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Breaking boundaries: Introducing cariprazine
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8 Cariprazine holds promise for transforming the clinical landscape of schizophrenia
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Practical insights into schizophrenia treatment: Case studies highlight effective strategies
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Breaking boundaries Introducing cariprazine
In 2023, Adcock Ingram introduced cariprazine, an antipsychotic prescribed for individuals living with schizophrenia.1 Schizophrenia is a multifaceted disorder, 2 marked by alterations in positive, negative, cognitive, and affective symptoms.2 Globally, it affects ~24 million individuals and ranks among the top 20 leading causes of years lost due to disability.2
Positive symptoms of schizophrenia include persistent delusions, hallucinations, disorganized thinking, speech, and behaviour. Conversely, negative symptoms include avolition, blunted or flat affect, psychomotor disturbances, as well as experiences of passivity and control. 2 While positive symptoms tend to naturally diminish over time, negative symptoms often persist, correlating with a poor prognosis. 2
Cognitive impairments associated with schizophrenia affect various domains, including sustained attention, early information processing, contextual processing, memory, verbal and non-verbal abilities, executive functioning, abstraction, and conceptual organization. 3
Affective symptoms such as depression and anxiety are prevalent among individuals with schizophrenia. Research indicates that up to 80% of individuals experience depressive symptoms, while the prevalence of any anxiety disorder is estimated to be around 38%, with social anxiety disorder being the most common. 4,5
Several launches took place over the past few months in South Africa. In our article on page 6, we highlight five pivotal aspects that distinguish cariprazine from other
antipsychotics:
1 Distinct pharmacological profile: Cariprazine exhibits a unique pharmacological profile compared to other atypical antipsychotics.
2 Extended half-life: The long half-life of cariprazine offers protection to individuals, even in cases of missed doses.
3 Broad-spectrum treatment: Cariprazine serves as a comprehensive treatment, effectively addressing both positive and negative symptoms.
4 Treatment of predominant negative symptoms: Cariprazine stands out as the sole antipsychotic with documented efficacy in treating predominant negative symptoms of schizophrenia.
5 Excellent safety profile: Cariprazine boasts an excellent safety profile, further distinguishing it from other antipsychotics.
In our article on page 12, Dr Pravesh Kassen, a practicing psychiatrist at Akeso Clinic in Pietermaritzburg, offers valuable insights from his experiences with cariprazine.
References
1. Professional Information. Reagila. Updated 2022. [Internet]. Available at: https://pipil-repository.sahpra.org.za/wp-content/ uploads/2022/08/Final_PIL_Reagila_Applicant. pdf
2. Masinga N, Nyamaruze P, Akintola, O. A retrospective study exploring how South African newspapers framed Schizophrenia and other psychotic disorders over an 11-year period (2004–2014). BMC Psychiatry 22, 667 (2022). https://doi.org/10.1186/s12888-022-04276-5
3. Srisudha B, Kattula D, Devika S, Rachana A. Cognitive dysfunction and disability in people living with schizophrenia. J Family Med Prim Care, 2022 Jun;11(6):2356-2362. doi: 10.4103/jfmpc. jfmpc_396_21. Epub 2022 Jun 30.
4. Morrissette DA, Stahl SM. Affective symptoms in schizophrenia. Drug Discovery Today: Therapeutic Strategies, Volume 8, Issues 1–2, doi. org/10.1016/j.ddstr.2011.
We hope you find this guide valuable in your journey toward understanding and managing schizophrenia. With the introduction of cariprazine, there is renewed hope for improved outcomes and enhanced quality of life for individuals living with this complex disorder.
