Depot (LAI) algorithm


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First-Line Choice of an Antipsychotic LAI:

A first-generation depot antipsychotic should be chosen from the NHSGG&C Formulary*

Current evidence indicates that zuclopenthixol decanoate is more effective in preventing relapse than other first generation antipsychotic depots1.

*Exception to first line choice of FGA LAI:

Where there is good evidence of effect and tolerability with a specific SGA oral medication favouring its use as an LAI and where adherence with the oral medication is problematic. (Note: Paliperidone LAI over risperidone LAI should be considered for people who have responded well to oral risperidone and fit the exception criteria).

Second-Line Choice of an Antipsychotic LAI:

In the event of treatment failure or emergent, intolerable side-effects with the first-line choice:

An alternative first-generation depot medicine should be chosen from NHSGG&C Formulary*

*Exception: If emergent side-effects include extrapyramidal side effects or tardive dyskinesia then consider a formulary SGA LAI.

The differential in acquisition costs of FGA LAIs vs SGA LAIs
therefore clearly favours the prescription of FGA LAI medicines.

New initiations for SGA LAIs will now be subject to approval by local clinical director.

Any new request to initiate a SGA LAI should be made in writing to the respective CD for the service with a clear rationale for the choice of a SGA LAI over a first line choice of a FGA LAI.



Shajahan et al2 compared the use of risperidone, flupentixol and zuclopenthixol LAIs with respect to loss of efficacy and adverse effects leading to treatment discontinuation. They concluded that overall zuclopenthixol was less likely to be discontinued than risperidone or flupentixol. Where efficacy was concerned, findings favoured zuclopenthixol over the other LAIs and adverse effects did not differ between the three LAIs.

Cordiner et al3 studied prescribing patterns and outcomes for zuclopenthixol, paliperidone and risperidone LAIs and found poorer outcomes for paliperidone over zuclopenthixol or risperidone.

A recent local study4 assessed LAI use in one GG&C CMHT that had similar number of patients prescribed FGA and SGA LAIs. Patients receiving FGA LAIs complained of significantly fewer adverse effects than those receiving SGA LAIs. Average doses of FGA LAI were less than 15% BNF maximum where as average SGA LAI doses were approximately 80% of the BNF maximum. This study indicated that FGA LAIs were better tolerated and at least as efficacious as SGA LAIs.

The Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS I)5 compared FGAs including FGA LAIs and oral SGAs, although it did not include any SGA LAIs. It concluded there was no disadvantage in terms of quality of life or symptom control over a one year period in commencing treatment with FGAs rather than non-clozapine SGAs in people with schizophrenia whose medication was being changed because of intolerance or inadequate response.

The differential in acquisition costs of FGA LAIs vs SGA LAIs therefore clearly favours the prescription of FGA LAI medicines.

Prescribing flowchart


Comparative costs


1. da Silva Freire Coutinho E, Fenton M, Quaraishi SN. Zuclopenthixol decanoate for schizophrenia and other serious mental illnesses. Cochrane Database of Systematic Reviews 1999, Issue 3. Art. No.: CD001164. DOI: 10.1002/14651858.CD001164.

2. Shajahan P, Spence E, Taylor, M Darlington D, Pelosi A. Comparison of the effectiveness of depot antipsychotics in routine clinical practice. Psych Bull 2010, 34: 273-279

3. Cordiner M, Shajahan P, McAvoy S, Bashir M, Taylor M. Effectiveness of long-acting antipsychotics in clinical practice : 1. A retrospective, 18-month follow up and comparison between paliperidone palmitate, risperidone long-acting injection and Zuclopenthixol decanoate. Ther Adv Psychopharmacol 2016; 6(2): 66

4. Watson, D. Evaluation of the prescribing practice of long acting injectable antipsychotics: A pilot study. MSc thesis 2016

5. Jones PB et al. Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry. 2006;63:1079-1087

Last reviewed: 10 May 2022

Next review: 01 December 2023

Author(s): PMG-MH

Version: 2

Approved By: PMG-MH

Reviewer Name(s): Lead Clinical Pharmacist, Clinical Effectiveness Pharmacist