1. Antipsychotic Long Acting
Injections
Dr V K SAHU
Resident Psychiatry

2. Headings
• Introduction
• Methods of improving outcome
• Antipsychotic Long Acting Injections (LAI)
• Pharmacology
• Individual Long Acting Antipsychotics
• Advantages & Disadvantages
• Conclusion
2

3. Introduction
• Schizophrenia is a major
psychiatric disorder, or cluster of
disorders, characterised by
psychotic symptoms that alter a
person's perception, thoughts,
mood and ehaviour
• Continuous, long-term treatment
to minimize relapse and provide
clinical benefit to patients.
• Non-adherence to medication is
a major risk factor for relapse
and re-hospitalization.
3

4. Introduction - Course of Schizophrenia
4
Robinson EJ,Birchwood M. ‘Theory of mind’ skills during an acute episode of psychosis and following
recovery. Psychological Medicine 1998 Aug; 28(05): 1101-1112

5. Introduction
• What constitutes maintenance phase and its treatment in
schizophrenia has not yet been established.
• Discontinuation and intermittent or targeted strategies are not
generally recommended.
• Controversy regarding dose reduction or lower dose therapy,
especially with regards to atypical antipsychotics.
5
Takeuchi H, Suzuki T, Uchida H, Watanabe K, Mimura M. Antipsychotic treatment for schizophrenia
in the maintenance phase: a systematic review of the guidelines and algorithms.. Schizophrenia
Research 2012 Feb; 134(2-3): 219-25

6. 6
• Cognitive behavioural therapy
• Compliance therapy
• More frequent and/or longer visits
• Patient/family psycho-education
• Symptom/side effect monitoring
• Dose correction to reduce side effects
• Simplified medication regimen
• First generation long-acting
injectable antipsychotics
• Second-generation long-acting
injectable antipsychotics
Pharmacologic
al
intervention
Psychosocial and
programmatic
interventions
Adherence

7. LAI & Adherence
• Non-adherence may be both a cause and consequence of
worsening of illness
• Long-acting injectable antipsychotic drugs can help to:
• Improve adherence
• Reduce relapse
• Lower hospitalization rates
7

8. Antipsychotic Long Acting Injections
(LAI)
• Two groups of LAIs: First generation LAIs and Second-
generation LAIs.
• First LAI – Fluphenazine Enantate- 1966.
• Second LAI- Fluphenazine decanoate.
• First of the second generation LAI –Risperidone
• Under trial LAI - iloperidone
8

9. LAI Classification-Delivery mechanism
9
CLASS DELIVERY AGENT
FGA OIL FLUPHENAZINE DECANOATE
HALOPERIDOL DECANOATE
FLUPENTIXOL/ZUCLOPENTHIXOL
PIPOTIAZINE PALMITATE
PERPHENAZINE DECANOATE
SGA MICROSPHERE RISEPERIDONE,ARPIPRAZOLE
CRYSTAL OLANAZAPINE PAMOATE
PALIPERIDONE PALMITATE

10. First-generation LAIs
• Flupentixol:
• Thioxanthine antipsychotic.
• LAI is formulated as flupentixol decanoate in a low-viscosity vegetable
oil (fractionated coconut oil).
• Peak plasma levels 3–7 days after IM injection
• Apparent half-life of 17 days.
• Steady-state plasma levels can be expected to be achieved after 2
months or so of regular dosing.
• In practice, plasma levels may show marked variability independent of
dose changes.4
10

11. First-generation LAIs
• Fluphenazine:
• Piperazine phenothiazine compound.
• Fluphenazine decanoate is available as an LAI in sesame oil.
• Plasma levels peak within 24 h of intramuscular injection
• Half-life is approximately 7–14 days.
• Plasma levels obtained vary up to 40-fold in patients receiving the
same dose.
• Smoking significantly reduces plasma fluphenazine levels.
11

12. First-generation LAIs
• Haloperidol:
• Butyrophenone
• Haloperidol decanoate in Sesame oil.
• Peak plasma levels are seen up to 7 days after intramuscular injection
• Plasma half-life is around 3 weeks.
• Steady-state plasma levels can be expected to be reached after 2–3
months of regular dosing.
• As with fluphenazine, clearance of haloperidol is significantly increased
by smoking.
• Variation in plasma levels is smaller than oral haloperidol.
12

