disorders,Fourth
Edition, Text Revision. Washington, DC. American
Psychiatric Association, 2000.
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Overlap of Mood Disorders and Psychotic Disorders
Psychosis
Bipolar Disorder
Depression w/ Psychotic Features
Bipolar Depression
Treatment- Resistant Depression
Depression
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History of Mood Disorders

• Kraepelin (1890s)
• manic-depressive insanity
• Included DSM-IV subtypes, mixed and rapid cycling
  states, many of the soft bipolar variations and
  also episodic depressions
• DSM-I (1960s)
• proposed a differentiation between major
  depression and manic-depressive illness
• Later DSMs
• unipolar - bipolar dichotomy
• Fieve and Dunner (1970s)
• discriminated bipolar I from bipolar II disorder
• a seminal event in the evolution of the soft
  bipolar spectrum

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Further Evolution

• KLERMAN'S BIPOLAR SUBTYPES (1981)
• Bipolar I Mania and depression
• Bipolar II Hypomania and depression
• Bipolar III Cyclothymic disorder
• Bipolar IV Hypomania or mania precipitated by
  antidepressant drugs
• Bipolar V Depressed patients with a family
  history of bipolar illness
• Bipolar VI Mania without depression unipolar
  mania

Psychiatric Annals 17 January 1987
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Current Thinking

• Hagop Akiskal nosologic pendulum is swinging
  back towards Kraepelinian original unitary
  concept of the bipolar spectrum of mood disorders
• He added four more subtypes according to some
  unique clinical features.

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AKISKAL'S SCHEMA OF BIPOLAR SUBTYPES

• Bipolar I full-blown mania
• Bipolar I ½ depression with protracted hypomania
• Bipolar II depression with hypomanic episodes
• Bipolar II ½ cyclothymic disorder
• Bipolar III hypomania due to antidepressant
  drugs
• Bipolar III ½ hypomania and/or depression
  associated with substance use
• Bipolar IV depression associated with
  hyperthymic temperament

Akiskal Pinto (1999) Psychiatric Clinics of
North America 223, 517-534
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AKISKAL'S SCHEMA OF BIPOLAR SUBTYPES

• Bipolar I full-blown mania
• Bipolar I ½ depression with protracted hypomania
• Bipolar II depression with hypomanic episodes
• Bipolar II ½ cyclothymic disorder
• Bipolar III hypomania due to antidepressant
  drugs
• Bipolar III ½ hypomania and/or depression
  associated with substance use
• Bipolar IV depression associated with
  hyperthymic temperament
• Proposed subtypes V and VI have not yet been
  characterized
• presumably will involve
• episodic anxiety disorders
• seasonal mood states
• mood disorders co morbid with various anxiety
  disorders of an episodic nature.

Akiskal Pinto (1999) Psychiatric Clinics of
North America 223, 517-534
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Complicated.? Thats not all..
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Liebers soft Bipolar Spectrum Disorders

• Episodic Mood Instability
• Episodic Atypical Depression
• Episodic Dysphoric Hypomania

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1. Episodic mood instability

• Lifelong episodes of mood swings starting around
  adolescence.
• The mood shifts unpredictably among several
  distinct mood poles
• brief depressions lasting hours to one or two
  days
• brief euphoria
• brief dysphoric or irritable episodes
• brief paranoid episodes
• brief episodes of rage or intense uncontrollable
  anger
• brief episodic anxiety equivalents (panic
  attacks, phobias or obsessive ruminations).
• This multiplicity of mood options multipolar
  mood disorder might be a more accurate
  designation for it.

