The first measurements of haloperidol (HL) and its reduced metabolite hydroxyhaloperidol (RH) in ... more The first measurements of haloperidol (HL) and its reduced metabolite hydroxyhaloperidol (RH) in plasma versus clinical response in five chronic schizophrenic patients are reported. HL and RH were measured by a radioimmunoassay with a low coefficient of variation. Patients were selected based on poor response or the need for high dosage and were rated with the Clinical Global Impression Scale. Daily HL dosage range was 0.5 to 1.5 mg/kg. HL plasma concentrations ranged from 14 to 98 ng/ml. RH plasma concentrations ranged from 10 to 319 ng/ml. Four patients did not respond to HL therapy; two of these improved dramatically when switched to fluphenazine. The four nonresponding patients had higher RH than HL concentrations. RH seems to be present in plasma in significant concentrations, and further investigation of the relationships of RH and HL plasma levels versus response is needed.
Tardive dyskinesia (TD) is an involuntary movement disorder induced by dopamine-receptor blocking... more Tardive dyskinesia (TD) is an involuntary movement disorder induced by dopamine-receptor blocking agents (DRBAs), including antipsychotics. Because the introduction of second-generation antipsychotics has reduced but not eliminated the risk for TD as had been hoped, recognizing and treating TD are important skills for clinicians. Many patients rely on DRBAs for chronic conditions. To minimize the risk of patients' involuntary movements becoming permanent, they must be detected early and treated. To improve the early recognition and diagnosis of TD, clinicians must know the risk factors, understand the functional impairment, regularly and systematically assess their patients, and appropriately apply diagnostic criteria.
The authors report on three chronic, treatment-refractory schizophrenic patients who dramatically... more The authors report on three chronic, treatment-refractory schizophrenic patients who dramatically improved when placed on very high doses of loxapine (300-500 mg/day). Numbness transiently appeared in two patients at very high doses of loxapine; it may be a frequently occurring but unreported side effect. The relative lack of serious side effects to very high dose loxapine suggests that this may be a useful intervention in carefully selected refractory patients. The authors recommend that controlled studies be done to elucidate the benefit to risk ratio.
We have evaluated the efficacy and safety of different dosing regimens of haloperidol decanoate (... more We have evaluated the efficacy and safety of different dosing regimens of haloperidol decanoate (HLD). Eighteen patients were evaluated as part of our ongoing Therapeutic Drug Monitoring Program. Diagnoses were chronic schizophrenia (n = 12), bipolar with psychosis (n = 3), and others (n = 3). Patients were assessed prior to each HLD dose using the Clinical Global Impressions (CGI) rating scale. The total monthly HLD dose for our population was calculated based on a target conversion ratio of 20 times the previously administered oral haloperidol dose given in divided doses of 100 mg to 150 mg every 3 to 7 days until the full amount was administered. This HLD dosing pattern was repeated during the second month, but at a lower dose to compensate for drug accumulation. Despite this loading dose paradigm, significantly greater haloperidol plasma concentrations were present during oral haloperidol than during the first month of HLD therapy. This regimen achieves therapeutically equivalen...
Antipsychotic (AP) medications are prescribed for various psychiatric diagnoses that require rout... more Antipsychotic (AP) medications are prescribed for various psychiatric diagnoses that require routine monitoring to ensure optimal use, effectiveness, adherence, and for potentially severe adverse effects. There is currently no comprehensive protocol for institutional supervision of prescribing and monitoring AP. Antibiotics (ABX) are commonly associated with stewardship programs aimed at optimizing use and mitigating harm. These programs have proven to result in positive outcomes in both safety and efficacy parameters for numerous institutions. Given that AP are also associated with significant adverse effects and often misused, the concept of stewardship can be applied to this class of agents to optimize their use and improve overall patient outcomes. The objective of this paper is to provide guidance for the implementation of antipsychotic stewardship programs (APSP) in the inpatient setting. The development of this APSP was designed based on ABX stewardship programs and the Cente...
Introduction Olanzapine (OLZ) is a second generation antipsychotic that is approved for the treat... more Introduction Olanzapine (OLZ) is a second generation antipsychotic that is approved for the treatment of schizophrenia, bipolar disorder type 1 as monotherapy (acute manic or mixed episodes, maintenance), or as an add-on to lithium or valproate (manic or mixed episodes). It is one of the most effective antipsychotics for the treatment of schizophrenia, but concerns remain due to its significant metabolic adverse effects. Notably, OLZ has one of the highest rates of weight gain among all antipsychotic drugs. Previous studies report on potential mitigation of weight gain with opioid antagonists. A systematic review was conducted to summarize the impact of these agents on weight and BMI when used as adjuncts to OLZ. Methods A systematic review of randomized controlled trials was conducted with 3 searches between March 2, 2021 and March 27, 2022. Results Six studies met inclusion criteria, 5 of which assessed OLZ and samidorphan (SAM) and 1 of which assessed OLZ and naltrexone compared ...