13. First-generation LAIs
• Perphenazine:
• Piperazine phenothiazine
• Perphenazine decanoate in sesame oil.
• Used mainly in northern europe and scandinavia.
• After intramuscular injection, peak plasma levels are obtained in 1–7
days
• Half-life is approximately 2 weeks.
• Steady-state levels are obtained after 3 months.
• Variations in plasma levels during regular dosing are small.
• Plasma levels are directly correlated with dose.
13

14. First-generation LAIs
• Pipotiazine:
• Piperidine Phenothiazine Antipsychotic.
• The Lai Formulation Contains Pipotiazine Palmitate In Coconut Oil.
• Provides Peak Plasma Levels After 1–2 Weeks Although No Drug Is
Released For At Least 3 Days.
• Plasma Half-life Is Around 2 Weeks
• Time To Steady State Is 2 Months.
14

15. First-generation LAIs
• Zuclopenthixol:
• Thioxanthine compound.
• LAI is formulated as the decanoate ester dissolved in thin vegetable oil
(fractionated coconut oil).
• Peak plasma levels of zuclopenthixol are achieved a week after
injection.
• Plasma half-life has been estimated at 7.4 days and 19 days.
• Shows moderate inter- and intra-individual differences in plasma levels
• Marked differences b/w peak and trough plasma levels when given
every 2 weeks (peak levels more than 3 times higher than trough).
• Steady-state plasma levels are achieved after around 2 months of
regular dosing
15

16. First Generation Antipsychotic long-acting
injections : suggested doses and frequencies
Drug Licensed
injection site
Test dose
(mg)
Dose range
(mg/week)
Dosing
Interval
(weeks)
Comments
Flupentixol
decanoate
Gluteal or thigh 20 12.5-400 2-4 Maximum
licensed
dose is very
high
relative to other
LAIs
Fluphenazine
decanoate
Gluteal 12.5 6.25-50 2-5 High EPS
Haloperidol
Decanoate
Gluteal 25 12.5-75 4 High EPS
Pipothiazine
palmitate
Gluteal 25 12.5-50 4 ? Lower
incidence of
EPS (unproven)
Zuclopenthixol
decanoate
Gluteal or thigh 100 100-600 2-4 ? Slightly higher
efficacy
16

17. Second-generation LAIs
• Risperidone:
• First ‘atypical’ drug to be made
available as depot
• Contains risperidone coated in
polymer to form microspheres.
• Have to be suspended in an
aqueous base immediately
before use.
• Stored in a fridge
• Available as doses of 25, 37.5
and 50 mg
17

18. • Unlike FGA-LAIs, Risperidone Long Acting Injections(RLAI)
breaks down into completely natural products (CO2 and H2O)
18

19. Second-generation LAIs
• Risperidone injection is not suitable for patients with treatment-refractory
schizophrenia.
• Peak release is at about 28 days.
• The long-acting injection also seems to be well tolerated: fewer than 10%
of patients experience EPS and fewer than 6% withdrew from a long-term
trial because of adverse effects.
• Doses of 25–50 mg every 2 weeks appear to be as effective as oral doses
of 2–6 mg/day.
• Prolactin levels appear to reduce somewhat following a switch from oral to
injectable risperidone.
• Rates of tardive dyskinesia are said to be low
19

20. Second-generation LAIs
• RLAI may improve the trajectory of myelination in first episode
patients and have a beneficial impact on cognitive performance
20
Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL "et al". Long Acting Injection Versus Oral
Risperidone in First-Episode Schizophrenia: Differential Impact on White Matter Myelination Trajectory.
Schizophrenia Reseaarch.Supplement 2011 Oct; 132(1): 35-41.

21. Second-generation LAIs
21
• Paliperidone
• Contains extended release
intramuscular extended-release
intramuscular Paliperidone
Palmitate
• Major active metabolite of
risperidone: 9-hydroxyrisperidone
• Active paliperidone plasma levels
are seen within a day or so,
therefore co- administration of oral
paliperidone or risperidone during
initiation is not required

22. Second-generation LAIs
• Paliperidone palmitate IM does not require cold storage.
• Prefilled syringes and does not require reconstitution
• No oral supplementation is required on initiation for paliperidone
palmitate.
• No test dose is required for paliperidone palmitate (but patients
should ideally be currently stabilised on or have previously
responded to oral paliperidone or risperidone).
• The median time to maximum plasma concentrations is 13 days.
• Treatment with paliperidone palmitate (100 mg eq.) was efficacious
and all doses tested were tolerable.
22
7. Bartzokis Gopal S1, Hough DW, Xu H, Lull JM, Gassmann-Mayer C, Remmerie BM, "et al". Efficacy and
safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized,
double-blind, placebo-controlled, dose-response study. International Clinical Psychopharmacology 2010

