Mood Disorders (18.19-2-2010)

1. By
Dr. Maged Al Adrousy
Lecturer of psychiatry- Cairo university

2. introduction
 Bipolar disorder is an episodic, potentially
life-long, disabling disorder that can be
difficult to diagnose.
 known as Manic Depression, Results in
pathological mood swings from mania to
depression, These mood swings occur
spontaneously.

3. Mania
Euthymia
Depression

4. History
 Bipolar Disorder
 200 CE First reports
 1654 Jean Pierre Falret
 “folie circulaire" (circular insanity)
 Familial illness
 1913 Emil Kraepelin
 Manic - Depressive
 1930’s ECT first used
 1949 Lithium first used
 1950 Chlorpromazine first used
 1952 Genetic link recognized
 1980 Bipolar Disorder term adopted
 1995 Depakote approved for BP
 2003 First atypical approved for BP

5. Types of Mood Disorders
10%
2%
 DSM IV
2% MDD
 Major Depressive Disorder
BP I
 Dysthymic Disorder
BP II
 Bipolar Disorder Type I
NOS
 Bipolar Disorder Type II 86%
 Cyclothymic Disorder
 NOS
 Mixed Phase
 Rapid Cyclers 33% MDD
BP I
 Bipolar Spectrum (BPS) 50%
BP II
BPS
15% 2%

6.  Bipolar disorder is a cyclical mood disorder
 Abnormally elevated mood or irritability
alternates with depressed mood
bipolar I – at least one manic or mixed episode
bipolar II – at least one major depressive episode
and at least one hypomanic episode
Cyclothymia = hypomania with “minor” depression
“Bipolar spectrum” = Depression + other complexities
 Bipolar NOS or Mood DO NOS

7. Structure of a Recurrent
Illness
Precipitant
Episode
Underlying illness

8. Spectrum of Illness Course
Episodic Unstable
Purely episodic course: Radical mood instability:
-interepisode stability -’interepisode’ instability
-no mixed states -mixed states
-infrequent episodes -frequent episodes
-good recovery -incomplete recovery
-low incidence of complications -high incidence of complications
-early onset
-stronger genetic loading?
Course of illness dictates response strategies for the acute episode

9. DIAGNOSTIC CRITERIA FOR MANIC
EPISODES
THREE TO FOUR OF THE FOLLOWING CRITERIA ARE REQUIRED
DURING THE ELEVATED MOOD PERIOD
Highly inflated or grandiose self-esteem
Decreased need for sleep, or rested after only a few hours of sleep
Pressured speech
Racing thoughts and flight of ideas
Easy distractibility, failure to keep attention
Increased goal-directed activity
High excess involvement in pleasurable activities (sex, travel, spending
money)
General criteria for a manic episode require a period of elevated, expansive,
or irritable mood that lasts 1 week or requires hospitalization. A general
medical condition and substance abuse must be ruled out before these
symptoms are considered mania.

10. Manic Episode:
Differential Diagnoses
Differential diagnosis Consider if . . .
Mood disorder due to a Major medical condition present
general medical
condition First episode at >50 years of age
Symptoms in context of intoxication
Substance-induced or withdrawal
mood disorder History of treatment for depression
Mood disturbance not severe
Hypomanic episode enough to require hospitalization
or impair functioning
Mixed episode Manic episode and MDE in 1 week

11. Manic Episode:
Differential Diagnoses (cont.)
Differential diagnosis Consider if . . .
AD/HD Early childhood mood disturbance onset
Chronic rather than episodic course
No clear onsets and offsets
No abnormally elevated mood
No psychotic features
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV). 4th ed. 1994.