BackgroundThe COVID-19 pandemic substantially impacted care of patients with schizophrenia treate... more BackgroundThe COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study examined how clinics adapted operations to maintain a standard of care for these patients after pandemic onset.MethodsOnline surveys were completed in October-November 2020 by one principal investigator (PI) or PI-appointed designee at 35 clinics participating in OASIS (NCT03919994). Items concerned pandemic impacts on clinic operations, particularly telepsychiatry, and on the care of patients with schizophrenia treated with LAIs.ResultsAll 35 clinics reported using telepsychiatry; 20 (57%) implemented telepsychiatry after pandemic onset. Telepsychiatry visits increased from 12%-15% to 45%-69% across outpatient visit types after pandemic onset; frequency of no-show and/or canceled telepsychiatry visits decreased by approximately one-third. Nearly half of clinics increased the frequency of telepsychiatry visits for patients w...
Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved tr... more Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP). This article reviews the safety, efficacy, and pharmacology data for pimavanserin and its role in therapy. Method of Research: Initial literature sources were identified via MEDLINE search (1946-September 2016) of pimavanserin and ACP-103 (original molecular designation). Reference review and search of FDA.gov and clinicaltrials.gov yielded additional studies. English-language studies of pimavanserin for PDP were evaluated. Animal studies were excluded. Randomized, controlled trials (RCTs) were prioritized. Results: Four RCTs were identified. In each, pimavanserin was well-tolerated with few adverse effects and no worsening of motor symptoms. A Phase II trial displayed a nonsignificant trend toward Scale for Assessment of Positive Symptoms (SAPS) improvement (p=0.09), with significant benefits in secondary efficacy markers. However, tw...
Tardive dyskinesia (TD) is an involuntary movement disorder induced by dopamine-receptor blocking... more Tardive dyskinesia (TD) is an involuntary movement disorder induced by dopamine-receptor blocking agents (DRBAs), including antipsychotics. Because the introduction of second-generation antipsychotics has reduced but not eliminated the risk for TD as had been hoped, recognizing and treating TD are important skills for clinicians. Many patients rely on DRBAs for chronic conditions. To minimize the risk of patients' involuntary movements becoming permanent, they must be detected early and treated. To improve the early recognition and diagnosis of TD, clinicians must know the risk factors, understand the functional impairment, regularly and systematically assess their patients, and appropriately apply diagnostic criteria.
The first measurements of haloperidol (HL) and its reduced metabolite hydroxyhaloperidol (RH) in ... more The first measurements of haloperidol (HL) and its reduced metabolite hydroxyhaloperidol (RH) in plasma versus clinical response in five chronic schizophrenic patients are reported. HL and RH were measured by a radioimmunoassay with a low coefficient of variation. Patients were selected based on poor response or the need for high dosage and were rated with the Clinical Global Impression Scale. Daily HL dosage range was 0.5 to 1.5 mg/kg. HL plasma concentrations ranged from 14 to 98 ng/ml. RH plasma concentrations ranged from 10 to 319 ng/ml. Four patients did not respond to HL therapy; two of these improved dramatically when switched to fluphenazine. The four nonresponding patients had higher RH than HL concentrations. RH seems to be present in plasma in significant concentrations, and further investigation of the relationships of RH and HL plasma levels versus response is needed.
Tardive dyskinesia (TD) is an involuntary movement disorder induced by dopamine-receptor blocking... more Tardive dyskinesia (TD) is an involuntary movement disorder induced by dopamine-receptor blocking agents (DRBAs), including antipsychotics. Because the introduction of second-generation antipsychotics has reduced but not eliminated the risk for TD as had been hoped, recognizing and treating TD are important skills for clinicians. Many patients rely on DRBAs for chronic conditions. To minimize the risk of patients' involuntary movements becoming permanent, they must be detected early and treated. To improve the early recognition and diagnosis of TD, clinicians must know the risk factors, understand the functional impairment, regularly and systematically assess their patients, and appropriately apply diagnostic criteria.
The authors report on three chronic, treatment-refractory schizophrenic patients who dramatically... more The authors report on three chronic, treatment-refractory schizophrenic patients who dramatically improved when placed on very high doses of loxapine (300-500 mg/day). Numbness transiently appeared in two patients at very high doses of loxapine; it may be a frequently occurring but unreported side effect. The relative lack of serious side effects to very high dose loxapine suggests that this may be a useful intervention in carefully selected refractory patients. The authors recommend that controlled studies be done to elucidate the benefit to risk ratio.
