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Biomedical subjects

M Tohen

Publications and source records attributed to M Tohen.

At least 73 records · Page 4Linked to original sources

Does intolerance or lack of response with fluoxetine predict the same will happen with sertraline?

BACKGROUND: The purpose of this study was to determine whether sertraline would be well tolerated and effective in patients who had failed fluoxetine therapy or were unable to tolerate the medication. METHOD: Hospital records were reviewed for 88 consecutive patients started on sertraline treatment at McLean Hospital from February 11, 1992 to August 28, 1992. Forty-two patients were identified who had received sertraline treatment and who had had previous trials of fluoxetine. Patients were contacted after discharge to determine sertraline efficacy and side effects. A variety of patient characteristics and outcome measures were compared. RESULTS: Thirty-nine subjects (93%) were available for follow-up interviews. The DSM-III-R diagnoses at discharge were as follows: major depression (N=25), bipolar depression (N=6), schizoaffective disorder (N=4), and obsessive-compulsive disorder (N=4). The sertraline discontinuation rate was 64% (25/39) by a mean +/- SD of 2.3 +/- 2.1 months. In patients with major depression (N=25) and bipolar depression (N=6) discharged on sertraline, only 13 (42%) were considered responders to sertraline therapy, and at follow-up, only 8 (26%) of 31 were considered responders to sertraline therapy. Patients who had previously discontinued fluoxetine because of side effects were significantly more likely to have side effects during sertraline treatment (p = .027), and to have discontinued sertraline at follow-up (p = .018). CONCLUSION: Sertraline was found to be modestly efficacious and associated with numerous side effects and discontinuation rates in patients who had previously discontinued fluoxetine.

1-Naphthylamine↗

The use of valproate in an elderly population with affective symptoms.

BACKGROUND: Little is known about the efficacy and tolerability of valproate in the elderly population with affective disorders. This pharmacoepidemiologic study was undertaken to determine the side effect profile and efficacy of valproate in an elderly population with psychiatric symptomatology. METHOD: This was a retrospective chart review of all elderly inpatients at McLean Hospital who received valproate between May 8, 1989, and May 8, 1992. Charts were reviewed to determine gender, discharge diagnosis, indication for the agent, and length of time on each medication. Charts were also reviewed for abnormalities in liver function tests, blood cell dyscrasias, sedation, nausea and vomiting, weight gain, impairment of cognition, tremor, and hair loss. The efficacy of the medication was also determined. RESULTS: Thirty-five elderly subjects who suffered from an affective disorder and who had received valproate were identified. The mean age was 71.3 years. The mean length of time the patient received valproate was 32.7 days. The mean dose was 743 mg/day, and the mean blood drug level was 52.9 mg/L. The valproate was rated as efficacious in 18 (62%) of the 29 patients who had had an adequate drug trial at discharge. Overall the medication was well tolerated. There were no reports of liver function test abnormalities. One patient experienced transient leukopenia. Other adverse events included two reports of nausea, two reports of sedation, and one complaint of confusion. None of the variables examined were found to be statistically significant in regard to efficacy. CONCLUSION: Valproate was well tolerated and efficacious in this elderly population with affective disorders. Further controlled studies are needed to confirm our results.

Affective Disorders, Psychotic↗

Risperidone in the treatment of mania.

BACKGROUND: Risperidone, a 5-HT2 and D2 antagonist, has been shown to be an effective antipsychotic in the treatment of schizophrenia but has unclear efficacy in the treatment of psychotic affective disorders. The purpose of the study was to assess the efficacy of risperidone in the treatment of acute mania with psychotic features. METHOD: We conducted an open-label pilot study of risperidone and concurrent mood-stabilizing drugs in the treatment of acute mania with psychotic features. Patients were diagnosed with the Structured Clinical Interview for DSM-III-R (SCID). Efficacy was measured weekly with the use of the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). RESULTS: Ten women and 5 men (mean age = 38 years) were included in the study. Of the 13 patients who completed 2 weeks of treatment, 8 of these 13 had a 50% improvement of the BPRS, and all 13 had at least a 25% improvement (p = .002, 95% confidence interval [CI] = 46.0 to 57.8). Of the 8 patients who completed 6 weeks of treatment, 7 of the 8 had a 50% improvement, and all 8 had a 25% improvement (p = .012, 95% CI = 52.4 to 69.3). Similar results were obtained with the YMRS. By the second week of treatment, 10 of the 13 patients remaining in treatment had at least a 50% improvement, and 12 of these 13 had a 25% improvement (p = .002, 95% CI = 55.1 to 89.9). By the sixth week, all of the 8 patients remaining in treatment had a 75% improvement (p = .012, 95% CI = 90.5 to 102.8). The medication was well tolerated, and no case worsened. CONCLUSION: When used with concomitant mood-stabilizing drugs, risperidone may be effective and well tolerated in patients with acute mania with psychotic features. Considering the open design, small sample size, and limited period of observation, further studies need to be conducted.