12. Major Depressive Episode:
DSM-IV Criteria
 Depressed mood and/or loss of interest
or pleasure ≥ 2 weeks duration
 Associated symptoms
 Physical: insomnia/hypersomnia, appetite/weight
change, decreased energy, psychomotor change
 Psychological: feelings of guilt or worthlessness,
poor concentration/indecisiveness, thoughts
of death/suicidal intentions (SI)

13. …and ≥4 of the following symptoms
 Physical  Psychological
 Sleep disorder  Low self
 Appetite change esteem/guilt
 Poor concentration/
 Fatigue
indecisiveness
 Psychomotor
 Thoughts of death/SI
retardation

14. Mixed Episode: Diagnostic
Criteria
 Criteria met for both manic episode + MDE
for ≥1 week
 Symptoms
 Are sufficient to impair functioning
or
 Necessitate hospitalization
or
 Are accompanied by psychotic features

15. Epidemiology
 Peak age of onset: adolescence through early 20s
 Onset of first manic episode after age 40 years is
“red flag” to consider substance use or general
medical condition
 Lifetime suicide rates range from 10% to 15%
 Seasonal variation
 Depression more common in spring and autumn
 Mania more common in summer

16. Bipolar Disorders:
Epidemiology
Characteristics BPD I BPD II
Prevalence ≤1.6% 0.5%
Ethnic/racial
differential None None
Gender
differential M=F F›M (?)

17. Bipolar Disorders: Epidemiology
Characteristics BPD I BPD II
Course Recurrent in >90% Hypomanic episodes in
of cases BPD II immediately
precede or follow MDEs
in 60% to
70% of cases
First-degree First-degree relatives
Familial pattern relatives have may have increased
increased rates of rates of BPD I, BPD II,
BPD I, BPD II, and and MDD
MDD

18. Diagnostic Dilemmas:
Unipolar Versus Bipolar
No evidence of hypomania,
Unipolar cyclothymia, hyperthymic personality,
or family history of BPD
≥1 manic episode
BPD I Recurrent major depression with
BPD II hypomania and/or cyclothymic
temperament
Recurrent major depression without
BPD NOS spontaneous hypomania but often with
hyperthymic temperament
and/or family history of BPD

19. Bipolar vs unipolar

20. BD II

21. CYCLOTHYMIC DISORDER
 Cyclothymic disorder is
a recurrent, chronic,
mild form of bipolar
disorder in which mood
typically oscillates
between hypomania
and dysthymia.
 If a manic episode or
depressive episode is
experienced,
cyclothymic disorder is
not diagnosed. http://www.allaboutdepression.com/cyclothymia/images/graph
ic2.gif

22. CYCLOTHYMIC DISORDER
EPIDEMIOLOGY ETIOLOGY
The lifetime prevalence of Genetic and familial studies reveal
cyclothymic disorder is 0.4% to 1%. an association with other mood
disorders
The rate appears equal in men and
women, although women are
usually more likely to seek
treatment

23. CLINICAL MANIFESTATIONS OF
CYCLOTHYMIC DISORDER
 Cyclothymic disorder is a milder form of bipolar
disorder consisting of recurrent mood
disturbances between hypomania and
dysthymic mood.
 A single episode of hypomania is sufficient
enough to diagnose cyclothymic disorder,
although most individuals also have dysthymic
periods.
 Cyclothymic disorder is never diagnosed when
there is a history of mania, major depressive
episode, or mixed episode.

24. Etiology

25. Heritability
 Evidence for heritability is much stronger for
bipolar than for unipolar disorders
 Specific genetic association has not been
consistently replicated

26. EVIDENCE FOR HERITABILITY OF
BIPOLAR DISORDER
 Family Studies- First degree relatives are 8 to 18
times more likely to have Bipolar I
 2 to 10 times to have MDD.
 Risk is 25% if one parent has illness, and 50% to
75% with both parents affected

27. FAMILY STUDIES
 The majority of individuals with bipolar disorder
have a positive family history of some type of
mood disorder
 About 50% of all bipolar I patients have at least
one parent with a mood disorder

28. ADOPTION STUDIES
 Prevalence of bipolar disorder in adopted away
offspring corresponds to rates in biological, but
not adoptive relatives
 Twin Studies- Concordance rate in MZ twins
is 33 to 90%, in DZ is 5 to 25%

