Administration Of Atypical Antipsychotic Drugs Research Articles

Medication-induced Psychotic Disorder. A Review of Selected Drugs Side Effects.

Medication-induced psychotic disorder (MIPD) is a diagnostic term for a syndrome with symptoms such as hallucinations and delusions directly related to drug intake. The purpose of this review is to report and comment on the current knowledge about pathomechanisms, risk factors, symptoms, and treatment of MIPD caused by selected widely used medications. PubMed, Scopus, and Google Scholar databases were searched for articles on MIPD published prior to January 2021 using search terms 'psychosis' OR 'psychotic disorder' AND 'side effects' combined with certain medications group. The initial search was then narrowed to medications with more pathomechanisms than only direct dopamine-inducing activity that are widely used by clinicians of various medical specialties. Steroids, antiepileptic drugs, antimalarial drugs, and antiretroviral drugs can induce psychosis with persecutory delusions and auditory hallucinations as the most frequently reported symptoms. Mood changes and anxiety may precede psychosis after steroids and antimalarials. Psychiatric history and female sex are risk factors for most of the MIPD. Treatment involves cessation of the suspected drug. Administration of atypical antipsychotic drugs may be helpful, although there is insufficient data to support this approach. The latter should be done with careful consideration of pharmacokinetic and pharmacodynamic interactions. MIPD is a rare condition. The appearance of psychotic symptoms during systemic treatment may be associated with administered medications, psychiatric comorbidity, or be a part of the clinical picture of a certain disorder. Furthermore, sometimes it may be challenging to distinguish MIPD from delirium. Therefore, we consider that the key to proper management of MIPD is a thorough differential diagnosis.

THE CLOZAPINE EFFECT ON BLOOD GLUCOSE LEVELS, LEUKOCYTES AND PLATELETS IN SCHIZOPHRENIC PATIENTS IN THE MENTAL SERVICE UNIT OF BANYUMAS HOSPITAL

Schizophrenia is a disorder of strange and disordered thoughts, delusions, hallucinations, inappropriate influences, and disorders of psychosocial functioning. One of the management of schizophrenia therapy is the administration of atypical antipsychotic drugs, namely clozapine. Clozapine is an antagonist of serotonin (5-HT2) and dopamine type 2 (D2) receptors. However, the risk of using clozapine provides a risk of side effects in the form of metabolic syndromes such as impaired blood glucose regulation and disorders of blood elements such as leukocytes and platelets. This study aims to determine the effect of using clozapine on blood glucose, leukocyte, and platelet levels in schizophrenia patients at Banyumas General Hospital. This research method was carried out by cross-sectional study in outpatient schizophrenia at Banyumas General Hospital who received clozapine therapy and had met the inclusion and exclusion criteria, taken by consecutive sampling, then examined blood glucose levels, leukocyte counts, and platelet counts before and after giving clozapine therapy. Samples were taken on day 1 and day 10 of drug use. Paired t-test statistical analysis was used to see the effect of using clozapine on glucose, leucocyte, and platelet levels. In the T-test, it was found that there was a relationship between the use of clozapine on the patient's blood glucose levels, the use of clozapine did not have a significant effect on the increase in leukocyte levels and there was also a relationship between the use of clozapine and the patient's platelet levels. The results showed that the patient had an increase in blood glucose levels by a percentage (100%), the patient had leukopenia by a percentage (63.5%), the patient had thrombocytopenia by a percentage (75%), while the other patients had thrombocytosis. Patients with hyperglycemia, leucopenia, and thrombocytopenia were those who used clozapine> 12 months

THE CLOZAPINE EFFECT ON BLOOD GLUCOSE LEVELS, LEUKOCYTES AND PLATELETS IN SCHIZOPHRENIC PATIENTS IN THE MENTAL SERVICE UNIT OF BANYUMAS HOSPITAL