5. Temmingh H, Stein DJ. Anxiety in Patients with Schizophrenia: Epidemiology and Management. CNS Drugs, 2015;29(10):819-32. doi: 10.1007/ s40263-015-0282-7. PMID: 26482261. SF
REAGILA® gives them hope. WHEN SCHIZOPHRENIA ALTERS THEIR LIVES,
Dear Healthcare Provider,
Introducing REAGILA®
REAGILA® contains cariprazine, an atypical antipsychotic with a unique pharmacological profile1,2 for the treatment of acute relapses of schizophrenia and maintenance therapy in adult patients.2 Although positive symptoms of schizophrenia are effectively managed, the primary negative symptoms generally do not respond well to currently available antipsychotics and remain an unmet medical need.3
Cariprazine is unique among antipsychotics in having a higher affinity for the D3 receptor than dopamine itself.1 Consistent broad-spectrum efficacy for positive and negative symptoms has been shown across 3 pivotal trials in the treatment of acute schizophrenia.4-6
Furthermore, it has proven superior efficacy over another atypical antipsychotic (risperidone) in patients with predominant negative symptoms.7,8 Four different dosage strengths enable easy dose titration to suit individual needs.2
Should you require any additional information, please do not hesitate to contact your helpful Adcock Ingram Sales Representative.
Yours sincerely,
Anneke Rice
Brand Manager: CNS
Adcock Ingram Healthcare (Pty) Ltd
Email: customer.care@adcock.com
https://www.health.gov.za/nhi-pee/. 3.
Schooler NR. Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment. Neuropsych Dis Treat 2020:16 519–534. http://doi.org/10.2147/NDT.S225643. 4. Durgam S, Starace A, Li D, et al An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: A phase II, randomized clinical trial. Schizophr Res 2014;152:450-457. http://dx.doi.org/10.1016/j.schres.2013.11.041. 5. Durgam S, Cutler AJ, Lu K, et al. Cariprazine in Acute Exacerbation of Schizophrenia: A Fixed-Dose, Phase 3, Randomized, Double-Blind, Placebo- and Active-Controlled Trial. J Clin Psychiatry 2015;76(12):e1574-e1582. Dx.doi.org/10.4088/JCP.15m09997. 6. Kane JM, Zukin S, Wang Y, et al Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia. Results From an International, Phase III Clinical Trial. J Clin Psychopharmacol 2015;35: 367–373. DOI: 10.1097/JCP.0000000000000346. 7. Barabassy A, Szatmári B, Laszlovszky I, et al. Negative Symptoms of Schizophrenia: Constructs, Burden, and Management [Internet]. Psychotic Disorders - An Update. InTech 2018. Chapter 4:43-62. http://dx.doi.org/10.5772/intechopen.73300. 8. Németh G, Laszlovszky I, Czobor P, et al. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial. Lancet 2017;389:1103-1113. DOI: http://dx.doi.org/10.1016/S0140-6736(17)30060-0. 9. REAGILA® professional information, November 2022. 10. Data on file SEP and SEP approval. S5 Reagila® 1,5 mg hard capsules. Each hard capsule contains cariprazine hydrochloride corresponding to 1,5 mg cariprazine. Reg. No.: 55/2.6.5/0097. S5 Reagila® 3 mg hard capsules. Each hard capsule contains cariprazine hydrochloride corresponding to 3 mg cariprazine. Each hard capsule contains 0,0003 mg Allura red AC (E129). Reg. No.: 55/2.6.5/0098.
ANXIETY
STRESAM
INDICATION
• STRESAM is indicated for psychosomatic manifestations of anxiety.1
CIPRALEX® DEPRESSION AND ANXIETY DISORDERS
INDICATIONS
CIPRALEX® has a broad range of indications making it suitable for a wide range of patients:2
• Major Depressive Episodes
• Panic Disorder with or without agoraphobia
• Social Anxiety Disorder (social phobia)
• Generalised Anxiety Disorder
• Obsessive-Compulsive Disorder
MEDIKINET® MR INDICATION
• MEDIKINET® MR is indicated as part of a comprehensive treatment programme for attention-deficit/hyperactivity disorder (ADHD) in children aged 6 years of age and over and adults with ADHD onset in childhood when remedial measures alone prove insufficient.3
• Treatment must be initiated and supervised by a doctor specialised in the treatment of ADHD.3
• AMFEXA® is indicated as part of a comprehensive treatment programme* for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 17 years when response to previous methylphenidate treatment is considered clinically inadequate.4
*Typically includes psychological, educational and social measures
• REAGILA® is indicated for the treatment of acute relapses of schizophrenia and maintenance therapy in adult patients.5
• XADAGO® is indicated for the treatment of adult patients with idiopathic Parkinson’s disease (PD) as add-on therapy to a stable dose of levodopa (L-dopa) alone or in combination with other PD medicines in mid-to late stage fluctuating patients.7
• TERIFLUNOMIDE ADCO® is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of relapses and delay the accumulation of physical disability.6
Cariprazine holds promise for transforming the clinical landscape of schizophrenia
This article summarises the presentations made by four prominent local psychiatrists and will highlight the five key advantages of cariprazine.
