Biomedical subjects

M Tohen

Publications and source records attributed to M Tohen.

At least 19 recordsLinked to original sources

PubMed2006

Psychopathology factors in first-episode affective and non-affective psychotic disorders.

BACKGROUND: Since the onset, prevalence, and course of specific psychopathological features rarely have been analyzed simultaneously from the start of dissimilar psychotic illnesses, we compared symptom-clusters in first-episode DSM-IV affective and non-affective psychotic disorders. METHODS: Subjects (N=377) from the McLean-Harvard First Episode Project hospitalized for first-lifetime primary psychotic illnesses were followed prospectively for 2 years to verify stable DSM-IV diagnoses. We ascertained initial symptoms from baseline SCID and clinical assessments, applying AMDP and Bonn psychopathology schemes systematically to describe a broad range of features. Final consensus diagnoses were based on intake and follow-up SCID assessments, family interviews, and medical records. Factor-analytic methods defined first-episode symptom-clusters (Factors), and multiple-regression modeling related identified factors to initial DSM-IV diagnoses and to later categories (affective, non-affective, or schizoaffective disorders). RESULTS: Psychopathological features were accommodated by four factors: I represented mania with psychosis; II a mixed depressive-agitated state; III an excited-hallucinatory-delusional state; IV a disorganized-catatonic-autistic state. Each factor was associated with characteristic prodromal symptoms. Factors I and III associated with DSM-IV mania, II with major depression or bipolar mixed-state, III negatively with delusional disorder, IV with major depression and negatively with mania. Factors I and II predicted later affective diagnoses; absence of Factor I features predicted non-affective diagnoses, and no Factor predicted later schizoaffective diagnoses. CONCLUSION: The findings contribute to descriptive categorizations of psychopathology from onset of dissimilar psychotic illnesses. This approach was effective in identifying and subtyping affective psychotic disorders early in their clinical evolution, but non-affective and schizoaffective conditions appear to be more complex and unstable.

Adult↗

PubMed2004

Scale matters: the need for a Bipolar Depression Rating Scale (BDRS).

OBJECTIVE: To briefly review the clinical and biological distinctions between unipolar and bipolar depression critiquing in particular currently available depression rating scales and discuss the need for a new observer-rated scale tailored to bipolar depression. METHOD: Relevant literature pertaining to the symptomatic differences between bipolar disorder and unipolar disorder as well as their measurement using existing assessment scales was identified by computerized searches and reviews of scientific journals known to the authors. RESULTS: Bipolar depression is distinct from unipolar depression in terms of phenomenology and clinical characteristics. These distinguishing features can be used to identify bipolarity in patients that present with recurrent depressive episodes. This is important because current self-report and observer-rated scales are optimized for unipolar depression, and hence limited in their ability to accurately assess bipolar depression. CONCLUSION: The development of a specific bipolar depression rating scale will improve the assessment of bipolar depression in both research and clinical settings and assist the development of better treatments and interventions.

Bipolar Disorder↗

PubMed2003

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design.

Adolescent↗

PubMed2003

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. II. Baseline characteristics of the "prodromal" sample.

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.

Adolescent↗

PubMed2002

What makes a drug a primary mood stabilizer?

The term 'mood stabilizer' has been applied to a number of medications for the treatment of patients with bipolar disorder. The operational definition of the properties of a mood-stabilizing medication has varied according to the properties of specific medications and the clinical characteristics of the illness. Randomized controlled trials of agents accepted or proposed as mood stabilizers are reviewed to marshall the available evidence in support of this claim. In addition, potential pharmacological mechanisms underlying mood-stabilizing effects of established compounds are reviewed.

Affect↗

PubMed2002

Treatment of bipolar I rapid cycling patients during dysphoric mania with olanzapine.

