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Biomedical subjects

Stephen R Marder

Publications and source records attributed to Stephen R Marder.

At least 37 records · Page 2Linked to original sources
PubMed2004

Posttraumatic stress disorder: psychopathology, medical management, and dental implications.

PTSD is a chronic mental illness that may arise after an individual experiences or witnesses a life-threatening event. Symptoms consist of persistent reexperiencing of the event, avoidance of reminders of the event, a numbing of positive emotions, and social withdrawal. A depressed mood and excessive use of alcohol and tobacco may accompany the disorder. PTSD afflicts approximately 5% of men and 11% of women. Dental disease may be extensive because of neglect of oral hygiene compounded by cigarette smoking. Dental treatment includes preventive education, oral cancer screening, and prescribing saliva substitutes or stimulants and anticaries agents to combat medication-induced xerostomia. Precautions must be taken when prescribing or administering certain analgesics, antibiotics, or sedative agents that may adversely interact with the psychiatric medications or when performing surgery because of the long-term effects of alcohol abuse.

Alcohol Drinking↗
PubMed2004

Do clozapine and risperidone affect social competence and problem solving?

OBJECTIVE: The purpose of this investigation was to evaluate the effects of clozapine and risperidone on social skill and problem solving in patients with schizophrenia. METHOD: The Wisconsin Card Sorting Test and the Maryland Assessment of Social Competence were administered at baseline, week 17, and week 29 of a multisite clinical trial. RESULTS: Despite evidence of clinical improvement with both medications, there was virtually no medication effect on either social competence or problem solving. CONCLUSIONS: These findings underscore the circumscribed nature of symptomatic improvement in the broader spectrum of clinical outcomes and suggest that new-generation medications may not be expected to produce substantial changes in social role functioning or social problem-solving capacity in the community. The generalizability of the findings should be viewed cautiously because of the low power of this trial, and replication is warranted.

Adult↗
PubMed2004

Physical health monitoring of patients with schizophrenia.

OBJECTIVE: Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings. METHOD: A consensus meeting including psychiatric and other medical experts assembled on October 17-18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis. Experts for each topic area formulated monitoring recommendations that were discussed by all of the participants until a consensus was reached. RESULTS: Consensus recommendations included regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction. Information from monitoring should guide the selection of antipsychotic agents. Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine. Patients who receive both first- and second-generation antipsychotic medications should be examined for extrapyramidal symptoms and tardive dyskinesia. Patients with schizophrenia should receive regular visual examinations. CONCLUSIONS: The conference participants recommended that mental health care providers perform physical health monitoring that typically occurs in primary care settings for their patients who do not receive physical health monitoring in those settings. This change in usual practice is recommended on the basis of the conference participants' belief that this additional monitoring will result in the earlier detection of common, serious risk factors that could, without detection and intervention, contribute to impaired health of patients with schizophrenia.

Adult↗
PubMed2004

Panic disorder: psychopathology, medical management and dental implications.

BACKGROUND: This article reviews the clinical features, epidemiology, pathophysiology, dental findings, and dental and medical management of the care of patients with panic disorder, or PD. TYPES OF STUDIES REVIEWED: The authors conducted a MEDLINE search for the period 1998 through 2003, using the key term "panic disorder" to define the pathophysiology of the disorder, its epidemiology and dental implications. The articles they selected for further review included those published in peer-reviewed journals. RESULTS: PD is a common and debilitating psychiatric disease in which a person experiences sudden and unpredictable panic attacks, or PAs, with symptoms of overwhelming anxiety, chest pain, palpitations and shortness of breath. Persistent concern about having another attack and worry that it may indicate a heart attack or "going crazy" impairs the person's social, family and working lives. Frequently accompanying the disorder is agoraphobia, depression and mitral valve prolapse, or MVP. CLINICAL IMPLICATIONS: In patients with PD, the prevalence of dental disease may be extensive because of the xerostomic effects of psychiatric medications used to treat it. Dental treatment consists of preventive dental education and prescribing saliva substitutes and anticaries agents. Precautions must be taken when prescribing or administering analgesics, antibiotics or sedative agents that may have an adverse interaction with the psychiatric medications. Because there is a connection between PAs and MVP, the dentist needs to consult with the patient's physician to determine the presence of MVP and whether there is associated mitral valve regurgitation. Patients with MVP and accompanying mitral valve regurgitation require prophylactic antibiotics when undergoing dental procedures known to cause a bacteremia and heightened risk of endocarditis.