Schizophrenia is a disorder of strange and disordered thoughts, delusions, hallucinations, inappropriate influences, and disorders of psychosocial functioning. One of the management of schizophrenia therapy is the administration of atypical antipsychotic drugs, namely clozapine. Clozapine is an antagonist of serotonin (5-HT2) and dopamine type 2 (D2) receptors. However, the risk of using clozapine provides a risk of side effects in the form of metabolic syndromes such as impaired blood glucose regulation and disorders of blood elements such as leukocytes and platelets. This study aims to determine the effect of using clozapine on blood glucose, leukocyte, and platelet levels in schizophrenia patients at Banyumas General Hospital. This research method was carried out by cross-sectional study in outpatient schizophrenia at Banyumas General Hospital who received clozapine therapy and had met the inclusion and exclusion criteria, taken by consecutive sampling, then examined blood glucose levels, leukocyte counts, and platelet counts before and after giving clozapine therapy. Samples were taken on day 1 and day 10 of drug use. Paired t-test statistical analysis was used to see the effect of using clozapine on glucose, leucocyte, and platelet levels. In the T-test, it was found that there was a relationship between the use of clozapine on the patient's blood glucose levels, the use of clozapine did not have a significant effect on the increase in leukocyte levels and there was also a relationship between the use of clozapine and the patient's platelet levels. The results showed that the patient had an increase in blood glucose levels by a percentage (100%), the patient had leukopenia by a percentage (63.5%), the patient had thrombocytopenia by a percentage (75%), while the other patients had thrombocytosis. Patients with hyperglycemia, leucopenia, and thrombocytopenia were those who used clozapine> 12 months

Association of the HTR2C-759C/T polymorphism and antipsychotic-induced weight gain: a meta-analysis

BackgroundAntipsychotic-induced weight gain (AIWG) is a crucial factor for the medication cessation of patients with schizophrenia. Multiple studies have shown that the functional polymorphism -759 C/T (rs3813929) in the HTR2C...

Trends in the use of antipsychotics in the Israeli inpatient population, 2004-2013.

BackgroundAlthough serious mental illneses are treated with both typical and atypical antipsychotic grugs, trends in their use in psychiatric inpatient population in Israel are unrecognized. The aim of this study was to detect trends in the use of typical and atypical antipsychotic drugs in the Israeli inpatient psychiatric population throughout the last decade.MethodsData regarding allocation of typical and atypical antipsychotics, over the period 2004 to 2013, were extracted from the electronic records of SAREL, Israel’s largest private supplier of drugs to healthcare and medical facilities. The data were converted to defined daily doses (DDD) per 1000 inpatients per day.ResultsUsage of the ten atypical antipsychotic agents allocated through Israel’s national health care system increased by 73 %, from 128.09 DDD/1000 inpatients/day in 2004 to 221.69 DDD/1000 inpatients/day in 2013. This rise from 2004 to 2013 was largely due to a 1.6-fold increase in the administration of olanzapine (48.31 to 79.57 DDD/1000 inpatients/day), a 4.4-fold increase of quetiapine (9.74 to 43.04 DDD/1000 inpatients/day) and 3.7-fold increase of amisulpride (5.54 to 20.38 DDD/1000 inpatients/day). At the same period, the total utilization of 12 main typical antipsychotics decreased by 15.5 %, from 148.67 DDD/1000 inpatients/day in 2004 to 125.57 DDD/1000 inpatients/day in 2013. Over the entire period, total DDDs of both classes of antipsychotics (typical and atypical) increased by 38 %.ConclusionsSimilar to trends in the treatment of psychiatric outpatients in other countries, there was a substantial increase in the administration of atypical antipsychotic drugs to the Israeli psychiatric inpatient population across the study period. A decrease in the use of typical antipsychotics (substitution), polypharmacy, administration for more indications (supplementation) and the use of larger doses of antipsychotics may account, in part, for this increase. The findings have implications for mental health policy in the context of the Mental Health Care System Reform. Systematic studies on appropriate dosing of antipsychotics and augmentation strategies are warranted.