Cape Town
Prof Lebo Phahladira, psychiatrist and senior lecturer, is a member of the Psychosis Research Programme of the Department of Psychiatry at Stellenbosch University
Prof Dana Niehaus, Head: Psychogeriatric Unit at Stikland Hospital and Stellenbosch University
Cariprazine’s unique pharmacological profile
Antipsychotics are classified according to which dopamine receptors (D1, D2, D3) they bind to. The neurobiological mechanism and clinical effects of agents depend on which dopamine receptor subtype they exert their action.1
Cariprazine is a dopamine D3 and D2 receptor partial agonist and has a ~10fold higher affinity for D3 receptors. D3 receptors are highly expressed in areas of the brain that play a role in the regulation of motivation and reward-related behaviour. 2,3
Studies show clinical antipsychotic efficacy with cariprazine is attained at about 60% to 75% occupancy of dopamine D2 receptors. Cariprazine also has a high affinity for serotonin or 5-hydroxytryptamine (5-HT). 2,4
According to Stahl, cariprazine is unique because of its high affinity for D3 receptors. Cariprazine works by blocking the release of D3 receptors, which is thought to improve dopaminergic neurotransmission.1,5 Furthermore, blocking D3 receptors can enhance acetylcholine release in the prefrontal cortex, which contribute to improvement in cognitive function.1
Cariprazine has the longest halflife of any atypical antipsychotic Cariprazine is a once-daily oral agent, which can be taken with, or without food. It has two major active metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). 6
Nakamura et al evaluated the pharmacokinetics of cariprazine, metabolites, and total active moieties (sum of cariprazine and two metabolites), as well as efficacy and safety. Participants were randomised to 3mg, 6mg, or 9mg/day. The study duration was 28-weeks. 6
They found that a steady state was reached within one to two weeks for cariprazine and DCAR, four weeks for DDCAR, and three weeks for total active moieties. Exposure was dose-proportional over the range of 3mg/day–9mg/day. 6
Cariprazine and DCAR levels decreased by >90% within one week after the last dose, DDCAR decreased by ~50% at one week, and total active moieties decreased by ~90% within four weeks. 6
The terminal half-lives of cariprazine, DCAR, and DDCAR ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446 hours, respectively. The effective half-life (calculated from time to steady state) of total active moieties was about a week. 6
According to Stahl, cariprazine has the longest half-life of any atypical antipsychotic. As a result, it takes about five half-lives to get to steady state, which means that the effective dose continues to rise over the course of a few weeks following initiation, even if the daily dose stays the same. 5
Stahl does caution that an unsuspecting clinician may increase the dose before arriving at steady state and overshoot the ideal dose, requiring some down-titration later. 5
Furthermore, when stopping treatment with cariprazine, it will be many weeks before the active drug is washed out. That could be a potential advantage in schizophrenia, a condition known to be characterised by poor adherence to treatment. 5
City of Tshwane
Dr Franco Colin, psychiatrist in private practice and part time consultant to the Department of Psychiatry, University of Pretoria
includes various clusters, including negative symptoms (such as blunted affect, anhedonia, and avolition), cognitive impairments, and mood disturbances (like depression). Symptoms may persist even in clinically stable patients, contributing to impaired social and occupational functioning, thus significantly impacting their daily lives.7
A limitation of currently approved antipsychotics is that they are only effective in addressing positive symptoms of schizophrenia and have limited efficacy in managing other symptom domains.7
So, apart from having to manage symptoms with agents that have limited efficacy, individuals living with schizophrenia also face a high burden of adverse effects (AEs) associated with older generation antipsychotics including weight gain, metabolic disruptions, and sexual dysfunction, leading to medication non-adherence that can potentially worsen symptoms, stressed Dr Colin. 8
The limitations of traditional antipsychotics underscored the urgent need for the development of innovative therapeutic approaches to effectively address the diverse symptoms of the disorder while minimising the adverse effects on patients’ well-being, added Dr Colin.8