Anti-Anxiety Agents↗
PubMed2004

The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update.

BACKGROUND: The Texas Medication Algorithm Project (TMAP) has been a public-academic collaboration in which guidelines for medication treatment of schizophrenia, bipolar disorder, and major depressive disorder were used in selected public outpatient clinics in Texas. Subsequently, these algorithms were implemented throughout Texas and are being used in other states. Guidelines require updating when significant new evidence emerges; the antipsychotic algorithm for schizophrenia was last updated in 1999. This article reports the recommendations developed in 2002 and 2003 by a group of experts, clinicians, and administrators. METHOD: A conference in January 2002 began the update process. Before the conference, experts in the pharmacologic treatment of schizophrenia, clinicians, and administrators reviewed literature topics and prepared presentations. Topics included ziprasidone's inclusion in the algorithm, the number of antipsychotics tried before clozapine, and the role of first generation antipsychotics. Data were rated according to Agency for Healthcare Research and Quality criteria. After discussing the presentations, conference attendees arrived at consensus recommendations. Consideration of aripiprazole's inclusion was subsequently handled by electronic communications. RESULTS: The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations. CONCLUSION: Consensus on algorithm revisions was achieved, but only further well-controlled research will answer many key questions about sequence and type of medication treatments of schizophrenia.

Algorithms↗
PubMed2003

Right lateral fusiform gyrus dysfunction during facial information processing in schizophrenia.

BACKGROUND: Patients with schizophrenia exhibit facial information processing deficits that likely contribute to their social dysfunction. Whether the deficits involve facial affect and/or identity processing or result from other cognitive abnormalities in schizophrenia remains controversial, and a brain dysfunction specifically related to them has never been reported. If such dysfunction existed, it should be consistently observed across groups of patients and during performance of different facial information processing tasks, independently of whether such tasks demand working memory (WM), semantic, or other cognitive processes. We hypothesized that the right lateral fusiform gyrus (rLFG), one of several human brain areas involved in facial information processing, would consistently show activation abnormalities during both facial affect and identity discrimination in schizophrenia. METHODS: We used functional magnetic resonance imaging to measure brain activation in two groups of six chronic, stable schizophrenic outpatients and two of six age- and gender-matched healthy controls. One group of patients and one of controls performed facial affect-with or without semantic processing-and identity discrimination tasks, and the other two groups WM tasks with facial expression cues and varying attentional demands. RESULTS: Patients from either group failed to activate the rLFG when compared to controls in any task. Other activation abnormalities were task-specific (i.e., seen only during performance of one set of tasks) and not consistently observed in both groups of patients, and thus could not be directly and solely linked to facial information discrimination. CONCLUSIONS: These results indicate a specific rLFG dysfunction during early facial information--identity or affect--processing, independent from other cognitive deficits, in schizophrenia.

Adult↗
PubMed2003

Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials.

Aripiprazole is a novel antipsychotic with a unique mechanism of action. Presented here is a pooled analysis of safety and tolerability data from all completed short-term, placebo-controlled trials in schizophrenia from the aripiprazole clinical development program. Data were analyzed from five 4- to 6-week double-blind multicenter studies of patients hospitalized with acute relapse of schizophrenia or schizoaffective disorder randomized to aripiprazole (n=932), placebo (n=416), or haloperidol (n=201). Daily aripiprazole doses ranged from 2 to 30 mg. Safety assessments included adverse event (AE) reports, EPS scales, ECGs, weight, and prolactin, glucose and cholesterol levels. Aripiprazole was well tolerated, with similar AE incidence rates to placebo, and lower rates than haloperidol for akathisia, extrapyramidal syndrome and somnolence. Objective EPS assessments demonstrated no significant differences between aripiprazole and placebo on Simpson-Angus Scale (SAS) scores, no dose-dependent effects on Barnes Akathisia scores, and significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores from baseline vs. placebo (p</=0.01). Haloperidol showed increased SAS and Barnes Akathisia scores over placebo (p</=0.01). There was minimal mean weight change with aripiprazole (+0.71 kg) and haloperidol (+0.56 kg), and a lack of QT(c) prolongation. Serum prolactin increased with haloperidol, but not aripiprazole. In conclusion, aripiprazole shows a favorable safety and tolerability profile with low potential for EPS, weight gain, prolactin elevation, QT(c) prolongation, and sedation. Aripiprazole's safety profile may offer benefits in schizophrenia treatment.

