Monoamine oxidase inhibitors. A review of antidepressant effectiveness.

Data from double-blind, placebo-controlled trials of the monoamine oxidase (MAO) inhibitors show that phenelzine is clearly effective in neurotic or atypical depressives, but the findings concerning its effect in endogenous depressives are inconclusive. Although few controlled studies have been done with tranylcypromine, similar conclusions are warranted. Studies have contrasted MAO inhibitors and tricyclic antidepressants (TCAs) to gain further information about the type of patients likely to respond to MAO inhibitors. We believe that simply contrasting the relative efficacy of TCAs and MAO inhibitors is outdated. Neurotic or atypical depression is probably a heterogeneous syndrome, and delineation of subtypes responsive to specific antidepressants is needed. The implications of fast acetylation, selective MAO inhibitors, types MAOA and MAOB, and measures of platelet MAO inhibition are discussed in this article.

Fluphenazine decanoate, oral fluphenazine, and placebo in treatment of remitted schizophrenics. II. Rating scale data.

This study of patients with remitted chronic schizophrenia in an aftercare clinic was designed to test whether such patients require maintenance antipsychotic medication. A previous report showed that the group receiving active medication, fluphenazine decanoate and oral fluphenazine, had far fewer relapses; but the former group had a high incidence of akinesia. This present report presents rating scale data substantiating these two findings: (1) patients terminated on clinical grounds because of a schizophrenic relapse showed rating scale changes consistent with that diagnosis; and (2) the patients removed due to severe akinesia showed a worsening on items selected a priori to measure akinesia, and when compared to survivors on the same items, showed significant differences--thus confirming our clinical judgments.

Very high dosage vs standard dosage fluphenazine in schizophrenia. A double-blind study of nonchronic treatment-refractory patients.

Previous work with chronic schizophrenic patients and a pilot study with nonchronic treatment-refractory schizophrenic patients indicated that very high doses of fluphenazine hydrochloride (1,200 mg/day) have a greater antipsychotic effect than do standard doses. Increased side-effects were not reported. In a double-blind six-week random assignment study, 18 nonchronic treatment-refractory patients received the very high dose and 13 the standard dose. The standard-dose treated patients had greater improvement on a variety of measures. Analysis of Inpatient Multidimensional Psychiatric Scale scores indicate that some patients taking very high doses had akinesia, and extrapyramidal side-effect that in part accounted for their inferior response.

Neurologic soft signs in schizophrenia and character disorders. Organicity in schizophrenia with premorbid asociality and emotionally unstable character disorders.

Previous studies indicated that for two subgroups of patients, schizophrenics with premorbid asociality (SPA) and individuals with emotionally unstable character disorders (EUCD), central nervous system damage may have etiologic significance. It was hypothesized that these two patient groups would also have an increased number of neurologic soft signs. The relationship of neurologic examination, tests of auditory-visual integration, and intelligence quotient, and diagnoses was studied for 350 patients. Tests of reliability and persistence for all observed signs were performed. The EUCD and SPA groups had increased evidence of neurologic soft signs. Differences in patterns of IQ scores also suggest that different forms of brain damage may be present in these two groups. When the two groups were removed from the larger patient sample, those patients with other types of schizophrenia and character disorder did not exhibit evidence of neurologic impairment. This study of neurologic soft signs adds to the validity of considering SPA and EUCD as separate diagnostic entities.

Prophylaxis of affective disorders. Current status of knowledge.

A review of all properly controlled studies clearly indicates that lithium carbonate is prophylactic for mania in bipolar patients; it is suggestive of prophylaxis for depression in both bipolar and unipolar patients. Studies are outlined that would clarify lithium carbonate's prophylactic effect for depression in these two patient groups. Continuation therapy with antidepressants reduces incidences of recurrence in unipolar depressives. The only controlled study indicates that tricyclic antidepressants may have prophylactic effect in unipolar patients. This finding needs confirmation. Data are insufficient for conclusions on prophylactic treatment for schizoaffective disorders.

Are prophylactic antiparkinson drugs necessary? A controlled study of procyclidine withdrawal.

Of 55 aftercare patients receiving long-term treatment with antipsychotic and antiparkinson (AP) drugs, 37 were switched to being given placebo, and 18 remained on a regimen of procyclidine hydrochloride. The dose of antipsychotic was kept constant. After three weeks extrapyramidal side effects (EPS) developed in 54% of those patients receiving placebo and in none of those receiving procyclidine (P less than .002): Twenty-seven percent of the placebo group had EPS without akinesia, and in the same percentage akinesia developed (P = .003). We believe the risk-benefit ratio favors the routine use of AP drugs for prophylaxis and maintenance so as to avoid misdiagnosing as psychopathology, unspontaneity due to akinesia, and to reduce unreliable pill-taking due to EPS.

Facial discrimination and emotional recognition in schizophrenia and affective disorders.

Current research demonstrates that patients with schizophrenia display deficits in a broad range of interpersonal skills. To investigate the ability of patients with schizophrenia and major depression and normal controls to process facial stimuli, four tasks were constructed from 21 photographs of faces representing standardized poses of fundamental emotions. Two tasks were designed to investigate facial identity matching independent of emotion expressed, and two tasks were designed to test emotion recognition and emotion labeling, respectively. Results indicate that while depressed patients differed from controls only on the emotion-labeling task, those with schizophrenia showed deficits on all four tasks when compared with controls and did worse than patients with depression on the emotion tasks. The findings suggest that patients with schizophrenia are impaired on a broader range of facial perception skills than those with depression, when compared with controls.

Dosage of haloperidol for schizophrenia.

Eighty-seven newly admitted inpatients with schizophrenia were randomized to receive 10, 30, or 80 mg/d of oral haloperidol. They were treated under double-blind conditions for 6 weeks, less if their acute symptoms remitted sooner. Survival analysis showed no differences among the three treatments. Side effects were minimal in all three treatment groups, and there were no differences in side effects among the groups. These results suggest that dosages higher than 10 mg/d of haloperidol for most patients have no additional beneficial effect in the treatment of acute or exacerbated schizophrenia.

Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics. I. Relapse rates after one year.

In a simple remitted, nonpsychotic schizophrenics, the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate. There were no differences in relapse rates between the two active drugs, but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally, entirely due to the fact that in 35% of patients receiving fluphenazine decanoate, severe akinesia developed.

Adjunctive imipramine in the treatment of postpsychotic depression. A controlled trial.

The efficacy of adjunctive imipramine hydrochloride treatment for syndromally defined postpsychotic depression was assessed in a six-week, double-blind, placebo-controlled study. All patients had been diagnosed as having schizophrenia or schizoaffective disorder, all were receiving stable doses of fluphenazine decanoate, and all had received benztropine mesylate in an attempt to rule out neuroleptic-induced akinesia. Patients randomized to imipramine therapy fared significantly better in terms of their global improvement and in terms of individual symptoms that are components of the depression syndrome. There were no significant differences in outcome psychosis ratings or side effects. This study indicates the existence of an identifiable syndrome of secondary depression in this patient group that is likely to respond favorably to treatment with adjunctive imipramine.

Prophylactic lithium carbonate with and without imipramine for bipolar 1 patients. A double-blind study.

The efficacy of lithium carbonate plus imipramine hydrochloride vs lithium carbonate plus placebo in preventing relapse was assessed in a prospective, random-assignment double-blind study of 75 bipolar 1 patients. Outcome measures included type of relapse, time until relapse, and subsequent illness course. Infrequent depression relapse in either treatment group precluded any demonstration of an advantage of adding imipramine to a lithium carbonate regimen. There was little evidence that the combination of lithium carbonate and imipramine caused adverse reactions. However, interactions between type of most recent episode, treatment condition, sex, and type of relapse showed that women and mania-prone patients treated with imipramine had an increased risk of mania. Life table analysis showed that the overall probability of remaining well was the same for both treatment groups and that two thirds of all relapses occurred in the first six months.

Long-acting oral vs injectable antipsychotic drugs in schizophrenics: a one-year double-blind comparison in multiple episode schizophrenics.

Sixty patients meeting the criteria established for schizophrenia who attained a clinical plateau following hospital discharge were randomized to receive for one year either penfluridol, 20 to 160 mg orally once each week, or fluphenazine decanoate, 0.5 to 4 ml every two weeks. The relapse rate for both treatments was low and equal. The rate of recurrence of psychosis for patients receiving penfluridol was 7% and for those receiving fluphenazine decanoate 10%. A retrospective comparison of the penfluridol group was made to a similar group of patients assigned to placebo in an earlier study. Placebo-treated patients had a relapse rate of 68%. Penfluridol patients had statistically fewer psychotic relapses. Questions about the possible carcinogenicity of penfluridol in animals will have to be resolved before it can be widely used. This study demonstrates the feasibility of using an oral, long-acting antipsychotic agent. It would be a useful psychopharmacologic addition in the treatment of outpatient schizophrenics.

Low-dose neuroleptic treatment of outpatient schizophrenics. I. Preliminary results for relapse rates.

In an attempt to begin to establish minimum effective dosage requirements for the maintenance treatment of schizophrenia, we undertook a double-blind comparison of low-dose fluphenazine decanoate (1.25 to 5.0 mg/2 wk) with the standard-dose regimen (12.5 to 50.0 mg/2 wk) in outpatient schizophrenics. For the first 126 patients studied, cumulative relapse rates at one year for the low dose were 56% and for the standard dose 7%, a significant difference. Despite the fact that very little dyskinetic symptomatology developed in the sample as a whole, the low-dose treatment appeared to have a significant advantage in producing fewer early signs of tardive dyskinesia. Severity of relapse and total cumulative dosage were also considered.

Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness: a prospective, placebo-controlled comparison.

Twenty-seven patients with recurrent unipolar depression and 22 with bipolar II illness in remission for at least six months were randomly assigned on a double-blind basis to treatment regimens using lithium carbonate, imipramine hydrochloride, lithium carbonate plus imipramine, or placebo. Lithium carbonate was found to help prevent depressive relapse among patients with unipolar disease, and relapse of any type among those with bipolar II disease. No effect or interaction of imipramine was found in either group. These results add to a growing body of data that suggest the usefulness of lithium carbonate in the prophylaxis of unipolar depressive illness. The relative usefulness of lithium carbonate and imipramine requires further study.

Fluphenazine vs placebo in patients with remitted, acute first-episode schizophrenia.

Twenty-eight patients who had recently recovered from an acute-onset, first-episode schizophrenic illness were randomly given fluphenazine hydrochloride or decanoate or placebo for a one-year period in a double-blind study. Seven of 17 patients(14%) receiving placebo experienced a psychotic relapse, whereas none of 11 drug-treated patients experienced a relapse. Eighteen (69%) of the 26 patients available for follow-up (mean interval, 3.5 years) experienced a second psychotic relapse either during the study or afterward, and 50% (14/28) of the original sample experienced a third episode.

Attitudinal changes of involuntarily committed patients following treatment.

Thirty-five involuntarily hospitalized psychiatric patients were interviewed immediately following admission and again prior to discharge to assess attitudinal changes and their relationship to patient characteristics and treatment outcome. The results indicate significant changes toward recognition of the original need for involuntary treatment. Those patients achieving remission of symptoms were most likely to have positive attitudes. Follow-up data indicate that the majority continued to receive outpatient treatment after the index episode, and among those readmissions that occurred, 92% were voluntary.

Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. I. Efficacy in short-term treatment.

Following promising preliminary evidence, the benzodiazepine-derivative alprazolam was studied in a large, placebo-controlled, eight-week, flexible-dose trial in patients with agoraphobia with panic attacks and panic disorder. Of 526 patients, 481 completed three weeks of treatment; however, significantly more placebo (102/234) than alprazolam (21/247) recipients subsequently dropped out of the trial, primarily citing ineffectiveness (of placebo) as the reason. Alprazolam was found to be effective and well tolerated. There were significant alprazolam-placebo differences in improvement for (1) spontaneous and situational panic attacks, (2) phobic fears, (3) avoidance behavior, (4) anxiety, and (5) secondary disability, all significant by the end of week 1. At the primary comparison point (week 4), 82% of the patients receiving alprazolam were rated moderately improved or better vs 43% of the placebo group. At that point, 50% of the alprazolam recipients vs 28% of placebo recipients were free of panic attacks.

Secondary depression in panic disorder and agoraphobia. I. Frequency, severity, and response to treatment.

Depressive symptomatology in 481 subjects with panic disorder and phobic avoidance was studied as part of an investigation of the efficacy of alprazolam in panic disorder. Subjects who had a major depressive episode (MDE) before the onset of their panic disorder were not included in the trial. With this exclusion criterion, 31% of subjects had a secondary MDE occurring after the onset of the panic disorder. The occurrence of secondary MDE was related to the length of time subjects were ill with panic disorder. Compared with the subjects without depression, those subjects with current MDE had higher scores on measures of anxiety and depression but not on the number of panic attacks per week. The presence of depression and the degree of phobic avoidance contributed independently to measures of the severity of the panic illness. Alprazolam was effective in reducing panic and depressive symptomatology in both depressed and nondepressed subjects with panic disorder. The presence of an MDE was not predictive of the outcome of treatment for the panic and phobic symptoms. Subjects with or without depression responded similarly to alprazolam.

Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. II. Patient acceptance, side effects, and safety.

In a multicenter placebo-controlled study, the safety, side effects, and patient acceptance of alprazolam for the treatment of panic disorder and agoraphobia were examined. A total of 525 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder were randomly assigned to receive alprazolam or placebo, which they took for eight weeks. The mean daily dose at the end of the study was 5.7 mg of alprazolam or 7.5 capsules of placebo daily. Potentially serious reactions to alprazolam occurred in ten of 263 subjects who received the drug. These included acute intoxication (three), hepatitis (two), mania (two), amnesia (one), aggressive behavior (one), and depression (one). Treatment-related side effects that were worse in patients taking alprazolam than in those taking placebo included sedation, fatigue, ataxia, slurred speech, and amnesia. Sedation was the most frequent but tended to subside with dose reduction or continued administration of the drug. Patient acceptance of alprazolam, as measured by the rate of completion for study participants, was high. Eighty-four percent of patients receiving active drug completed the study compared with 50% receiving placebo.

The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics.

Thirty-six remitted schizophrenics who participated in an outpatient study of fluphenazine decanoate or oral fluphenazine vs placebo given for a year were examined for the effect of drug treatment upon social and vocational functioning. Only the period prior to any clinical relapse was evaluated. We found no difference between those on drug or placebo, and conclude that antipsychotic drugs, at least in the context of an aftercare clinic offering a rich spectrum of nonpharmacological services, and when combined with antiparkinson medication, do not interfere with social and vocational functioning.