Effects of co-administration of fluoxetine and risperidone on properties of peritoneal and pleural macrophages in rats subjected to the forced swimming test

BackgroundLiterature data show that administration of atypical antipsychotic drug, risperidone (RIS), enhances antidepressive action of fluoxetine (FLU). As antidepressive treatments also regulate immune functions, we examined whether combined administration of FLU and RIS to rats subsequently subjected to a forced swimming test (FST) modifies parameters of macrophage activity that are directly related to their immunomodulatory functions, i.e., arginase (ARG) activity and nitric oxide (NO) synthesis. MethodsAntidepressive action of the drugs was assessed with FST. Peritoneal and pleural cells were eluted and selected parameters of immunoreactivity were assessed colorimetrically. ResultsWe found that the concomitant administration of FLU (10mg/kg) and RIS (0.1mg/kg) produced antidepressive-like effects in the FST, whereas the drugs were ineffective if administered separately. Stress related to the FST affected immune cell redistribution and changed some of the metabolic and immunomodulatory properties of macrophages. FLU administered to rats at a suboptimal dose for antidepressive action potently influenced macrophage immunomodulatory properties and redirected their activity toward antiinflammatory M2 functional phenotype, as manifested by changes in the ARG/NO ratio. These effects resulted from a direct cellular influence of the drug, as well as its action via neuroendocrine pathways, as evidenced in peritoneal and pleural cells. Addition of RIS did not augment immunomodulatory action of FLU, though the combination showed antidepressant-like activity in the FST. ConclusionsOur results suggest that when the drugs were administered together, FLU was potent enough to redirect macrophages toward M2 activity. It is also postulated that drug-induced changes in the immune system are not so closely related to antidepressant-like effects or might be secondary to those produced in the neuroendocrine system.

Six-month treatment with atypical antipsychotic drugs decreased frontal-lobe levels of glutamate plus glutamine in early-stage first-episode schizophrenia

ObjectiveTo study the effects of treatment with atypical antipsychotic drugs on brain levels of glutamate plus glutamine in early-stage first-episode schizophrenia.ParticipantsSixteen patients (eight males, eight females; aged 30 ± 11 years) completed the study.MethodsWe used administered 6 months of atypical antipsychotic drugs and used proton magnetic resonance spectroscopy to evaluate the results.ResultsWe found that the administration of atypical antipsychotic drugs for 6 months decreased the glutamate plus glutamine/creatine ratio in the frontal lobe. These results suggest that the administration of atypical antipsychotic drugs for at least 6 months decreased glutamatergic neurotransmissions in the frontal lobe in early-stage first-episode schizophrenia, but there was no difference in frontal-lobe levels between patients and control subjects before administration.ConclusionTaking these findings into account, the glutamatergic and GABAergic neurons are implicated in early-stage first-episode schizophrenia, but in complex ways.

Neural circuits underlying the inhibition of sympathetically‐mediated thermogenesis in brown adipose tissue (BAT) induced by atypical antipsychotic drugs

Administration of atypical antipsychotic drugs suppresses sympathetic activation of metabolism in BAT, which may contribute to the weight gain observed with maintenance on these medications. This study investigated the neural circuitry responsible for the antipsychotic drug‐evoked inhibition of the sympathetic outflow to BAT. In urethane/chloralose anesthetized rats, the increase in BAT sympathetic nerve activity (SNA) evoked by cooling the core temperature to ~35.5°C was completely inhibited by the atypical antipsychotic drug, Clozapine (Cloz; 3mg/kg, iv). Bilateral microinjection of muscimol (2mM, 120nl/side) into the ventrolateral medulla (VLM) reversed or prevented the Cloz‐evoked inhibition of BAT SNA. In contrast to the effect of Cloz on the cooling response, the increase in BAT SNA evoked by blockade of GABAA receptors within the rostral raphe pallidus (RPa) was not inhibited by Cloz (3–6mg/kg, iv). These results suggest that neurons within the VLM play a role in the inhibition of BAT SNA evoked by atypical antipsychotic drugs, possibly by activating a GABAergic input to the RPa. Supported by NIH grant DK082558 and an American Heart Association SDG.