23. Paliperidone dose and administration
information
Dose Route
Initiation
Day 1
Day 8 (+/−2 days)∗ 150 mg IM Deltoid only
100 mg IM Deltoid only
Maintenance
Every month (+/− 7 days)
thereafter 50–150 mg IM∗∗ Deltoid or gluteal
23
∗The second initiation dose may be given 2 days before or after day 8 (after the first initiation dose on day 1).2 Similarly the
manufacturer recommends that patients may be given maintenance doses up to 7 days before or after the monthly time point.2
This flexibility should help to minimise the number of missed doses.
∗∗The maintenance dose is perhaps best judged by consideration of what might be a suitable dose of oral risperidone and then
giving paliperidone palmitate in an equivalent dose IM, intramuscular

24. Approximate dose equivalence of
risperidone and paliperidone
Risperidone oral
(mg/day)
(bioavailability =
70%)
Paliperidone
oral
(mg/day)
(bioavailability =
28%)
Risperidone
LAI (Consta)
(mg/2 weeks)
Paliperidone
palmitate
(mg/month)
2 4 25 50
3 6 37.5 75
4 9 50 100
6 12 - 150
24

25. Second-generation LAIs
• ILOPERIDONE:
• Microencapsulated depot
formulations of iloperidone and
a poly-glycolide polylactide
glucose star polymer.
• Under trial
25

26. Second-generation LAIs
26
• Olanzapine
• Crystal salt made of Olanzapine & Palmoic
acid.
• Each 15 mg of Olanzapine LAI must be
dissolved in 0.1 ml of water.
• Max- 3.0 ml or 450 mg Olanzapine
• 3 hr monitoring after giving injection
• Post Injection Syndrome or Post Injection
Delirium Syndrome

27. Second-generation LAIs
27
• Post Injection Syndrome or Post Injection Delirium Syndrome:
• Mimics Olanzapine overdosage
• Sedation, dizziness, slurred speech, agitation, confusion, ataxia, weakness ,
unconsciousness
• Majority occurs in first hr post-injection, progressing from mild to
severe presentations
• No period of unique liability to PDSS, may occur in 1st to 66th
injection.
• Mechanism: Olanzapine LAI is highly soluble in blood compared to
muscle.
• Hypothesized that direct or partial injection into vasculature or bleeding
around injection site leading to direct contact of Olanzapine with blood
Peter Haddad, Tim Lambert, John Lauriello. Antipsychotic long-acting injections. Oxford: Oxford
University Press; 2011.

28. Second-generation LAIs
• Aipiprazole:
• First dopamine D2 partial
agonist given regulatory
clearance as a once-monthly
injection
• Microsphere long-acting
injectable (similar to RLAI)
28

29. Second-generation LAIs
• The most frequently reported adverse events were akathisia, insomnia
and injection-site pain.
• Injection-site reactions were generally mild to moderate in severity and
resolved over time.
• Extrapyramidal symptoms were reported more frequently with
aripiprazole 400 mg or 300 mg prolonged-release injection than oral
aripiprazole
29

30. Choice of antipsychotic medication
• The choice of antipsychotic medication should be made by the
service user and healthcare professional together
• Views of the carer if the service user agrees.
• Provide information and discuss the likely benefits and possible side
effects of each drug, including:
• Metabolic (including weight gain and diabetes)
• Extrapyramidal (including akathisia, dyskinesia and dystonia)
• Cardiovascular (including prolonging the QT interval)
• Hormonal (including increasing plasma prolactin)
• Other (including unpleasant subjective experiences)
30

31. Combined antipsychotic drugs
31
• Prescribed in the short term(for example, cross-tapering while
switching from one antipsychotic to another)
• In the longer term (for example, as a strategy to improve symptom
control or reduce side-effects.
• With respect to longer-term use, there is no good objective evidence
that combined antipsychotics (that do not include clozapine) offer
any efficacy advantage over the use of a single antipsychotic.
• More harm - increased prevalence of EPS, severe EPS, increased
metabolic side-effects, paralytic ileus, grand mal seizures and
prolonged QTc.

