Relapse prevention: Role of LAI

Why treat Schizophrenia ? Outcome in Schizophrenia

What is Relapse ?

The Cost of Relapse

2 to 5 times more than non-relapsed patients
Direct
- Rehospitalization
- emergency room visits
Indirect
- Loss of productivity
- QOL of the patient & relatives

Relapse Fuels the Progression of Illness With each relapse

Recovery can be slower and less complete

More frequent admissions to hospital
Illness can become more resistant to treatment
Increased risk of self-harm and homelessness
Regaining previous level of functioning is harder
Loss of self-esteem
Social and vocational disruption
Greater use of healthcare resources
Increased burden on families, caregivers

Lieberman JA. European Neuropsychopharmacol. 1996;6(Supplement 3):155.

Szymanski S et al., Am J Psychiatry. 1995;152(5):698-703.
Lieberman J. et al., Arch Gen Psychiatry. 1993;50(5):369- 76.

Is Relapse Immune
Mediated?

THE JOURNAL OF L I F ELONG LEARNING IN PSYCHIATRY

Spring 2012, Vol. X, No. 2

Relapse prevention is the main goal of the

maintenance treatment of schizophrenia

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Clinical Data: Antipsychotics

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What do we expect from an antipsychotic?

Treat psychosis

Reduce symptoms
Reduce symptoms below a threshold to
make a diagnosis : Symptom resolution
Maintain the patient with no more than
mild positive or negative symptoms for > 6
months : Remission
Recovery is the ultimate goal
Antipsychotics reduce relapse rates by 30-40%
Prophylactic effect in fully remitted patients
Maintain current functional status in partially remitted patients

Davis, J.M. et al.,Drugs.1994;47:741-73

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Depot vs. Oral

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Current status of LAI SGAs

RLAI

Olanzapine
pamoate

Paliperidone
palmitate

Administered
intramuscularly every 2
weeks1

Approved for use in the

EU and other countries2

Once-monthly deltoid or
gluteal administration,
approved in several
countries including the
USA3 and EU4

Available for deltoid and

gluteal administration

Risk of PDSS*

No refrigeration
or reconstitution

Iloperidone depot5 and aripiprazole depot6 are under development

*PDSS adverse events with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium, have been
reported following injections of olanzapine pamoate. After each injection, patients must be observed by a healthcare professional for at least 3 hours
LAI, long-acting injectable; SGA, second-generation antipsychotic; RLAI, risperidone long-acting injectable;
EU, European Union; PDSS, post-injection delirium/sedation syndrome
1. Risperdal Consta SmPC; 2. ZypAdhera SmPC; 3. Invega Sustenna US Prescribing Information; 4. Xeplion EU SmPC;
5. Study NCT01348100, www.ClinicalTrials.gov, accessed August 2011; 6. Study NCT00706654 www.ClinicalTrials.gov, accessed August 2011

Impact of LAI antipsychotics early in disease course

Risk of re-hospitalization in
nationwide cohort of
consecutive patients with
schizophrenia hospitalized for
the first time in Finland
Data obtained from national
databases of hospitalization,
mortality and AP prescriptionsa

Risk of re-hospitalization by antipsychotic

treatment pattern (n=2588)
Haloperidol, depot
Clozapine
Olanzapine
Other antipsychotics
Risperidone, depot
Perphenazine, depot
Polypharmacy
Zuclopenthixol, depot
Risperidone, oral

Risk of re-hospitalization for patients

receiving LAI medications was about
one-third of that for patients receiving
oral medicationsb

Perphenazine, oral
Quetiapine
No treatment
Haloperidol, oral
Zuclopenthixol, oral
0

Hazard ratio with 95% CI

aCalculated

hazard ratios were adjusted for effects of sociodemographic and clinical variables, temporal sequence of APs used, and the choice of
the initial AP for each patient; bPairwise comparison [adjusted hazard ratio=0.36, 95% CI=0.170.75)]
LAI, long-acting injectable; AP, antipsychotic; CI, confidence interval
Reproduced with permission

