Schizophrenia is a chronic disease that requires lifelong medical care and supervision. There is a high rate of relapse, mostly caused by poor adherence to oral antipsychotics. Long-acting injectable (LAI) antipsychotics have proved effective in schizophrenia and other severe psychotic disorders due to the stable blood levels, leading to a reduction of the risk of relapse. LAIs are associated with better functioning, quality of life, and patient satisfaction. In Treatment-resistant schizophrenia the combination of antipsychotics is a common practice. Nevertheless, the combination of two different long-acting injectable antipsychotics is not frequent.

A case of a 34-year-old man is presented, previously diagnosed of Schizophrenia, with highly disabling chronic positive symptoms. With no in-sight and no will in receiving treatment. Has been stable for a year while being in treatment with paliperidone 525mg LAI/ 10 weeks, and aripiprazole 400mg LAI/28 days.

The patient was closely observed and given oral paliperidone, after 5 days long-acting paliperidone was introduced. He was discharged with mild improvement of his psychiatric symptoms. While being in treatment with Paliperidone 525mg, he kept vivid delusions and hallucinations. The patient still refused to take any oral medications. Long-acting aripiprazole 300mg was added to the treatment.

He showed clinical improvement after a month. He has been stabilized for one year.

Treating resistant schizophrenia is among the most challenging clinical endeavors. A very helpful approach to improve adherence in schizophrenia is the use of long-acting injectable (LAI) antipsychotics. A major effort on scientific research of combination of LAI is needed.

No significant relationships.

A growing number of published cases has showed that hypersexual behavior may arise with treatment with second-generation antipsychotics, including aripiprazole and olanzapine. Aripiprazole is a second-generation antipsychotic commonly used to treat schizophrenia and bipolar disorder. It has a unique pharmacologic profile acting as a partial agonist of the dopamine D2 receptor, as a partial agonist at the 5-HT1A receptor, and as an antagonist at the 5-HT2A receptor. Literature shows that medication with partial dopaminergic agonistic activity can cause compulsive behaviors, such as pathological gambling, compulsive eating, compulsive shopping, and hypersexuality. Although it is difficult to predict who would develop these behaviors, the literature suggests that patients at a higher risk of developing impulsive behaviors include those with a personal or family history of obsessive-compulsive disorder, impulse control disorder, bipolar disorder, impulsive personality, alcoholism, drug abuse, or other addictive behaviors.

Here, we present a case of a 32-year-old male who developed hypersexuality symptoms after receiving aripiprazole as treatment for bipolar disorder.

We have done a literature review using the MeSH terms Aripiprazole and hypersexuality in the “PubMed”.

After switching Aripiprazole to Risperidone the hypersexuality symptoms started to decrease and got almost complete relief after 2 weeks.

This case highlights the rare hypersexuality side effect that can arise in patients receiving aripiprazole for bipolar disorder treatment. Clinicians should be aware of the increased risk of hypersexuality and other impulsive behaviors as they can significantly impair a patient’s daily functioning.

No significant relationships.

Aripiprazole (ARI) is an atypical antipsychotic drug with D2 partial agonist properties, usually prescribed to treat mood disorders (major depression or bipolar disorder) and schizophrenic disorder (schizophrenia or schizoaffective disorder). Dopamine receptor agonists, as is ARI, have been implicated in some cases of impulse-control problems, such as gambling disorder (GD), increased spending, hypersexuality and compulsive eating.

Currently, it is hypothesized that aripiprazole may cause impulse-control problems because it can produce a hyperdopaminergic state in the mesolimbic pathway (reward system) through its predominant action on dopamine D3 receptors. We intend to do a non-systematic review of the scientific information regarding this subject.

The authors revised the published literature about this topic, selecting relevant articles, systematic reviews and case reports, with the topic words: “aripiprazol”, “gambling disorder” and “dopamine receptor” in scientific data base.

Overall, a few cases of ARI-induced pathological gambling as well as ARI-induced hypersexuality have been reported. In one study it was verified that comorbid psychiatric and substance use disorders were common among those who have experienced GD or worsened GD after beginning ARI treatment. In another study, it was verified that the group of patients who reported this alleged side-effect were mostly young (mean age, 33.6 years), mostly men (88.2%) and most lived alone.

Attributing to dopamine agonists the only factor that can explain the onset of GD is simplistic and dangerous. Many other potential risk factors, including individual vulnerability factors (temperament, genetics) as well as environmental factors, must be considered.

No significant relationships.

41 years-old man diagnosed of schizophrenia and peripheral spondyloarthropathy HLA-B27 (-) in treatment with methotrexate. Psychiatric background: First psychotic episode at 18, with no further medical monitoring. In 2018 he underwent a new episode consisting in auditory hallucinations, delusional ideas and clinophilia of months of evolution. He was sent to a Psychiatric Rehabilitation Unit and prescribed aripiprazole 20mg. The routine blood analysis revealed triglycerides level of 414mg/dL, with previous normal levels (123 mg/dL), without no other cause to justify it.

To study the relationship between aripiprazole treatment and acute hypertriglyceridemia.

A clinical case is presented and available bibliography about the relation between aripiprazole and acute hypertriglyceridemia is reviewed.

Hypertriglyceridemia was confirmed in the second analysis, so we concluded it was due to the start of aripiprazole, after rejecting other potential causes. Aripiprazole was replaced by cariprazine 3mg because of its similar profile. The analysis was repeated after a month and the normalization of the triglyceridemia (159mg/dL) was verified, while cholesterol levels remain stable. Moreover, the patient experienced an improvement in akathisia and sedation.

