What is Aripzolmin?

• Aripzolmin is the brand name of Domina’s new antipsychotic (expanding the antipsychotic family to 8 medications)
• The active ingredient is aripiprazole
• It is available as 5, 10, and 15mg oral tablets
• One Aripzolmin box has 30 tablets

What is Aripzolmin FDA approved for?

1. FDA approved for symptomatic management of psychosis in patients with schizophrenia. Aripiprazole was shown to be well tolerated and effective in short, intermediate, and long-term trials
2. FDA approved for acute manic episodes associated with bipolar disorder as monotherapy or adjunctive therapy. Aripiprazole was shown to be well tolerated and effective in combination with mood stabilizers or as monotherapy
3. FDA approved for autistic spectrum disorder (ASD). According to studies, short-term treatment of aripiprazole in ASD patients reduced irritability, hyperactivity, and the number of repetitive, pointless behaviours (stereotyped behaviours)
4. FDA approved for tourette syndrome and major depressive disorder as adjunctive treatment 

What makes Aripzolmin different than other antipsychotic drugs?

Aripiprazole is a second-generation atypical antipsychotic drug. The distinguishing characteristic of aripiprazole from first generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) is that it has partial agonistic activity at dopamine D₂ receptors.

What is Aripzolmin’s mechanism of action (MOA)?

1. Partial agonist at D₂, D₃, and 5-HT_1A receptors
2. Antagonist at 5-HT_2A receptors
3. Has low binding affinity for other receptors such as muscarinic and histaminic receptors

Hence, it is efficacious against negative, positive, and cognitive symptoms of schizophrenia.

How can Aripzolmin’s MOA contribute to its clinical activity?

To achieve best clinical outcome, two problems should be considered:

1. Dopaminergic hyperactivity results in psychosis
2. Dopaminergic hypoactivity results in cognitive dysfunction

The improvement of psychotic symptoms is due to the inhibition of more than 80% of dopamine D₂ receptors; however, this is accompanied by an increased prevalence of motor adverse effects and increased prolactin levels. This issue occurs more with FGAs than SGAs. Aripiprazole, on the other hand, is better than other SGAs as it has a high affinity and high occupancy of dopamine D₂ receptors without causing extrapyramidal symptoms. 10mg Aripiprazole results in >80% receptor occupancy, whereas higher doses (30mg) cause 90%-94%. Thus, Aripiprazole improves psychosis without causing dopaminergic hyperactivity.

The decrease of cognitive function is usually due to the reduced dopaminergic activity at the prefrontal cortex. This dysfunction is related to the dopaminergic antagonism of other antipsychotics. Since Aripiprazole is a partial agonist, it may correct such deficient neurotransmission, resulting in a stabilization of the dopaminergic signal. Thus improving cognitive function.

Does Aripzolmin cause less side effect than other SGAs?

Yes, the side effect profile of Aripiprazole is better than other FGAs and SGAs due to being a partial agonist. Aripiprazole has been shown to:

1. Decrease motor (tardive dyskinesia) and metabolic (lipid and glucose blood concentrations, cardiovascular risk factors) functions, psychiatric hospitalization rates, orthostatic hypotension, and prolactin levels
2. Decrease alcohol craving in patients with dependence
3. Cause less weight gain due to the moderate affinity of aripiprazole for H₁-histamine receptors
4. Cause sedation in less than 10% of patients
5. Improve cognitive and sexual function

Thus, making aripiprazole a valid alternative for patients struggling with persistent side effects or low efficacy of their current drug.

What pharmacological factors should be considered when switching to Aripzolmin?