29. Genetic Polymorphism
 A functional polymorphism is a genetic variant
that appears in at least 1% of a population and
alters the biological functioning of the individual
 Some types of polymorphisms in Mood
Disorders
 Serotonin transporter
 Serotonin 2A receptor
 MTHF reductase
 Catachol -o- methyl tranferase (COMT)
 Tyrosine hydroxylase
 Cytochrome P450 metabolism of medications

30. Biological factors
 Dysregulation in levels catecholamines (++
levels of dopamine and norepinephrine).
 -- levels of serotonoine ??
 Neuroendocrinal factors:
• HPA axis (cortisol hypersecreation) may
affect BDNF.
• Throid dysfucntion.
 EEG changes (kindling model)
 Degenerative structural brain changes.

31. Psychosocial factors
 Life time events.
 Behavioral models .
 Psychological theories.

32. Impact of BD
 Higher rates of mortality from other medical conditions
 Increased substance abuse risk
 Lifetime suicide attempt risk (.02% in general populatio
 Bipolar Disorder Type I – 17%
 Bipolar Disorder Type II – 24%
 90% of completed suicides can be traced back to a
Mood Disorder
 High rates of cognitve defeicets affecting Working
memory Sustained attention, Abstract reasoning,
Visuomotor skills, Verbal memory, Verbal fluency,
Cognitive flexibility

33. Management

34. A- psychopharmacology
 Mood stabilizers
 Atypical antipsychotics.
 Benzodiazepines.
 Channel blockers.
 Others
 Combination therapy is more effective than
monotherapy

35. Mood stabilizers
 Lithium
 Conventional anti-epileptics as
carbamazepine and Na valproate.
 New anti-epileptics lamotrigene
gababentine, and topiramate

36. What Exactly Is a Mood
Stabilizer?
• Some authorities suggest 2 out of 3 of the
following properties:
– Antimanic, antidepressive, prophylactic
• Other experts are more stringent—requiring:
– Treatment of acute mania,
– Treatment of acute depression, AND
– Prevention of recurrent mania and depression
– Dosen’t ppt mania or depression.
• Lithium remains the gold standard

37. Lithium
 Widely recommended treatment for
Bipolar Disorder
 60-80% success in reducing acute manic
and hypomanic states
 However… issues in non-compliance to
take medication, side effects, and relapse
rate with its use are being examined in
terms of being the best option

38. Pharmacokinetics:
 Peak blood levels reached in 3 hrs, fully
absorbed in 8 hrs
 Absorbed rapidly and completely orally
 Efficacy correlates with blood levels
 Crosses blood-brain barrier slowly and
incompletely
 Usually taken as a single daily dose

39. Kinetics Cont.
 Approx. 2 wks to reach a steady state
within the body
 ½ of oral dose excreted in 18-24 hrs,rest
within 1-2 wks
 Recommended 0.8-1.2 mEq/L, optimum
would be 0.6-0.8 mEq/L, with 2 mEq/L
displaying toxicity .
 Monovalent ion not metabolized in liver,
excreted by the kidney.

40. Pharmacodynamics
 No psychotropic effect on non-Bipolars
 Affects nerve membranes, multiple receptor
systems and intracellular 2nd messenger
impulse transduction systems.
 Interacts with serotonin
 Potential to regulate CNS gene expression,
stabilizing neurons w/ associated multiple
gene expression change.

41. How does a simple ion do all of
this?
 Even as a simple ion, it has complex
effects on multiple transmitter systems
and mood stabilizing attributes
 This is due to a latter effect reducing a
neuron’s response to synaptic input, and
therefore stabilizing the membrane

42. Side Effects and Toxicity
 Relate to plasma concentration levels, so
constant monitoring is key
 Higher concentrations ( 1.0 mEq/L and up
produce bothersome effects, higher than 2
mEq/L can be serious or fatal
 Symptoms can be neurological,
gastrointestinal, enlarged thyroid, rash,
weight gain, memory difficulty, kidney
disfunction, cardiovascular
 Not advised to take during pregnancy, affects
fetal heart development

43. Side effects of Li
1. GIT symptoms (diarrhea intially)
2. Hypokalaemia…….cardiotoxic.
3. Polyuria and D.insipius (ADH).
4. Tremors.
5. Epileptogenic.
6. Teratogenic.
7. hypothyroidism
8. Li toxicity may occure (ttt?)