Tiihonen et al. Am J Psychiatry 2011;168:603609

Relapse in patients treated with injectable vs oral

formulations
Study or
subgroup

LAI/Depot

Risk ratio
MH, random, 95% CI

Oral

Events

Total

Events

Total

Arango 2005
Barnes 1983
Del Guidice 1975
Falloon 1978
Gaebel 2010
Hogarty 1979
Li 1996*
Potapov 2008
Rifkin 1977
Schooler 1979
Total (95% CI)

10
3
21
8
54
22
32
4
2
26

26
19
27
20
355
55
155
20
23
143
843

6
3
30
5
102
32
52
8
3
35

20
17
31
24
355
50
137
20
28
147
829

Total events

182

276

Weight
(%)
5.2
1.9
22.8
4.2
18.6
14.8
15.1
3.6
1.4
12.4
100.0
0.01

0.1

Favours depot

10

100

Favours oral

Significantly fewer (21.6%) participants in the depot than in the

oral group (33.3%) relapsed
*In Li et al. the allocation of 28 out of 320 participants was unclear, reducing the total number of participants from 1700 to 1672; Fluphenazine depot, risperidone
long-acting-injectable, haloperidol-decanoate and zuclopenthixol-depot; Fluphenazine, pimozide, zuclopenthixol, quetiapine, olanzapine and any antipsychotic;
LAI, long-acting injectable; CI, confidence interval; MH, MantelHaenzel estimate

Reproduced with permission

Leucht et al. Schizophr Res 2011;127:8392

RLAI in FES

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Reduction in relapse with paliperidone palmitate

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Reduction in relapse with paliperidone palmitate in

recently diagnosed patients

p<0.0001

p=0.0025
50

44%

40
30
20

20%

10
0

Paliperidone
palmitate
(n=70)

Placebo
(n=75)

5 years since diagnosis (n=145)

Subjects with recurrence (%)

Subjects with recurrence (%)

Recurrence rate, by time since diagnosis and treatment

48%

50
40

30
20

13%

10
0

Paliperidone
palmitate
(n=135)

Placebo
(n=128)

>5 years since diagnosis (n=263)

Following initial 33-week,

open-label paliperidone
palmitate transition and
maintenance phase,
remitted patients entered
a variable-length,
randomized, double-blind,
placebo-controlled relapse
prevention phase
At randomization:
35% (n=145) patients with
recently diagnosed
schizophrenia
(5 years since diagnosis)

The recurrence rate was significantly lower in paliperidone

palmitate-treated compared with placebo-treated subjects,
regardless of the time since diagnosis
Alphs et al. Poster presented at APA, May 1621 2009, San Francisco, CA, USA

Improved symptoms with paliperidone palmitate in

recently diagnosed patients
Post hoc analysis of a 13-week trial. All groups received paliperidone palmitate 150 mg eq. on
Day 1 or matching placebo

p<0.001
p=0.0031

Significant symptomatic improvements were observed in paliperidone

palmitate-treated subjects, regardless of the time since diagnosis
PANSS, Positive and Negative Syndrome Scale

Bossie et al. Ther Adv Psychopharmacol 2011;1:111124

Treatment algorithm for acute schizophrenia potential role for

LAI SGA
Patients in acute phase of schizophrenia
Early psychosis

Good adherence
profile
Consider
patients choice
Explain chronic
disease model

Relapse
(due to poor adherence)
Poor adherence
risk profile*

Prior exposure
to neuroleptic

Consider LAI SGA ( oral or

short-acting IM antipsychotic
and/or benzodiazepines, as
needed)
Use oral antipsychotic if appropriate
and preferred by patient

LAI, long-acting antipsychotic; SGA, second-generation antipsychotic

Highly aroused
and agitated
Neuroleptic
naive

Proceed as per
local or
institutional
acute arousal
guidelines

Newton et al. Curr Med Res Opin. 2012;28:559567

Benefits of Long Acting Antipsychotics

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Disadvantages of Long Acting Antipsychotics

28

Depot Antipsychotics: Busting the Myths

29

Guidelines Recommendation

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Thanks !

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