Long-acting injectables – a major advance in the treatment of schizophrenia

Lorem ipsum dolor sit amet, consectetur adipiscing elit. Ut elit tellus, luctus nec ullamcorper mattis, pulvinar dapibus leo.

Psychosis is described as an amalgamation of psychological symptoms resulting in a loss of contact with reality.5 

How do you differentiate between the different psychotic spectrum disorders?  

Schizophrenia is the most prevalent psychotic disorder6 and is characterised by positive and negative symptoms of at least six months’ duration, including at least one month of active-phase positive and negative symptoms:3 

  • Delusions: strange beliefs and ideas which are resistant to rational/logical dispute or contradiction from others 
  • Hallucinations: typically auditory, or less frequently, visual 
  • Disorganised speech: incoherence, irrational content 
  • Disorganised or catatonic behaviour: repetitive, senseless movements, or adopting a pose which may be maintained for hours. The individual may be resistant to efforts to move them into a different posture or will assume a new posture in which they are placed. 

Negative symptoms include a decrease or loss in normal functioning, and their components can commonly be confused with those of depressive disorders. The prodrome phase of schizophrenia commonly presents with negative symptoms. Patients can present as inexpressive or emotionally blunted and can be described as having a ‘flat affect’.5  

They can exhibit simplistic or prosodic speech patterns, along with alogia (poverty of speech). Psychomotor retardation, lack of energy, interest, concentration, and pleasure in activities once found pleasurable (anhedonia) are all potential features as well.5 

The prevalence and symptoms of schizophreniform disorder overlap with that of schizophrenia. However, the distinction is that symptoms are present for less than six months.7  

In schizoaffective disorders, patients present with both psychotic symptoms (similar to schizophrenia) and either a major depression or manic episode. The patient experiences either delusions or hallucinations for at least two weeks when they are not having a depressive or manic episode. The symptoms that meet criteria for manic episodes are present for >50% of the illness duration.7 

Delusional disorder is characterised by the presence of at least one delusion a month. The patient’s function is not impaired outside the specific impact of delusion and the duration of any depressive or manic episodes have been brief, relative to the duration of the delusion/s.7 

The diagnostic criteria for brief psychotic disorder is the presence of one or more of the following symptoms for at least one day, but less than one month: Delusions, hallucinations, disorganised speech, grossly disordered or catatonic behaviour.7   

Schizotypal personality disorder is characterised by one or more of the following symptoms in an attenuated form: delusions, hallucinations, or disorganised speech. Symptoms must have occurred at least once a week for the past month and must have started or gotten worse in the past year. Symptoms are not better attributed to another disorder, substance use or a medical condition.7 

Preventing relapses, readmissions, and suicide 

The management patients living with psychosis vary greatly depending on the origins of the psychosis. Any patient experiencing an episode of psychosis should be evaluated.5  

Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders.5 The goal of treatment is remission, which is defined as a period of six months with no symptoms or mild symptoms that do not interfere with a person’s behaviours.6 

Antipsychotics have demonstrated to be most effective in managing positive symptoms discussed earlier. However, they are less useful for negative symptoms. Second-generation or atypical antipsychotics are recommended by guidelines.5 

Briefly, the 2020 American Psychiatry Association guidelines recommend pharmacotherapy and psychosocial for the effective treatment  of schizophrenia. Pharmacotherapy recommendations include:8 

  • Antipsychotic medication with monitoring for effectiveness and side effects. Continuation of medication for those whose symptoms have improved 
  • Clozapine for patients with treatment-resistant schizophrenia or those with substantial risk of suicide or suicide attempts 
  • Long-acting injectable (LAI) antipsychotics for those who prefer them. 

Recommended psychosocial interventions include coordinated specialty care programmes for patients experiencing a first episode of psychosis,  cognitive-behavioural therapy for psychosis, psychoeducation and supported employment services.8 

Treatment complications as a result of non-adherence 

Treatment of schizophrenia is complicated because of non-adherence. It is estimated that between 26% and 44% of patients discontinue treatment and that around 66% are partially non-adherent. Disruption in treatment has been associated with relapse and increased risk of hospitalisation. About 80% of patients experience multiple relapses over the first five years of treatment.11,12 

Relapse increases the risk of suicide. The suicide rate for patients with schizophrenia spectrum disorders is more than 20 times higher than that for the general population. The risk is highest during the early stage of the illness or the first episode. The lifetime risk of suicide in patients living with schizophrenia is around 5%.13  

Preventing relapse in the early phases of the disorder 

Second-generation oral antipsychotic drugs are often suggested as a first-line treatment during the acute phase of early psychosis. Following control of the acute phase of psychosis, some have highlighted the benefits of switching patients to LAIs.10 

A 2022 review by Lian et al found that the use of LAIs in recent-onset, first-episode, and early psychosis patients is superior to oral antipsychotics in terms of reducing relapse and hospitalisation rates in early psychosis patients.10 

Haung et al (2021) suggest that LAI use in patients with newly diagnosed schizophrenia is associated with decreased all-cause mortality and suicide risk. Furthermore, early treatment with LAIs within the first two years of oral antipsychotic initiation was associated with a decrease in suicide mortality risk. Thus, LAI use in the early stage of treatment should be actively considered for patients with newly diagnosed schizophrenia.13 

Available LAIs 

LAI formulations are available for risperidone, olanzapine, aripiprazole, and paliperidone.11 In South Africa, paliperidone is available in once-monthly and three-monthly formulations. Paliperidone once-monthly, indicated for the prevention of relapse, is available in pre-filled syringes in 50mg, 75mg, 100mg and 150mg dosages.14 

