Risperidone for Extended-Release Injectable Suspension (Perseris)

CADTH recommends that Perseris should be reimbursed by public drug plans for the treatment of schizophrenia in adults if certain conditions are met. Perseris should be covered by public drug plans in a similar manner to other long-acting injectable atypical antipsychotic drugs for the treatment of adults with schizophrenia. Perseris should only be reimbursed if the total monthly dose is not more than 120 mg and is not used in combination with other long-acting injectable antipsychotic drugs. Perseris should not cost more than other long-acting injectable (LAI) atypical antipsychotic drugs.

Mechanism of Action of Atypical Antipsychotic Drugs in Mood Disorders

Atypical antipsychotic drugs were introduced in the early 1990s. Unlike typical antipsychotics, which are effective only against positive symptoms of schizophrenia, atypical antipsychotics are effective against negative and cognitive symptoms as well. Furthermore, they are effective not only in psychotic but also in affective disorders, on their own or as adjuncts to antidepressant drugs. This review presents the neural mechanisms of currently existing atypical antipsychotics and putative antipsychotics currently being investigated in preclinical and clinical studies and how these relate to their effectiveness in mood disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD). Typical antipsychotics act almost exclusively on the dopamine system. Atypical drugs, however, modulate serotonin (5-HT), norepinephrine, and/or histamine neurotransmission as well. This multimodal mechanism of action putatively underlies the beneficial effect of atypical antipsychotics in mood and anxiety disorders. Interestingly, novel experimental drugs having dual antipsychotic and antidepressant therapeutic potential, such as histamine, adenosine, and trace amine-associated receptors (TAAR) ligand, are also characterized by a multimodal stimulatory effect on central 5-HT, norepinephrine, and/or histamine transmission. The multimodal stimulatory effect on central monoamine neurotransmission may be thus primarily responsible for the combined antidepressant and antipsychotic therapeutic potential of certain central nervous system (CNS) drugs.

A propensity score matching analysis for cardio metabolic risk of antipsychotics in patients with schizophrenia using Japanese claims data

Background The aim of this study was to evaluate the cardio-metabolic risk in schizophrenia patients treated by atypical antipsychotic drugs compared with that in those treated without atypical antipsychotic drugs using a nationwide insurance claims database and medical examination database in Japan. Methods Eligible patients were defined as those meeting the following two criteria: (i) A diagnosis of schizophrenia (ICD-10 code: F20) was made between 1 January 2005 and 31 December 2017, with data available for at least 6 months before the diagnosis was made (index month), and (ii) health check-up data were available within ±3 months of the index month. The primary endpoint was changes in cardio-metabolic risk based on the Suita score at 1 year, and the secondary endpoints were changes in medical examination data related to cardio-metabolic risk (total cholesterol [TC], triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body mass index [BMI], and hemoglobin A1c) at 1 year. The primary endpoint was evaluated by multivariate analysis, with the cumulative chlorpromazine equivalent amount and the baseline Suita score added as covariates. Results One-hundred eighty five pairs of propensity score (PS)-matched patients were evaluated. Patients receiving atypical antipsychotic drugs exhibited a greater change in the Suita score and a risk of coronary heart disease based on the Suita score of 0.530 and 0.098%, respectively, than patients not receiving atypical antipsychotic drugs, but there was no significant difference (p = 0.412 and 0.610). The significant changes in TC and BMI were determined as 6.525 mg/dL and 0.380 kg/m2 greater, respectively, in patients treated with atypical antipsychotic drugs (p = 0.037 and 0.011). Conclusions There were no significant increases in changes in the Suita score at 1 year by treatment with atypical antipsychotic drugs compared with treatment without atypical antipsychotic drugs. However, the TC and BMI were significantly higher in patients treated with atypical antipsychotic drugs.

Mechanism of Action of Atypical Antipsychotic Drugs in Mood Disorders

Atypical antipsychotic drugs were introduced in the early 1990th. Unlike typical antipsychotics, which are effective only against positive symptoms of schizophrenia, atypical antipsychotics show effectiveness against negative and cognitive symptoms as well. Furthermore, they are effective not only in psychotic, but also in affective disorders, by their own or as adjuncts to antidepressant drugs. While typical antipsychotics act, almost exclusively, via dopamine-2 (D2) receptors, atypical target serotonin-1A/1B/2A/2C (5-HT1A/1B/2A/2C), α1/2-adrenergic, and/or histamine-1 (H1) receptors as well. Blocking of 5-HT1A/1B autoreceptors, inducing their early desensitization, and/or activation of α1-adrenoceptors, allow some atypical drugs to enhance 5-HT transmission. Blocking of 5-HT2A/2C and/or α2-adrenoceptors enable some atypical antipsychotics to stimulate catecholamine transmission and/or diminish the inhibition of catecholamine neurons induced by some antidepressants. It is possible, that the activation of H1 and/or blocking of H3 boost monoamine transmission as well, via a mechanism involving stimulation of firing activity of dopamine neurons. The experimental drugs with antipsychotic potential, acting on adenosine and trace amino associated (TAAR) receptors, might be effective in mood disorders as well, because of the ability to modulate the excitability of monoamine-secreting neurons and to potentiate extracellular concentrations of monoamines in the limbic areas of the brain.