Thomas A. Ban

The history of the psychopharmacology of schizophrenia

Objective: To review the historical development of the psychopharmacological treatment of schizophrenia. Method: A chronological literature review of the clinical practices and theoretical models that have controlled drug treatment of schizophrenia at different times. Results: Effective treatment of schizophrenia was achieved only after the introduction of antipsychotic drugs, in the 1950s, and is still progressing. Conclusion: Close collaboration between basic neuroscience and careful and informed clinical practice are likely to lead to continued progress.

Flexible System Criteria in chronic schizophrenia

Abstract In a multinational study of chronic hospitalized schizophrenia, the 12 items of the Flexible System Criteria were employed in addition to clinical diagnosis for admission. Comparisons with the more acutely ill patients of the International Pilot Study of Schizophrenia (IPSS) suggest a possible shift to a greater percent of chronic patients having negative symptoms.

Nimodipine in the treatment of old age dementias

1. In a multicenter, placebo-controlled, double-blind clinical study in 178 elderly patients with cognitive decline, nimodipine, a calcium antagonist was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with 90 mg of nimodipine administered orally in divided doses for 12 weeks was significantly superior to an inactive placebo on all outcome measures including the Wechsler Memory Scale, the Mini Mental State Examination, the Global Deterioration Scale, the Sandoz Clinical Assessment Geriatric Scale, the Plutchik Geriatric Rating Scale, the Severity of Illness and Global Improvement Scales of Clinical Global Impression, and the Hamilton Psychiatric Rating Scale for Depression. 3. Adverse effects with nimodipine were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.

Clinical efficacy of reboxetine: a comparative study with desipramine, with methodological considerations

The efficacy and tolerability of 4–8 mg reboxetine, a selective noradrenaline reuptake inhibitor (NARI) was verified in a 4‐week, double‐blind, placebo‐ and desipramine‐controlled study in hospitalised patients with major depression. Two‐hundred‐and‐fifty‐eight patients were recruited and randomised to treatment with 4–8 mg reboxetine, 100–200 mg desipramine or placebo on a fixed, changing dosage regimen. The therapeutic response rate (<50% reduction in mean efficacy rating scale total scores) was significantly higher with reboxetine than with placebo (p<0·05). The onset of therapeutic effect [when mean efficacy rating scale total scores became significantly (p<0·05) lower (better) than placebo] was consistently earlier with reboxetine than desipramine. From the three adverse events encountered with significant (p<0·05) difference among the groups, dryness of mouth and blurred vision were reported more frequently with desipramine than with reboxetine and placebo, whereas urinary hesitancy was reported more frequently with reboxetine than placebo. No clinically significant changes were observed in laboratory parameters and vital signs. The mean scores on the CGI‐Efficacy Index in the reboxetine group was significantly (p<0·05) higher (better) than in the desipramine and placebo groups. CODE‐DD demonstrated the broadness of the DSM‐III‐R diagnosis of major depression and provided information for designing studies for the detection of the treatment responsive population of reboxetine. In conclusion, reboxetine administered for 4 weeks in the daily doses of 4–8 mg was effective and well tolerated in treating hospitalised patients with major depression.

International study of expert judgement on therapeutic use of benzodiazepines and other psychotherapeutic medications: II. Pharmacotherapy of anxiety disorders

OBJECTIVE To assemble expert clinical experience and judgement in the treatment of anxiety and related disorders in a systematic, quantitative manner. METHODS A panel of internationally recognized Experts in treating anxiety and depression was constituted by multistage peer nomination. 90% completed a questionnaire. This report focuses on case vignettes of 7 anxiety disorders followed by questions about relevant therapeutic options. RESULTS Panelists usually recommended both psychological and pharmacological interventions. Most favored antidepressants, usually tricyclic, for agoraphobia, panic and OCD; beta-blockers for specific social phobia; and benzodiazepines for GAD and adjustment disorder. Some Experts favored polypharmacy, usually an antidepressant and a benzodiazepine. The majority usually advocated pharmacotherapy for 6 months or more. They recommended the same duration of treatment with benzodiazepines and other medications, except for GAD. CONCLUSIONS The responses of the Expert Panel imply that; (1) most anxiety disorders are serious and merit vigorous, prolonged pharmacotherapy; and (2) antidepressants and benzodiazepines are effective and safe for long-term treatment of these conditions. This outcome contrasts with the widespread apprehension about long-term pharmacotherapy, especially with benzodiazepines, and some regulatory views.