Enter cariprazine, a broad-spectrum antipsychotic that has been shown to effectively manage positive and negative symptoms. Marder et al evaluated the mean change from baseline to week six in Positive and Negative Syndrome Scale (PANSS)-derived symptom factors. Positive, negative, cognitive (eg disorganised thought), hostility (uncontrolled hostility/excitement), and affective (anxiety/depression) symptoms were analysed and the effects of cariprazine were compared to placebo.7
In the pooled analyses at week six, the difference in mean change from baseline was statistically significant in favour of cariprazine (1.5mg/d-9mg/d) compared to placebo across all five PANSS factors.7
Cariprazine is a broad-spectrum treatment effective in managing positive and negative symptoms The symptomatology of schizophrenia
The largest treatment effect was observed in the disorganised thought factor (effect size [ES]=0.47, P<0.0001). Similar treatment effects were found for the negative symptom (ES=0.39, P<0.0001), positive symptom (ES=0.37, P<0.0001), and uncontrolled hostility/excitement (ES=0.34, P<0.0001) factors.7
A dose-response analysis was conducted using pooled data from two fixed-dose studies. The difference in mean change from baseline in PANSS total score, negative symptom factor score, and disorganised thought factor score was
statistically significant in favour of all doses of cariprazine (1.5mg/d, 3mg/d, 4.5mg/d and 6mg/d) compared to placebo.7
Slightly larger treatment effects were observed with cariprazine 4.5mg/d and 6mg/d than with cariprazine 1.5mg/d and 3mg/d on PANSS total, negative symptom, positive symptom, and disorganised thought factor scores.7
On the PANSS positive factor, the differences between the three highest doses of cariprazine and placebo were statistically significant, while all doses except cariprazine 4.5mg/d were significantly different from placebo on the uncontrolled hostility/excitement factor.7
Cariprazine is the only antipsychotic with proven efficacy in the treatment of predominant negative symptoms of schizophrenia
Németh et al conduced a randomised, double-blind, phase IIIb trial, enrolling adults living with stable schizophrenia and predominant negative symptoms (>6 months) at 66 study centres in 11 European countries.9
Participants (n=533) were randomly assigned (1:1) to 26 weeks of monotherapy with fixed-dose oral cariprazine (3mg, 4.5mg [target dose], or 6mg/d) or risperidone (3mg, 4mg [target dose], or 6mg/d). Previous medication was discontinued over two weeks.9
The primary outcome was the change from baseline to week 26 or end of treatment on the PANSS-factor score for negative symptoms (PANSS-FSNS), analysed in a modified intention-to-treat population of patients who had follow-up assessments within five days after the last receipt of study agents.9
Cariprazine led to greater least squares mean change in PANSS-FSNS from baseline to week 26 than risperidone (−8.90 points for cariprazine vs −7.44 points for risperidone, least squares mean difference −1.46, 95% CI −2.39 to −0.53, p=0.0022, effect size 0.31).9
The authors concluded that their results support the efficacy of cariprazine in the treatment of predominant negative symptoms of schizophrenia.9
Dr Colin concluded that cariprazine has the potential to change clinical practice by providing a treatment option for patients with predominant negative symptoms of schizophrenia. Treatment with cariprazine monotherapy not only improved predominant negative symptoms in patients with schizophrenia, but the effect was also clinically meaningful, as shown by improvement in patient functioning. 8
Johannesburg
Dr Viresh Chiman, a psychiatrist practising at Akeso Parktown
Modern psychopharmacology is increasingly emphasising the importance of pharmacotherapy’s tolerability to enhance the quality of life (QoL) for individuals living with schizophrenia. This focus includes factors such as functionality, sustained remission, and overall recovery, noted Dr Chiman.10
He emphasised that poor adherence rates to antipsychotic treatment is high among individuals living with schizophrenia, with adherence rates ranging between 56% and 60%.11
Non-adherence is the most frequent cause of exacerbation, relapse (75% to 90%), re-hospitalisation, or increased use of emergency psychiatric services, functional decline, and an increased risk of death, as well as increasing the care burden on their families.11
Non-adherence tends to occur more frequently when patients disagree with the necessity of treatment. Furthermore, complex treatment regimens and the presence of AEs deemed ‘unbearable and unacceptable’ by patients contribute significantly to nonadherence, said Dr Chiman.10
