Background
Methods
Questionnaire development
LAI second-generation antipsychotics | Risperidone microsphere |
---|---|
Olanzapine pamoate | |
LAI first-generation antipsychotics
|
Haloperidol decanoate
|
Zuclopenthixol decanoate
| |
Flupentixol decanoate
| |
Fluphenazine decanoate
| |
Pipotiazine palmitate
|
Rating scale
Expert selection
-
Clinical activity in the field of schizophrenia or bipolar disorder.
-
Publication (s) or communication (s) of research work in the field of LAI antipsychotics in national or international congresses.
Data analysis
-
First-line treatment/strategy was defined if at least 50% of the answers to the question were in the zone 7–9 and less than 20% were in the zone 0. The treatment/strategy of choice was kept if at least 50% of the experts had rated it 9.
-
Second-line treatment/strategy was defined if less than 50% of the answers to the question were in the zone 7–9, at least 50% were in the cumulated zones 7–9 and 4–6, and less than 20% were in the zone 0.
-
Third-line treatment/strategy was defined if less than 50% of the answers to the question were in the cumulated zones 7–9 and 4–6, and less than 20% were in the zone 0.
-
Contraindication was defined if at least 50% of the answers were in the zone 0.
Percentage of answers in the zones | ||||
---|---|---|---|---|
0 | 1-3 | 4-6 | 7-9 | |
< 20% | - | < 50% | ≥ 50% | → First-line treatment/strategy |
< 20% | < 50% | ≥ 50% and < 100% | → Second-line treatment/strategy | |
< 20% | - | < 50% | → Third-line treatment/strategy | |
≥ 50% | - | - | - | → Contraindication |
Results
Description of the expert population
Age (years) | N | 42 |
---|---|---|
Mean ± SD | 46.81 ± 9.82 | |
Min; Max | 31; 63 | |
Median | 46 | |
Years of practice
| N | 41 |
Mean ± SD | 17.29 ± 10.20 | |
Min; Max | 2; 37 | |
Median | 16 | |
Treatment of patients in outpatients
| N | 41 |
Mean ± SD | 68.90 ± 22.43 | |
Min; Max | 25; 100 | |
Median | 75 | |
Treatment of patients in hospital
| N | 41 |
Mean ± SD | 31.10 ± 22.43 | |
Min; Max | 0; 75 | |
Median | 25 | |
During the last 5 years, in the field of LAI FGA/LAI SGA
| N | 42 |
Clinical activity | 42 (100.0%) | |
Research projects | 18 (42.9%) | |
Publications | 12 (28.6%) | |
Communications
| N | 36 |
Conferences | 22 (61.1%) | |
Congress | 24 (66.7%) | |
Teaching | 22 (61.1%) |
Target population
Indications
LAI FGA | LAI SGA |
---|---|
1
st
line treatment
| |
Schizophrenia | |
Delusional disorder | |
Schizoaffective disorder | |
2
nd
line treatment
| |
Schizophrenia | Bipolar disorder |
Delusional disorder | Personality disorder |
Schizoaffective disorder | |
Personality disorder |
-
as 1st line treatment in schizophrenia, delusional disorder and schizoaffective disorder.
-
as 2nd line treatment in bipolar disorder and personality disorders.
-
as 2nd line treatment in schizophrenia, delusional disorder, schizoaffective disorder and personality disorders.
Most appropriate introduction period during the illness
LAI FGA | LAI SGA |
---|---|
Schizophrenia
| |
LAI FGA are not recommended in the initial phase of the disorder. | Very early introduction of LAI SGA is recommended (eventually from the 1st psychotic episode). |
LAI FGA can be used during the maintenance treatment in the case of the efficacy of the oral form and when the benefit/risk ratio is considered as satisfactory. | It is recommended that an LAI SGA be introduced from the 1st recurrent psychotic episode (if the patient was not treated with an LAI antipsychotic). |
Bipolar disorder
| |
LAI FGA are not recommended. | LAI SGA are not recommended in the initial phase of bipolar disorder. |
-
They are recommended from the first psychotic episode.