Switching the patient from antipsychotic to Aripiprazole should be considered when:

1. There is a lack of tolerability of the antipsychotic’s side effects
2. There is a lack of efficacy of the antipsychotic

Switching to Aripiprazole from an antipsychotic should be done cautiously because:

1. There is a risk of psychotic relapse
2. Aripiprazole may not work on all the receptors the other antipsychotic is binding to

Switching the patient from an antipsychotic with high antagonism at a specific receptor to an antipsychotic with diminished action on that receptor must be done cautiously as the risk of psychotic relapse may increase. In these circumstances, a slow cross-tapering between the two antipsychotics is required, or the new antipsychotic (aripiprazole) must reach its plateau dose before the first medication may be tapered off. 

Other antipsychotics may be strong antagonists to muscarinic acetylcholine and histamine H₁ receptors whereas Aripiprazole has little affinity to these receptors. When moving from these antipsychotics to aripiprazole, two distinct effects can be expected:

1. It is anticipated that after the switch, adverse effects would get better in terms of weight gain and metabolic impacts. This was shown in a 4-month research where patients switched from olanzapine to aripiprazole and found a significant reduction in lipids and weight in overweight patients
2. When switching to aripiprazole, rebound agitation and insomnia may follow. In this situation, the likelihood of these side effects may be decreased or prevented by slow tapering the antipsychotic and/or by adding anti-histaminergic medications or benzodiazepines, if necessary

When should Aripzolmin be used with a benzodiazepine?

In the initial phase it is better to combine aripiprazole with a benzodiazepine (Midazolam Domina, Diazepam Domina, CLONA-RIL, Lexo-Zepam, and Lorativan), as aripiprazole has low sedation properties which is necessary during acute psychotic or manic episodes. The benzodiazepine can then be withdrawn when the acute episode is over.

What are the advantages of switching to Aripzolmin?

• Reduction of adverse effects such as hyperprolactinemia, extrapyramidal symptoms, weight gain, and high lipid and glucose blood levels
• Improves sexual function. According to a meta-analysis, switching to aripiprazole, compared to other antipsychotics, was more often related with remission of sexual dysfunction among patients who suffered sexual dysfunction secondary to antipsychotic medicine
• Improves the wellbeing of patients. A study has shown that patients switched from antagonist antipsychotics (olanzapine, risperidone) to aripiprazole showed improvement in their subjective wellbeing
• Improves clinical effectiveness and adherence
• Once daily dosing due to its long half-life (75 hours)
• Given anytime of the day due to its minimal sedative effects

 

References:

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2.  Gettu N, Saadabadi A. Aripiprazole 2023 [Available from: https://www.ncbi.nlm.nih.gov/books/NBK547739/.

3. Stip E, Tourjman V. Aripiprazole in schizophrenia and schizoaffective disorder: A review. Clin Ther. 2010;32 Suppl 1:S3-20.

4.  Hirsch LE, Pringsheim T. Aripiprazole for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2016;2016(6):Cd009043.

5. Jibson MD, Marder S, Friedman M. Second-generation antipsychotic medications: Pharmacology, administration, and side effects 2023 [Available from: https://www.uptodate.com/contents/second-generation-antipsychotic-medications-pharmacology-administration-and-side-effects?search=aripiprazole&source=search_result&selectedTitle=7~72&usage_type=default&display_rank=7.

6.  Newcomer JW, Campos JA, Marcus RN, Breder C, Berman RM, Kerselaers W, et al. A multicenter, randomized, double-blind study of the effects of aripiprazole in overweight subjects with schizophrenia or schizoaffective disorder switched from olanzapine. J Clin Psychiatry. 2008;69(7):1046-56.

7.  La Torre A, Conca A, Duffy D, Giupponi G, Pompili M, Grözinger M. Sexual dysfunction related to psychotropic drugs: a critical review part II: antipsychotics. Pharmacopsychiatry. 2013;46(6):201-8.

8. Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Int Clin Psychopharmacol. 2011;26(3):130-40.

9. Mizrahi R, Mamo D, Rusjan P, Graff A, Houle S, Kapur S. The relationship between subjective well-being and dopamine D2 receptors in patients treated with a dopamine partial agonist and full antagonist antipsychotics. Int J Neuropsychopharmacol. 2009;12(5):715-21.