The simultaneous presentation of manic and depressive symptoms in the same patient is fairly common. The terms and have been used as equivalents to mixed states. Pharmacotherapy is less effective in this group of patients. The aim of this study is to determine the effectiveness and safety of olanzapine as an add-on therapy in patients with bipolar disorder with a rapid cycling course during a dysphoric mania episode. Thirteen patients treated with mood stabilizers for at least 1 year and diagnosed with a mixed episode were included in an open trial. All had at least 4 episodes in the last year. Patients with organic diseases, including altered thyroid function, were excluded from the research. Patients were evaluated at inclusion and at day 28. Response was defined as a decrease of 50% in the Young Mania Rating Scale and the Hamilton Rating Scale for Depression concomitant with a Clinical Global Impression improvement of 1 or 2. All patients completed the study. The doses of olanzapine were 16.15 +/- 5.82 mg/day. There was a reduction in the manic and depressive symptoms in all patients. Ten of the 13 patients were considered to have responded to the treatment according to the response definition. Adverse effects included somnolence (23.08%) and weight gain (0.81 +/- 1.96 kg in women, 2.20 +/- 2.28 kg in men). Our results suggest that olanzapine combined with mood stabilizers is safe and effective in the treatment of the manic and the depressive symptoms of dysphoric mania with a rapid cycling course.

Adult↗

PubMed2002

Olanzapine versus haloperidol in the treatment of acute mania: clinical outcomes, health-related quality of life and work status.

We aimed to compare clinical outcomes, health-related quality of life (HRQOL) and work status associated with olanzapine and haloperidol treatment in patients with bipolar disorder. This double-blind, randomized controlled trial, comparing flexible dosing of olanzapine (5-20 mg/day, n = 234) to haloperidol (3-15 mg/day, n = 219), consisted of a 6-week acute phase, followed by a 6-week continuation phase. Symptomatic remission rates were similar for olanzapine- and haloperidol-treated patients at weeks 6 and 12. At week 6, significant changes in five dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) [general health (P = 0.010), physical functioning (P < 0.001), role limitations due to physical problems (P < 0.001), social functioning (P < 0.05) and vitality (P < 0.01)] and the SF-36 physical components summary score were found in favour of olanzapine compared to haloperidol. At week 12, olanzapine treatment maintained the significantly favourable HRQOL changes. At the end of week 12, patients on olanzapine showed significantly greater improvement than haloperidol in work activities impairment and household activities impairment scores on the Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation (SLICE/LIFE) activities impairment scores. Subgroup analyses revealed that olanzapine treatment significantly increased a proportion of employed patients and their weekly paid working hours. In conclusion, compared to haloperidol, olanzapine treatment was comparably effective in the remission of bipolar mania and significantly improved HRQOL and work status in patients with bipolar I disorder.

Acute Disease↗

PubMed2001

A meta-analysis of the use of typical antipsychotic agents in bipolar disorder.

BACKGROUND: The potential benefits of typical antipsychotic agents in bipolar disorder are offset by serious treatment-associated side effects. Despite these concerns and the availability of mood stabilizing agents, the treatment of bipolar disorder with typical antipsychotic agents appears to be widespread. METHODS: A Medline search identified 16 publications that outlined medication use among 2378 bipolar disorder patients. Meta-analysis was used to estimate a weighted average of the relative proportions of the treatment use, where the weights were the reciprocals of the estimated variances for each study. RESULTS: Overall, 84.7% of bipolar patients received typical antipsychotic agents, with a loading toward a greater in-patient (90.7%) relative to out-patient (65.3%) use. Monotherapy accounted for 53.8% of typical antipsychotic use, and typical antipsychotic/mood stabilizer combination therapy accounted for 47.4%. In four studies where length of treatment data were available, the median of minimum typical antipsychotic use was 2.5 months, with 96.0% of the patients receiving typical antipsychotic agents. LIMITATIONS: The meta-analytic technique employed in this analysis is limited by the possible inclusion of studies with unreliable study designs or biased treatment practices, publication bias in which some studies may not have been reported, and possible lack of identification of all relevant studies. CONCLUSIONS: Typical antipsychotic agents are commonly used in the treatment of bipolar disorder, possibly due to dissatisfaction with mood stabilizer monotherapy especially in psychotic mania, the high prevalence of psychotic symptoms in acute mania, inappropriate continuation of typical antipsychotic agents after initial stabilization, and/or unavailability or unfamiliarity with new treatments. These findings also suggest that typical antipsychotics may have not only antipsychotic effects in mania but perhaps also antimanic properties.