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2. Episodic atypical depression (EAD)

• shows atypical depressive features
• eating too much, sleeping too much, feeling worse
  towards evening and intense tiredness or
  lethargy.
• mood responsive
• Temporary response to favourable circumstances
  (hours to a day or two) before returning to the
  depressed state.
• co-existing anxiety and its subtypes (phobias,
  panic attacks, OCD )

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Subtypes of Episodic Atypical Depression

• (distinguished by special features)
• seasonal affective disorder
• winter-onset atypical depressions
• premenstrual dysphoric disorder
• a/w irritability, mood swings and dysphoria
  (irritability)
• a week to ten days on either side of the
  menstrual period
• hysteroid dysphoria
• mainly in women with histrionic personality
  features
• episodes precipitated by romantic rejection
• abulic depression
• a/w a deficit syndrome (apathy, amotivation, lack
  of will power, lack of energy, lack of pleasure
  in life, emotional blunting )

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3. Episodic Dysphoric Hypomania

• NB Hypomania
• Two types euphoric and dysphoric (irritable)
• Two durations episodic and protracted
• Episodic dysphoric hypomania
• Irritability, emotional discomfiture,
  impulsiveness, temper dyscontrol and impaired
  judgment
• Interfere with interpersonal relationships and to
  limit productivity at work
• Sense of inner speeding combined with restless
  over activity and racing thoughts, which can lead
  to a state of desperation.
• Episodes of depression and mood instability
  almost always present sometimes brief euphoric
  episodes.
• Triad irritable episodes alternating with rage
  episodes and paranoid episodes is characteristic
  of dysphoric hypomania.

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Mixed Bipolar Disorder

• Simultaneous occurrence of both depressive
  symptoms and mania/ hypomania and rapid cycling
  bipolar disorder
• Frequent switches from depression to
  mania/hypomania and back
• Found in bipolar I, bipolar II and bipolar
  spectrum disorders.
• They are more common in women, often associated
  with
• thyroid abnormalities
• lack of response to lithium
• antidepressant-induced worsening of symptoms
• Diagnosis of mixed states is most likely after
• failing to respond to outpatient treatment
• becomes worse on antidepressant medications
• Misdiagnosis of these conditions is all too
  common, leading to delays in effective treatment
  and a higher risk of suicide.

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A Proposed Definition of Bipolar Spectrum Disorder

• At least 1 major depressive episode
• No spontaneous hypomanic or manic episodes
• Either
• 1 of the following plus at least 2 of D
• or 2 of the following, plus 1 item from D
• Family history of bipolar disorder in 1st degree
  relatives
• Antidepressant induced mania or hypomania

Ghaemi SN et al (2002) Can J Psychiatry.
47(2)125-134
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A Proposed Definition of Bipolar Spectrum Disorder

• If no items from C are present, 6 / 9 of below
  are needed
• Hyperthymic personality (at baseline,
  non-depressive state)
• Recurrent major depressive episodes (gt3)
• Brief major depressive episodes (ave lt3 months)
• Atypical depressive symptoms
• Psychotic major depressive episodes
• Early age of onset of major depressive episodes
  (ltage 25)
• Postpartum depression
• Antidepressant wear-off (acute, but not
  prophylactic response)
• Lack of response to 3 antidepressants trial

Ghaemi SN et al (2002) Can J Psychiatry.
47(2)125-134
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COMORBIDITY

• A high percentage of bipolar mood disorders,
  perhaps more than 50, are comorbid with other
  medical and/or psychiatric conditions.

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Thyroid disorders

• Hyperthyroidism resembles hypomania/ mania and
  it can worsen pre-existing mania/ hypomania
• Hypothyroidism resembles clinical depression and
  it can cause pre-existing depression to be
  unresponsive to antidepressant medications
• Treatment with lithium can produce hypothyroidism
• Subtle or subclinical hypothyroidism is often
  associated with the development of mixed and
  rapid cycling bipolar disorders.

