1

Mood stabilisers

• At least:• A treatment that is effective in augmenting the management of

mania and/or depression without causing switching into the opposite pole

• Not toxic

• Ideally:• Effective in preventing both mania and depression• Useful in both the acute situation and in relapse prevention• Well tolerated to increase compliance

2

Olanzapine 1

• Has a bipolar license

• Strongly anti-manic

• Found to have mood elevating effects• Less potent than SSRI’s1, though Olanzapine plus fluoxetine

demonstrated superior efficacy for treating resistant depression compared to either agent alone

1. Shelton RC et al. Am J Psych 158: 131-134

3

Olanzapine 2

• Further studies (open label, retrospective case note reviews and case reports) show the benefit of olanzapine in the treatment of depression1,2,3,4,5,6, both as monotherapy and in combination with SSRI’s

• Conflicting evidence regarding metabolic effects:• Weight gain• Abnormal glucose metabolism• Raised cholesterol levels

1. Dube S et al. Biological Psychiatry 51(8 Suppl.) 66S. 20022. Adli M et al. Nervenarzt 70(1): 68-713. Tohen M. et al. European Neuropsychopharmacology 9 (Suppl. 5), S246. 19994. Konig F et al. Neuropsychobiology 43(3), 170-4, 20015. Rothschild AJ et al. Journal of Clinical Psychiatry 60(2), 116-8. 19996. Shelton R et al. Schizophrenia Research 36 (1-3), 297-8. 1999

4

Lamotrigine (1)

• Inhibition of Na channels, inhibit glutamate release

• Clear evidence for efficacy in bipolar depression1 (licensed in 24 countries)

• Studies underway suggestive of and seeking clarity for benefit in rapid cycling bipolar disorder1. Less evidence for efficacy in mania

• Open studies & anecdotal reports of benefit in unipolar and treatment resistant depression2

• No risk of manic switching (highest with tricyclics) – a true mood stabiliser3

• Caution with dose escalation – rash

1. Macdonald KJ & Young LT. CNS Drugs (2002) 16(8): 549-622. Barbee JG & Jamhour NJ. J Clin. Psych. (2002) 63(8) 737-413. Calabrese JR et al. Am J Psych (1999) 156(7): 1019-23

5

Lamotigine – Any Mood Episode1

1. Calabrese et al 2002

6

Lamotigine – Manic Episode1

1. Calabrese et al 2002

7

Lamotigine – Depressive Episode1

1. Calabrese et al 2002

8

Olanzapine

Therapeutic indications

• Olanzapine is indicated for treatment of moderate to severe manic episode1

• In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder1

• If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimisation as needed), with supplementary therapy to treat mood symptoms, as clinically indicated

1. Zyprexa (olanzapine) Summary of Product Characteristics

9

In patients without psychotic featuresPrimary measures: YMRS or remissions rates

Mea

n c

han

ge

in Y

MR

S s

core

OlanzapineHaloperidolVal Ref (s) : Tohen M et al (2001) Poster presented at the APA, New Orleans 2001 Tohen M et al (2002) Am J Psychiatry 159: 1011-1017

0

-2

-4

-6

-8

-10

-12

-14

-16

Olz vs Val3 weeks

60

50

40

30

20

10

0

Olz vs Haloperidol6 weeks

p=0.043p=<0.001

41.6%n=89

41.6%n=89

56.7%n=10456.7%n=104

-14.11n=63

-14.11n=63

-8.69n=72-8.69n=72

%

Pat

ien

ts i

n r

emis

sio

n

10

Time to Relapse into Depression:Based on Symptomatic Rating Scale Criteria*

* HAMD-21 total score >15

Tohen M et al (2002).Presented at 3rd European Stanley Foundation Conference on Bipolar Disorder, Germany, 13 Sept. 2002

p=0.889

OlanzapineLithium

0 50 100 150 200 250 300 350 4000

20

40

60

80

100

Time to relapse of depression (days)

% p

rob

ab

ility

of

rem

ain

ing

in r

em

iss

ion

11

Weight change

Mean change in weight

Change to endpoint

N Mean (kg) SD p-value

Open label Olanzapine / lithium combination

532 2.74 3.8 <0.001

Double-blind OlanzapineLithium

215214

1.79-1.38

5.825.01

<0.001

Tohen M et al (2002).Presented at 3rd European Stanley Foundation Conference on Bipolar Disorder, Germany, 13 Sept. 2002

12

*defined as 7% change from baseline over 52 weeks follow up

Weight change

Potentially clinically significant change in weight following 6–12 weeksof lithium / olanzapine combination treatment*

N n % p-value

Gain OlanzapineLithium

215214

6421

29.89.8

<0.001

Loss OlanzapineLithium

215214

2041

9.319.2

0.004

Tohen M et al (2002).Presented at 3rd European Stanley Foundation Conference on Bipolar Disorder, Germany, 13 Sept. 2002