Paliperidone three-monthly is indicated for maintenance therapy once patients are stable on the once-monthly formulation for four months or more. The three-monthly formulation is available in pre-filled syringes in 175mg, 263mg, 350mg and 525mg dosages.14 

Ostuzzi et al found paliperidone are among the best choices for the maintenance treatment of schizophrenia and other psychotic spectrum disorders.15 


The majority of patients living with schizophrenia recover from the initial acute phase, but only 14% to 20% recover fully. Others will improve but will continue to have recurrent episodes or relapses, the timing of which are related to stress, adversity, social isolation, and poor take-up of treatments.16  

Antipsychotic drugs have been the mainstay of treatment of schizophrenia since the 1950s. In the treatment and management of schizophrenia, antipsychotics are currently recommended for the treatment of acute episodes, for relapse prevention, for the emergency treatment of acute behavioural disturbance (rapid tranquillisation) and for symptom reduction.16  

The introduction of long-acting injectable formulations (‘depot’) of antipsychotic medication in the 1960s was heralded as a major advance in the treatment of established schizophrenia.16 

LAIs possess several important features that may help improve adherence in individuals with schizophrenia/schizoaffective disorder or bipolar disorder, including elimination of the need for daily administration, enabling healthcare providers (HCP) to be alerted and intervene if the LAI is not taken, and a guarantee of administration and transparency of adherence.17  

When an individual is being administered an LAI and relapse does occur, the HCP knows that relapse is due to a reason other than nonadherence. Importantly, LAIs reduce the risk of relapse and hospitalisation, which can affect health outcomes, quality of life, and healthcare cost.17  


  1. Wang J, Stone WS. Clinical high risk for psychosis provides new opportunities for schizophrenia intervention strategies. General Psychiatry, 2022. 
  2. Charlson FJ, et al. Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophrenia Bulletin, 2018. 
  3. Porter D. Schizophrenia Disorder DSM-5 295.90 (F20.9). 
  4. Perrotta G. Psychotic spectrum disorders: Definitions, classifications, neural correlates, and clinical profiles. Annals of Psychiatry and Treatment, 2020. 
  5. Calabrese J, Al Khalili Y. Psychosis. [Updated 2022 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. 
  6. Holder SD, Wayhs A. Schizophrenia. Am Fam Physician. 2014. 
  7. Barch DM. Schizophrenia Spectrum Disorders. 
  8. Keepers GA et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. The American Journal of Psychiatry, 2020. 
  9. Correll CU. Systematic literature review of schizophrenia clinical practice guidelines on acute and maintenance management with antipsychotics. Nature Schizophrenia, 2022. 
  10. Lian L, et al. Long-acting injectable antipsychotics for early psychosis: A comprehensive systematic review. PLoS ONE, 2022. 
  11. Emsley R, Kilian S. Efficacy, and safety profile of paliperidone palmitate injections in the management of patients with schizophrenia: an evidence-based review. Neuropsychiatric Disease and Treatment, 2018. 
  12. Correll CU, et al. Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview. CNS Drugs, 2021. 
  13. Huang C-Y, et al. Comparison of Long-Acting Injectable Antipsychotics With Oral Antipsychotics and Suicide and All-Cause Mortality in Patients With Newly Diagnosed Schizophrenia. JAMA Network Open, 2021. 
  14. MIMS. Atypical Antipsychotics.  
  15. Ostuzzi G, et al. Oral and longacting antipsychotics for relapse prevention in schizophreniaspectrum disorders: a network metaanalysis of 92 randomized trials including 22,645 participants. World Psychiatry, 2022. 
  16. NICE. Psychosis and Schizophrenia in adults The NICE Guideline On Treatment And Management. 
  17. Sajatovic M, et al. Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder – expert consensus survey part 2. Neuropsychiatric Disease and Treatment, 2018. 

Suggested Articles

Suggested Clinical & CPD content

CPD: 1pt

Related articles

Welcome to Medical Academic​

Get the most out of Medical Academic by telling us your occupation. This helps us create more great content for you and the community.


1000’s of Clinical and CPD content compiled by Key Opinion Leaders and our expert medical editors.


Access to medical webinars and events

Group 193

Access medical journals from industry leaders and expert medical editorials.

Congratulations! Your account was successfully created.

Please check your email for an activation mail. Click the activation link to activate your account

Stay up to date

Search for anything across CPD, webinars and journals

1000’s of Clinical and CPD content compiled by Key Opinion Leaders and our expert medical editors.


Access to medical webinars and events

Group 193

Access medical journals from industry leaders and expert medical editorials.

Congratulations! You have successfully booked your seat.

All webinar details will be emailed to your email address.

Did you know, you can book future webinars with a single click if you register an account with Medical Academic.

Congratulations! Your account was successfully created.

Your webinar seat has been booked and all webinar details will be emailed to your registered email address

Why not register for Medical Academic while booking your seat for this webinar?

Future Medical Academic webinars can be booked with a single click, all with a Medical Academic account… and it’s FREE.

Book webinar & create your account

* (Required)


1000’s of Clinical and CPD content compiled by Key Opinion Leaders and our expert medical editors.


Access to medical webinars and events

Group 193

Access medical journals from industry leaders and expert medical editorials.

Congratulations! Your account was successfully created.

Thank you for registering. You can now log in to your account.

Create your account

* (Required)

Login with One Time Pin (OTP)

Enter your registered email address to receive an OTP

A verification code will be sent to your email address. Please ensure that is on your safe sender list.

We've sent your OTP