Acute Disease↗

Substance abuse and the chronically mentally ill: a description of dual diagnosis treatment services in a psychiatric hospital.

Between 20% and 70% of psychiatric patients have a co-occurring substance use disorder and rates of substance abuse among patients with psychotic disorders are especially high. Patients with co-existing psychosis and substance use disorders typically have poorer outcomes than patients diagnosed with either disorder alone. Frequently, treatment services for such dually diagnosed patients are not integrated and organizational barriers may impede the appropriate detection, referral, and treatment of these patients. This article reviews the epidemiology and treatment outcome for patients dually diagnosed with chronic mental illness (usually psychotic disorders) and substance use disorders. The article then presents a description of a dual diagnosis referral and treatment service in a large private, non-profit psychiatric hospital.

Comorbidity↗

Blood dyscrasias with carbamazepine and valproate: a pharmacoepidemiological study of 2,228 patients at risk.

OBJECTIVE: The purpose of this study was to determine the occurrence of leukopenia and other blood dyscrasias associated with psychiatric use of carbamazepine and valproate. METHOD: Rates of WBC counts of 3,000-4,000/mm3 (moderate leukopenia) and < 3,000/mm3 (severe leukopenia), platelet counts of < 100,000/mm3, and hematocrit < 30% were identified among 2,228 treated patients at risk among 11,720 patients admitted to McLean Hospital over 4 years (1989-1993). Patients who received carbamazepine or valproate and had a blood dyscrasia not associated with a relevant medical condition were compared to patients treated with imipramine or desipramine. RESULTS: Of 977 patients treated with carbamazepine, 2.1% experienced leukopenia (16 moderate cases, five severe). Time to 50% risk was 16 days, and recovery occurred within about 6 days after carbamazepine was stopped. For 1,251 patients given valproate, the occurrence of leukopenia was 0.4% (three moderate cases, two severe). The occurrence of leukopenia in 1,031 patients given the tricyclic antidepressants was 0.3% (two moderate cases, one severe). The observed occurrence of moderate leukopenia with carbamazepine was 6.9 and 7.3 times higher than that with valproate and antidepressants, respectively. CONCLUSIONS: Severe blood dyscrasias were uncommon in psychiatric patients given carbamazepine and were about as rare with valproate as with imipramine or desipramine. Most important, in this cohort of 2,228 patients exposed to carbamazepine and valproate, there were no life-threatening cases.

Adolescent↗

Temporal lobe proton magnetic resonance spectroscopy of patients with first-episode psychosis.

OBJECTIVE: The authors measured the ratio of N-acetyl aspartate (a putative neuronal marker) to creatine-phosphocreatine in patients with first-episode psychosis by using proton magnetic resonance spectroscopy (MRS). METHOD: Temporal lobe 1H MRS was performed bilaterally on 13 patients with first-episode psychosis and 15 comparison subjects. The N-acetyl aspartate/creatine-phosphocreatine and choline/creatine-phosphocreatine ratios were determined. RESULTS: The N-acetyl aspartate/creatine-phosphocreatine ratio of the psychotic patients was significantly lower than that of the comparison subjects. CONCLUSIONS: These preliminary data suggest that abnormalities in temporal lobe N-acetyl aspartate concentration are present early in psychotic illness.

Adult↗

Occurrence of seizures related to psychotropic medication among psychiatric inpatients.