Acute Disease↗
PubMed2003

Prefrontal-posterior parietal networks in schizophrenia: primary dysfunctions and secondary compensations.

BACKGROUND: Working memory (WM) deficits are well known in schizophrenia and have been associated with abnormal activation patterns of the prefrontal cortex (PFC) during cognitive performance. The magnitude and particularly the direction of the PFC activation -- i.e., increased (hyperfrontality) or decreased (hypofrontality) -- in schizophrenia, as well as its pathophysiological implications, remain controversial. Working memory is supported by a distributed neural network, whose main components are the PFC and the posterior parietal (PPC) cortices. Monkey studies indicate that, during WM performance, PFC functional lesions may be compensated by the PPC if task demands center mainly on anticipating responses, but not if they center on remembering cues. We hypothesized that a primarily dysfunctional PFC in schizophrenia might show hypofrontality or hyperfrontality as a result, respectively, of efficient or inefficient PPC compensation, as dictated by task demands. To test our proposition, we biased the demands of WM tasks toward anticipating responses or remembering cues and measured its impact on the PFC-PPC functional balance in a group of schizophrenic patients and one of normal control subjects. METHODS: We used functional magnetic resonance imaging to measure correlates of neuronal activity in the PFC and PPC of schizophrenic patients and control subjects performing WM tasks that either demanded information retention or allowed for response anticipation. RESULTS: When compared to control subjects, schizophrenic patients exhibited decreased PFC activation and increased PPC activation during anticipatory WM performance, and increased PFC activation during mnemonic WM performance. CONCLUSIONS: In schizophrenia, a PFC dysfunction results in hypo- or hyperfrontality as a function of whether other alternate areas of a PFC-PPC network for WM are available and efficacious in supporting specific task demands.

Adult↗
PubMed2003

Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder.

BACKGROUND: Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors. This multicenter trial examined the efficacy, safety, and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder. METHODS: In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n = 101) or 30 mg/d (n = 101) of aripiprazole, placebo (n = 103), or 6 mg/d of risperidone (n = 99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval. RESULTS: Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/d) were significantly better than placebo on all efficacy measures. Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole. There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone. Mean change in QTc interval did not differ significantly from placebo with any active treatment group. Aripiprazole and risperidone groups showed a similar low incidence of clinically significant weight gain. CONCLUSIONS: Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder. It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders.

Adult↗
PubMed2003

Intra- and interindividual variations in steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients treated chronically with various doses of risperidone.

The intra- and interindividual variability in apparent steady-state plasma levels of risperidone (RSP) and its metabolite 9-hydroxyrisperidone (9-OHRSP) in schizophrenic patients was investigated. Patients (n = 46, age 26.4 +/- 5.3 years) with diagnosed schizophrenia were treated with a fixed daily oral dose of RSP (1-12 mg/d). The steady-state plasma samples from these patients were collected over a period of 5 years and a total of 549 visits. Plasma concentrations of RSP and 9-OHRSP were determined using a highly sensitive and specific LC-MS-MS method with a detection limit of 0.1 ng/mL. All plasma samples had measurable amounts of 9-OHRSP; however, RSP was nondetectable (<0.1 ng/mL) in 18% of the plasma samples. 9-OHRSP levels were, on average, approximately 22 times higher than those of RSP. The plasma levels of RSP and 9-OHRSP varied widely among patients receiving similar doses of RSP, and the intra- and interindividual variations of RSP and 9-OHRSP plasma levels were found to be large. The data indicated that there was no significant change in the steady-state levels of either RSP or 9-OHRSP during the treatment period. Similarly, the dose-normalized concentration did not vary significantly during the treatment period or with the administered dose. The absence of RSP in many plasma samples (<0.1 ng/mL) and presence of 9-OHRSP at severalfold higher concentrations than RSP indicate that measuring plasma levels of RSP alone may lead to erroneous interpretation in plasma level monitoring studies. The current data support the fact that it is important to measure steady-state levels of total active moiety by analyzing both RSP and 9-OHRSP for plasma drug monitoring.