Furthermore, when looking at it from the patient perspective, they rated metabolic consequences of medication as contributing to morbidity, low QoL, and low satisfaction with care and from a caregiver perspective, sedation and weight gain were rated as important factors contributing to non-adherence, said Dr Chiman.10
Cariprazine’s safety profile
Numerous studies have assessed the safety and tolerability of cariprazine in a wide spectrum of patient subgroups. Earley et al (2017) conducted a post-hoc safety and tolerability analysis using data from four acute trials within the cariprazine schizophrenia clinical development programme.12
The analysis included the overall safety population, comprising all patients who received at least one dose of the study drug, as well as modal daily dose subgroups (1.5mg/d–3mg/day, 4.5mg/d–6mg/day, and 9mg/d–12mg/day).12
The study found that cariprazine was generally well tolerated. The incidence of treatment-emergent AEs compared to placebo was similar for the 1.5mg/d–3mg/day subgroup, but higher for the 4.5mg/d–6mg/ day and 9mg/d–12mg/day subgroups.12
A dose-response relationship was observed for akathisia, extrapyramidal symptoms, and diastolic blood pressure. However, the mean changes in metabolic parameters were generally similar between cariprazine-treated and placebo-treated patients.12
Notably, there were no increases in prolactin levels or QTc values greater than 500ms. Small increases in mean body weight (~1kg-2kg) were observed compared to placebo.12
To further elucidate the long-term safety profile of cariprazine, Nasrallah et al (2017) conducted post-hoc analyses by pooling data from two 48-week openlabel, flexible-dose extension studies. These analyses focused on outcomes in the pooled safety population, comprising patients who received at least one dose of cariprazine during an open-label extension period. Descriptive statistics were utilised to summarise findings for the overall cariprazine group and modal daily dose subgroups (1.5mg/d–3mg/day, 4.5mg/d–6mg/day, and 9mg/day).13
AEs such as akathisia, insomnia, weight increased, and headache were reported in ≥10% of the overall population. Notably, mean prolactin levels decreased across all dose groups (overall −15.4ng/mL).13
Clinically insignificant changes in aminotransferase levels and alkaline phosphatase were observed, with no evident dose-response relationship observed.13
Additionally, metabolic parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels, exhibited mean decreases, without any doseresponse relationship noted. Moreover, changes in cardiovascular parameters, including blood pressure and pulse, were generally deemed not clinically significant.13
AEs related to extrapyramidal symptoms occurred in ≥5% of patients, including akathisia, tremor, restlessness, and extrapyramidal disorder. Nasrallah et al concluded that these post-hoc pooled analyses demonstrated the overall safety and tolerability of cariprazine.13
Barabássy et al (2021) conducted posthoc analyses to assess the safety profile of cariprazine within the recommended dose range of 1.5mg/d-6 mg/d for schizophrenia, using data (n=2048) from eight clinical trials.14
The most reported AEs (>10%) in patients treated with cariprazine included akathisia (14.6%), insomnia (14.0%), and headache (12.1%). Most AEs were considered mild (71.0%) or moderate (26.5%). Akathisia, the most common cariprazine-related AE, was predominantly mild/moderate (97.5%) and
managed with rescue medications (56.3%) or dose reduction (18.3%).14
The metabolic profile of cariprazine showed minimal weight gain (mean of 1kg) and an AE of weight increased reported for 5.1% of patients. Other AEs of special interest that occurred at >3% included extrapyramidal disorder (7%), sedation (3.7%), and somnolence (3.1%). Prolactin elevation, cognition impairment, sexual dysfunction, suicidality, and QT prolongation were reported at ≤1%.14
The authors concluded that cariprazine within the recommended dose range demonstrated a favourable safety profile and was generally well tolerated in individuals living with schizophrenia.14
Dr Chiman pointed out that longerterms studies (76 weeks) showed an average of only 1kg weight gain.10 A 2020 meta-analysis of 83 studies compared 18 different antipsychotics (18 750 patients) with placebo (4210 patients). The authors found no evidence of weight gain with cariprazine when compared with placebo.15
Cariprazine’s mode of action
Discover how cariprazine works to manage the symptoms of schizophrenia. In this short video, we delve into its unique mode of action, exploring its high affinity for D3 receptors and how this translates to potential cognitive, antidepressant, and symptom-relief benefits. Click here or scan the QR code.