OBJECTIVE: Seizures associated with psychotropic medication are serious and reportable adverse drug reactions. This study examined the occurrence of seizures associated with psychotropic medication during psychiatric hospitalization. METHODS: Among 10,994 admissions to a psychiatric teaching hospital over a 30-month period between 1990 and 1993, 29 patients were identified by a specially trained quality assurance nurse as having seizures that were probably related to psychotropic medication. These cases were verified by a clinical pharmacist and a psychopharmacologist. Two patients were excluded, and the records of 27 patients were reviewed in detail. RESULTS: Nineteen of the 27 patients (70 percent) whose seizures were related to psychotropic medication had a preexisting seizure disorder, and eight had new-onset seizures. Psychotropic medications were primarily implicated as being associated with seizures in the cases of three of the 19 patients with preexisting seizure disorders (15.8 percent) and five of the eight patients with new-onset seizures (62.5 percent). In the group with preexisting seizure disorders, six patients (32 percent) had subtherapeutic blood levels of antiseizure medication, and four (21 percent) experienced pseudoseizures. CONCLUSIONS: Seizures among inpatients on psychotropic medication were infrequent (.3 percent of psychiatric admissions); the majority (70 percent) occurred in patients with preexisting seizure disorders. Seizures were directly attributed to psychotropic medications in less than .1 percent of admissions.

Anticonvulsants↗

Clozapine in severe mood disorders.

BACKGROUND: A growing literature suggests that the atypical antipsychotic agent clozapine may be effective in schizoaffective and psychotic mood disorders. METHOD: To evaluate the efficacy and tolerability of clozapine in severe mood disorders, we reviewed published studies on clozapine in schizophrenia, bipolar disorder, schizoaffective disorder, major depression, and organic disorders with psychotic or major affective syndromes, identified through the MEDLINE data base. RESULTS: Patients in manic or psychotic phases of schizoaffective or bipolar disorder were significantly more likely to respond to clozapine than patients with schizophrenia (p = .006) or severe depressive syndromes (unipolar, bipolar, and schizoaffective depression combined; p = .001). There was no significant difference in the side effect profile secondary to clozapine in patients with severe mood disorders compared to patients with schizophrenia. CONCLUSION: Clozapine appears to be effective and well-tolerated in the short-term and maintenance treatment of severe or psychotic mood disorders, particularly in the manic-excited phases of schizoaffective and bipolar disorders, even in patients who have not responded well to conventional pharmacotherapies.

Bipolar Disorder↗

Prescribing trends of antidepressants in bipolar depression.

BACKGROUND: This study utilizing pharmacoepidemiologic methods was undertaken to determine the prescribing patterns of antidepressants particularly in bipolar depression. METHOD: From pharmacy records of the McLean Hospital, the number of patients receiving antidepressants and given electroconvulsive therapy (ECT) from June 1, 1987, to May 8, 1993, was determined. We later linked these data bases with patients who were diagnosed with DSM-III-R bipolar depression (296.5) during the same period of time. RESULTS: During the 6-year period, it was determined that 3829 inpatients had received tricyclic antidepressants (TCAs), 2981 fluoxetine, 2603 trazodone, 809 bupropion, 743 monoamine oxidase inhibitors (MAOIs), 592 stimulants, 588 sertraline, 48 paroxetine, and 894 ECT. There were significant increases over time in prescriptions of MAOIs compared with fluoxetine (chi 2 = 14.36, p = .006), and bupropion compared with TCAs (chi 2 = 6.45, p = .04). There was a trend for bupropion to be prescribed more over time compared with fluoxetine (chi 2 = 5.09, p = .08). There were no significant changes in the prescribing of other antidepressants or in the use of ECT. CONCLUSION: At our center, prescribing of bupropion and MAOIs in bipolar depression has increased significantly. This may be related to the reports in the literature of the low switch rates to mania with the use of these drugs.

Adult↗

Is clozapine a mood stabilizer?

BACKGROUND: Clozapine has been increasingly shown to be effective in the acute and maintenance treatment of bipolar disorders. For this reason, we studied whether clozapine alone is effective as a mood stabilizer in patients with refractory bipolar disorders. METHOD: Subjects were part of a long-term follow-up study cohort of 193 patients with refractory mood disorders who were treated with clozapine at McLean Hospital prior to July 1, 1992. Patients included in this study were those older than 16 years with bipolar disorder (manic or mixed) and schizoaffective disorder, bipolar type, discharged taking clozapine alone (N = 17). Hospital records on all patients were reviewed by trained raters blind to "best-estimate" diagnoses. Response to clozapine was determined by the Clinical Global Impressions-Improvement (CGI-I) scale. Patients were contacted at least 6 months after clozapine initiation for semistructured follow-up interviews by raters blind to diagnosis and baseline information. RESULTS: Seventeen subjects were contacted 16.1 +/- 5.6 months after clozapine initiation. Most of the 17 patients had previously failed trials of lithium, valproate, carbamazepine, neuroleptics, combinations of these, and electroconvulsive therapy; or had tardive dyskinesia. Of these patients, 65% (11/17) continued to be on clozapine therapy alone at follow-up and had no subsequent rehospitalization or affective episode. At follow-up, there was a significant decrease in the rehospitalization rate (p = .025) than before starting clozapine and a significant improvement in CGI-I scores (p = .02). CONCLUSION: Clozapine monotherapy is an effective mood stabilizer, reducing both the number of affective episodes and rehospitalizations in patients with severe refractory bipolar illness.