Adult↗
PubMed2003

Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes.

OBJECTIVE: Most controlled studies comparing second-generation and conventional antipsychotics have focused on the acute treatment of schizophrenia. The authors compared symptom outcomes, side effects, and social adjustment in stable schizophrenia outpatients who received 2 years of maintenance treatment with risperidone or haloperidol. METHOD: This was a 2-year, randomized, double-blind comparison of 6 mg of risperidone versus haloperidol in 63 patients with stabilized DSM-IV schizophrenia. Study patients also received 15 months of standard behavioral skills training or enhanced training with a case manager who promoted patients' use of their skills in the community. RESULTS: The risk of psychotic exacerbations and the risk of leaving the study were similar for both drug treatment groups. However, patients who received both risperidone and the enhanced community-based skills training were more likely to remain in the study than those in the other treatment groups. Patients demonstrated significant improvement in score on the Brief Psychiatric Rating Scale over time with both medications. There were no between-group differences in cluster scores for thought disturbance, hostile-suspiciousness, and withdrawal-retardation. A significant between-group difference favoring risperidone was found for the anxious-depression cluster. Risperidone resulted in significantly greater reductions in tremor and akathisia and greater improvements in most items on the SCL-90-R. CONCLUSIONS: When compared with patients given a low dose of haloperidol, risperidone-treated patients experienced similar improvements in positive and negative symptoms and similar risks of psychotic exacerbations. However, risperidone-treated patients appeared to feel subjectively better, as indicated by less anxiety and depression and fewer extrapyramidal side effects.

Adolescent↗
PubMed2003

Alcohol abuse and dependence: psychopathology, medical management and dental implications.

BACKGROUND: The authors review the clinical features, epidemiology, pathophysiology, medical management, dental findings and dental treatment of patients with alcoholism. LITERATURE REVIEWED: The authors conducted a MEDLINE search for 1995 through 2001 using the key terms of alcoholism, epidemiology, pathophysiology, treatment and dentistry. Reports selected for further review included those published in English in peer-reviewed journals. The authors gave preference to articles reporting randomized, controlled trials. CONCLUSIONS: Alcoholism is a chronic and progressive psychiatric illness that afflicts more than 14 million Americans. It is characterized by a loss of control over the use of alcohol, resulting in impaired social functioning, and the consequent development of medical illnesses. The disease arises in genetically vulnerable people when they are overwhelmed by their cravings for the alcohol-associated euphoria that results from the actions of several neurotransmitter systems in the brain's pleasure center. New medications to counteract alcohol-induced neurotransmission imbalance may assist patients in reducing their craving. CLINICAL IMPLICATIONS: The prevalence of dental disease usually is extensive because of a disinterest in performing appropriate oral hygiene techniques and diminished salivary flow. Concurrent abuse of tobacco products worsens dental disease and heightens the risk of developing oral cancer. Identification of the alcohol-abusing patient, a cancer-screening examination, preventive dental education, and use of saliva substitutes and anticaries agents are indicated. Special precautions must be taken when performing surgery and when prescribing or administering analgesics, antibiotics or sedative agents that are likely to have an adverse interaction with alcohol or psychiatric medications.

Alcohol Deterrents↗
PubMed2003

Overview of partial compliance.