Antimanic Agents↗

PubMed2001

Olanzapine versus haloperidol in schizoaffective disorder, bipolar type.

BACKGROUND: The present analysis was performed on data from a subsample of patients with schizoaffective disorder, bipolar type, who participated in a multicenter, double-blind study comparing olanzapine to haloperidol. METHODS: Patients with schizoaffective disorder bipolar type, characterized as currently manic, mixed, depressed, or euthymic, were assessed weekly for 6 weeks during treatment with either olanzapine or haloperidol. Manic symptoms were measured using the sum of six items of the BPRS, and depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale. In addition, cognitive functioning was measured using the sum of seven items from the PANSS. Repeated measures analyses were performed using random coefficients regression of the serial measurement of manic, cognitive, and depressive symptoms. RESULTS: A significant treatment difference was detected overall, indicating that olanzapine was significantly more effective than haloperidol in reducing symptoms of depression and improving patients' cognitive symptoms. The superiority of olanzapine over haloperidol in the reduction of manic symptoms did not reach statistical significance (P=.052). The greatest improvement in both manic and cognitive symptoms was seen in the olanzapine-treated 'currently manic' subgroup, and least improvement in the haloperidol-treated 'euthymic' subgroup. Depressive symptoms were most improved in the olanzapine-treated 'depressed' subgroup, and least improved in the corresponding haloperidol subgroup. CONCLUSIONS: Overall, olanzapine was superior to haloperidol with respect to thymoleptic effects in patients with schizoaffective disorder, bipolar type.

Administration, Oral↗

PubMed2001

Use of olanzapine in dysphoric mania.

BACKGROUND: The simultaneous presentation of both manic and depressive symptoms has long been recognized. Nevertheless, a variable prevalence of dysphoric mania has been reported. The aim of this study was to estimate the prevalence of dysphoric mania among hospitalized patients and to assess the effectiveness of olanzapine in this type of patients. METHODS: Eighty-six patients who met DSM-IV criteria for mania were evaluated at admission with a protocol that included McElroy's criteria for dysphoric mania [Am. J. Psychiatry 149 (1992) 1633]. Treatment was administered according to clinical need, using mood stabilizers combined with antipsychotics. Sequential assessments were conducted throughout the study. RESULTS: Forty-four patients (51.2%) fulfilled McElroy's criteria for dysphoric mania. Fourteen of these dysphoric patients were treated with olanzapine in combination with mood-stabilizers. All patients improved in manic symptoms but patients treated with olanzapine improved significantly more than those treated with other antipsychotics in depressive symptoms. LIMITATIONS: The lack of randomization is a methodological limitation of this study, so these findings should be considered as preliminary. CONCLUSIONS: Dysphoric symptoms are common in this population of manic patients. Olanzapine in combination with mood-stabilizers may be effective in these patients. Additional controlled studies are needed to replicate these results.

Adult↗

PubMed2001

A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder.

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Abdominal Pain↗

PubMed2001

Olanzapine as alternative therapy for patients with haloperidol-induced extrapyramidal symptoms: results of a multicenter, collaborative trial in Latin America.

