Long-Acting Injectable Antipsychotics: A Practical Guide for Prescribers
- 1 Advantages and disadvantages of long-acting antipsychotics
- 2 Clinical questions answered
- 3 Tables summarizing individual agents
- 4 Practical considerations
- 5 References
Author: Flavio Guzman, MD
Last updated: September 25, 2017
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  reviewed the role of long-acting injectables in schizophrenia. They summarized the key advantages and disadvantages of LAIs in clinical practice.
- 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
- 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
- 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  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|
|Otsuka/ Lundbeck||300,400 mg vials, prefilled syringes||400 mg once/month||Requires a period of 2 weeks of overlap with oral aripiprazole.|
|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.
|Lilly||210, 300, 405 mg vials||150–300 mg q2 weeks
300–405 mg once/month
|Requires monitoring post injection (3 hours)|
(Invega Sustenna, Xeplion)
|Janssen||39,78,117,156 or 234 mg prefilled syringes||117 mg once/month||Oral supplementation not necessary.|
|Janssen||273, 410, 546, 819 mg prefilled syringes||410 mg q3 months||Use in patients already treated with Invega Sustenna|
|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|
- Aripiprazole monohydrate requires a period of overlap of 2 weeks with oral aripiprazole.
- Available as a lyophilized powder which needs to be reconstituted.
- Aripiprazole lauroxil requires a period of overlap of 3 weeks with oral aripiprazole.
- Available as a prefilled syringe that does not require reconstitution.
- 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
- Paliperidone palmitate does not need overlap with oral paliperidone.
- Requires two separate loading dose injections during the first week.
- 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.
- Risperidone microspheres requires a period of overlap of 3 weeks with oral risperidone.
- It has a 2-week dosing interval.
Acknowledgements: Thanks to Dr. Leslie Lundt for correcting an earlier version of this article.
- 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. ↩
- Castillo, E. G., & Stroup, T. S. (2015). Effectiveness of long-acting injectable antipsychotics: a clinical perspective. Evidence Based Mental Health, ebmental–2015. ↩
Gopalakrishna, G., Aggarwal, A., & Lauriello, J. (2013). Long-acting injectable aripiprazole: how might it fit in our tool box?. Clinical schizophrenia & related psychoses, 7(2), 87-92.
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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