Bipolar Disorder in DSM 5/ Impact of Bipolar Depression /Bipolar Depression vs. Unipolar Depression /Pharmacotherapy of Bipolar Depression

1. Mohamed sedky
Psychiatric specialist
BMHH
Dec 2014

2.  Bipolar Disorder in DSM 5
 Impact of Bipolar Depression Impact of Bipolar Depression
 Bipolar Depression vs. Unipolar Depression
 Pharmacotherapy of Bipolar Depression

3. Bipolar Disorder in DSM 5

4. Bipolar and Related Disorders are separated from
Depressive Disorders and placed between DepressiveDepressive Disorders and placed between Depressive
Disorders and Schizophrenia Spectrum and Other
Psychotic Disorders to recognize their place as a bridge
in terms of symptoms, family history, and genetics.

7. DSM IV-TR DSM-5
Bipolar I Disorder Bipolar I Disorder
Bipolar II Disorder Bipolar II Disorder
Cyclothymic Disorder Cyclothymic Disorder
Substance-Induced Mood Disorder Substance/Medication-Induced Bipolar
and Related Disorder
Mood Disorder Due to General Medical
Condition
Bipolar and Related Disorder Due to
Another Medical Condition
Other Specified Bipolar and Related
Disorder
Bipolar Disorder NOS Unspecified Bipolar and Related Disorder

8. Mania and Hypomania
Add to Criterion A: “and abnormally and
persistently increased activity or energy”
 Increased activity or energy became a core symptom Increased activity or energy became a core symptom
of mania hypomania.
 Rationale: this will make explicit the requirement of increased
energy/activity in order to diagnose bipolar I or II disorder
(which is not required under DSM-IV) and will improve the
specificity of the diagnosis.

9. Mania and Hypomania:
“Antidepressant switching”
 A full manic/hypomanic episode that emerges
during antidepressant treatment (e.g., medication,during antidepressant treatment (e.g., medication,
electroconvulsive therapy) but persists at a fully
syndromal level beyond the physiological effect
of that treatment is now sufficient evidence for a
manic/hypomanic episode and, therefore, a
bipolar diagnosis.

13. No more “Mixed episode”
“Mixed episode” is replaced with a “with mixed
features” specifier for manic, hypomanic, andfeatures” specifier for manic, hypomanic, and
major depressive episodes (> 3 symptoms from other pole).
– Rationale: DSM-IV criteria excluded from diagnosis the
sizeable population of individuals with subthreshold mixed states
who did not meet full criteria for major depression and mania,
and thus were less likely to receive treatment.

14. OLD & NEW BIPOLAR SPECIFIERS
Moderate

15. “With anxious distress” also added as a specifier
for bipolar (and depressive) disorders
 – Rationale: the co-occurrence of anxiety with– Rationale: the co-occurrence of anxiety with
depression is one of the most commonly seen
comorbidities in clinical populations. Addition of this
specifier will allow clinicians to indicate the presence
of anxiety symptoms that are not reflected in the core
criteria for depression and mania but nonetheless may
be meaningful for treatment planning.

16. • The presence of at least two of the following symptoms
during the majority of days of the current or most recent
episode of mania, hypomania or depression:
 Feeling keyed up or tense
 Feeling unusually restless Feeling unusually restless
 Difficulty concentrating because of worry
 Fear that something awful may happen
 Feeling that the individual might lose control of himself or herself
• Higher levels of anxiety associated with higher suicide
risk, longer duration of illness and greater likelihood of
treatment nonresponse.

18.  With Peripartum onset. Can be applied to
current/most recent episode of mania, hypomania, or
depression in Bipolar I or II if onset of mood symptoms
was during pregnancy or in the 4 weeks following
delivery.delivery.
 With Seasonal pattern. Regular temporal
relationship between onset (and remission) of manic,
hypomanic, or depressive episodes and a particular time of
year. Does not include cases where there is an obvious
psychosocial stressor related to the season.

22.  Numerous periods with hypomanic symptoms Numerous periods with hypomanic symptoms
that do not meet criteria for a hypomanic
episode and numerous periods with depressive
symptoms that do not meet criteria for a major
depressive episode, for at least 2 years (at least
1 year in children and adolescents).

