Mohamed sedkyPsychiatric specialist

BMHHDec 2014

Bipolar Disorder in DSM 5

Impact of Bipolar Depression Impact of Bipolar Depression

Bipolar Depression vs. Unipolar Depression

Pharmacotherapy of Bipolar Depression

Bipolar Disorder in DSM 5

Bipolar and Related Disorders are separated fromDepressive Disorders and placed between DepressiveDepressive Disorders and placed between DepressiveDisorders and Schizophrenia Spectrum and OtherPsychotic Disorders to recognize their place as a bridgein terms of symptoms, family history, and genetics.

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 MedicalCondition

Bipolar and Related Disorder Due to Another Medical Condition

Other Specified Bipolar and Related Disorder

Bipolar Disorder NOS Unspecified Bipolar and Related Disorder

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.

Mania and Hypomania:

“Antidepressant switching”

A full manic/hypomanic episode that emergesduring antidepressant treatment (e.g., medication,during antidepressant treatment (e.g., medication,electroconvulsive therapy) but persists at a fullysyndromal level beyond the physiological effectof that treatment is now sufficient evidence for amanic/hypomanic episode and, therefore, abipolar diagnosis.

No more “Mixed episode”

“Mixed episode” is replaced with a “with mixed features” specifier for manic, hypomanic, and features” 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.

OLD & NEW BIPOLAR SPECIFIERS

Moderate

“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.

• 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.

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 followingdelivery.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.

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).

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

There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiologicalconsequence of another medical condition.consequence of another medical condition.

Specify if: With manic features

With manic- or hypomanic-like episode

With mixed features

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)

used in situations in which the clinician chooses not to specify the reason that the criteria are not met for a specific bipolar and related not 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).

It's A Serious Illness

9%6%

46%

1% 2%

AsymptomaticDepressedManic/hypoman

% of Weeks

146 bipolar I patients146 bipolar I patientsfollowed 12.8 yearsfollowed 12.8 years

86 bipolar II patients86 bipolar II patientsfollowed 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

High Suicide RiskBipolar Depression

Risk of suicide is higher during:

Bipolar Depression ˃ Bipolar Mania

Bipolar Depression ˃ Unipolar Depression

5146

39

40

50

60

Percent of

Anxiety

Substance Use39

10 80

10

20

30Percent of

Patients

Disorders

Substance Use

Psychosis

ADHD

Eating

Kogan et al., 2004

Is It Unipolar Or Bipolar Or Bipolar Depression ?!!

Trigger ManiaAnd

AnxietyUnopposed Antidepressants in Bipolar Depression

Unopposed Antidepress-

ants

Poor Response

Increase Risk Of Suicide

Induce Rapid

Cycling

Depression

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

The most commonly Prescribed drugs in the USA for Bipolar Disorders are ……Disorders are ……

Antidepressants ‼

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 for to 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.

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

2004•Symbyax (Prozac and Zyprexa)

2007•Seroquel (Quetiapine)

2013•Latuda (Lurasidone)

An atypical antipsychotic developed by Dainippon Sumitomo Pharma and marketed by Sunovion in the USA.

FDA approved in 2010FDA approved in 2010

Indicationso 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.

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.

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.

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.

1999 - 2012

72 RCTs

9,006 Patients

Statisticallysuperior to placebo

Not statisticallysuperior to placebo

Not higher than placebo

Lurasidone Imipramine oAripiprazoleLurasidoneValproateQuetiapineCombined Olanzapine /FluoxetineOlanzapinelamotrigine

ImipramineLithiumMoclobemideParoxetineziprasidone

oAripiprazole

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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).

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.

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 unipolarpatients, and five studies were prospective. Remission patients, 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.

Some studies suggest that response to ECT occurs more rapidly in bipolar major depression than unipolar major rapidly 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.

Don’t forget ECT when your patient: medication resistant

psychotic signs psychotic signs

catatonic features

Suicidal

pregnant

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