32. Practical issues concerning LAI
administration
DRUG INJEC
TION
SITE
STORAGE RECONSTITUTION & ADMINISTRATION
FGAs Gluteal Oil in vial • Z- track injection technique to avoid post-
injection leak
• Concentrates where available may
reduce injection volume
• Nodule formation with repeated injection
• Essential to rotate sites
Risperdon
e
Gluteal
or
deltoid
Powder;
special kits
• Requires cold chain storage
• Special kits & training
• Z tracking not required
32

33. Practical issues concerning LAI
administration
DRUG Injection
Site
Storage Reconstitution & administration
Paliperidone Deltoid or
Gluteal
Pre-filled
syringe kit
• Choice of needle based on weight
• Longer needle for > 90 kg
• Deltoid achieves rapid uptake
• Z-tracking not required
Olanzapine Gluteal Powder,
special kits
• Special kits & training required
• Large volume at top doses
• Z- tracking not required
• 3 hr observation in health care due to possibility of Post-
injection syndrome
Aripiprazole Gluteal Pre-filled
dual
chamber
syringe
• Not indicated for the treatment of people with dementia-
related psychosis
• Z-tracking not required
33

34. Equivalence of specific SGAs in oral &
LAI form
SGA-LAI Drug Target oral equivalent dose LAI Dose & Frequency
Risperidone < 3 mg oral 25 mg 2 – weekly
3 mg to 5 mg oral 37.5 mg 2- weekly
> 5 mg oral 50 mg 2 -weekly
Paliperidone(a) 6 mg 117 mg 4 -weekly
9 mg 156 mg 4- weekly
Olanzapine 10 mg 150 mg 2 -weekly
300 mg 4- hrly
15 mg 210 mg 2 -weekly
405 mg 4- weekly
20 mg 300 mg 2 - weekly
No 4 weekly equivalent
34
(a)- 39 mg, 78 mg, 117 mg, 156 mg, 234 mg equivalent to 25 mg, 50 mg, 75 mg, 100 mg &
150 mg of marketed Paliperidone

35. Schizophrenia Guideline Relation to non-adherence and/or relapse.
Consider an LAI if :
LAI indicated if patient
expresses preference
for this treatment
American Psychiatric
Association(Lehman et al. 2004a)
Partial to full non-adherence leading to recurrent
relapses
-
Canadaian Clinical Practise
Guidelines (Canadian Psychiatric
Association 2005
Non-adherence in multi-episode patients or those
with persistent positive symptoms
-
NICE (National Institute of Clinical
Excellence) 2009
Avoidant of covert non-adherence is a priority Yes
Patient Outcomes Research
Team(PORT) Recommendations
(Lehman et al. 2004b)
Frequent Relapses on oral medication or a history
of problems with poor adherence on oral medication
Yes
RANZAP (Royal Australian & New
Zealand College of Psychiatrists)
2005
Despite psychosocial adherence interventions a
patient repeatedly fails to adhere to necessary
medication and relapses frequently
Yes
Texas Medication Algorithm (Miller et
al. 2004)
Inadequate adherence at any stage -
Peter Haddad, Tim Lambert, John Lauriello. Antipsychotic long-acting injections. Oxford: Oxford University
Press; 2011
35

36. Advice on prescribing long-acting
injections of antipsychotic drugs
• For FGAs, give a test dose. For SGAs, test doses are not
required (less propensity to cause EPS and aqueous base not
known to be allergenic).
• Begin with the lowest therapeutic dose.
• Administer at the longest possible licensed interval.
• Adjust doses only after an adequate period of assessment.
Doses may be reduced if adverse effects occur, but should be
increased only after careful assessment over at least 1 month,
preferably longer.
• Not recommended for those who are antipsychotic-naive
36

37. Reducing dose of depots
• If it has not already been done, oral antipsychotic medication should
be discontinued first.
• The interval between injections should be increased to up to 4
weeks before decreasing the dose given each time. Note: not with
risperidone.
• The dose should be reduced by no more than a third at any one
time. Note: special considerations apply to risperidone.
• Decrements should, if possible, be made no more frequently than
every 3 months,preferably every 6 months.
• Discontinuation should be seen as the endpoint of the above
process
37