44. Na valproate
 Tab 200mg and 500 mg
 Dose 50-150 mg%
 Best for rapid-cycling and acute-mania
 Actions: through GABA potentiation, Ca
channel blockade, Na channel blockade,
glutamat antagonist.

45.  Side effects
2. Hepatotoxic.
3. Wt gain
4. Hair loss.
5. GIT symptoms.
6. Tremors and sedation
7. Neural tube defects

46. carbamazepine
 Tab 200mg 400 mg
 Dose 5-15 µg/L
 Action similar to valproate.
 Superior to lithium for rapid-cycling, regarded
as a second-line treatment for mania
 Correlation between therapeutic and plasma
levels (estimated between 5-10 Mg/L)
 Side effects:
7. Agranulocytosis
8. Skin reaction
9. Teratogenic
10.Liver enzyme induction

47. Gabapentin
 Primarily an anti-convulsant, yet also “off
label,” or without FDA approval for treatment
of Bipolar and many other anxiety, behavioral
and substance abuse problems, possibly pain
disorders
 GABA analogue
 not bound to plasma proteins, not
metabolized, few drug interactions
 Half-Life is 5-7 hours
 Side Effects include
sleepiness,dizziness,ataxia and double vision

48. Lamotrigine
 Reported effective with Bipolar,
Borderline Personality, Schizoaffective,
Post-Traumatic Stress Disorders
 98% of administered drug reaches
plasma
 Half-Life is 26 hrs.
 Inhibits neuronal excitability and
modifies synaptic plasticity
 Side Effects may include dizziness,
tremor, headache, nausea, and rash

49. Topiramate and Tiagabine
 Two newer anti-convulsants that have
potential for use in the treatment of
Bipolar disorder

50. Anticonvulsants: Efficacy in
BD
 Probably effective:
 Lamotrigine, CBZ, oxycarbazepine, valproate
 Possibly effective:
 Gabapentin, zonisamide, phenytoin,
levetiracetam
 Ineffective/problematic:
 Topiramate, tiagabine, vigabatrin

51. Calcium Channel Blockers
 Modulate transmitter release & plasticity
 Most not consistently effective, possibly due to
inconsistent uptake into brain
 Nimodipine reported effective in rapid-cycling,
including refractory & ultra-rapid

52. Atypical Anti-psychotics
 Risperidone seems more anti-depressant
than anti-psychotic
 Clozapine is effective, yet not readily
used due to potential serious side effects
 Olanzapine is approved for short-term
use in acute mania
 Quatiapine is now approved as a broad
spectrum medication in BD esp (Bipolar
depression).

53. Acetylcholinesterase Inhibitors
 Potentiating the action of acetylcholine
may exert relief from mania
 This potentiation is the result of
inhibiting the enzyme acetylcholine
esterase

54. Omega-3 Fatty Acids
 Obtained from plant or marine sources
 Known to dampen neuronal signaling
transduction systems in a variety of cell
systems
 Being investigated as a treatment for
Bipolar Disorder

55. Three Phases of Treatment
Episode Continuation Maintenance
0-2 months 2-12 months Indefinite
Symptomatic Functional Stability/adaptive
Each phase has specific goals
Each phase has specific pharmacological and nonpharmacological rx
Treatment must be harmonized across phases

56. Nonpharmacologic
Treatments
 ECT
 Reports of effectiveness in mania, depression, &
refractory mixed states
 Bilateral generally more effective
 Continuation ECT may prolong recovery;
maintenance?
 Transcranial magnetic stimulation
 Psychotherapy : May include cognitive
behavioral, psychodynamically oriented, family,
couples, interpersonal, and self-help group
therapies

57. Thank you