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Substance misuse

• Psychoactive effects on the brain and can worsen
  the bipolar condition
• Interfere with effective treatment
• Can mimic both depression and hypomanic states
• Unmask a pre- existing depression or bipolar
  disorder
• Can be secondary to self-medication of bipolar
  disorder

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ADHD

• ADHD is now known to often persist into adulthood
  and symptoms may overlap with bipolar spectrum
  disorder
• Overlapping symptoms
• Restlessness
• Motor hyperactivity
• Easy distractibility
• Impulsiveness
• Inability to concentrate or focus attention
• Temper dyscontrol
• Differentiation ADHD continuous vs bipolar
  conditions episodic
• Incidence of their co morbidity is unknown.
• Stimulants (eg Ritalin), tend to worsen the
  symptoms of bipolar spectrum disorder

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Borderline Personality Disorder (BPD)

• Stormy and unstable lifestyle, overly dramatic,
  intense but unstable relationships, and exhibit
  self-defeating and often self-destructive
  behaviours
• Recent years a high percentage of these patients
  have co morbid bipolar spectrum disorders.
• 75 of these patients will respond to
  combination pharmacotherapy using SSRI, a mood
  stabilizer and an atypical antipsychotic (e.g.
  olanzapine).
• Once the mood has become stable, they can then
  benefit from competent psychotherapy to deal with
  their emotional backwash.
• Better prognosis with this treatment approach?

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Mood Disorder Questionnaire (MDQ) Bipolar
Spectrum Disorder Scale (BSDS)
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Hirschfield RM (2002) J Clin Psych. 4 9-11
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Bipolar Spectrum Disorder Scale (Ghaemi Pies
2003)

• Read the following paragraph all the way through
  first, then follow the instructions which appear
  below it.
• Some individuals noticed that their mood and/or
  energy levels shift drastically from time to time
  ______ .  These individuals notice that, at
  times, their moody and/or energy level is very
  low , and at other times, and very high______.
  During their " low" phases, these individuals
  often feel a lack of energy, a need to stay in
  bed or get extra sleep, and little or no
  motivation to do things they need to do______ . 
  They often put on weight during these
  periods______ .  During their low phases, these
  individuals often feel "blue," sad all the time,
  or depressed______ .  Sometimes, during the low
  phases, they feel helpless or even suicidal 
  _____ .  Their ability to function at work or
  socially is impaired ______ .  Typically, the low
  phases last for a few weeks, but sometimes they
  last only a few days ______ .  Individuals with
  this type of pattern may experience a period of
  "normal" mood in between mood swings, during
  which their mood and energy level feels "right"
  and their ability to function is not disturbed
  ______ .  They may then noticed they marked shift
  or "switch" in the way they feel ______ .  Their
  energy increases above what is normal for them,
  and they often get many things done they would
  not ordinarily be able to do ______ .  Sometimes
  during those "high" periods, these individuals
  feel as if they had too much energy or feel
  "hyper" ______ .  Some individuals, during these
  high periods, may feel irritable, "on edge," or
  aggressive ______.  Some individuals, during the
  high periods, take on too many activities at once
  ______.  During the high periods, some
  individuals may spend money in ways that cause
  them trouble______ .  They may be more talkative,
  outgoing or sexual during these periods ______ . 
  Sometimes, their behavior during the high periods
  seems strange or annoying to others ______ . 
  Sometimes, these individuals get into difficulty
  with co-workers or police during these high
  periods ______ .  Sometimes, they increase their
  alcohol or nonprescription drug use during the
  high periods ______ .

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Scoring the BSDS

• Add total of check marks from the first 19
  sentences. To that total, add the number in
  parentheses below for the line you selected 
• this story fits me very well, or almost perfectly
  (6)
• this story fits me fairly well (4)
• this story fits me to some degree, but not in
  most respects (2)
• this story doesn't really describe me at all (0)
• The maximum is 19 plus 6, for 25 points.  
• Interpretation 
• 19 or higher bipolar spectrum disorder highly
  likely
• 11-18 moderate probability of bipolar
  spectrum disorder.
• 6-10 low probability of bipolar
  spectrum disorder
• lt6 bipolar spectrum disorder
  very unlikely

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Bipolar Disorder Treatment Strategies Revisited
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Treatment of Bipolar Disorder
Treats the highs (mania)
Helps prevent the highs and lows (maintenance)
Helps manage the lows (depression)
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Long-term Treatment Goals