38. LAI FGA and LAI SGA Indications
according to the DSM-IV-TR criteria
38
Pierre ML, Mocrane A, Philippe C, Sebastien G, Sylvie L,Ludovic, Guidelines for the use and management of
long-acting injectable antipsychotics in serious mental illness, BMC Psychiatry 2013,(13) 340
LAI FGA LAI SGA
1st Line Treatment
Schizophrenia
Delusional disorder
Schizoaffective disorder
2nd Line Treatment
Schizophrenia
Delusional disorder
Schizoaffective disorder
Personality Disorder
Bipolar disorder
Personality disorder

39. Use of LAI FGA and LAI SGA according
to the period of 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).
Biploar Disorder
LAI FGA are not recommended LAI SGA are not recommended in
the initial phase of bipolar disorder.
39
Pierre ML, Mocrane A, Philippe C, Sebastien G, Sylvie L,Ludovic, Guidelines for the use and management of
long-acting injectable antipsychotics in serious mental illness, BMC Psychiatry 2013,(13) 340

40. Indications of LAI FGA and LAI SGA according
to clinical characteristics of the illness
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
LAI SGA
• Non-adherence (partial/full)
• Patient preference
• Positive depot experienced
LAI SGA • Cognitive deficits Social
isolation
2nd Line LAI FGA or
SGA
Positive symptoms 2nd Line • BD I
• Manic polarity
• Rapid cycler
• Hazard risk for others
• Low insight
LAI SGA • Negative symptoms 40

41. Benefit/risk ratio for LAI FGA and LAI
SGA in Schizophrenia
Prevention of psychotic
recurrence
1st Line of Treatment Risperidone LAI
2nd Line of Treatment Olanzapine pamoate
Haloperidol decanoate
Zuclopenthixol decanoate
Flupentixol decanoate
Fluphenazine decanoate
Pipotiazine palmitate
Pierre ML, Mocrane A, Philippe C, Sebastien G, Sylvie L,Ludovic, Guidelines for the use and management
of long-acting injectable antipsychotics in serious mental illness, BMC Psychiatry 2013,(13) 340

42. Benefit/risk ratio for LAI FGA and LAI
SGA in Bipolar disorder
Prevention of manic
recurrence
Prevention of
depressive
recurrence
1st Line Treatment - -
2nd 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
42
Pierre ML, Mocrane A, Philippe C, Sebastien G, Sylvie L,Ludovic, Guidelines for the use and
management of long-acting injectable antipsychotics in serious mental illness, BMC Psychiatry

43. Disadvantages of LAI over oral
antipsychotics
1. Understanding the pharmacokinetics & dosing require specific LAI
knowledge.
i. Delayed time until steady state is reached
ii. Clinical improvement may be delayed after dose increase
iii. Elimination may take weeks to months
2. Adverse effects may persist after stopping/reducing dose
3. Less scope of dynamic titration.
4. Injection related adverse effects e.g. pain, nodules
5. Some patient rehards LAI as indicating a lack of control or autonomy
6. Organised community system to deliver LAIs
7. LAI storage, reconstitution & administration may require special
precautions, &/or training
8. SGA-LAI have high acquisition costs
Peter Haddad, Tim Lambert, John Lauriello. Antipsychotic long-acting injections. Oxford: Oxford
University Press; 2011
43

44. Advantages of depot antipsychotics
over oral antipsychotic
1. Improved treatment adherence, overt non-adherence can be addressed
2. Easier early detection of relapse, improved relapse prevention and
reduced rehospitalisation rates
3. Enhanced consistency between the drug prescription and drug delivery
4. More predictable and stable serum concentrations
5. Less variability between patients in steadystate blood levels for a given
dose
6. Lowest effective dose principle more safely achieved with depots (step-
wise reduction)
7. Reduced risk of accidental or deliberate selfpoisoning (overdose)
8. Less risk of overdose
9. Bypasses pharmacokinetic hurdeles of absorption & first pass hepatic
elimination
Thomas R.E. Barnes. Why aren't depot antipsychotics prescribed more often and what can be
done about it?. Advances In Psychiatric Treatment 2005; (11): 211-213.
44

45. Tackling myths about depot drugs
1. Risk of neuroleptic malignant syndrome is not higher for depot than oral drugs
2. No evidence to suggest that neuroleptic malignant syndrome is a
contraindication for subsequent depot use
3. For the same drug, the risk of tardive dyskinesia is not higher for depot than
oral formulations
4. Patients already on depot like this formulation and many prefer depot to oral
drugs
5. Clinicians perceive a stigma to be associated with depots but this may be
based on the worst characteristics of typical drugs (e.g. unacceptable side-
effects) rather than on intramuscular long-acting injections per se
6. Most nursing staff are aware of the benefits of depots but their training
experiences and pressure of time may adversely affect systematic monitoring
of potential side-effects
45
Thomas R.E. Barnes. Why aren't depot antipsychotics prescribed more often and what can be done
about it?. Advances In Psychiatric Treatment 2005; (11): 211-213.