Conventional antipsychotic agents can induce extrapyramidal symptoms (EPS) that may be alleviated by switching patients to novel agents such as olanzapine. Patients with schizophrenia and related disorders (ICD-10) who were taking haloperidol (N = 94; mean dose = 12.7 mg/day) and had EPS (Simpson-Angus Scale [SAS] > 3) were directly switched to 6 weeks of open-label olanzapine treatment (mean dose = 11.4 mg/day). There were significant mean improvements (p <0.001 for all measurements) from baseline to endpoint on the SAS (-9.69+/-5.33; percentage change, 87.2%), the Barnes Akathisia Scale (-1.00+/-1.19; percentage change, 82.5%), and the Abnormal Involuntary Movement Scale (-1.48+/-2.89; percentage change, 81.1%), and anticholinergic use decreased from 47.9% to 12.8% (mean baseline to endpoint change: -1.52+/-1.91-mg equivalents of benztropine; p < 0.001). Significant mean baseline to endpoint improvements (p < 0.001 for all measurements) were observed on the Positive and Negative Syndrome Scale (PANSS; -25.28+/-18.67; percentage change, 30.3%), the PANSS-extracted Brief Psychiatric Rating Scale (0-6 scale, -13.41+/-10.16; percentage change, 54.4%), and the Clinical Global Impressions Severity scale (-1.16+/-1.19; percentage change, 26.4%). Spontaneously reported treatment- emergent adverse events with a greater than 5% incidence were somnolence (16.0%), increased appetite (14.9%), weight gain (11.7%), headache (8.5%), anxiety (7.4%), dizziness (6.4%), and insomnia (5.3%). Criteria for a successful switch were met by 90.5% of patients. Psychotic symptom exacerbation was experienced by 30.9% of patients at any time during the study and by 11.7% of patients at endpoint. Results suggest that a direct switch to olanzapine is a therapeutic option when patients with haloperidol-induced EPS are unable to tolerate a more gradual switch.

Adolescent↗

PubMed2001

A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania.

There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania.

Adult↗

PubMed2001

Olanzapine as long-term adjunctive therapy in treatment-resistant bipolar disorder.

The aim of this study was to estimate the long-term effectiveness of olanzapine as adjunctive therapy in patients with bipolar disorder who exhibited an inadequate response to mood stabilizers. Twenty-three Research Diagnostic Criteria (RDC) patients with bipolar I and II were assessed by means of the Schedule for Affective Disorders and Schizophrenia and entered if they gave their consent to participate. All of them had experienced frequent relapses, residual subsyndromal symptoms, and inadequate responses to other drugs, such as lithium, valproate, or carbamazepine. While maintaining other drugs, they all received open-label, increasing doses of olanzapine, until achieving clinical response. Other drugs were maintained. The patients were assessed several consecutive times from baseline to the endpoint with the Clinical Global Impressions (CGI) scale for use in bipolar illness. Records of recurrences, hospitalizations, and side effects were also collected. The last-observation-carried-forward analysis showed that there was a significant reduction of CGI scores after the introduction of olanzapine, either in manic symptoms (p = 0.0015), depressive symptoms (p = 0.0063), or global symptoms (p = 0.0003). The most frequent adverse events were somnolence (17%) and weight gain (13%). The mean dose of olanzapine at the end of the 43-week follow-up was 8.1 mg/day. Olanzapine may be a useful medication for the long-term adjunctive treatment of patients with bipolar disorder who exhibit a poor response to mood stabilizers, such as lithium, valproate, or carbamazepine. These results suggest mood-stablizing properties of olanzapine.

Adult↗

PubMed2001

A novel augmentation strategy for treating resistant major depression.

OBJECTIVE: Treatment-resistant depression is a significant public health concern; drug switching or augmentation often produce limited results. The authors hypothesized that fluoxetine could be augmented with olanzapine to successfully treat resistant depression. METHOD: An 8-week double-blind study was conducted with 28 patients who were diagnosed with recurrent, nonbipolar, treatment-resistant depression without psychotic features. Subjects were randomly assigned to one of three groups: olanzapine plus placebo, fluoxetine plus placebo, or olanzapine plus fluoxetine. RESULTS: Fluoxetine monotherapy produced minimal improvement on various scales that rate severity of depression. The benefits of olanzapine monotherapy were modest. Olanzapine plus fluoxetine produced significantly greater improvement than either monotherapy on one measure and significantly greater improvement than olanzapine monotherapy on the other measures after 1 week. There were no significant differences between treatment groups on extrapyramidal measures nor significant adverse drug interactions. CONCLUSIONS: Olanzapine plus fluoxetine demonstrated superior efficacy for treating resistant depression compared to either agent alone.