We have evaluated the efficacy and safety of different dosing regimens of haloperidol decanoate (... more We have evaluated the efficacy and safety of different dosing regimens of haloperidol decanoate (HLD). Eighteen patients were evaluated as part of our ongoing Therapeutic Drug Monitoring Program. Diagnoses were chronic schizophrenia (n = 12), bipolar with psychosis (n = 3), and others (n = 3). Patients were assessed prior to each HLD dose using the Clinical Global Impressions (CGI) rating scale. The total monthly HLD dose for our population was calculated based on a target conversion ratio of 20 times the previously administered oral haloperidol dose given in divided doses of 100 mg to 150 mg every 3 to 7 days until the full amount was administered. This HLD dosing pattern was repeated during the second month, but at a lower dose to compensate for drug accumulation. Despite this loading dose paradigm, significantly greater haloperidol plasma concentrations were present during oral haloperidol than during the first month of HLD therapy. This regimen achieves therapeutically equivalen...
Antipsychotic (AP) medications are prescribed for various psychiatric diagnoses that require rout... more Antipsychotic (AP) medications are prescribed for various psychiatric diagnoses that require routine monitoring to ensure optimal use, effectiveness, adherence, and for potentially severe adverse effects. There is currently no comprehensive protocol for institutional supervision of prescribing and monitoring AP. Antibiotics (ABX) are commonly associated with stewardship programs aimed at optimizing use and mitigating harm. These programs have proven to result in positive outcomes in both safety and efficacy parameters for numerous institutions. Given that AP are also associated with significant adverse effects and often misused, the concept of stewardship can be applied to this class of agents to optimize their use and improve overall patient outcomes. The objective of this paper is to provide guidance for the implementation of antipsychotic stewardship programs (APSP) in the inpatient setting. The development of this APSP was designed based on ABX stewardship programs and the Cente...
Introduction Olanzapine (OLZ) is a second generation antipsychotic that is approved for the treat... more Introduction Olanzapine (OLZ) is a second generation antipsychotic that is approved for the treatment of schizophrenia, bipolar disorder type 1 as monotherapy (acute manic or mixed episodes, maintenance), or as an add-on to lithium or valproate (manic or mixed episodes). It is one of the most effective antipsychotics for the treatment of schizophrenia, but concerns remain due to its significant metabolic adverse effects. Notably, OLZ has one of the highest rates of weight gain among all antipsychotic drugs. Previous studies report on potential mitigation of weight gain with opioid antagonists. A systematic review was conducted to summarize the impact of these agents on weight and BMI when used as adjuncts to OLZ. Methods A systematic review of randomized controlled trials was conducted with 3 searches between March 2, 2021 and March 27, 2022. Results Six studies met inclusion criteria, 5 of which assessed OLZ and samidorphan (SAM) and 1 of which assessed OLZ and naltrexone compared ...
BackgroundThe COVID-19 pandemic substantially impacted care of patients with schizophrenia treate... more BackgroundThe COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study examined how clinics adapted operations to maintain a standard of care for these patients after pandemic onset.MethodsOnline surveys were completed in October-November 2020 by one principal investigator (PI) or PI-appointed designee at 35 clinics participating in OASIS (NCT03919994). Items concerned pandemic impacts on clinic operations, particularly telepsychiatry, and on the care of patients with schizophrenia treated with LAIs.ResultsAll 35 clinics reported using telepsychiatry; 20 (57%) implemented telepsychiatry after pandemic onset. Telepsychiatry visits increased from 12%-15% to 45%-69% across outpatient visit types after pandemic onset; frequency of no-show and/or canceled telepsychiatry visits decreased by approximately one-third. Nearly half of clinics increased the frequency of telepsychiatry visits for patients w...
Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved tr... more Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP). This article reviews the safety, efficacy, and pharmacology data for pimavanserin and its role in therapy. Method of Research: Initial literature sources were identified via MEDLINE search (1946-September 2016) of pimavanserin and ACP-103 (original molecular designation). Reference review and search of FDA.gov and clinicaltrials.gov yielded additional studies. English-language studies of pimavanserin for PDP were evaluated. Animal studies were excluded. Randomized, controlled trials (RCTs) were prioritized. Results: Four RCTs were identified. In each, pimavanserin was well-tolerated with few adverse effects and no worsening of motor symptoms. A Phase II trial displayed a nonsignificant trend toward Scale for Assessment of Positive Symptoms (SAPS) improvement (p=0.09), with significant benefits in secondary efficacy markers. However, tw...
Tardive dyskinesia (TD) is an involuntary movement disorder induced by dopamine-receptor blocking... more Tardive dyskinesia (TD) is an involuntary movement disorder induced by dopamine-receptor blocking agents (DRBAs), including antipsychotics. Because the introduction of second-generation antipsychotics has reduced but not eliminated the risk for TD as had been hoped, recognizing and treating TD are important skills for clinicians. Many patients rely on DRBAs for chronic conditions. To minimize the risk of patients' involuntary movements becoming permanent, they must be detected early and treated. To improve the early recognition and diagnosis of TD, clinicians must know the risk factors, understand the functional impairment, regularly and systematically assess their patients, and appropriately apply diagnostic criteria.
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Papers by Stephen Saklad