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Schizophrenia is associated with impairments of sensorimotor and sensory gating as measured by prepulse inhibition (PPI) of the acoustic startle response and P50 suppression of the auditory event-related potential respectively. While serotonin and dopamine play an important role in the pathophysiology and treatment of schizophrenia, their role in modulating PPI and P50 suppression in humans is yet to be fully clarified. To further explore the role of serotonin and dopamine in PPI and P50 suppression, we examined the effects of acute tryptophan depletion (to decrease serotonin) and acute tyrosine/phenylalanine depletion (to decrease dopamine) on PPI and P50 suppression in healthy human participants. In addition, we also examined for the first time, the effects of simultaneous serotonin and dopamine depletion (ie combined monoamine depletion) on PPI and P50 suppression. The study was a double-blind, placebo-controlled cross-over design in which 16 healthy male participants completed the PPI and P50 paradigms under four acute treatment conditions: (a) balanced/placebo control, (b) acute tryptophan depletion, (c) acute tyrosine/phenylalanine depletion, and (d) acute tyrosine/phenylalanine/tryptophan depletion (combined monoamine depletion). Selective depletion of dopamine had no significant effect on either PPI or P50 suppression, whereas selective serotonin depletion significantly disrupted PPI, but not P50 suppression. Finally, the simultaneous depletion of both serotonin and dopamine resulted in significant reduction of both PPI and P50 suppression. We suggest these results can be explained by theories relating to optimal levels of monoaminergic neurotransmission and synergistic interactions between serotonergic and dopaminergic systems for normal 'gating' function. These findings suggest that a dysfunction in both serotonin and dopamine neurotransmission may, in part, be responsible for the gating deficits observed in schizophrenia, and their normalization following administration of atypical antipsychotic drugs.

Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

Antipsychotic drugs have been used effectively for the treatment of schizophrenia symptoms, but they are often associated with metabolic side effects such as weight gain and endocrine disruptions. To investigate the possible mechanisms of antipsychotic-induced metabolic effects, we studied the impact of chronic administration of a typical antipsychotic drug (haloperidol) and an atypical antipsychotic (risperidone) to male rats on food intake, body weight, adiposity, and the circulating concentrations of hormones and metabolites that can influence energy homeostasis. Chronic (28 days) haloperidol administration had no effect on food intake, weight gain or adiposity in male rats, whereas risperidone treatment resulted in a transient reduction in food intake and significantly reduced body weight gain compared to vehicle-treated control rats. Whereas neither antipsychotic had any effect on serum lipid profiles, glucose tolerance or the circulating concentrations of hormones controlled by the hypothalamo-pituitary-thyroid (free T4), -adrenal (corticosterone), -somatotropic (IGF-1), or -gonadotropic axes (testosterone), haloperidol increased circulating insulin levels and risperidone increased serum glucagon levels. This finding suggests that haloperidol or risperidone induce distinct metabolic effects. Since metabolic disorders such as obesity and type 2 diabetes mellitus represent serious health issues, understanding antipsychotic-induced endocrine and metabolic effects may ultimately allow better control of these side effects.

Rimonabant enhances clozapine‐induced neurochemical and histochemical responses in the rat

Acute administration of atypical antipsychotic drugs, such as clozapine, produces an increase in the efflux of catecholamines preferentially in the prefrontal cortex (PFC) and a characteristic expression of Fos-like immunoreactivity (Fos-li) in the forebrain of experimental animals. We examined the effects of the CB-1 receptor antagonist rimonabant on clozapine-induced increases in the efflux of dopamine (DA) and norepinephrine (NE) in the PFC, and Fos-li in the PFC, nucleus accumbens shell (NAc-shell) and core (NAc-core) and dorsolateral striatum (DL-Str) in the rat. Rimonabant and clozapine dose-dependently increased cortical efflux of DA and NE. Pretreatment (30min) with rimonabant (3mg/kg, IP) significantly enhanced the clozapine (10mg/kg, SC)-induced increase in catecholamine efflux in the PFC. Clozapine (8mg/kg, SC) significantly increased the Fos-li in the PFC and NAc-shell. Rimonabant (10mg/kg, IP) significantly increased the Fos-li in the PFC. Rimonabant pretreatment (30min) significantly enhanced the clozapine-induced Fos-li in the PFC and NAc-shell. Clozapine alone and the combination of rimonabant and clozapine demonstrated a positive atypical index (based on the difference in the Fos-li in the NAc-shell versus the DL-Str) indicating atypicality of antipsychotic-like activity. The present results indicate that rimonabant enhances the neurochemical and histochemical effects of clozapine and that this combined administration reveals an atypical antipsychotic-like profile of drug action. Funded by: Eli Lilly and Co.

