Major Research Findings

Aripiprazole has been shown to be effective in treating schizophrenia in clinical settings; however, its mechanisms of action are not fully understood. Aripiprazole differentially affects dopaminergic transmission in the mesolimbic and nigrostriatal pathways, which may contribute to its long-term efficacy in controlling schizophrenia symptoms with reduced extrapyramidal side-effects. 4

Aripiprazole, a novel antipsychotic drug, is metabolized by CYP3A4 and CYP2D6, mainly forming its active metabolite dehydroaripiprazole. In this study, serum levels of aripiprazole and dehydroaripiprazole in psychiatric patients were measured and correlated with dose, comedication, and clinical effects, including therapeutic and side effects. Patients were treated with mean doses of 20 +/- 8 mg/day of aripiprazole (median 15 mg, range 7.5-60 mg). Serum levels correlated significantly with the dose (r = 0.419; P < 0.01), with a mean value of aripiprazole of 214 +/- 140 ng/ml. Mean concentrations of the active metabolite dehydroaripiprazole amounted to 40% of the parent compound. Comedication with CYP3A4 and CYP2D6 inducers or inhibitors changed serum levels up to 51%. Improvement was best in patients with a serum level between 150 and 300 ng/ml. No or only mild side effects were detected in patients, with aripiprazole plasma concentrations between 110 and 249 ng/ml. A total of 32% of the patients who received no other antipsychotic drug besides aripiprazole reported side effects; tension being the most frequent one. Since serum levels of aripiprazole and dehydroaripiprazole were highly variable between individuals, and distinct ranges were associated with good therapeutic response and minimal side effects, it seems likely that therapeutic drug monitoring can be helpful to improve the antipsychotic drug therapy. 6

Aripiprazole, due to its partial agonism of D2 and 5-HT1A receptors, is considered to have a low incidence of extrapyramidal side effects (EPS). However, EPS has been reported in adults and children during treatment with therapeutic doses of aripiprazole. To the best of our knowledge, no cases of EPS with low doses (5 mg) have been reported until now. In this article, we present an 11-year-old child who developed EPS on low doses (5 mg) aripiprazole. This case emphasizes the need for careful surveillance for the development of EPS in patients treated even with low doses of aripiprazole. 2

Reasons for side effects

Side effects of aripiprazole are thought to be due to its pharmacological actions, particularly its effects on dopamine receptors. Aripiprazole acts as a partial agonist of dopamine receptors, meaning that it exhibits both activating and inhibiting effects on these receptors. This action can contribute to the development of EPS and other side effects.

Common side effects

Extrapyramidal symptoms (EPS)

Aripiprazole, while having a lower incidence of EPS compared to other antipsychotics, still has the potential to cause EPS. Symptoms of EPS include dystonia, parkinsonism, akinesia, and akathisia. 7 2

Oculogyric Crisis

Oculogyric crisis is a rare type of acute dystonia characterized by spasmodic upward deviation of the eyes lasting for a few minutes to several hours. It is commonly seen with the administration of first-generation antipsychotics and rarely reported in patients taking second-generation antipsychotics. Although aripiprazole, a second-generation antipsychotic, is known for its low potential for extrapyramidal side effects (EPS), there are multiple case reports of it resulting in acute dystonia, especially OGC. In this paper, we report a case of aripiprazole-induced OGC in a 16-year-old female patient after a suicide attempt by taking 40 mg of aripiprazole and 5 g of acetaminophen. The necessary investigations were ordered, and the patient's dystonic symptoms resolved completely after administering parenteral diazepam and benztropine. 8

Nausea and Vomiting

Aripiprazole can cause gastrointestinal side effects such as nausea and vomiting. 3

Weight Gain

Aripiprazole can cause metabolic side effects such as weight gain. 3

Sexual dysfunction

Aripiprazole can cause sexual dysfunction, including decreased libido, erectile dysfunction, and ejaculatory dysfunction. 1

Anxiety

Aripiprazole can cause mental side effects such as anxiety. 3

Insomnia

Aripiprazole can cause sleep problems such as insomnia. 3

Fatigue

Aripiprazole can cause common side effects such as fatigue. 3

Side effect management

Extrapyramidal symptoms (EPS)

If EPS occurs, anticholinergic medications (such as benztropine, diphenhydramine) may be administered.

Oculogyric Crisis

If OGC occurs, benzodiazepines or anticholinergic medications may be administered. 8

Nausea and Vomiting

If nausea and vomiting occur, antiemetics may be administered. 3

Weight Gain

To prevent weight gain, a healthy diet and regular exercise are important. 3

Sexual dysfunction

If sexual dysfunction occurs, reducing the dose of aripiprazole or switching to another antipsychotic may be considered. 1

Anxiety

If anxiety occurs, anxiolytics may be administered. 3

Insomnia

If insomnia occurs, hypnotics may be administered. 3

Comparison of Studies

Commonalities of Studies

Many studies have shown that aripiprazole can cause side effects such as EPS. 7 2

Differences in Studies

Some studies have observed differences in the incidence and types of side effects associated with aripiprazole. This may be due to factors such as the age, sex, type of illness, dose, and concomitant medications of the study participants. 3

Real-Life Applications: Precautions

Aripiprazole is an effective medication for treating mental health conditions such as schizophrenia. However, it can cause EPS and other side effects. Therefore, it is important to follow your doctor's instructions carefully and be aware of potential side effects while taking aripiprazole. If you experience any side effects while taking aripiprazole, consult your doctor immediately. Do not stop taking aripiprazole or change your dosage without your doctor's consent. 7 2

Limitations of Current Research

Research on the side effects of aripiprazole has limitations such as a small sample size and short follow-up periods. Therefore, further research on the side effects of aripiprazole is needed. 3

Future Research Directions

Future research on the side effects of aripiprazole could include studies with larger sample sizes and longer follow-up periods, as well as studies that investigate the types and incidence of side effects in more detail. 3

Conclusion

Aripiprazole is an effective medication for treating schizophrenia, but it can cause side effects such as EPS. It is important to follow your doctor's instructions carefully and be aware of potential side effects. If you experience any side effects, consult your doctor immediately. 7 2