References
1. Stahl S. Drugs for psychosis and mood: unique actions at D3, D2, and D1 dopamine receptor subtypes. CNS Spectrums, 2017.
2. Kiss B, Horvath A, Nemethy Z, et al Cariprazine (RGH-188), a Dopamine D3 Receptor-Preferring, D3/D2 Dopamine Receptor Antagonist–Partial Agonist Antipsychotic Candidate: In Vitro and Neurochemical Profile. Journal of Pharmacology and Experimental Therapeutics, 2010.
3. Girgis RR, Slifstein M, D’Souza D, et al Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [(11)C]-(+)-PHNO. Psychopharmacology (Berl), 2016.
4. Edinoff A, Ruoff MT, Ghaffar YT, et al Cariprazine to Treat Schizophrenia and Bipolar Disorder in Adults. Psychopharmacol Bull, 2020.
5. Stahl S. Mechanism of action of cariprazine. CNS Spectrums, 2016.
6. Nakamura T, Kubota T, Iwakaji A, et al Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment). Drug Des Devel Ther, 2016.
7. Marder S, et al Efficacy of cariprazine across symptom domains in patients with
Receptor Affinity and Function: Antipsychotics are categorised by their binding affinity to dopamine receptors (D1, D2, D3). Cariprazine is unique as a dopamine D3 and D2 receptor partial agonist, showing a ~10-fold higher affinity for D3 receptors.
D3 receptor Role: D3 receptors are prominently expressed in brain regions associated with motivation and reward-related behaviors, making cariprazine particularly effective in these areas.
Clinical efficacy: Studies demonstrate that cariprazine achieves clinical antipsychotic efficacy at 60% to 75% occupancy of dopamine D2 receptors. Additionally, it has a high affinity for serotonin or 5-HT receptors.
Mechanism of action: Cariprazine’s high affinity for D3 receptors and its partial agonism are thought to enhance dopaminergic neurotransmission, thereby improving symptoms of schizophrenia.
Ten key messages
Cognitive Benefits: Blocking D3 receptors with cariprazine can increase acetylcholine release in the prefrontal cortex, contributing to better cognitive function.
Long half-life: Cariprazine boasts the longest half-life among atypical antipsychotics, with its active metabolites maintaining therapeutic levels for extended periods, which aids in maintaining steady-state levels and potentially improving treatment adherence.
Dosing and metabolism: Cariprazine is taken once daily and can be consumed with or without food. Its active metabolites, DCAR and DDCAR, contribute to its prolonged action and efficacy.
Treatment of negative symptoms: Cariprazine has shown efficacy in treating both positive and negative symptoms of schizophrenia, setting it apart from many antipsychotics that primarily address positive symptoms.
Safety profile: Cariprazine is generally well-tolerated, with common adverse events being mild to moderate. It shows minimal metabolic side effects, such as slight weight gain, and has a low impact on prolactin levels and QTc intervals.
