Depot Antipsychotic Injections Long acting antipsychotics

1. Depot Antipsychotics (LAI)
Kapil Kulkarni
ST4 Gosfield ward
Clinical Supervisor: Dr Hem Raj Pal

2. Contents
1. Introduction and compliance issues
2. Course of illness and strategies in maintenance phase

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 behaviour.
• Non-compliance to medication is a major risk factor for relapse and re-
hospitalization.
• Continuous, long-term treatment to minimize relapse and provide clinical benefit
to patients.

4. Course of Schizophrenia
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. • 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.
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. Psychosocial and
programmatic
interventions
Pharmacologic
al
intervention
Adherence
• 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

7. Introduction
• Remission has been defined as a level of
symptomology that does not interfere
with an individual’s behaviour, and is
also below that required for a diagnosis
of schizophrenia. Symptom
improvements should last for a minimum
of six months in order for remission to be
reached.
• Treatment-resistant schizophrenia (TRS)
affects ~30% of people with a diagnosis
of schizophrenia
Meltzer HY. Treatment-resistant schizophrenia–the role of clozapine. Curr
Med Res Opin. 1997;14(1):1–20.

8. • Non-compliance may be both a cause and consequence of worsening of illness
• Around 50% of relapses are due to non-compliance to treatment.*
• Long-acting injectable antipsychotic drugs can help to:
1) Improve adherence
2) Reduce relapse
3) Lower hospitalization rates
LAI & Adherence
* Factors associated with relapse in schizophrenia Kazadi N.J.B. Moosa M.Y.H. Jeenah F.Y. South African
Journal of Psychiatry. 2008. Volume 14, Issue 2

9. Antipsychotic Long Acting Injections (LAI)
• First FGA LAI?
• First SGA LAI?

10. Antipsychotic Long Acting Injections (LAI)

11. 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, Lurasidone,

12. Antipsychotic Long Acting Injections (LAI)
CLASS DELIVERY AGENT
FGA OIL FLUPHENAZINE DECANOATE
HALOPERIDOL DECANOATE
FLUPENTIXOL/ZUCLOPENTHIXOL
PIPOTIAZINE PALMITATE
PERPHENAZINE DECANOATE
SGA MICROSPHERE RISEPERIDONE,ARPIPRAZOLE
CRYSTAL OLANAZAPINE PAMOATE
PALIPERIDONE PALMITATE

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

14. First-generation LAIs
Haloperidol:
• Butyrophenone
• Haloperidol decanoate in Sesame oil.
• Peak plasma levels- up to 7 days after IM injection
• Plasma half-life is around 3 weeks.
• Steady-state plasma levels- 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.

15. First-generation LAIs
Flupentixol:
• Thioxanthene antipsychotic.
• LAI of Flupentixol decanoate- 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- after 2 months or so of regular dosing.

16. First-generation LAIs
Flupentixol:
• In practice, plasma levels may show marked variability independent of dose
changes.
• Dose of depot is 8 times of total oral dose.
• It has mood elevating property, may worsen agitation.

17. First-generation LAIs
Zuclopenthixol:
• Thioxanthene compound.
• LAI as Zuclopenthixol Decanoate- dissolved in thin vegetable oil (fractionated
coconut oil).
• Peak plasma levels- after 1 week of IM injection.
• Plasma half-life- around 2 weeks. (7.4 to 19 days)
• Steady-state plasma levels - after around 2 months of regular dosing
• 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).

18. First-generation LAIs
Perphenazine:
• Piperazine phenothiazine
• Perphenazine decanoate in sesame oil.
• Used mainly in northern Europe and Scandinavia.
• After intramuscular injection, peak plasma levels- 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.

19. First-generation LAIs
19
Pipothiazine:
• Piperidine Phenothiazine antipsychotic.
• The LAI formulation contains Pipotiazine Palmitate in coconut oil
• Although no drug is released after 3 days; the peak plasma level- 1 – 2 weeks.
• Plasma half-life is around 2 weeks
• Time to steady state is 2 months.

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

21. Second-generation LAIs
Risperidone:
• First ‘atypical’ drug to be made available as depot
• Contains Risperidone coated in polymer to form microspheres.
• Peak release is at about 28 days.
• Have to be suspended in an aqueous base immediately before use.
• Stored in a fridge

22. Second-generation LAIs
• The long-acting injection also seems to be well tolerated: fewer than 10% of
patients experience EPS in long-term trial because of adverse effects.
• Rates of tardive dyskinesia are said to be low.
• Prolactin levels appear to reduce somewhat following a switch from oral to
injectable risperidone.

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

24. Second-generation LAIs
• RLAI may improve the trajectory of
myelination in first episode patients
and have a beneficial impact on
cognitive performance
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.

25. Second-generation LAIs
Paliperidone:
• Major active metabolite of Risperidone: 9-hydroxyrisperidone
• Contains extended release intramuscular Paliperidone Palmitate
• Active paliperidone plasma levels- within a day or so
• Therefore co- administration of oral paliperidone or risperidone during initiation
is not required.
• The median time to maximum plasma concentrations is 13 days.