46. Metanalysis of LAI efficacy
• Kirson NY et al:
• Comparative effectiveness of antipsychotic formulations is sensitive to research
design
• Depot formulations displayed significant advantages in nonrandomized
observational studies. In RCTs no difference was observed
• Lafeuille MH et al:
• Meta-analysis, including studies with both interventional and non-interventional
designs and using meta-regressions
• LAIs are associated with higher reductions in hospitalization rates for
schizophrenia patients compared to oral antipsychotics.
46
Lafeuille MH, Dean J, Carter V, Duh MS, Fastenau J, Dirani R, Lefebvre P. Systematic review of long-acting
injectables versus oral atypical antipsychotics on hospitalization in schizophrenia. Current Medical Research
and Opinion 2014; 30(08): 1643-1655.
Kirson NY, Weiden PJ, Yermakov S, Huang W, Samuelson T, Offord SJ "et al". Efficacy and effectiveness of
depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. The
Journal of Clinical Psychiatry 2013 Jun; 74(06): 568-75

47. Conclusion
• When selecting a specific LAI, consider class similarities and individual
antipsychotic differences.
• Individualize the dose and dosing interval based on patient response,
peak-related adverse effects (time to peak is approximately 5 half-lives for
most drugs), and possible reduced symptom control at the end of the
dosing interval
• Although some LAIs are expensive, they potentially reduce the financial
burden of schizophrenia and improve quality of life.
• Do not rule out first-generation LAIs.
47

48. Conclusion
• Consider a loading dose strategy to minimize the time a patient
has to take an oral and LAI antipsychotic combination.
• If antipsychotic polypharmacy is necessary, document your
rationale.
• Keep other reasons for non-adherence in mind & intervene
accordingly.
48

49. References
1. Peter Haddad, Tim Lambert, John Lauriello. Antipsychotic long-acting injections. Oxford:
Oxford University Press; 2011.
2. Stephen M Stahl. Antipsychotic agents. In: (eds.)Stahl's essential psychopharmacology.
4th ed. Cambridge: Cambridge; 2013. p129-236
3. Thomas R.E. Barnes. Why aren't depot antipsychotics prescribed more often and what
can be done about it?. Advances In Psychiatric Treatment 2005; (11): 211-213.
4. Maxine X. Patel and Anthony S. David. Why aren’t depot antipsychotics prescribed more
often and what can be done about it?. Advances in Psychiatric Treatment 2005; (11):
203-211.
5. John M. Kane, Carlos Garcia-Ribera. Clinical guideline recommendations for
antipsychotic long-acting injections. The British Journal of Psychiatry.Supplement 2009
Nov; (195): s63–s67.
6. Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL "et al". Long Acting
Injection Versus Oral Risperidone in First-Episode Schizophrenia: Differential Impact on
White Matter Myelination Trajectory. Schizophrenia Research.2011 Oct; 132(1): 35-41.
49

50. 7. Bartzokis Gopal S1, Hough DW, Xu H, Lull JM, Gassmann-Mayer C, Remmerie BM, "et
al". Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic
schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study.
International Clinical Psychopharmacology 2010 Sep; 25(5): 247-56.
8. Robinson EJ,Birchwood M. ‘Theory of mind’ skills during an acute episode of psychosis
and following recovery. Psychological Medicine 1998 Aug; 28(05): 1101-1112
9. Lafeuille MH, Dean J, Carter V, Duh MS, Fastenau J, Dirani R, Lefebvre P. Systematic
review of long-acting injectables versus oral atypical antipsychotics on hospitalization in
schizophrenia. Current Medical Research and Opinion 2014; 30(08): 1643-1655.
10. Pierre ML, Mocrane A, Philippe C, Sebastien G, Sylvie L,Ludovic, Guidelines for the use
and management of long-acting injectable antipsychotics in serious mental illness, BMC
Psychiatry 2013,(13) 340
50