Impact on clinical practice: Cariprazine’s efficacy in treating predominant negative symptoms and its favourable safety profile position it as a potential game-changer in clinical practice, offering a comprehensive treatment option for schizophrenia with fewer side effects and better patient adherence.
acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies. Eur Neuropsychopharmacol, 2019.
8. Franco C. Now Available in South Africa – Reagila® (Cariprazine): A New Atypical Broad-spectrum Antipsychotic with a unique pharmacological profile. Presentation, [date].
9. Németh G, Laszlovszky I, Czobor P, et al. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, doubleblind, controlled trial. Lancet, 2017
10. Chiman V. Now Available in South Africa – Reagila® (Cariprazine): A New Atypical Broad-spectrum Antipsychotic with a unique pharmacological profile. Presentation, 15 May 2024.
11. Chauhan N, Chakrabarti S, Grover S. Detecting
medication non-adherence in schizophrenia: A comparison of different methods among outpatients from a North Indian center. Ind Psychiatry J, 2023.
12. Earley W, Durgam S, Lu K, et al Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebocontrolled studies. Int Clin Psychopharmacol, 2017.
13. Nasrallah HA, Earley W, Cutler AJ, et al. The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis. BMC Psychiatry, 2017
14. Barabássy Á, Sebe B, Acsai K, et al Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies. Neuropsychiatr Dis Treat, 2021.
15. Pillinger T, McCutcheon RA, Vano L, et al
Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry, 2020. SF
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Practical insights into schizophrenia treatment: Case studies highlight effective strategies
Explore the insights of Dr Pravesh Kassen, a dedicated psychiatrist specialising in schizophrenia treatment at Akeso Clinic in Pietermaritzburg, KwaZulu-Natal, as he shares two illuminating case studies.
Case Study #1
Patient profile
Patient A is a 20-year-old male residing in Pietermaritzburg, currently a first-year BSc student. He has no prior medical or surgical history but has a six-year history of cannabis abuse, which he ceased four months before the onset of severe psychiatric symptoms. Notably, his mother had been treated for depression ten years earlier.
Case presentation
Over the past five months, significant behavioural changes were observed by the patient’s parents, including reduced socialisation, withdrawal and isolation, poverty of speech and content, aggressive behaviour towards parents, paranoia and distrust of friends, self-talk, hyperreligiosity, and fragmented sleep patterns. The patient reported auditory hallucinations with a running commentary
and command hallucinations. Despite ceasing cannabis use, his symptoms did not improve. In December 2023, severe aggression, violent outbursts, and worsening paranoia necessitated a threeweek admission to hospital. The primary diagnosis was paranoid schizophrenia. Initial treatment
The patient was initially treated with 10mg of olanzapine taken in the evenings,
CNS FORUM | Cariprazine
resulting in partial improvement but with severe cognitive blunting, drowsiness, and slowness. He was unable to tolerate the medication and was weaned off over two weeks with family assistance.
Clinical reassessment
By mid-January 2024, the patient’s symptoms re-emerged, including blunted affect, slow and lethargic demeanor, poor eye contact, poverty of speech, and distraction by auditory hallucinations.
Treatment plan
The treatment approach was re-evaluated, considering the patient’s poor response to olanzapine and the need for effective management of both positive and negative symptoms. After discussion with the patient and his family, it was decided to initiate cariprazine, a newer antipsychotic known for its efficacy in treating schizophrenia with a favourable side effect profile.
The patient started on a low dose of cariprazine, 1.5mg in the mornings for five days, followed by an increase to 3mg daily thereafter. This gradual titration aimed to minimise side effects while maximising therapeutic benefits.
Follow-up and outcome
A follow-up assessment on 26 March 2024 revealed significant improvement and remission of psychotic symptoms. The patient reported feeling more engaged with his studies, exhibiting improved communication and social interactions. His parents noted a marked reduction in aggression and paranoia, with a return to previous interests and activities.
Feedback from the patient and his parents highlighted enhanced academic performance, increased spontaneity, and the absence of auditory hallucinations and paranoid thoughts. The treatment with cariprazine was well-tolerated, with minimal adverse effects reported during follow-up visits.
