Relapse_Prevention-_The_Role_of_LAI.ppt

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Relapse prevention: Role of LAI


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Why treat Schizophrenia ? Outcome in Schizophrenia

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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

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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.


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Is Relapse ImmuneMediated?

THE JOURNAL OF L I F ELONG LEARNING IN PSYCHIATRY

Spring 2012, Vol. X, No. 2


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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?

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Treat psychosis

Reduce symptoms

Reduce symptoms below a threshold tomake a diagnosis : Symptom resolution

Maintain the patient with no more thanmild positive or negative symptoms for > 6months :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

Administeredintramuscularly every 2

weeks1

Available for deltoid andgluteal administration

Olanzapinepamoate

Approved for use in theEU and other countries2

Risk of PDSS*

Paliperidonepalmitate

Once-monthly deltoid or

gluteal administration,approved in several

countries including theUSA3and EU4

No refrigerationor reconstitution

Iloperidone depot5and aripiprazole depot6are under development

LAI, long-acting injectable; SGA, second-generation antipsychotic; RLAI, risperidone long-acting injectable;

EU, European Union; PDSS, post-injection delirium/sedation syndrome

*PDSSadverse events with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium, have beenreported following injections of olanzapine pamoate. After each injection, patients must be observed by a healthcare professional for at least 3 hours

1. RisperdalConstaSmPC; 2. ZypAdheraSmPC; 3. InvegaSustennaUS Prescribing Information; 4. XeplionEU SmPC;5. Study NCT01348100, www.ClinicalTrials.gov, accessed August 2011; 6. Study NCT00706654 www.ClinicalTrials.gov, accessed August 2011


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Impact of LAI antipsychotics early in disease course

Risk of re-hospitalization by antipsychotictreatment pattern (n=2588)

Risk of re-hospitalization for patients

receiving LAI medications was aboutone-third of that for patients receiving

oral medicationsb

aCalculated hazard ratios were adjusted for effects of sociodemographic and clinical variables, temporal sequence of APs used, and the choice ofthe initial AP for each patient; bPairwise comparison [adjusted hazard ratio=0.36, 95% CI=0.170.75)]

Risk of re-hospitalization innationwide cohort ofconsecutive patients withschizophrenia hospitalized forthe first time in Finland

Data obtained from nationaldatabases of hospitalization,mortality and AP prescriptionsa

LAI, long-acting injectable; AP, antipsychotic; CI, confidence interval

Haloperidol, depot

Clozapine

Olanzapine

Other antipsychotics

Risperidone, depot

Perphenazine, depot

Polypharmacy

Zuclopenthixol, depot

Risperidone, oral

Perphenazine, oral

Quetiapine

No treatment

Haloperidol, oral

Zuclopenthixol, oral

0 1 3 42

Hazard ratio with 95% CI

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


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Relapse in patients treated with injectable vs oral

formulations

Study or

subgroup

LAI/Depot Oral

Events Total Events TotalWeight

(%)

Arango 2005 10 26 6 20 5.2

Barnes 1983 3 19 3 17 1.9

Del Guidice 1975 21 27 30 31 22.8

Falloon 1978 8 20 5 24 4.2

Gaebel 2010 54 355 102 355 18.6

Hogarty 1979 22 55 32 50 14.8

Li 1996* 32 155 52 137 15.1

Potapov 2008 4 20 8 20 3.6

Rifkin 1977 2 23 3 28 1.4

Schooler 1979 26 143 35 147 12.4

Total (95% CI) 843 829 100.0

Total events 182 276

Risk ratioMH, random, 95% CI

0.01 0.1 1 10 100

Favours depot Favours oral

Leucht et al. Schizophr Res 2011;127:8392

*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, risperidonelong-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

Significantly fewer (21.6%) participants in the depot than in theoral group (33.3%) relapsed

Reproduced with permission


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RLAI in FES

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Reduction in relapse with paliperidone palmitate

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R d i i l i h li id l i i


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Reduction in relapse with paliperidone palmitate in

recently diagnosed patients

Subjectswithrecurrence(%)

The recurrence rate was significantly lower in paliperidonepalmitate-treated compared with placebo-treated subjects,

regardless of the time since diagnosis

Recurrence rate, by time since diagnosis and treatment

Alphs et al. Poster presented at APA, May 1621 2009, San Francisco, CA, USA

50

40

30

20

10

0

20%

44%


(n=70)5 years since diagnosis (n=145)

Placebo(n=75)

p=0.0025

50

40

30

20

10

0

13%

48%


(n=135)>5 years since diagnosis (n=263)

Placebo(n=128)

p


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Improved symptoms with paliperidone palmitate in

recently diagnosed patients

Significant symptomatic improvements were observed in paliperidonepalmitate-treated subjects, regardless of the time since diagnosis

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

PANSS, Positive and Negative Syndrome Scale

p=0.0031

p


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Treatment algorithm for acute schizophrenia potential role for

LAI SGA

Patients in acute phase of schizophrenia

Early psychosis Highly arousedand agitated

Relapse(due to poor adherence)

Poor adherencerisk profile*

Good adherenceprofile

Neurolepticnaive

Prior exposureto neuroleptic

Considerpatients choice Consider LAI SGA (oral or

short-acting IM antipsychoticand/or benzodiazepines, asneeded)

Proceed as per

local orinstitutionalacute arousal

guidelines

Explain chronicdisease model

Use oral antipsychotic if appropriateand preferred by patient

Newton et al. Curr Med Res Opin. 2012;28:559567LAI, long-acting antipsychotic; SGA, second-generation antipsychotic


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Benefits of Long Acting Antipsychotics

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Disadvantages of Long Acting Antipsychotics

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Depot Antipsychotics: Busting the Myths

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Guidelines Recommendation

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Thanks !

Relapse_Prevention-_The_Role_of_LAI.ppt

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