Ambulatory Care↗

PubMed2001

Cycling into depression from a first episode of mania: a case-comparison study.

OBJECTIVE: The characteristics of patients who cycle from mania to major depression and the frequencies of these cycles remain poorly understood. METHOD: This study compared 28 patients with a first episode of mania who cycled into a major depressive episode without recovery from their index episode and 148 patients with first-episode mania who did not cycle into depression. Patients were given extensive assessments at baseline and 6-, 12-, and 24-month follow-ups. Comparisons between the two groups were made on demographic variables, clinical ratings, and outcome variables. RESULTS: Approximately 16% of the patients with a first episode of mania cycled into major depression. Patients who cycled into depression were more likely to have higher depressive scores at admission and tended to have the mixed subtype of bipolar disorder. CONCLUSIONS: Patients with first-episode mania who score high for depression at admission may be at greater risk of cycling into a major depressive episode.

Adult↗

PubMed2001

Medication prescribing patterns for patients with bipolar I disorder in hospital settings: adherence to published practice guidelines.

OBJECTIVE: The purposes of this paper were to examine the medication prescribing patterns for bipolar I disorder in hospital settings and to compare them to recently published expert consensus guidelines for medication treatment of bipolar disorder. METHODS: Data were obtained from the 1996-2000 CQI+SM Outcomes Measurement System, on patients age 18 or older admitted to psychiatric inpatient units from over 100 medical-surgical hospitals. A total of 1864 patients with a primary discharge diagnosis of bipolar I or II disorder were identified from a large cohort of hospitalized patients. Patient characteristics were assessed at hospital admission and medication usage, at discharge. The medication analysis focused on the 1471 individuals with bipolar I mania or bipolar I depression (with or without psychotic features), representing 54% and 25% of admitted bipolar patients, respectively. RESULTS: At admission, the typical bipolar patient (mean age 57) had experienced a relatively severe and chronic course of illness. The array of psychotropic agents used was broad, with no single prescribing pattern predominant. Only one in three bipolar I (manic or depressed) patients with psychotic features was discharged on medications recommended by expert guidelines as preferred or alternate recommended treatment. Absent psychotic features, this dropped to one in six patients. Surprising was the relatively high use of antidepressants for patients with mania, particularly those without psychotic symptoms. CONCLUSIONS: Results suggest that a substantial proportion of patients with bipolar I disorder are discharged from hospitals on medications not generally recommended by current practice guidelines.

Adolescent↗

PubMed2000

First-episode schizophreniform disorder: comparisons with first-episode schizophrenia.

BACKGROUND: Schizophreniform disorder remains poorly understood and has been reported probably to be a heterogeneous group of psychotic disorders. METHOD: This study compared first-episode schizophreniform disorder (N=12) and schizophrenia (N=18) patients. The authors propose that schizophreniform disorder has a different type of onset and outcome than schizophrenia. Patients were given extensive assessments at initial evaluation, 6 month follow-up, and 24 month follow-up. Comparisons between the two groups were made on type of onset, demographic, clinical ratings and outcome variables. RESULTS: Patients with schizophreniform disorder compared to patients with schizophrenia were more likely to have an acute onset (P=0.003), and have recovered by 6 months (P=0.03). However, there were no differences in outcome at 24 months. Furthermore, all schizophreniform cases except for two were re-diagnosed at 24 months as having schizophrenia. CONCLUSIONS: The findings suggest that the initial differences of schizophreniform disorder compared to schizophrenia were not apparent at 24 months follow-up. Schizophreniform disorder did not emerge as a highly distinctive and stable form of psychosis that merits a diagnostic classification separate from schizophrenia.

Adult↗