26. Second-generation LAIs
• Paliperidone palmitate IM does not require cold storage.
• Prefilled syringes and does not require reconstitution.
• 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).
• 3 monthly injections available
Bartok’s 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 randomize2d2, double-blind, placebo-controlled,
dose-response study. International Clinical Psychopharmacology 2010

27. • Paliperidone LAI 3‐monthly Paliperidone LAI 3‐monthly is indicated
for patients who are clinically stable on paliperidone LAI 1‐monthly
(preferably for 4 months or more) and do not require dose
adjustment.7 Paliperidone LAI 3‐monthly is generally well tolerated,
with a tolerability profile similar to the 1‐monthly preparation,8,9 and
is non‐inferior to paliperidone 1‐monthly in terms of relapse rate.8
When initiating paliperidone LAI 3‐monthly, give the first dose in
place of the next scheduled dose of paliperidone LAI 1‐monthly. The
dose of paliperidone LAI 3‐monthly should be based on the previous
paliperidone LAI 1‐monthly dose, see Table 1.17.

28. • Table 1.17 Dosing of paliperidone LAI 3‐monthly7
• Dose of paliperidone LAI 1‐monthly Dose of paliperidone LAI
3‐monthly
• 50mg 175mg
• 75mg 263mg
• 100mg 350mg
• 150mg 525m

29. 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
∗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

30. 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

31. Second-generation LAIs
Olanzapine:
• Crystal salt made of Olanzapine & Palmoic acid. (Olanzapine pamoate)
• Plasma peak- 2-4 days
• Half life- 2-4 weeks
• Time for steady level 2-3 months
• Each 150 mg of Olanzapine LAI must be dissolved in 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

32. Second-generation LAIs
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.

33. Second-generation LAIs
Aripiprazole:
• First dopamine D2 partial agonist given regulatory clearance as a once-monthly
injection
• Microsphere long-acting injectable (similar to RLAI)
• The most frequently reported adverse events were akathisia, insomnia and
injection-site pain.

34. Second-generation LAIs
• 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

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

36. Practical issues concerning LAI administration
DRUG
36
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 so
eessential to rotate sites
Risperdon
e
Gluteal
or
deltoid
Powder;
special kits
• Requires cold chain storage
• Special kits & training
• Z tracking not required

37. Practical issues concerning LAI administration
37
DRUG Injection
Site
Storage Reconstitution & administration
Paliperidone Deltoid or Pre-filled • Choice of needle based on weight
Gluteal syringe kit • Longer needle for > 90 kg
• Deltoid achieves rapid uptake
• Z-tracking not required
Olanzapine Gluteal Powder, • Special kits & training required
special kits • 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 • Not indicated for the treatment of people with dementia-
dual related psychosis
chamber • Z-tracking not required
syringe

38. 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- weekly
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

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

40. Pierre ML, MocraneA, Philippe C, Sebastien G, Sylvie L,Ludovic, Guidelines for the use and
management of long-acting injectable antipsychotics in serious mental illness, BMC Psychiatry

41. 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, MocraneA, 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. 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

43. 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, MocraneA, 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

44. 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
Olanzapine
Pamoate
Risperidone LAI
Olanzapine
Pamoate
42
Pierre ML, MocraneA, Philippe C, Sebastien G, Sylvie L,Ludovic, Guidelines for the use and
management of long-acting injectable antipsychotics in serious mental illness, BMC Psychiatry

45. 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:
1. Metabolic (including weight gain and diabetes)
2. Extrapyramidal (including akathisia, dyskinesia and dystonia)
3. Cardiovascular (including prolonging the QT interval)
4. Hormonal (including increasing plasma prolactin)
5. Other (including unpleasant subjective experiences)
• Initiate with small dose as per BNF
• Discuss monitoring at regular interval
NICE Guidelines, 2014

46. Moudsley guidelnes

47. Advice on prescribing long-acting injections of
antipsychotic drugs
48
• FFor 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

48. • There is no simple formula for deciding when or whether to reduce the dose of maintenance antipsychotic treatment; therefore, a risk–benefit analysis must be done for
• every patient. Many patients, it should be noted, prefer to receive depots/LAIs.12 When
• considering dose reduction, the following prompts may be helpful:
• ■ Is the patient symptom‐free and, if so, for how long? Long‐standing, non‐distressing
• symptoms which have not previously been responsive to medication may be excluded.
• ■ What is the severity of the adverse effects (EPS including TD, metabolic adverse
• effects including obesity, etc.)? When patients report no or minimal adverse effects it
• is usually sensible to continue treatment and monitor closely for signs of TD.
• ■ What is the previous pattern of illness? Consider the speed of onset, duration and
• severity of past relapses and any dangers or risks posed to self or others.
• ■ Has dosage reduction been attempted before? If so, what was the outcome?
• ■ What are the patient’s current social circumstances? Is it a period of relative stability,
• or are stressful life events anticipated?
• ■ What is the potential social cost of relapse (e.g. is the patient the sole breadwinner for
• a family)?
• ■ Is the patient able to monitor his/her own symptoms? If so, will he/she seek help?

49. • If, after consideration of the above, the decision is taken to reduce
medication dose, the
• patient’s family should be involved and a clear explanation given of
what should be
• done if symptoms return or worsen. It would then be reasonable to
proceed in the
• following manner:

50. Reducing dose of depots
51
• If it has not already been done, oral antipsychotic medication should be discontinued
first.
• Where the product labelling allows, 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. The slower the rate of withdrawal, the longer the time to
relapse.
• Discontinuation should not be seen as the ultimate aim of the above process although it
sometimes results. NICE (2014) now suggests that intermittent treatment
(symptom‐triggered) is preferable to no treatment.

51. 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

52. 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

53. 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.

54. • When and how to use long-acting injectable antipsychotics

55. Conclusion
56
• 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.

56. Conclusion
57
• 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.