LAIs: old, classic, vintage or valuable?

Professor Dana Niehaus, a psychiatrist at Stikland Hospital recently shared insights around the psychopharmacology of the long acting injectables (LAIs), also known as depot medication. The roadshow was held in four venues across the country (Pretoria, Johannesburg, Cape Town and Durban) and attracted just over 80 delegates from the state sector as well as several doctors from neighbouring countries.

The use of depot medication can result in better outcomes for the patient – an increased time to medicine discontinuation and subsequent relapse, higher remission rates, greater reduction in symptoms and a shorter time to sustained remission.

Key treatment targets in schizophrenia include sustained symptomatic and functional remission to prevent relapse. The majority of patients will require long term, continuous treatment with an antipsychotic. Traditionally, guidelines have classed depot medication for patients in the chronic stage of the disease, those who are poorly adherent to their oral medication and those who have had multiple relapses. However, more recent guidelines have suggested that LAIs should be considered in recent onset schizophrenia. In current practice less than 10% of patients will receive a depot when they present with first episode psychosis, despite evidence for earlier use.

Prof Niehaus explored factors favouring the use of depots, concentrating specifically on clinician willingness. In a study of United Kingdom psychiatrists, 91% believed LAIs were efficacious, 81% believed they increased adherence and 94% agreed that they prevent relapse. However, 48% of the same group of psychiatrists also believed there was a stigma attached to the use of this medicine formulation, and 69% believed it would be less acceptable to the patient. Following this, the doctors were asked to portray depots in a negative light when speaking to the first group of patients, and in a positive light when speaking to a second group of patients. The difference was astounding – when communicated in a negative light, there was a 33% uptake in the use of depots, but when communicated in a positive light, there was a 96% uptake.

Practical information discussed included factors which affect the release and subsequent absorption of a depot medication, and the importance of understanding the pharmacokinetics of a given product.

There are several factors which affect the release and absorption rate of a depot medication. First and foremost is the injection site, the injection volume and the needle gauge – the average layer of gluteal fat is approximately 3.5 cm but a large proportion of patients, especially women, tend to have a greater layer of gluteal fat, which may result in an intramuscular injection not going directly into the muscle. The implications of this are slower release and slower absorption of the medicine. Other factors to consider include the rate of bioconversion from a pro to a parent drug, the absorption, distribution and spreading of the oil vehicle, and partitioning of the drug between the oil and tissue fluid.

Finally, Prof Niehaus spoke on the concept of drug forgiveness. This is the ability of a medication to maintain therapeutic activity despite non-compliant dosing behaviour. In a trial by Hughes et al (2008), equivalent doses of risperidone tablets (2mg daily) versus risperidone injection (25mg every two weeks), were compared. There was an above average adherence rate of 79% (presumably due to the clinical trial setting). When the pharmacokinetic coverage of these patients was measured, the patients on the depot were adequately covered 76% of the time, as opposed to the patients in the oral group who only had adequate coverage 35% of the time.

The presentation was informative and practical, and thoroughly enjoyed by all who attended. We hope this educational initiative will be of use to the attendees in their day to day practices.

 

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