Lack of tolerable treatment options for patients with schizophrenia

Abstract

PurposeAtypical antipsychotics (AAs), an effective treatment for schizophrenia, have a range of pharmacologic properties leading to differences in tolerability as well as heterogeneity in treatment response. Individual patient characteristics must be considered when making treatment choices, especially from an adverse event (AE) or tolerability perspective. Despite the availability of numerous AAs, after appraising patient characteristics at the time of treatment selection, physicians may quickly run out of tolerable treatment options.Patients and methodsAE risk factors, defined as having either a prior history of an AE or a risk factor for that AE, were determined for Medicaid-insured and Commercially insured patients using database analysis. Patients receiving AA treatment between January 1, 2010 and December 31, 2012 defined the index date of first observed AA prescription during this period. Nine AAs were evaluated for association with AE risk factors as informed by drug prescribing information from the different manufacturers and published meta-analyses. The proportion of patients with pre-index AE risk factors prescribed an AA associated with that risk factor was then determined.ResultsA high proportion of patients (>80%) were prescribed an AA associated with extrapyramidal symptoms or akathisia despite experiencing extrapyramidal symptoms or akathisia prior to AA treatment initiation. Similar trends were observed among patients with diabetes (>60%) and obesity (>40%). From the nine treatment options available, the number of optimal choices for individual patient segments were limited based on their prior history, including those with cardiometabolic and cardiovascular comorbidities (four); experiencing prolactin elevation-related problems (seven); needing to avoid excessive sedation (four); or at risk of extrapyramidal symptoms or akathisia (two). Options were then further restricted among patients in more than one segment when multiple pre-index AE risk factors were combined.ConclusionWhen combining patient risk profile with antipsychotic AE profile, physicians may quickly run out of tolerable treatment options for individual patients, despite the availability of many AAs, suggesting a need for additional treatment options with better tolerability and without compromising efficacy.

Initial Clinical Experience of RP5063 Following Single Doses in Normal Healthy Volunteers and Multiple Doses in Patients with Stable Schizophrenia

“…7,19,20 Coupled with other existing or treatment-induced comorbidities (e.g., EPSs or akathisia [>80%], QT interval prolongation [40%], and hyperprolactinemia [>25%]), these underlying conditions can quickly limit the clinician's choice when considering the side effects with available medications. 4 Furthermore, approved treatments are associated with varying degrees of EPS and hyperprolactinemia, 7,21 leading to endocrine disruptions (e.g., breast enlargement, increase the risk of breast cancer, and a decrease in or loss of sexual interest) directly through hyperprolactinemia and indirectly through D 2 receptor antagonism. Although reduced sexual activity is associated with the onset of psychosis, antipsychotic-induced hyperprolactinemia is linked with reductions in sexual interest, activity, and satisfaction.…”

“…Management involves antipsychotic therapy, with all approved treatments blocking dopamine (D) receptors, particularly D 2 , and second‐generation products blocking serotonin (5‐hydroxytryptamine, 5‐HT), notably 5_HT 2A 2. Present treatments are limited by side effects, such as extrapyramidal symptoms (EPS), metabolic and cardiovascular issues, hyperprolactinemia, as well as sexual and endocrine dysfunctions, that undermine compliance 3, 4, 5, 6, 7…”

Approaches to neuromodulation for schizophrenia

“…These side effects include: extrapyramidal symptoms related to movement (34%–58%), hyperprolactinaemia (31%–39%), akathisia (7%–35%), sedation (47%), fatigue (60%) and sexual dysfunction (30%–80%) 3. Other life-threatening side effects include agranulocytosis, impaired glucose metabolism, myocarditis, neuroleptic malignant syndrome, seizures and significant weight gain 3.…”

“…These side effects include: extrapyramidal symptoms related to movement (34%–58%), hyperprolactinaemia (31%–39%), akathisia (7%–35%), sedation (47%), fatigue (60%) and sexual dysfunction (30%–80%) 3. Other life-threatening side effects include agranulocytosis, impaired glucose metabolism, myocarditis, neuroleptic malignant syndrome, seizures and significant weight gain 3. In summary, novel therapeutic interventions for the treatment of SZ are needed for the 19%–25% of individuals with poor outcome, 19%–30% of individuals who consistently relapse and 15% of individuals experiencing intolerable or life-threatening antipsychotic side effects.…”

Modelo animal de epilepsia e psicose comórbida: aspectos neuropatológicos, corportamentais e modulação pelo tratamento com nitroprussiato de sódio

“…Como uma desordem mental e comportamental está entre as 10 principais causa de incapacidade por anos vividos (Hallak, 2009). Associada a comorbidade médica e índices de mortalidade, pacientes com esquizofrenia apresentam duplo risco de mortalidade comparado a controles saudáveis (Citrome et al, 2015). Poucos estudos têm estimando a prevalência da doença no país, e a maior parte foram conduzidos há mais de 10 anos atrás (Matos et al, 2015).…”