-
Their introduction from the first recurrent psychotic episode is also recommended (if the patient was not treated with an LAI antipsychotic).
Choice criteria for an LAI FGA or LAI SGA according to the clinical characteristics of patient
Schizophrenia | Bipolar disorder | ||||
---|---|---|---|---|---|
1st line
|
LAI FGA or LAI SGA
| Frequent relapses Non-adherence (partial/full) Hazard risk for others Low insight Patient preference Positive depot experienced |
1st line
| Non-adherence (partial/full) Patient preference Positive depot experienced | |
LAI SGA
| Cognitive deficits Social isolation |
LAI SGA
| |||
2
nd
line
|
LAI FGA or SGA
| Positive symptoms |
2
nd
line
| BD I Manic polarity Rapid cycler Hazard risk for others Low insight | |
LAI SGA
| Negative symptoms Suicidal risk |
Schizophrenia
-
Patients presenting frequent relapses, poor adherence or non-acceptance of a long-term treatment.
-
Patients presenting dangerous behavior.
-
Patients presenting a low level of insight about illness and need for treatment.
-
Patients wishing treatment by LAI antipsychotic and/or having a history of effective treatment by LAI FGA or LAI SGA.
-
Patients presenting cognitive impairment with an impact on their functioning.
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Socially and family isolated patients.
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Patients receiving outpatient care without consent.
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Patients presenting a predominant clinical dimension.
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Patients presenting a high level of suicide intention.
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Patients presenting a high level of insight about their illness.
Bipolar disorder
-
Patients presenting poor adherence with non-acceptance of a long-term oral treatment.
-
Patients wishing for an LAI SGA treatment and/or having a history of effective treatment with LAI SGA for bipolar disorder symptoms.
-
Patient presenting particular clinical characteristics.
-
Patients presenting a dangerous behavior or a history of impulsive behavior.
Benefit/risk balance for LAI FGA and LAI SGA depending on the psychiatric disorder
In patients with schizophrenia
Prevention of psychotic recurrence | |
---|---|
1
st
line treatment
| Risperidone LAI |
2
nd
line treatment
| Olanzapine pamoate |
Haloperidol decanoate | |
Zuclopenthixol decanoate | |
Flupentixol decanoate | |
Fluphenazine decanoate | |
Pipotiazine palmitate |
In patients with bipolar disorder
Prevention of manic recurrence | Prevention of depressive recurrence | |
---|---|---|
1
st
-line treatment
| - | - |
2
nd
-line treatment
|
In monotherapy or in combination with a mood stabilizer
|
Always in combination with a mood stabilizer
|
Risperidone LAI | Risperidone LAI | |
Olanzapine pamoate | Olanzapine pamoate |
Procedures for prescribing and use
Patients stabilized by an antipsychotic treatment
Switch from an oral form antipsychotic (FGA or SGA) to an LAI form
Switch from an LAI antipsychotic (FGA or SGA) to another LAI antipsychotic
Practical procedures for the introduction and for the injection reminders
-
1 st line strategies, using telephone reminders and agenda given to the patient (follow-up diary).
-
2 nd line strategies, by letter or eventually by text messages.
-
deep intramuscularly (gluteal or deltoid muscle) (strategy of choice).
-
by changing the injection site each time (as 1st line strategy).
-
by proposing a local transdermal anaesthetic (cream or patch) before the injection in order to reduce the pain at the injection site (as 2nd line strategy).
Specific therapeutic strategies according to the psychiatric disorder or its co-morbidities
Schizophrenia and delusional chronic disorder
- In the acute phase
-
Optimization of the current LAI antipsychotic.
-
Combination of an oral antipsychotic with the current LAI antipsychotic.
- After stabilization of the psychotic episode
Residual symptoms with LAI antipsychotics justifying a reassessment
-
in 1st line strategies: to optimize the treatment by LAI FGA or LAI SGA.
-
in 2nd line strategies.
Bipolar disorder
Manic episode with LAI SGA
-
in 1st line strategy: to combine the current LAI SGA with an oral anti-manic mood stabilizer (without recommendation of a specific medication).