Torsade de pointes in a patient with complex medical and psychiatric conditions receiving low‐dose quetiapine

Describe potential cardiac complications of low-dose quetiapine and other atypical antipsychotic drugs. We present a case report of a 45-year-old Black woman with multiple medical and psychiatric problems taking low-dose quetiapine. Coincident with a generalized seizure, the patient developed 'ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. A cardiac electrophysiologist was concerned that the very slow shortening of the prolonged QTc interval after magnesium replacement implicated quetiapine as a risk factor for QTc interval prolongation and torsade de pointes. A psychosomatic medicine consultant asserted that the fragmented medical and psychiatric care almost certainly contributed to the patient's medical problems. We discuss other cases of QT interval prolongation by newer antipsychotic drugs and previous reports by our group concerning the association of psychotropic drugs, QT interval prolongation, and torsade de pointes. Atypical antipsychotic drug administration, when accompanied by risk factors, may contribute to cardiac arrhythmias including torsade de pointes.

Influence of Aging on the Improvement of Subjective Sleep Quality by Atypical Antipsychotic Drugs in Patients With Schizophrenia: Comparison of Middle-Aged and Older Adults

The authors investigated the influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia. Subjects were 86 inpatients (mean age: 61.4 years) who had been receiving treatment with conventional antipsychotic drugs and who met DSM-IV criteria for schizophrenia. Their antipsychotic medication was changed from conventional antipsychotics to one of four atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, or risperidone). Patients were grouped by age (older or younger than 65 years). Subjective sleep quality and psychopathology were assessed twice: 1) at baseline, and 2) 8 weeks after switching to the atypical antipsychotic drugs. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the Positive and Negative Syndrome Scale (PANSS) was used to measure psychopathology. The proportion of the patients who experienced improved subjective sleep quality was significantly higher in the elderly than in the middle-aged group. Logistic-regression analysis revealed that the improvement in subjective sleep quality through administration of atypical antipsychotic drugs was predicted by increased age, daytime dysfunction, and longer sleep latency at baseline. These results demonstrate that atypical antipsychotic drugs are beneficial to the quality of sleep in elderly patients with schizophrenia.

Influence of Aging on the Improvement of Subjective Sleep Quality by Atypical Antipsychotic Drugs in Patients With Schizophrenia: Comparison of Middle-Aged and Older Adults

Objective The authors investigated the influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia. Methods Subjects were 86 inpatients (mean age: 61.4 years) who had been receiving treatment with conventional antipsychotic drugs and who met DSM-IV criteria for schizophrenia. Their antipsychotic medication was changed from conventional antipsychotics to one of four atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, or risperidone). Patients were grouped by age (older or younger than 65 years). Subjective sleep quality and psychopathology were assessed twice: 1) at baseline, and 2) 8 weeks after switching to the atypical antipsychotic drugs. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the Positive and Negative Syndrome Scale (PANSS) was used to measure psychopathology. Results The proportion of the patients who experienced improved subjective sleep quality was significantly higher in the elderly than in the middle-aged group. Logistic-regression analysis revealed that the improvement in subjective sleep quality through administration of atypical antipsychotic drugs was predicted by increased age, daytime dysfunction, and longer sleep latency at baseline. Conclusions These results demonstrate that atypical antipsychotic drugs are beneficial to the quality of sleep in elderly patients with schizophrenia.

Effects of Changing From Typical to Atypical Antipsychotic Drugs on Subjective Sleep Quality in Patients With Schizophrenia in a Japanese Population

To investigate the effects of the atypical antipsychotic drugs risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of sleep in patients with schizophrenia. Subjects were 92 inpatients (mean age = 59.9 years) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects were randomly assigned to receive 1 of 4 atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality and psychopathology were assessed twice: at baseline and 8 weeks after switching. Data were collected from June 2001 to December 2001. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS). Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine, risperidone, or quetiapine, but not with perospirone, in comparison with conventional antipsychotic drugs. Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline. In addition, improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS. These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs, suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement. These improvements were correlated with improvement of negative symptoms.