• Facilitating compliance
• Tolerability of adverse effects of medications
• Denial of illness
• Recognizing signal events that indicate
• Patient has returned to baseline functioning
• Patient is at a risk for relapse
• Family Involvement
• To pick up early warning signs of patient
  relapsing
• To assess the familys expectations

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World Federation of Societies of Biological
Psychiatry (WFSBP) 2003 Guidelines

• Acute bipolar mania, mild to moderate
• Acute bipolar mania, severe
• Bipolar depression

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World Federation of Societies of Biological
Psychiatry (WFSBP) 2003 Guidelines

• Acute bipolar mania, mild to moderate
• First line
• Lithium
• Valproate
• Atypical antipsychotic (best evidence olanzapine
  or risperidone)
• Carbamazepine (limited data)
• Second line
• Combine mood stabiliser with 2nd mood stabiliser
  or atypical antipsychotic -or- change mood
  stabiliser
• Adjunctive treatment with benzodiazepines and/or
  low potency/atypical antipsychotics when
  indicated

Grunze H, Kasper S, Goodwin G et al. World J Biol
Psychiatry 200345-13.
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World Federation of Societies of Biological
Psychiatry (WFSBP) 2003 Guidelines (cont.)

• Acute bipolar mania, severe
• First line
• Lithium
• Valproate
• Carbamazepine (limited data)
• Second line
• Combination of 2 mood stabilisers (preferably
  anticonvulsant lithium)
• Third line
• ECT
• Adjunctive treatment with benzodiazepines and/or
  atypical antipsychotic/high potency antipsychotic
  (also injectable) when indicated

Grunze H, Kasper S, Goodwin G et al. World J Biol
Psychiatry 200345-13.
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World Federation of Societies of Biological
Psychiatry (WFSBP) 2002 Guidelines

• Bipolar depression
• First line
• SSRI or bupropion plus lithium or lamotrigine
• Valproate or carbamazepine or selective MAOI
  (limited data)
• Second line
• Combination of 2 mood stabilisers (limited data)
• Third line
• Change AD, consider TCA or irreversible MAOI
• Combination of 2 mood stabilisers, consider
  adding thyroxine
• Fourth line
• ECT
• Adjunctive treatment with benzodiazepines, sleep
  deprivation, atypical antipsychotics when
  indicated

Grunze H, Kasper S, Goodwin G et al. World J Biol
Psychiatry 20023115-124.
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Treatment Strategies for Bipolar Spectrum
Disorder Lieber (2003)?

• Present with predominantly anxiety or depression
  symptoms
• Start initially on an SSRI (e.g. Fluoxetine)
• If symptoms of hypomania occur during the course
  of treatment, add a mood stabilizer (e.g. Sodium
  Valproate)
• If the patient fails to respond to the SSRI
  within four weeks or is unable to tolerate it due
  to side effects, I will switch to a dual
  neurotransmitter antidepressant (Effexor,
  Welbutrin, Remeron, Serzone).
• Once the patient is mood stable and without
  symptoms, monitor at one to three-month
  intervals. Advise to continue the same dose to
  prevent recurrence

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Treatment Strategies for Bipolar Spectrum
Disorder Lieber (2003)?

• Present with either euphoric or dysphoric
  hypomania/ uncontrollable rage/violent outbursts
• Start on a mood stabilizer.
• If necessary, an antidepressant drug can be added
  later after the mood has been stabilized.
• Patients with mixed or rapid cycling states
• Usually respond to combination therapy with mood
  stabilizers and antidepressants.

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Unanswered Questions

• Does bipolar spectrum disorder routinely require
  mood stabilisers?
• How safe are antidepressants in bipolar spectrum?
• What is the optimal duration of treatment?

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Conclusion

• Bipolar Spectrum Disorders are only recently
  recognized
• May explain difficulties in treating mood
  disorder patients
• Treatment strategies need to be optimized
  depending on presenting problems and may need to
  be revised from time to time

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Thank You