-
in 2nd line strategies.
-
in 1st line strategy: to optimize the dose of the oral anti-manic mood stabilizer.
-
in 2nd line strategies.
- After stabilization of the manic episode
Depressive bipolar episode with LAI SGA
- In the acute phase
-
in 1st line strategy: to combine the current LAI SGA with an oral mood stabilizer with antidepressant effect (i.e. lamotrigine, quetiapine, lithium).
-
in 2nd line strategies.
-
in 1st line strategies.
-
in 2nd line strategies.
- After stabilization of the depressive episode
Psychiatric co-morbidities associated with a schizophrenic or bipolar disorder with an LAI antipsychotic
Addiction to a psychoactive substance (alcohol, opiates…)
Procedures for follow-up and monitoring
Pre-therapeutic LAI antipsychotic summary
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Personal and family medical history (diabetes, dyslipidaemia).
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Healthy lifestyle (eating habits, physical activity, substance use, smoking).
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Weight, Body Mass Index calculation, umbilical circumference.
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Blood pressure.
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1st line paraclinical exams:
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Complete blood count, blood electrolyte (+ urea, creatinine, fasting glucose).
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Liver function tests.
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Lipid profile.
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Beta hCG.
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Electrocardiogram.
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Paraclinical exams depending on the clinical state of patient (as 2nd line):
-
Thyroid function test.
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Prolactinaemia.
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Electroencephalogram.
Monitoring procedures
Specific populations
Women during pregnancy
In the case of discovering a pregnancy
Elderly patients
-
Dosage adjustment according to weight, liver or renal function tests.
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A longer titration than in adults with a lower “target” dose.
-
Close medical follow-up (strategy of choice).
-
Closer tolerance monitoring than in adults (strategy of choice).
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Prescription only by a psychiatrist.
Subjects in precarious situations
Subjects incarcerated in prison
Discussion
Evidence-based guidelines vs. consensus-based guidelines
-
No or insufficient level of evidence addressing the question.
-
Possibility to decline the topic in easily identifiable clinical situations.
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Need to identify and select the strategies deemed appropriate by an independent panel from amongst several alternative options.
Indications of LAI antipsychotics
-
Schizophrenia.
-
Schizoaffective disorder.
-
Delusional disorder.
-
Bipolar disorder.
-
Personality disorder.
Use of LAI antipsychotics during the different phases of the illness
What is the specific clinical profile of patients using LAI antipsychotics in clinical practice?
LAI FGA vs LAI SGA
Use of LAI antipsychotics in clinical practice guidelines
Conclusion
Appendix 1: Scientific support of the project
Initiation of the formal consensus guidelines
-
French Association of Biological Psychiatry and Neuropsychopharmacology (Association Française de Psychiatrie Biologique et Neuropsychopharmacologie - AFPBN -).
Coordination
-
Professor Pierre-Michel Llorca/Doctor Ludovic Samalin.
Project scientific committee
-
Doctor Mocrane Abbar.
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Professor Philippe Courtet.
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Professor Pierre-Michel Llorca.
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Doctor Sebastien Guillaume.
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Doctor Ludovic Samalin.
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Sylvie Lancrenon.
Independent scientific committee (ISC)
-
Professor Emmanuel Haffen.
-
Professor Christophe Lançon.
-
Professor Pierre Thomas.
Appendix 2: list of experts
Appendix 3: key points
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1. Long-acting injectable (LAI) antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder.
-
2. LAI second-generation antipsychotics (SGA) are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics (FGA) (depot neuroleptics) are not recommended in the early course of schizophrenia and must be avoided in bipolar disorder.
-
3. LAI antipsychotics have long been viewed as a treatment that could only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated.
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4. According to their efficacy and tolerability:
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5. In order to improve the acceptance and understanding of the benefits of an LAI antipsychotic, it is recommended to deliver to each patient specific information concerning the advantages and inconveniences of the LAI formulation, in the framework of shared decision-making.
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6. Process for switching to LAI antipsychotic. Two main situations are identified:
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7. Medication management: