Cardiac effects of antidepressants.

Cardiac effects of tricyclics and tetracyclics, while common, are most frequently benign and well-tolerated. For older patients with underlying disease, however, closer clinical monitoring is needed. The most common effect of MAOIs in healthy adults taking normal dosages is orthostatic hypotension. The most serious reaction to MAOIs is hypertensive crisis, which may be fatal.

Cognitive changes in acute schizophrenia with brief neuroleptic treatment.

The authors studied 44 acutely decompensated, hospitalized schizophrenic patients who were placed on a double-blind basis for 10 days in three treatment groups: patients given high, moderate, and standard doses of haloperidol. To assess changes in the patients' concentration, abstract thinking, and ability to respond appropriately they administered two clinical rating scales and three psychological tests. Patients in all three treatment groups showed similar and significant improvements according to both clinical and psychological ratings after haloperidol administration. Normal control subjects showed no change in psychological test scores over time. The authors conclude that brief treatment with neuroleptics produces measurable improvement in schizophrenic thinking.

Amoxapine and amitriptyline in the outpatient treatment of endogenous depression.

This double-blind investigation compared onset of action, efficacy, and safety of amoxapine and amitriptyline in 46 endogenously depressed outpatients. Statistical analysis demonstrated relatively few significant differences in improvement between the two groups. Most of the differences favored amoxapine, however, and on all measures there were clear trends favoring amoxapine for more rapid onset of action or greater overall efficacy or both.

Haloperidol for acute schizophrenic patients. An evaluation of three oral regimens.

The relative efficacy of three oral regimens of haloperidol was compared in a ten-day, double-blind study of 63 acutely ill schizophrenic patients newly admitted to the hospital. One group of patients received 20 mg of haloperidol on day 1, then increasing increments of 20 mg a day, reaching a maximum dosage of 100 mg daily on day 5. Another group received 10 mg of haloperidol on day 1, then increasing increments of 10 mg daily, reaching 100 mg daily on day 10. A third group of patients received a fixed dosage of 10 mg daily for ten days. Haloperidol was well tolerated by the patients; there were no serious adverse reactions. The data indicated that the regimens had similar therapeutic efficacy, suggesting that acutely ill schizophrenic patients respond to a wide range of doses of haloperidol but that onset of response and efficacy are not increased in most patients by providing a high initial loading dosage. Adequate, safe dosage must be determined in each case.

Primary affective disorders.

This paper reviews the diagnosis and medical treatment of the major affective disorders. Patients with severe mood disturbances are frequently seen by the family physician. The diagnosis may be delayed since the patient may focus predominantly on somatic concerns which may mimic physical illness. The characteristics, course, and differential diagnosis of depression and mania are discussed. Antidepressants and lithium therapy greatly improve the prognosis of these disorders; monoamine oxidase inhibitors and neuroleptics are indicated for special subtypes of depression. Dosage schedules, interactional effects, adverse and toxic effects are reviewed for tricyclic antidepressants and lithium.

Clobazam versus placebo for anxiety and tension in psychoneurotic outpatients. A multicenter collaborative study.

Clobazam, a 1,5-benzodiazepine, was compared with placebo in 190 psychoneurotic outpatients with prominent symptoms of anxiety and tension of at least two weeks of duration. The design was one of double-blind parallel groups treated for one week. Clobazam subjects began on 40 mg daily in divided dosage, which was increased to 80 mg daily be day 3 if the drug was well tolerated. Two patients receiving clobazam had laboratory chemistry abnormalities which were possibly drug related. Adverse effects occurred more frequently in the clobazam group and were typical of those of marketed benzodiazepines. This study indicates that clobazam is an effective anxiolytic agent demonstrating its clinical effects during the first week of treatment.

Overview: efficacy and safety of the rapid neuroleptization method with injectable haloperidol.

The authors review the literature on the rapid neuroleptization (titration) method with I.M. haloperidol. Most of the approximately 650 predominantly schizophrenic and manic patients represented in the studies calmed down rapidly on medication, and some demonstrated an early reduction in core psychotic symptoms. The initial doses varied widely, ranging from 1 to 30 mg, with a maximum total daily dosage of 100 mg. The medication seemed to have been well tolerated in all cases, with no reported major complications. The authors conclude that the method shows definite merit with agitated and belligerent patients. However, they make a number of specific recommendations for further research to clearly establish the effectiveness and safety of this method of neuroleptic administration.

Factors influencing clinical response to psychotropic drugs. Imipramine in depression.

Numerous factors are involved in determining the efficacy of tricyclic antidepressant agents in the treatment of depression. The list includes diagnosis and patient selection; pharmacodynamics, bioavailability and tissue sensitivity; natural history; placebo response, nonspecific factors; compliance and adverse effects; the effects of concurrent life events, illness and treatment, and the bias in evaluating the outcome of treatment. Physicians should be aware of the factors that influence clinical response so they can maximize therapeutic effects and utilize the agents properly.

High vs standard dosage fluphenazine HCL in acute schizophrenia.