Adult↗

Substance abuse in psychotic disorders: associations with affective syndromes. DSM-IV Field Trial Work Group.

In a sample of 412 patients with psychotic disorders, the authors examined whether comorbid substance use can be reliably diagnosed, is associated with increased rates of affective symptoms and syndromes and specific psychotic symptoms, and is associated with lowered reliability of the DSM-III-R principal diagnosis. Data from the DSM-IV Field Trial for Schizophrenia and Other Psychotic Disorders was analyzed. In this dataset, substance use was scored on a 4-point ordinal scale and reliability was determined using weighted kappa scores. The associations of significant substance use with affective syndromes and symptoms, and psychotic symptoms were analyzed. Kappa statistics were calculated for principal psychotic disorder diagnoses for patients with and without significant substance use. Weighted kappa scores for substance use ratings ranged from 0.27 to 0.96 (median = 0.85). Syndromal depression was significantly associated with current alcohol use in the entire sample and in the subgroup with schizophrenia alone. Grandiose delusions were also associated with substance use. Significant comorbid substance use was not associated with lowered reliability of diagnosing the principal psychotic disorder. These findings support the hypothesis that comorbid substance abuse can be reliably diagnosed and that alcohol abuse is associated with depressive syndromes in patients with psychotic disorders.

Adult↗

First-episode mania in late life.

Among 14 elderly patients (mean age = 74.6 years) with first-episode mania who were followed for 3 to 10 years, men had a higher risk of mortality. Compared to 36 elderly patients with multiple episodes of mania, patients with first-episode mania were twice as likely to have a comorbid neurological disorder (71% [N = 10] versus 28% [N = 10]). Mania in the elderly appears to be a heterogeneous disorder.

Age of Onset↗

One hundred years of schizophrenia: a meta-analysis of the outcome literature.

OBJECTIVE: This study was undertaken to assess the twentieth-century literature on outcome in schizophrenia for historical trends that might be associated with changes in diagnostic and therapeutic practice and to test the hypothesis that both improved biological treatment and changes in diagnostic criteria have influenced outcome. METHOD: Meta-analysis of the international literature on outcome in schizophrenia or dementia praecox from 1895 to 1992 identified 821 studies; 320 of these, with 51,800 subjects in 368 cohorts, met the inclusion criteria for the study. RESULTS: Only 40.2% of patients were considered improved after follow-ups averaging 5.6 years (range = 1-40). Outcome was significantly better when patients were diagnosed according to systems with broad criteria (46.5% were improved) or undefined criteria (41.0% were improved) rather than narrow criteria (27.3% were improved). The proportion of patients who improved increased significantly after mid-century (for 1956-1985 versus 1895-1955, 48.5% versus 35.4%), probably reflecting improved treatment as well as a broadened concept of schizophrenia. However, in the past decade, the average rate of favorable outcome has declined to 36.4%, perhaps reflecting the re-emergence of narrow diagnostic concepts. CONCLUSIONS: Overall, less than half of patients diagnosed with schizophrenia have shown substantial clinical improvement after follow-up averaging nearly 6 years. Despite considerable gains in improvement rates after mid-century, there has been a decline since the 1970s. These historical changes probably reflect improved treatment, shifts in diagnostic criteria, and selection bias related to changes in health care.

Cohort Studies↗

Antidepressant-associated mania: a controlled comparison with spontaneous mania.