A substantial proportion of patients with psychiatric and nonpsychiatric chronic illnesses fail to take their medications as prescribed. A number of studies suggest that 50% or more of individuals with schizophrenia are noncompliant with medications at some time during their illness. In most cases, patients are partially compliant, taking only a portion of their prescribed medications. Noncompliance is probably the most important element contributing to relapse in schizophrenia. Factors contributing to the rate of noncompliance include medication side effects, the severity of psychotic symptoms, impaired cognition, and an inadequate understanding of the role of medication for preventing relapse. In addition, both patients and clinicians overestimate patients' compliance. Strategies for managing partial compliance include the treatment of medication side effects, the education of patients about their illness, and the use of long-acting antipsychotic formulations.

Antipsychotic Agents↗
PubMed2002

Sexual side effects of novel antipsychotic medications.

BACKGROUND: The novel antipsychotic medications offer a more favorable extrapyramidal side effect profile than conventional agents. It is uncertain that the novel antipsychotics have a benefit in terms of sexual side effects. METHODS: We prospectively administered a survey of sexual functioning to 25 male patients with DSM-IV schizophrenia, taking conventional and novel antipsychotics. Contrasts were made between three treatment groups: clozapine (CLOZ), risperidone (RIS), and a combined haloperidol/fluphenazine (HAL/FLU) group. RESULTS: A decrease in overall sexual functioning was reported in all medication groups (40-71%). The majority of subjects taking RIS or HAL/FLU reported a decline in one or more aspects of sexual functioning. Examining specific aspects of sexual functioning revealed that, a decline in sexual interest was significantly less common on CLOZ compared to RIS (0 vs. 64%; chi(2)=6.1, df=1, p=0.01) or HAL/FLU (0 vs. 67%; chi(2)=5.2, df=1, p=0.02), while a decline in the erectile frequency was significantly more common on RIS compared to CLOZ (40 vs. 93%; chi(2)=6.2, df=1, p=0.01) or HAL/FLU (50 vs. 93%; chi(2)=4.8, df=1, p=0.03) (0%). For enjoyment of orgasm and ejaculatory volume, significantly fewer CLOZ compared to RIS subjects reported a decline (20 vs. 86%; chi(2)=7.4, df=1, p=0.01). CONCLUSIONS: Sexual side effects are common clinically pertinent adverse effects associated with both novel and conventional antipsychotic medications. They deserve increased attention in clinical work and future research with emerging antipsychotic drugs.

Adult↗
PubMed2002

The neurocognitive effects of low-dose haloperidol: a two-year comparison with risperidone.

BACKGROUND: Neurocognitive deficits are core features of schizophrenia that are linked to functional outcome for the disorder. Recent studies and reviews have concluded that newer antipsychotic medications are better for neurocognitive deficits than conventional antipsychotic medications; however, one difficulty in interpreting this literature is that the comparisons have mainly been with high doses of conventional medications. This study examined the neurocognitive effects of low-dose haloperidol compared with risperidone over a 2-year period. METHODS: Sixty-two patients were randomly assigned to medication (starting at 6 mg of each medication) and administered neurocognitive batteries six times over the course of follow-up. At 6 months, the mean dose of haloperidol was 5.0 mg, and the mean dose of risperidone was 6.0 mg. Neurocognitive data were reduced into cluster scores and a global summary score. RESULTS: We found no significant overall differences in treatment effects on the cluster scores or the global score. The global score revealed a significant group by time interaction, reflecting the fact that the haloperidol group tended to improve initially and then stay stable, whereas the risperidone group improved more gradually over the follow-up period. CONCLUSIONS: This study did not provide support for neurocognitive advantages of a newer antipsychotic medication over a low-dose conventional medication. We speculate that conventional medications may have neurocognitive benefits at low doses that are neutralized or reversed at higher doses.

Adult↗
PubMed2002

Can clinical practice guide a research agenda?

Articles from this issue of the Bulletin indicate that clinicians are frequently adopting clinical practices that have not been supported by an evidence base. Examples of these practices are prescribing more than one antipsychotic and reserving clozapine for patients who have had multiple antipsychotic trials. This commentary suggests that these practices can be used to define important research questions.

Antipsychotic Agents↗