Long-Acting Injectable Antipsychotics: A Practical Guide for Prescribers

Author: Flavio Guzman, MD
Last updated: February 10, 2018
Competing interests: none

This article summarizes the most clinically relevant features of long-acting injectable antipsychotics (LAIs, previously known as depot antipsychotics). We discuss general concepts as well as key prescribing facts of individual agents.
The guide also includes two new formulations: aripiprazole lauroxil (Aristada) and 3-month paliperidone palmitate (Invega Trinza).

Advantages and disadvantages of long-acting antipsychotics

Brissos and colleagues [1] reviewed the role of long-acting injectables in schizophrenia. They summarized the key advantages and disadvantages of LAIs in clinical practice.

Potential advantages

  • Early identification of non-adherence
  • Providing a mechanism for monitoring adherence with injections
  • No need to remember to take medication every day
  • Regular interactions between patient and medical staff
  • Reduced relapse frequency and rehospitalization rates
  • Clear attribution of the cause of relapse or non-response, discriminating between non adherence or lack
    of response
  • Reduce the risk of accidental or deliberated overdose
  • Treating patients with more stable plasma concentrations than oral medications
  • Avoidance of first-pass metabolism – better relationship between dose and blood level of drug
  • Lower and less frequent peak plasma level – reduced side effects

Potential disadvantages

  • Slow dose titration
  • Longer time to achieve steady state levels
  • Less flexibility of dose adjustment
  • Delayed disappearance of distressing and/or severe side effects
  • Pain at the injection site can occur, and leakage into the subcutaneous tissue and/or the skin may cause irritation and lesions (especially for oily long-acting injectable)
  • Burden of frequent travel to outpatient clinics or home visits by community nurses for their administration
  • Risperidone long-acting injectable needs refrigeration, which may be cumbersome in some latitudes
  • Perception of stigma

Clinical questions answered

Castillo and Stroup [2] reviewed the effectiveness of LAIs and addressed the following questions:

Who should receive LAIs?

Consider LAIs for patients with recent-onset schizophrenia and those with risk factors for medication non-adherence: history of non-adherence, severe symptoms, comorbid substance use, cognitive impairment, ambivalence or negative attitudes towards medications, and poor insight.

Are the newer LAIs more effective?

The effectiveness of newer LAIs (aripiprazole, olanzapine, paliperidone and risperidone) and older LAIs (haloperidol,fluphenazine, flupenthixol) is similar.

Tables summarizing individual agents

First-generation antipsychotics available as long-acting injectable medications


Drug Starting dose (mg) Maintenance dose (mg)
Haloperidol decanoate 50 50–200 every 3–4 weeks
Fluphenazine decanoate 12.5 12.5 – 50 every 2–3 weeks
Flupenthixol decanoate 20 50–300 every 2–4 weeks
Zuclopenthixol decanoate 100 200–500 every 1–4 weeks

Second-generation antipsychotics available as long-acting injectable medications

Drug (Brand name) Manufacturer Available formulations Injection interval Comments
Aripiprazole monohydrate
(Abilify Mantenna)
Otsuka/ Lundbeck 300,400 mg vials, prefilled syringes 400 mg once/month Requires a period of 2 weeks of overlap with oral aripiprazole.
Aripiprazole lauroxil
Alkermes 441, 662, 882 mg prefilled syringes 441–882 mg once/month
882 mg q 6 weeks
The 882 mg dose can be administered every 6 weeks.
Requires a period of 3 weeks of overlap with oral aripiprazole.
Olanzapine pamoate
(Zyprexa Relprevv)
Lilly 210, 300, 405 mg vials 150–300 mg q2 weeks
300–405 mg once/month
Requires monitoring post injection (3 hours)
Paliperidone palmitate
(Invega Sustenna, Xeplion)
Janssen 39,78,117,156 or 234 mg prefilled syringes 117 mg once/month Oral supplementation not necessary.
Paliperidone palmitate
(Invega Trinza)
Janssen 273, 410, 546, 819 mg prefilled syringes 410 mg q3 months Use in patients already treated with Invega Sustenna
Risperidone microspheres

(Risperdal Consta)

Janssen 12.5, 25, 37.5 or 50 mg vials 25 mg q2 weeks Requires a period of 3 weeks of overlap with oral risperidone

Practical considerations

Abilify Mantenna

  • Aripiprazole monohydrate requires a period of overlap of 2 weeks with oral aripiprazole.
  • Available as a lyophilized powder which needs to be reconstituted.

See full prescribing information (PDF)


  • Aripiprazole lauroxil requires a period of overlap of 3 weeks with oral aripiprazole.
  • Available as a prefilled syringe that does not require reconstitution.

See full prescribing information (PDF)

Highlights of prescribing information

Zyprexa Relprevv

  • Olanzapine pamoate does not need overlap with oral olanzapine.
  • It has a small risk of post-injection syndrome (0.07% of injections):
    • Symptoms include sedation, confusion, agitation, anxiety, aggressiveness, dizziness, ataxia and extrapyramidal symptoms
    • This risk limits use olanzapine pamoate use
    • After injection, the patient must be monitored for three hours by a healthcare professional
    • In the US, prescribers who administer Zyprexa Relprevv must enroll in a national registry that documents the incidence of this adverse effect

See full prescribing information (PDF)

Invega Sustenna

  • Paliperidone palmitate does not need overlap with oral paliperidone.
  • Requires two separate loading dose injections during the first week.

See full prescribing information (PDF)

Invega Trinza

  • The 3-month paliperidone palmitate (PPM–3) formulation can only be used if the patient has been receiving 1-month paliperidone palmitate injections for at least 4 months.
  • It is administered 4 times a year, providing the longest interval of any approved LAI.

See full prescribing information (PDF)

Risperdal Consta

  • Risperidone microspheres requires a period of overlap of 3 weeks with oral risperidone.
  • It has a 2-week dosing interval.

See full prescribing information (PDF)

Acknowledgements: Thanks to Dr. Leslie Lundt for correcting an earlier version of this article.


  1. Brissos, S., Veguilla, M. R., Taylor, D., & Balanzá-Martinez, V. (2014). The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal. Therapeutic advances in psychopharmacology, 2045125314540297.  ↩
  2. Castillo, E. G., & Stroup, T. S. (2015). Effectiveness of long-acting injectable antipsychotics: a clinical perspective. Evidence Based Mental Health, ebmental–2015.  ↩
  3. Gopalakrishna, G., Aggarwal, A., & Lauriello, J. (2013). Long-acting injectable aripiprazole: how might it fit in our tool box?. Clinical schizophrenia & related psychoses7(2), 87-92.
  4. Citrome, L. (2015). Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.Expert review of clinical pharmacology, 1-18.

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