Long-term antipsychotic use and its association with outcomes in schizophrenia - the Northern Finland Birth Cohort 1966.

BACKGROUND: Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes. METHODS: The sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers. RESULTS: During the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score. CONCLUSIONS: In our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes.

Neurochemistry and delirium.

Acute confusional state or delirium is one of the most common organic brain syndromes especially in the elderly. It develops suddenly, within hours or days, and often during a period of hospitalization. In this paper we review the results of our studies on the neurochemistry of delirium.

A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder.

BACKGROUND: The objective of this study was to evaluate the efficacy and tolerability of citalopram in the long-term treatment of adult outpatients with panic disorder with or without agoraphobia. METHOD: Patients in this double-blind, parallel-group trial were assigned to 1 of 3 fixed dosage ranges of citalopram (10 or 15 mg/day, 20 or 30 mg/day, or 40 or 60 mg/day), 1 dosage range of clomipramine (60 or 90 mg/day), or placebo. After the completed 8-week acute treatment period, the eligible patients could continue the treatment for up to 1 year. Of the 475 patients who were randomly assigned for the short-term trial, 279 agreed to continue double-blind treatment at their assigned doses. The primary efficacy measure used was the Clinical Anxiety Scale panic attack item, and the response was defined as no panic attacks (score of 0 or 1). The other key measures used were the Physician's Global Improvement Scale, the Patient's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety (HAM-A). RESULTS: In all drug-treated groups, except the group receiving the lowest citalopram dose, the treatment outcome was generally better than with placebo. As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo (p < .05), with citalopram 20 or 30 mg/day demonstrating the best response. Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up. Analysis of the difference in the number of patients in different treatment groups remaining in the study (perhaps the best measure of long-term efficacy) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients (p < .0002 and p < .004, respectively). HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients. All treatment groups showed no new or exceptional adverse event clusters. CONCLUSION: Citalopram in the dosage range of 20 to 60 mg/day is effective, well tolerated, and safe in the long-term treatment of patients who have panic disorder.

The effect of citalopram in panic disorder.

BACKGROUND: Citalopram is a serotonin reuptake inhibitor which has been demonstrated to be highly selective and with a superior tolerability profile to the classical tricyclic antidepressants. This study was designed to test whether there was any difference in efficacy in the management of panic disorder (PD) between citalopram and placebo. METHOD: This was a double-blind, placebo and clomipramine controlled, parallel group eight-week study. A total of 475 patients with PD, with or without agoraphobia, were randomised to treatment with either placebo, clomipramine 60 or 90 mg/day, or citalopram 10 or 15 mg/day, or 20 or 30 mg/day, or 40 or 60 mg/day. Doses were increased over the first three weeks, stabilised during the fourth week and fixed between weeks five and eight. RESULTS: Treatment with citalopram at 20 or 30 mg, 40 or 60 mg and clomipramine were significantly superior to placebo, judged by the number of patients free of panic attacks in the week prior to the final assessment. All rating scales examined suggested that citalopram 20 or 30 mg was more effective than citalopram 40 or 60 mg. CONCLUSION: The most advantageous benefit/risk ratio for the treatment of PD was associated with citalopram 20 or 30 mg/day.

Fluvoxamine increases the clozapine serum levels significantly.

In this case report we describe an interaction between clozapine and fluvoxamine in two physically healthy patients meeting the DSM-IIIR criteria for paranoid schizophrenia. The substantial rise of clozapine serum levels suggest that caution should be exercised when combining fluvoxamine with clozapine as the clozapine concentration may increase by a factor of 5-10.

A long-term follow-up study of cerebrospinal fluid somatostatin in delirium.

Cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined for elderly delirious patients during the acute stage and after 1- and 4-year follow-up periods, and the SLI levels were compared with age-equivalent controls. As a whole group, and also when the group was subdivided according to the severity of cognitive decline at the acute stage, type of delirium or the central nervous system disease, delirious patients showed significant reduction of SLI as compared with the controls. In the follow-up, we observed a further reduction of CSF SLI together with significant correlations in the second, third and fourth samples between SLI levels and Mini-Mental State Examination scores. Our results suggest a role for somatostatinergic dysfunction in the genesis of some symptoms of delirium, and this dysfunction may be linked to the long-term prognosis of delirious patients.

A long-term follow-up study of cerebrospinal fluid acetylcholinesterase in delirium.

Cerebrospinal fluid acetylcholinesterase (CSF AChE) was determined for elderly delirious patients during the acute stage and after a 1- and 4-year follow-up periods, and the AChE levels were compared with age-equivalent controls. The AChE levels measured during the index admission correlated with the length of life after delirium, suggesting that cholinergic dysfunction may have prognostic significance in delirious patients. Although the CSF AChE concentrations measured during the index admission were in the same range as in controls, we observed a declining trend in patients with various structural brain diseases during the follow-up period. The decreasing levels may reflect the progression of the underlying dementia in these patients.

A long-term follow-up study of cerebrospinal fluid 5-hydroxyindoleacetic acid in delirium.

Cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) was determined for elderly delirious patients during the acute stage and after a 1-year follow-up period, and the 5-HIAA levels were compared with age-equivalent controls. As compared with the controls, the 5-HIAA levels were significantly higher at the beginning of the index admission in patients with multi-infarct dementia and patients with no apparent CNS disease. The 5-HIAA levels were also higher in the latter subgroup in the 1-year sampling, but no other differences between delirious patients and controls were observed. The one-way procedure showed no differences between the subgroup means of delirious patients when divided according to the severity of cognitive decline or type of delirium in any of the samples. The 5-HIAA levels measured during the index admission correlated with the length of life after delirium suggesting that serotonergic dysfunction may have prognostic significance in delirious patients.

Neuroleptic malignant syndrome during remoxipride treatment. A case report.

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening complication of neuroleptic treatment. The authors describe a case of NMS during treatment with a new atypical neuroleptic, remoxipride. To their knowledge, there are no previously reported cases.

A prospective study of delirium in elderly patients admitted to a psychiatric hospital.

Seventy consecutive elderly patients meeting the DSM-III criteria for non-alcohol delirium were examined during the acute stage and followed to four years later. The mean age of the patients at the beginning of the index admission was 74.8 +/- 6.4 years. The most common aetiologies for delirium were stroke, infections and metabolic disorders. Coexistent structural brain disease predisposing to delirium was found in 57 cases (81%). During the index admission, the cognitive dysfunction associated with delirium ameliorated significantly (mean +/- S.D. Mini Mental State Examination score 9.7 +/- 6.6 at admission and 13.9 +/- 7.2 at discharge, P < 0.001), but during the follow-up period of four years progression of the basic central nervous system disease was observed together with declining cognition and deteriorating functions of daily living. Four patients died during the index admission and 42 patients during the follow-up period. In decreased patients there was a statistically significant connection between the levels of cognitive functioning and functions of daily living at the end of the index admission and the life span after delirium.

Clinical picture and long-term course of epileptic seizures that occur during clozapine treatment.

Clozapine is an atypical neuroleptic drug that has proved to be effective in alleviating psychotic symptoms refractory to treatment with standard neuroleptic drugs. In addition to hematological side effects, an increased susceptibility to epileptic seizures during clozapine treatment has previously been described. In this report, we describe the clinical picture and electroencephalographic findings of 12 schizophrenic patients who have had from one to six clozapine-associated epileptic convulsions.