OBJECTIVE: Antidepressants have been associated with the induction of mania and rapid cycling. This study examined whether antidepressant-associated manic states differ in any way from spontaneous mania. METHOD: Forty-nine consecutive inpatients with antidepressant-associated manic states were compared with 49 matched inpatients with spontaneous mania in a blind, retrospective chart review. RESULTS: Across virtually every clinical measure examined, the patients with antidepressant-associated manic states experienced milder and more time-limited manic episodes than the patients with spontaneous mania. The patients with antidepressant-associated manic states were subject to frequent checking by nurses and hall restriction for a significantly shorter period of time than the patients with spontaneous mania. The patients with antidepressant-associated manic states also had significantly less severe levels of delusions, hallucinations, psychomotor agitation, and bizarre behavior, according to a standard rating instrument, than the patients with spontaneous mania. For further study the patients with antidepressant-associated mania were divided into subgroups taking four individual classes of antidepressant drugs: tricyclics (N = 19), fluoxetine (N = 13), monoamine oxidase inhibitors (MAOIs) (N = 8), and bupropion (N = 6); three patients taking combinations of drugs were not included in these analyses. The patients with MAOI- and bupropion-associated mania had a slightly lower overall rating of severity of psychopathology at admission than the subgroups with fluoxetine- and tricyclic-associated mania. CONCLUSIONS: Antidepressant-associated mania appears to be a milder and more time-limited syndrome than spontaneous mania and may represent a distinct clinical entity. MAOIs and bupropion may be associated with milder manic states than either tricyclic drugs or fluoxetine.

Adult↗

Unipolar mania reconsidered: evidence from an elderly cohort.

Earlier studies have failed to differentiate the unipolar manic subtype from bipolar patients with both manic and depressive episodes. This retrospective cohort study of 50 elderly manic in-patients identified six patients (12%) who met strict criteria for a course of unipolar mania. Significant differences emerged in age at onset, with a mean of 41.2 years for unipolar mania compared with 64.7 years for the others. Consequently, clinical course was significantly longer, 27.7 v. 7.4 years. Elderly patients pursuing a unipolar manic course are among the very few elderly 'bipolars' whose illness begins early in life. Recent neuroradiological investigations and data from geriatric studies suggest that the concept of unipolar mania is worthy of further investigation.

Aged↗

Childhood abuse in first-episode psychosis.

Of 38 adult patients admitted for first-episode psychosis, 20 reported childhood abuse, with equal prevalence in men and women. Patients with histories of childhood abuse had significantly more dissociative symptoms, but not more severe psychiatric symptoms. Childhood abuse was not related to rate of recovery and was only marginally related to longer stays in hospital. Although childhood abuse did not affect recovery during first-episode psychosis, it may contribute to a chronic course in some patients.

Adolescent↗

Neurologic factors predict a favorable valproate response in bipolar and schizoaffective disorders.

The hypothesis that neurologic factors influence the response to valproate (divalproex sodium) in bipolar and schizoaffective disorders was tested. In 115 predominantly lithium-refractory inpatients, neurologic findings were recorded, and blind raters assessed valproate response from the medical record. Patients with a seizure history were much more likely to have a robust response to valproate (70%), when compared with patients without such history (34.6%). History of head injury and abnormal electroencephalographic findings also tended to be more common in those patients with good response. Overall, the group of patients with any neurologic abnormality exhibited a significantly higher rate of good response to valproate (43.6%) than did the neurologically normal group (24.3%). Bipolar or schizoaffective patients with abnormal neurologic features may represent a distinct subtype of illness and appear to be good candidates for valproate therapy.

Bipolar Disorder↗

A double-blind trial of bupropion versus desipramine for bipolar depression.

BACKGROUND: Although treatment of bipolar depression is a frequent clinical problem, double-blind studies of the treatment of bipolar depression are scarce. Some case series and uncontrolled data suggest antidepressants may differ in their propensity to induce mania or their efficacy for bipolar depression. METHOD: The authors conducted a prospective double-blind trial to assess efficacy and rate of treatment-emergent mood elevation in depressed bipolar patients when bupropion or desipramine was added to an ongoing therapeutic regimen of lithium or an anticonvulsant. Results were assessed after 8 weeks of acute treatment and during maintenance treatment up to 1 year. RESULTS: No difference was found for acute efficacy between the two drugs. Mania/hypomania was observed in 5 of 10 desipramine-treated patients, but only 1 of 9 bupropion-treated patients. The occurrence of hypomania or mania was correlated with treatment group (Kendall's tau correlation = 0.42; Z = -2.5, p < .012). CONCLUSION: These pilot findings suggest that bupropion is less likely to induce mood elevation than desipramine. For treatment of bipolar depression, bupropion and desipramine appear to have similar antidepressant efficacy.

Adult↗