Although metabolic impact is not expected with aripiprazole, after reviewing the bibliography we have found a clinical trial and a case series that described this adverse effect. Our case highlights the importance of closely monitoring of patients in whom an antipsychotic treatment is started due to the high mortality and morbidity related to cardiovascular diseases.

No significant relationships.

The significant clinical efficacy of lithium and lamotrigine in the described patients is consistent with the hypothesis that microdeletion of the SHANK3 gene may be associated with bipolar disorder.

The described phenotypes were characterized by intellectual disability, general speech underdevelopment, muscle hypotonia, and developmental dyspraxia. Their causal relationships with epileptic encephalopathy, schizophrenia, bipolar and hyperkinetic disorders have been analyzed.

Prospective studies of two patients with Phelan McDermid syndrome (22q13.3 microdeletions of the SHANK3 gene) within 10-12 years after genome scanning allowed describing the clinical polymorphism of developmental disorders. The sensitivity of psychotic symptoms to antipsychotic and mood stabilizer therapy has also been studied.

Manifest psychotic disorders in patients did not reveal an affinity for therapy with amisulpride, haloperidol, quetiapine, which demonstrated a partial therapeutic response to treatment with aripiprazole, which cast doubt on the possibility of qualifying psychotic symptoms in patients as the debut of schizophrenia. The partial therapeutic efficacy of combination therapy with aripiprazole and benzodiazepines (clonazepam/diazepam) qualified psychotic episodes in two patients with 22q13.3 syndrome as pediatric delirium. The significant clinical efficacy of lithium and lamotrigine in the described patients is consistent with the hypothesis that microdeletion of the SHANK3 gene may be associated with bipolar disorder.

The combination of lithium and lamotrigine may be recommended for the treatment of polymorbid mental disorders in patients with ASD and 22q13.3 syndrome. If lithium salts are poorly tolerated, a combination of lamotrigine and aripiprazole may be used to treat polymorbid mental disorders with confusion and catatonic symptoms in ASD.

No significant relationships.

Los ensayos naturalistas sobre la efectividad de los antipsicóticos atípicos son necesarios para aportar una información más amplia sobre la eficacia, la seguridad y la tolerabilidad en pacientes con esquizofrenia tratados en un centro médico de la comunidad.

En este estudio multicéntrico abierto de 26 semanas, diversos pacientes con esquizofrenia, que necesitaron un cambio en la medicación antipsicótica porque no toleraban bien la medicación actual y/o porque los síntomas clínicos no estaban bien controlados, se aleatorizaron para recibir aripiprazol o un tratamiento estándar (TE) con un antipsicótico atípico (por ejemplo, olanzapina, quetiapina o risperidona en función del juicio del investigador sobre el tratamiento óptimo de cada paciente individual y la respuesta previa del paciente a la medicación antipsicótica). El objetivo principal fue comparar la efectividad de un tratamiento de 26 semanas con aripiprazol con el TE, medido por la puntuación total del Cuestionario de Evaluación del Investigador (IAQ) en la última observación arrastrada (UOA) de la semana 26 (variable primaria), una medida validada que controla el alivio o el empeoramiento de 10 síntomas clave asociados con la psicopatología de la esquizofrenia y los efectos secundarios del tratamiento antipsicótico. Los objetivos secundarios fueron evaluar la efectividad usando las escalas Impresión Clínica Global - Mejoría Global (CGI-I) e Impresión Clínica Global - Gravedad de la Enfermedad, para evaluar el tiempo transcurrido hasta la suspensión del tratamiento, la preferencia del paciente respecto a la medicación, y la calidad de vida y la tolerabilidad de aripiprazol comparado con el TE.

El tratamiento con aripiprazol (n=268) fue significativamente más eficaz que el TE (n = 254; P < 0,001; UOA de la semana 26), evidenciado por la puntuación IAQ total, desde la semana 4 (primera fase de evaluación) y se mantuvo hasta la semana 26. Una relación similar se demostró en los pacientes que terminaron el estudio (análisis de casos observados); aripiprazol se asoció con una efectividad significativamente mayor en todas las fases de evaluación con un mayor efecto diferencial de TE con el tiempo. Los pacientes tratados con aripiprazol también tuvieron mejorías significativamente mayores en la escala CGI-I (tasa de rspuesta, P = 0,009 en la UOA de la semana 26), y en la calidad de vida (puntuación total en la escala de Calidad de Vida; P < 0,001 en la semana 26). Además, una proporción significativamente mayor de pacientes que recibieron aripiprazol calificaron la medicación del estudio como “mucho mejor” en la escala del Cuestionario de Preferencias de Medicación (POM) que la medicación anterior al estudio comparados con los pacientes tratados con TE (P < 0,001; semana 26). El tiempo hasta la suspensión del tratamiento y las tasas de suspensión debidas a episodios adversos fueron similares en los dos grupos de tratamiento. La incidencia de pacientes con uno o varios síntomas extrapiramidales (por ejemplo, acatisia, distonía, episodios parkinsonianos y episodios residuales) fue mayor en los pacientes que recibieron aripiprazol comparados con los pacientes tratados con TE (13,5% frente a 5,6%); sin embargo, una proporción mayor de pacientes del grupo TE tuvo un aumento de peso clínicamente significativo (21,2% frente a 7,3% para aripiprazol) y de las concentraciones séricas (potencialmente importantes desde el punto de vista clínico) de colesterol total, colesterol de lipoproteínas de baja densidad, triglicéridos y prolactina comparados con los pacientes que recibieron aripiprazol.

Aripiprazol es un antipsicótico atípico eficaz para el tratamiento de la esquizofrenia, que ha demostrado más efectividad que los fármacos estándar usados en este estudio en pacientes que necesitaban un cambio en la medicación antipsicótica.