Extended-release vs immediate-release quetiapine

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BMD affects 4.4% of the population and is ranked fourth in terms of global causes of morbidity and mortality among people <25-years. Schizophrenia affects between 0.3% and 0.7% of the global population.3 

Correct diagnosis is extremely important because it informs the management approach to these two disorders. It should be noted that schizoaffective disorder (SZD) has similar symptoms as schizophrenia and BMD and is important to rule out as a possible diagnosis.4  

According to Wilson et al, SZD ‘occupies an intermediate position on the continuum of disease severity, between schizophrenia and mood disorders, in particular BMD’.4  

Patients living with SZD present with schizophrenic (eg delusions, hallucinations, disorganised speech) as well as mood symptoms (eg depressive or manic episodes). The lifetime prevalence of SZD is 0.3%.4,5 

According to Wy and Saadabadi, time frames often give clues towards differentiating between SZD and schizophrenia. Symptom course also plays a role: did mood symptoms or psychotic symptoms come first? For how long did the symptoms last?5 

There must be a definite period of at least two weeks in which there are only psychotic symptoms (delusions and hallucinations) without mood symptoms to diagnose SZD.5  

However, a major mood episode (depression or mania) is present for most of the total duration of the illness. Once the psychotic symptoms predominate most of the total duration of the illness, the diagnosis leans towards schizophrenia. Also, schizophrenia requires six months of prodromal or residual symptoms. SZD does not require this criterion.5 

For the purposes of this article, we will focus on schizophrenia and BMD.  

Overlap between symptoms of schizophrenia and BMD 

To add to the complexities of diagnosis, schizophrenia and BMD mania also share an overlap of symptoms, but it is extremely important to keep in mind that these are two distinct psychiatric disorders each requiring a different treatment approach.6  

Similar symptoms between the two disorders include for example psychotic episodes or hallucinations (the hallmark of schizophrenia), paranoia, and cognitive deficits. More than 50% of patients living with BMD experience psychotic episodes or hallucinations (the hallmark of schizophrenia) throughout life.7  

However, in schizophrenia, auditory hallucinations are more common, whereas in BMD, grandiosity and excitement are more prevalent. While paranoia can be present in both conditions, it is more systematic in schizophrenia.7  

Furthermore, Jiménez-López et al showed that patients living with schizophrenia or BMD have similar neurocognitive deficits. However, neurocognitive deficits in patients living with schizophrenia are more severe and pervasive compared to those living with BMD.7   

Studies also show that the two diseases share a similar genetic profile and risk factors. Lichtenstein et al showed that heritability for schizophrenia and BMD was 64% and 59%, respectively.6,8 

Canetta et al showed that maternal serological influenza exposure was related to a significant five-fold greater risk of BMD with psychotic features. A previous study showed an association between prenatal influenza exposure and schizophrenia.8 

Differentiating between schizophrenia and BMD 

Treating schizophrenia and BMD mania 


The goals in treating schizophrenia include targeting symptoms, preventing relapse, and increasing adaptive functioning so that the patient can be integrated back into the community.10 

 Standard management of schizophrenia includes the use of antipsychotic medications such as quetiapine to help control acute psychotic episodesand prevent relapses.11  

 Early intervention in the first episode of psychosis has the potential to improve outcomes. Such intervention could result in attenuation, delay or even prevention of the onset of psychosis in some individuals.11  

Although pharmacotherapy is the mainstay of schizophrenia management, but residual symptoms may persist. For that reason, non-pharmacological treatments, such psychotherapy, are also important.12  

BMD mania 

A manic episode is defined as an emotional state where a person is unusually irritable in an extreme way, most of the day for most days, has more energy than usual for at least one week. The change in mood is uncharacteristic of the person’s usual state or behaviour. A hypomanic episode is like a manic episode however, the symptoms are less severe and may only last four consecutive days.13 

The Council for Medical Schemes’ BMD treatment algorithm recommends the use of the following:13 

  • Antimanic agents 
  • Bipolar depression agents 
  • Maintenance agents. 

Antimanic agents include anticonvulsants, lithium, and antipsychotics. Second-generation atypical antipsychotics are generally well tolerated with less side effects compared to first-generation agents. Atypical antipsychotics are recommended as prescribed minimum benefit level of care.13 

IR vs XR quetiapine: What are the differences? 