24. Develops during or soon after (within 1 month)
substance intoxication or withdrawal or after
exposure to a medication
 Sedative, hypnotic or anxiolytic
 Amphetamine
 Cocaine
 Alcohol
 Phencyclidine
 Hallucinogens

26. There is evidence from the history, physical
examination, or laboratory findings that the
disturbance is the direct pathophysiological
consequence of another medical condition.consequence of another medical condition.
Specify if:
 With manic features
 With manic- or hypomanic-like episode
 With mixed features

28.  Short-duration hypomanic episodes (2–3 days) and
major depressive episodes
 Hypomanic episodes with insufficient symptoms and Hypomanic episodes with insufficient symptoms and
major depressive episodes
 Hypomanic episode without prior major depressive
episode
 Short-duration cyclothymia (less than 24 months)

30. used in situations in which the clinician chooses
not to specify the reason that the criteria are
not met for a specific bipolar and relatednot met for a specific bipolar and related
disorder
Includes presentations in which there is insufficient information
to make a more specific diagnosis (e.g., in emergency room
settings).

32. It's A Serious Illness

33. 9%
6%
46%
1% 2%
Asymptomatic
Depressed
Manic/hypoman
% of Weeks
146 bipolar I patients146 bipolar I patients
followed 12.8 yearsfollowed 12.8 years
86 bipolar II patients86 bipolar II patients
followed 13.4 yearsfollowed 13.4 years
53%
32%
46%
50%
Judd et al (2002) Archives of General
Psychiatry (59) 530-537
Judd et al (2002) Archives of General
Psychiatry (59) 530-537
Judd et al (2003) Archives General
Psychiatry. (60) 261-269
Judd et al (2003) Archives General
Psychiatry. (60) 261-269
Cycling / mixed

34. High Suicide RiskBipolar Depression

35. Risk of suicide is higher during:
Bipolar Depression ˃ Bipolar Mania
Bipolar Depression ˃ Unipolar Depression

36. 51
46
39
40
50
60
Percent of
Anxiety
Substance Use39
10 8
0
10
20
30
Percent of
Patients
Disorders
Substance Use
Psychosis
ADHD
Eating
Kogan et al., 2004

37. Is It Unipolar
Or BipolarOr Bipolar
Depression ?!!

39. Trigger
Mania
And
AnxietyUnopposed
Antidepressants
in Bipolar
Depression Unopposed
Antidepress-
ants
Poor
Response
Increase
Risk Of
Suicide
Induce
Rapid
Cycling
Depression

40.  Risk of switching to mania:
 Bupropion 5-10%
 SSRIs 7-9% SSRIs 7-9%
 SNRIs 15-29%
 TCAs 43%
 Switching more common with bipolar I than II

41. The most commonly Prescribed
drugs in the USA for Bipolar
Disorders are ……Disorders are ……
Antidepressants ‼

43.  Antidepressant monotherapy should be avoided in bipolar
disorder.
 Adjunctive antidepressants may be used for an acute bipolar
depression when there is a history of previous positive response
to antidepressants. And patient should be closely monitored forto antidepressants. And patient should be closely monitored for
signs of hypomania or mania and increased psychomotor
agitation, in which case antidepressants should be discontinued.
 Maintenance treatment with adjunctive antidepressants may
be considered if a patient relapses into a depressive episode after
stopping antidepressant therapy.

44.  Adjunctive antidepressants should be avoided in
bipolar disorder:
During manic episodes
During depressive episodes with mixed features.
In the presence of psychomotor agitation or rapid cycling.In the presence of psychomotor agitation or rapid cycling.
History of “Antidepressant switching”
 tricyclics, tetracyclics, and SNRIs should be avoided

45. 2004
•Symbyax (Prozac and Zyprexa)
2007
•Seroquel (Quetiapine)
2013
•Latuda (Lurasidone)

46.  An atypical antipsychotic developed by Dainippon
Sumitomo Pharma and marketed by Sunovion in the
USA.
 FDA approved in 2010FDA approved in 2010
 Indications
o Treatment of schizophrenia in adults
o Treatment of depressive episodes in bipolar disorder in adults as both
monotherapy and adjunctive therapy
 Mechanism of action thought to be a combination of
dopamine D2 and serotonin 5HT2 receptor blockade
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.