Recommendations
Based on the positive response and remission of symptoms observed with cariprazine, continued treatment at 3mg daily in the morning was recommended. Regular follow-ups every four months were advised to monitor the patient’s progress, adjust medication as necessary, and provide ongoing support.
Concluding remarks
The case of Patient A underscores the complexity of treating paranoid schizophrenia in young adults, particularly in managing both positive and negative
symptoms effectively. The initial challenges with olanzapine highlight the variability in individual response to antipsychotic medications and the importance of personalised treatment approaches. Cariprazine emerged as a valuable therapeutic option, demonstrating significant efficacy in achieving complete remission of symptoms with fewer side effects compared to previous treatments. This case exemplifies the critical role of ongoing clinical assessment, adaptive treatment strategies, and patient-centred care in achieving positive outcomes in schizophrenia management.
Case study #2
Patient profile
Patient B is a 47-year-old male who has been under care since 2019. He initially presented with catatonia and a prior history of schizophrenia. His treatment history included multiple modalities with poor response, characterised by symptoms of paranoia, auditory hallucinations, and a sensation of pressure on the brain.
Case
presentation
Initially diagnosed >15-years ago, Patient B’s condition deteriorated over time, marked by recurrent psychotic episodes and episodes of catatonia. Upon presentation in 2019, he exhibited severe catatonia, with a flat affect and mutism, requiring extensive support for basic activities.
Initial treatment
Treatment commenced with ziprasidone 20mg twice daily and clonazepam 0.5mg twice daily to manage his psychotic symptoms and catatonic features. However, the initial pharmacological approach exacerbated his condition, leading to a deterioration in mental state and necessitating hospitalisation in a catatonic state.
Following hospitalisation, the treatment plan was adjusted to olanzapine 10mg orally at night and amisulpride 50mg orally twice daily. This regimen aimed to address both positive and negative symptoms of schizophrenia while improving the patient’s overall functional capacity and reducing catatonic features.
Clinical reassessment
Over the course of three years, Patient B showed gradual improvement in cognitive and psychotic symptoms, though persistent negative symptoms posed ongoing challenges. Despite the therapeutic benefits of olanzapine and amisulpride in managing his condition, the patient experienced significant medication-related
side effects, including drowsiness, substantial weight gain, and metabolic complications such as raised cholesterol and pre-diabetes.
Treatment plan
In January 2024, a comprehensive review of Patient B’s treatment regimen and health status prompted discussions with his family and healthcare team regarding the need for optimising therapeutic outcomes while minimising adverse effects. Together, they decided to introduce cariprazine, a novel antipsychotic known for its efficacy in managing schizophrenia symptoms with a potentially lower risk of metabolic side effects.
The treatment transition involved gradually tapering off olanzapine while initiating cariprazine at a low dose. Close monitoring of the patient’s response and side effects guided adjustments in medication dosage and scheduling to ensure optimal therapeutic outcomes.
Follow-up and outcome
By mid-2024, significant improvements were noted in Patient B’s overall health and symptom management. He exhibited a notable reduction in sedation, a 10kg weight loss, and improved metabolic markers, including stabilised blood pressure and cholesterol levels. The patient reported reduced anxiety, improved mood, and enhanced social engagement and functional capacity.
Recommendations
Continued monitoring and adjustment of cariprazine dosage were recommended to maintain stability in symptom management and overall health. Regular follow-up appointments every three months were scheduled to assess treatment efficacy, address any emerging issues, and provide ongoing support to the patient and his family.
Concluding remarks
Patient B’s case highlights the complexities and challenges inherent in managing chronic schizophrenia, particularly in patients with long-standing and treatmentresistant symptoms. The decision to introduce cariprazine represented a pivotal step in optimising therapeutic outcomes while addressing the patient’s persistent medication-related side effects and metabolic complications.
This case highlights the importance of personalised treatment approaches, continuous evaluation of treatment strategies, and collaborative decisionmaking in achieving positive outcomes in schizophrenia management. SF
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