Dopamine supersensitivity psychosis and dopamine partial agonist: A retrospective survey of failure of switching to aripiprazole in schizophrenia

Samaha

et al. 2017

Psychother Psychosom

Self Cite

223

227

The first-line treatment for psychotic disorders remains antipsychotic drugs with receptor antagonist properties at D₂-like dopamine receptors. However, long-term administration of antipsychotics can upregulate D₂ receptors and produce receptor supersensitivity manifested by behavioral supersensitivity to dopamine stimulation in animals, and movement disorders and supersensitivity psychosis (SP) in patients. Antipsychotic-induced SP was first described as the emergence of psychotic symptoms with tardive dyskinesia (TD) and a fall in prolactin levels following drug discontinuation. In the era of first-generation antipsychotics, 4 clinical features characterized drug-induced SP: rapid relapse after drug discontinuation/dose reduction/switch of antipsychotics, tolerance to previously observed therapeutic effects, co-occurring TD, and psychotic exacerbation by life stressors. We review 3 recent studies on the prevalence rates of SP, and the link to treatment resistance and psychotic relapse in the era of second-generation antipsychotics (risperidone, paliperidone, perospirone, and long-acting injectable risperidone, olanzapine, quetiapine, and aripiprazole). These studies show that the prevalence rates of SP remain high in schizophrenia (30%) and higher (70%) in treatment-resistant schizophrenia. We then present neurobehavioral findings on antipsychotic-induced supersensitivity to dopamine from animal studies. Next, we propose criteria for SP, which describe psychotic symptoms and co-occurring movement disorders more precisely. Detection of mild/borderline drug-induced movement disorders permits early recognition of overblockade of D₂ receptors, responsible for SP and TD. Finally, we describe 3 antipsychotic withdrawal syndromes, similar to those seen with other CNS drugs, and we propose approaches to treat, potentially prevent, or temporarily manage SP.

Section: Clinical Characteristics and Consequences Of Sp In The Era Osupporting

confidence: 89%

“…We will review 3 studies [34,35,36], 2 specifically focusing on TR schizophrenia (online suppl. Table 2).…”

Section: Clinical Characteristics and Consequences Of Sp In The Era Omentioning

confidence: 99%

Section: Clinical Characteristics and Consequences Of Sp In The Era Omentioning

confidence: 99%

Section: Clinical Characteristics and Consequences Of Sp In The Era Omentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy

Samaha

et al. 2017

Psychother Psychosom

Self Cite

223

227

Association of Aripiprazole With the Risk for Psychiatric Hospitalization, Self-harm, or Suicide

et al. 2019

IMPORTANCE Some reports have raised concerns regarding a potential psychiatric worsening associated with first-time use of aripiprazole in patients already treated with other antipsychotic medications. Whether aripiprazole use, particularly in the long term, increases the risk for serious psychiatric events is unclear. OBJECTIVE To assess whether switching to or adding aripiprazole is associated with serious psychiatric treatment failure compared with switching to or adding another antipsychotic drug in patients previously exposed to antipsychotic medications. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study was conducted from January 1, 2005, to March 31, 2015. Data were obtained from the United Kingdom Clinical Practice Research Datalink, one of the world's largest computerized databases linked to the Hospital Episodes Statistics repository and the Office for National Statistics (ONS) mortality database. Within a base cohort of new users of antipsychotic drugs, patients switching or adding aripiprazole (n = 1643) were propensity matched 1:1 to patients switching to or adding another antipsychotic medication (n = 1643). All patients were followed up until psychiatric treatment failure, for 365 days (1 year) after cohort entry, until death from any cause other than suicide, until end of registration or linkage with the databases, or end of the study period (March 31, 2016). MAIN OUTCOMES AND MEASURES Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of serious events of psychiatric treatment failure (psychiatric hospitalizations, self-harm, or suicide) associated with switching to or adding aripiprazole compared with other antipsychotic drugs. In addition to propensity score matching, all models were adjusted for age, number of psychiatric hospitalizations or self-harm events in the 6 months before cohort entry, number of different antipsychotic drugs before cohort entry, and quintiles of the Index of Multiple Deprivation. RESULTS The study cohort included 1643 patients (949 [57.8%] were women with a mean [SD] age of 42.1 [16.8] years) starting aripiprazole use; they were matched 1:1 to 1643 patients (871 [53.0%] were women with a mean [SD] age of 42.4 [17.1] years) starting use of another antipsychotic drug. During 2692 person-years of follow-up, 391 incident serious psychiatric treatment failures occurred, with a crude incidence rate of 14.52 (95% CI, 13.16-16.04) per 100 person-years. First-time use of aripiprazole was not associated with an increased rate of psychiatric treatment failure (HR, 0.87; 95% CI, 0.71-1.06), psychiatric hospitalizations (HR, 0.85; 95% CI, 0.69-1.06), or self-harm or suicide (HR, 0.96; 95% CI, 0.68-1.36) compared with starting use of another antipsychotic drug. Results were consistent across several sensitivity analyses. CONCLUSIONS AND RELEVANCE Initiating aripiprazole use, compared with another antipsychotic medication, after a previous antipsychotic exposure did not appear to be associated with psychiatric hospital...

Continuation rate for asenapine and brexpiprazole treatment in patients with schizophrenia

Inoue¹,

Suzuki

Hibino

et al. 2021

Brain and Behavior

Introduction The current study sought to compare the treatment continuation rates of asenapine and brexpiprazole while specifically investigating the factors influencing this index and the clinical efficacy of brexpiprazole. Methods Retrospective study on patients with schizophrenia who were prescribed either asenapine (n = 73) or brexpiprazole (n = 136), as part of their routine medical care. Results The treatment continuation rates for asenapine and brexpiprazole were 19.0% and 38.6% at 52 weeks, with that of brexpiprazole found to be significantly higher than that of asenapine (p = .002). Moreover, age was found to be a significant factor affecting the treatment continuation rate for brexpiprazole (p = .03). Additionally, patients with a longer continuation duration had significantly lower Clinical Global Impression‐Severity of Illness (CGI‐S) scale scores compared to those who discontinued early (p = .04). The continuation rate was also significantly higher for those who began using the drug as outpatients compared to those first administered the drug as inpatients (p = .04). Furthermore, disease duration, CGI‐S scale, and continuation duration significantly affected the clinical efficacy of brexipiprazole (p < .05 for all). Conclusions The continuation rate for brexpiprazole increases as the age of the patient increases, as disease severity decreases, and if the patient first uses the drug as an outpatient. Shorter disease duration and longer drug administration may lead to improved clinical efficacy. These results suggest that brexpiprazole is an effective treatment option for maintenance therapy of schizophrenia.