This rater blind project compared the efficacy and safety of using an oral rapid or neuroleptization method (maximum 80 mg./day) versus fixed standard dosage (20 mg./day) fluphenazine, a commonly used neuroleptic. There were 32 hospitalized, acutely decompensated schizophrenic patients in the experiment; the study period for each patient was a maximum of 7 days. The data were collected using the Benjamin Proverb Test and rating scales for psychopathology and adverse effects. Data analysis by means of the analysis of covariance demonstrated few significant differences between the 2 treatment methods: both methods produced a similar reduction in psychopathological symptoms and incidence of adverse effects. The authors conclude that the rapid neuroleptization method is not superior to the fixed standard dosage method in treating acute schizophrenia.

The schizophrenias: medical diagnosis and treatment by the family physician.

About one percent of the population will develop schizophrenic symptoms sometime during their life. Etiologies are poorly understood and the course is highly variable. The differential diagnosis and medical treatment of the schizophrenias are discussed. Neuroleptic drugs are the most effective single treatment, for they allow most patients to be treated on an ambulatory basis, under the care of community physicians. Adverse effects of neuroleptic agents are common and often subjectively annoying. They may be prevented or minimized by agent selection, dosage schedules, or contra-active treatment.

A twelve month comparison of penfluridol and trifluoperazine in chronic schizophrenic outpatients.

This investigation is a 52-week double-blind study comparing the efficacy and safety of penfluridol and trifluoperazine in 25 chronic schizophrenic outpatients. Penfluridol was administered once weekly and trifluoperazine daily. Measurements were made at baseline, various fixed intervals during the study period and termination. The data reveals that both agents were similarly effective in maintaining control of the symptoms of chronic schizophrenic patients at a level commensurate with or better than that provided by their previous medication. Besides being effective, medications were also well tolerated. The side effects were characteristic of marketed neuroleptics. Akathisia was more common with penfluridol but readily controlled with anti-parkinsonian medication. Other side effects were similar in severity and occurrence between study-drug groups. Both agents had low autonomic liability, and neither agent was depressogenic.

Successful suicides with thioridazine and mesoridazine: a result of probable cardiotoxicity.

Five cases of successful suicides from thioridazine and mesoridazine occurred. The clinical course and management are outlined. A sixth case of reversible total heart block associated with thioridazine is presented giving further evidence that the deaths from overdose probably resulted from drug cardiotoxicity.

Pimozide versus fluphenazine in ambulatory schizophrenics: A 12-month comparison study.

In this study, chronic schizophrenic outpatients who had been maintained on various neuroleptics for an average of about 4 years had their previous medications (approximately equivalent to 695 mg of chlorpromazine per day) changed abruptly to either pimozide or fluphenazine given in single daily oral doses on a double-blind basis for a period of 52 weeks. Average daily doses were pimozide 9.6 mg and fluphenazine 12.5 mg. Measurements of the therapeutic effects of the two drugs were made immediately prior to starting the study, at the end of the 2nd and 4th weeks, and thereafter every 4th week to the end of the study. Three psychometric scales were used for evaluation: Brief Psychiatric Rating Scale (BPRS); Evaluation of Social Functioning (ESFR); and Clinical Global Impressions (CGI). In addition, patients participated in a Social Adjustment Inventory (SAI) evaluation. Statistical analysis with the use of several statistical techniques for between- and within-drug group comparisons revealed that pimozide and fluphenazine were equally effective in maintaining control of symptomatology of chronic schizophrenics at a level commensurate with or better than that provided by their previous medication. Side effects were characteristic of marketed neuroleptics, similar in severity and occurrence between study-drug groups, mainly extrapyramidal symptoms, and readily controlled with antiparkinsonian medication. Pimozide, slightly more potent than fluphenazine, proved to be equally effective for the long-term management of chronic schizophrenic patients.

Depression and the reintegration phase of acute schizophrenia.

The authors found moderate to severe depression in 60% of a group of schizophrenic patients experiencing acute decompensations (N=30). The course of the depression was followed over an 8-week period8,during which patients were treated with depot fluphenazines. There was a statistically significant reduction in depression that closely paralleled the correction of the cognitive disorder. The authors discuss problems in identifying and quantifying depression during acute schizophrenic decompensation and suggest that the Hamilton scale anxiety/depression factor and the BRPS depression factor may be useful diagnositc tools.

Neuroleptic induced extrapyramidal symptoms.

All currently marketed neuroleptics induce extrapyramidal symptoms (EPS). These EPS are a function of biological sensitivity, neuroleptic molecular structure, dose, age, sex, and duration of neuroleptic treatment. Because of their association with EPS, at times irreversible, and their modest efficacy in the non-schizophrenic patients, neuroleptic administration should be limited predominantly to schizophrenic patients. Furthermore EPS should not be used as a guideline for the efficacy of neuroleptics as formerly assumed. For EPS may occur at subtherapeutic doses of neuroleptics and may be absent in patients experiencing clinical response. Neuroleptic dose should be the lowest efficacious dose required to provide symptom remission. In addition, antiparkinsonian (AP) agents should be administered predominently contraactively and not routinely in combination with neuroleptics. With the judicious administration of neuroleptic agents and AP medication, distressing EPS can be prevented or minimized, while providing control of schizophrenic symptoms.