Quetiapine is available as an IR formulation that requires twice-daily dosing, and an XR formulation that allows once-daily dosing and has a faster dose titration schedule. Antipsychotics are recommended as first-line treatment for both schizophrenia and BMD.2,11,13 

Quetiapine XR has a simple and fast titration. This is of significant benefit where there is often urgency for reaching therapeutic dose and steady state in the acute phase of illness, with quetiapine XR more often used in therapeutic doses compared with IR, and its once-daily dosing enhances adherence with less treatment cessation in patients prescribed quetiapine MR.15 

The pharmacokinetic characteristics of once-daily quetiapine XR demonstrate that the formulation provides continuous drug release over time with fewer peaks and troughs than the same total daily dose of twice-daily quetiapine IR. Quetiapine XR is characterised by sustained drug exposure (20 hours) compared to quetiapine IR (seven hours).14   

Once-daily quetiapine XR has a similar area under the plasma concentration–time curve (AUC), minimum plasma concentration (Cmin) and a slightly lower maximum plasma concentration (Cmax) than the equivalent dose of quetiapine IR given twice daily.14  

In a crossover, head-to-head study, total daily exposure, measured by AUC at steady state, was less variable with quetiapine XR versus quetiapine IR (39.2% versus 51.2%, respectively).14  

Compared with fasting, a high-fat meal increased the AUC and Cmax for quetiapine XR, whereas a light meal had no significant effect on these parameters. Quetiapine XR exhibits a less pronounced D2 receptor occupancy peak and receptor occupancy levels remain higher for longer compared with quetiapine IR.14  

Benefits of quetiapine XR 

According to Bui et al patients with schizophrenia or BMD often fail to take their medication as prescribed. Non-adherence rates as high as 50% have been reported in patients with schizophrenia, and more than 40% in patients with BMD.14    

Partial adherence or non-adherence to treatment is often a major contributory cause of relapse in both these patient populations. Patients who relapse typically experience poorer clinical outcomes and incur an increased financial and logistical burden on healthcare systems when compared with patients who remain in remission.14 

Barriers to medication adherence are multifactorial, including factors such as impaired cognitive function and lack of insight, but also importantly treatment related including frequency of dose and effectiveness, undesirable side-effects (eg sedation), as well as treatment delivery and form.15 

Studies show that cessation of treatment due to non-adherence was less common in patients receiving quetiapine XR than in those receiving quetiapine IR (3.4% and 12%, respectively.14  

Quetiapine XR has a more favourable tolerability profile and is associated with fewer common side effects, including dry mouth, dizziness, headaches, and nausea.15 

Furthermore, with quetiapine XR, the impact of daytime somnolence can be minimised by evening dosing, which is not possible with twice-daily dosing of quetiapine IR.14 

Factors to take into consideration when prescribing an antipsychotic 

According to Kelbrick, antipsychotic medication choice should be individualised. Important factors to take into consideration include:15  

  • Efficacy 
  • Tolerability 
  • Previous treatment choice and response  
  • Presenting symptom profile (eg where, in addition to psychotic symptoms, there is a need for mood-stabilising properties, or to address sleep difficulties and comorbid anxiety) 
  • Urgency for achieving therapeutic dose 
  • Risk profile 
  • Individual personal circumstances (employment, driving, etc)  
  • Individual antipsychotic side effect profile (both undesirable and advantageous side-effects).  


  1. MIMS. Atypical antipsychotics. 
  2. Riedel M, Schmitz M, Østergaard PK. Comparison of the effects of quetiapine extended-release and quetiapine immediate-release on cognitive performance, sedation, and patient satisfaction in patients with schizophrenia: A randomised, double-blind, crossover study (eXtRa). Schizophrenia Research, 2015. 
  3. Léger M, Wolff V, Kabuth B, Albuisson E, Ligier F. The mood disorder spectrum vs. schizophrenia decision tree: EDIPHAS research into the childhood and adolescence of 205 patients. BMC Psychiatry, 2022. 
  4. Wilson JE, Nian H, Heckers S. The schizoaffective disorder diagnosis: a conundrum in the clinical setting. Eur Arch Psychiatry Clin Neurosci, 2014. 
  5. Wy TJP, Saadabadi A. Schizoaffective Disorder. [Updated 2022 May 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: 
  6. Lichtenstein P, Yip BH, Björk C, et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet, 2009. 
  7. Jiménez-López E, Aparicio AI, Sánchez-Morla EM, et al. Neurocognition in patients with psychotic and non-psychotic bipolar I disorder. A comparative study with individuals with schizophrenia. J Affect Disord, 2017. 
  8. Canetta SE, Bao Y, Co MD, et al. Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring. Am J Psychiatry, 2014. 
  9. American Psychiatric Association. DSM-5. 
  10. Barnes TR, et al. Evidence-based guidelines for the pharmacological treatment of schizophrenia: updated recommendations from the British Association for Psychopharmacology.J Psychopharmacol, 2020.  
  11. American Psychiatric Association.Practice Guideline for the Treatment of Patients With Schizophrenia, 3rd edn, 2021. 
  12. Patel KR, Cherian J, Gohil K, et al. Schizophrenia: Overview and Treatment Options. P&T, 2014.  
  13. Council for Medical Schemes. PMB definition guidelines for bipolar mood disorder Version 1: 30.09.2020. 
  14. Bui K, Earley W, Nyberg S. Pharmacokinetic profile of the extended-release formulation of quetiapine fumarate (quetiapine XR): clinical implications. Current Medical Research and Opinion, 2013. 
  15. Kelbrick M. Quetiapine modified-release versus immediate-release in early psychosis. Progress in Neurology and Psychiatry, 2019. 

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