47.  As monotherapy
 A 6-week trial vs. placebo for symptom reduction in
bipolar depression showed that both doses of Lurasidone
studied were superior to placebo at 6 weeks
As an adjunct As an adjunct
 A 6-week trial of patients who were still symptomatic on
lithium or valproic acid were given placebo or lurasidone.
At 6 weeks, there was a superior symptom reduction in the
Lurasidone group vs. the placebo group
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.

50.  Metabolic changes and weight gain
 Possibly the most weight and metabolic neutral
 EPS – akathisia more common than others
 QTc prolongation QTc prolongation
 Sedation or somnolence
 Nausea and vomiting
 Rarer side effects – agranulocytosis, seizures, and
orthostasis
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.

51.  For bipolar depression, starting dose is 20
mg/day with a range of 20-120 mg/day
 All doses should be taken with a meal of at All doses should be taken with a meal of at
least 350 calories to improve absorption
 Dosing is recommended in the evening due to
the possibility of sedation and somnolence
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.

52. 1999 - 2012
72 RCTs
9,006 Patients

53. Statistically
superior to placebo
Not statistically
superior to placebo
Not higher than
placebo
Lurasidone Imipramine oAripiprazoleLurasidone
Valproate
Quetiapine
Combined Olanzapine
/Fluoxetine
Olanzapine
lamotrigine
Imipramine
Lithium
Moclobemide
Paroxetine
ziprasidone
oAripiprazole

56. Replace
Replace
Replace
Replace
Replace
Replace Replace

59. A review conducted by the US Food and Drug
Administration concluded that the evidence for treating
bipolar major depression with ECT is strong.bipolar major depression with ECT is strong.
 Goodman WK. Electroconvulsive therapy in the spotlight. N Engl J Med 2011; 364:1785.
 FDA Executive Summary: Prepared for the January 27-28, 2011 meeting of the Neurological
Devices Panel. Meeting to Discuss the Classification of Electroconvulsive Therapy Devices
(ECT).

60. Open label randomized trials suggest that for patients with
bipolar major depression, ECT is superior to
pharmacotherapy.
 Loo C, Katalinic N, Mitchell PB, Greenberg B. Physical treatments for bipolar disorder: a review
of electroconvulsive therapy, stereotactic surgery and other brain stimulation techniques. J Affect
Disord 2011; 132:1.

61. A pooled analysis of six observational studies compared
the efficacy of ECT in bipolar major depression (n =
316) with the efficacy in unipolar major depression (n =
790 patients); each study included bipolar and unipolar
patients, and five studies were prospective. Remissionpatients, and five studies were prospective. Remission
rates were similar for bipolar and unipolar patients (53
and 51 percent).
 Dierckx B, Heijnen WT, van den Broek WW, Birkenhäger TK. Efficacy of
electroconvulsive therapy in bipolar versus unipolar major depression: a meta-analysis.
Bipolar Disord 2012; 14:146.

62. Some studies suggest that response to ECT occurs more
rapidly in bipolar major depression than unipolar majorrapidly in bipolar major depression than unipolar major
depression.
 Daly JJ, Prudic J, Devanand DP, et al. ECT in bipolar and unipolar depression: differences
in speed of response. Bipolar Disord 2001; 3:95.
 Sackeim HA, Prudic J. Length of the ECT course in bipolar and unipolar depression. J ECT
2005; 21:195.

63. Don’t forget ECT when your patient:
 medication resistant
 psychotic signs psychotic signs
 catatonic features
 Suicidal
 pregnant

65.  In DSM 5: No more “Mixed episode” and increased activity or energy
became a core symptom of mania/ hypomania.
 The treatment of bipolar depression is a major challenge.
 Bipolar Disorder Symptoms are Chronic and Predominantly Depressive.
 Bipolar depression encompasses a high suicide risk.
 Antidepressant monotherapy should be avoided in bipolar depression
 Combined Olanzapine /Fluoxetine, Quetiapine, and Lurasidone are the FDA
approved drugs for bipolar depression.
 The evidence for treating bipolar major depression with ECT is strong