Neurotoxicity with combined administration of lithium and a neuroleptic

Abstract Case reports of neurotoxicity with lithium-neuroleptic combinations were reviewed with the objective of identifying the characteristics and predictors of the neurotoxic reaction. The investigation revealed that a reversible neurotoxic reaction characterized by organic psychopathological symptoms, extrapyramidal signs, cerebellar signs and fever may appear within a fortnight following the concurrent medication with lithium and neuroleptic(s) even though serum lithium levels are maintained at therapeutic or subtherapeutic values.

Trends in recommendations for the pharmacotherapy of anxiety disorders by an international expert panel, 1992-1997.

Abstract A follow-up survey in 1997 to a 1992 study of the recommendations of an international expert panel on the use of benzodiazepines (BZDs) and other psychotherapeutic medications in the treatment of anxiety disorders suggests that the BZDs remain a mainstay of pharmacotherapy for most of these conditions. BZDs were mentioned more often than any other class of drugs as preferred first-line therapy for anxiety disorders, except obsessive compulsive disorder. The introduction of the selective serotonin reuptake inhibitors (SSRIs) did not significantly affect the experts’ recommendations for the use of BZDs as first-line pharmacotherapy. Rather, the SSRIs displaced the tricyclic antidepressants. Some implications of the continuing recommendations for the use of BZDs in anxiety disorders are discussed.

The prevalence of abnormal involuntary movements among chronic schizophrenics.

In an international survey of chronic schizophrenia, data were collected on the Abnormal Involuntary Movements Scale (AIMS) to ascertain the prevalence of tardive dyskinesia. Abnormal movements were found to present in 28% of the sample of 739 patients. Using the more stringent Research Criteria for Tardive Dyskinesia (RD-TD) the prevalence rate was found to be 13.6%. Statistically significant differences were obtained between patients meeting RD-TD criteria and patients with abnormal movement who did not meet RD-TD criteria on total score, global severity, degree of incapacity and patient awareness--all reflecting greater severity in the RD-TD group. A much lower rate of moderate/severe tardive dyskinesia than that reported in the literature was obtained in this sample. Using the Leonhard classification of chronic schizophrenia, it was found that patients with prominent negative symptomatology had a high prevalence of tardive dyskinesia--confirming the previous reported relationship between these variables. Prevalence differences, possibly related to specific psychopathological syndromes, were also obtained.

Glycosaminoglycan polysulfate (ateroid) in old-age dementias: effects upon depressive symptomatology in geriatric patients

1. Glycosaminoglycan polysulfate is a mixture of sulfo-muco-polysaccharides with hypolipidemic activity. A number of clinical studies have indicated that it is effective in improving psychopathology in patients with cardiac and/or cerebral disease associated with arteriosclerosis. 2. A multicenter clinical trial was performed to compare the effects of two different dosages of glycosaminoglycan polysulfate upon depressive symptomatology in patients with multi-infarct dementia and primary degenerative dementia. 3. A total of 39 patients were treated in an 18-week clinical trial which followed a single-blind parallel design. 4. Results indicated that patients with both diagnoses improved significantly in depressive symptomatology over the course of treatment, with particular improvement noted in cognitive disturbance. Drug dosage was not a significant determinant of treatment response for either diagnostic group.

Prolegomenon to the clinical prerequisite: Psychopharmacology and the classification of mental disorders

Introduction Historical Development: Preclinical Neuropharmacology Present Status: Clinical Psychopharmacology 527 556 556 557 559 (Final form, April 1987)