Postpsychotic depressive symptoms in hospitalized schizophrenic patients.

Through chart review, we examined the incidence of depression-like symptoms and syndromes during the postpsychotic period of hospitalization in 50 patients whose conditions were diagnosed by Research Diagnostic Criteria (RDC) as being schizophrenia. Twenty patients (40%) reported experiencing substantial subjective sadness, and 17 (34%) were observed by staff to appear depressed. In 11 (22%), symptoms were noted in a pattern that would satisfy RDC for a minor depressive syndrome, and in an additional three patients (6%) the symptom pattern met criteria for a major depressive syndrome. These findings indicate that postpsychotic depressive symptomatology occurs relatively often in patients with schizophrenia diagnosed by stringent criteria, but that full syndromal manifestations of depression occur less frequently.

Use of antidepressant drugs in schizophrenia.

This review surveys the therapeutic efficacy of tricyclic antidepressants and monoamine oxidase inhibitors in schizophrenic patients. In general, the use of these drugs alone was found not to be warranted in schizophrenia, except perhaps in the so-called pseudoneurotic subgroup. In most cases, combinations of antidepressants and phenothiazines were not more beneficial than phenothiazines alone. In particular, the conditions of agitated patients and patients with histories of social deviance dating back to childhood were often made worse by the addition of an antidepressant. However, when the patients who demonstrated symptoms of clinical depression other than anergia were isolated from several of these studies, it was found that they constituted a subgroup that was often benefited by use of these combinations. Favorable and unfavorable clinical response patterns are discussed, and recommendations for future research are outlined.

Depression and immunity. Lymphocyte function in ambulatory depressed patients, hospitalized schizophrenic patients, and patients hospitalized for herniorrhaphy.

Mitogen-induced lymphocyte stimulation responses in ambulatory patients with major depressive disorder did not differ from those of matched controls. Lymphocyte responses in hospitalized schizophrenic patients and in patients hospitalized for elective herniorrhaphy similarly did not differ from responses of controls. The number of peripheral-blood T cells was decreased among the ambulatory depressed patients but not in the schizophrenic patients. These findings, together with previously reported decreased lymphocyte function in hospitalized depressed patients, suggest that decreased lymphocyte function is associated specifically with depression and not related to hospital effects or nonspecifically to other psychiatric disorders. The results also suggest that altered immunity in depression may be related to severity of depressive symptoms.

Maintenance imipramine therapy for secondary depression in schizophrenia. A controlled trial.

BACKGROUND: Although recent studies have documented the benefit of adjunctive antidepressant medication for the short-term treatment of certain patients with operationally defined syndromes of postpsychotic depression, the value of maintenance adjunctive antidepressant treatment in this circumstance has not been properly established. METHODS: This study examined 24 schizophrenic or schizoaffective patients with postpsychotic depression or negative symptoms. These patients had all been benefited over the short term by the addition of adjunctive imipramine hydrochloride to their ongoing fluphenazine decanoate/benztropine mesylate regimens, and this adjunctive treatment had been successfully continued for 6 months. In a randomized double-blind protocol, treatment with adjunctive imipramine hydrochloride (mean, 233 +/- 72 mg/d) was then either maintained or tapered to placebo for an ensuing 1-year trial, while treatment with fluphenazine and benztropine continued. RESULTS: Significantly more patients who received placebo substitution relapsed into depression (P < .001). Patients who received placebo substitution were also more likely to experience relapses into psychosis (P < .02). CONCLUSIONS: These results support the clinical value of maintenance adjunctive imipramine therapy among initially responsive patients with postpsychotic depressions.

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.

Plasma norepinephrine and dopamine-beta-hydroxylase activity in schizophrenia.

Plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) activity may be altered by changes in posture, pulse rate, and BP. Twenty-three drug-free schizophrenic, ten schizoaffective, and 24 normal control subjects, and a separate group of eight schizophrenic patients treated with chlorpromazine hydrochloride and haloperidol comprised the sample. Drug-free schizophrenic patients showed higher plasma NE levels while standing and higher pulse rates when supine and standing than normal subjects. Following chlorpromazine therapy, but not following haloperidol treatment, plasma NE level increased with patients supine and standing, pulse rate increased with patients standing, and systolic BP decreased with patients standing. These findings suggest (1) a decreased peripheral alpha-adrenergic postsynaptic receptor sensitivity in schizophrenia and (2) a peripheral alpha-adrenergic blocking mechanism in chlorpromazine-induced hypotension.

Depression in schizophrenia: perspective in the era of "Atypical" antipsychotic agents.

OBJECTIVE: The author sought to provide a contemporary understanding of depression in schizophrenia and promote a treatment orientation. METHOD: Computer and library-based resources were used to review the literature on depression in schizophrenia. RESULTS: Despite multiple definitions of "depression," a substantial rate of depression has consistently been found in patients with schizophrenia. A differential diagnosis can be used to advance the understanding and treatment of depression in schizophrenia, and changes in response to the advent of atypical antipsychotic agents can be understood in the context of this differential diagnosis paradigm. CONCLUSIONS: Depression is an important co-occurring syndrome in schizophrenia. In at least some schizophrenic patients, the stress-vulnerability model has potential as an integrating concept concerning the relationship between depression and psychosis.

Comparative side effects of imipramine, benztropine, or their combination in patients receiving fluphenazine decanoate.

Patients receiving fluphenazine decanoate who were switched from adjunctive benztropine to imipramine in a double-blind trial experienced marked exacerbations of extrapyramidal side effects. No substantial increase in anticholinergic side effects occurred, however, when imipramine was added to fluphenazine decanoate and benztropine.

Intrapsychic structural effects of psychiatric research.

The authors observed that many psychotic patients on a clinical/research ward incorporated various aspects of research organization into their own evolving intrapsychic structures. This process had either beneficial or deleterious clinical effects, depending on the attributes of the research and the specific mental functions to which these attributes became attached. The observations resulted in the development of a set of recommendations for maximizing the therapeutic usefulness of this phenomenon and minimizing its countertherapeutic drawbacks.

Adjunctive imipramine maintenance treatment in schizophrenic patients with remitted postpsychotic depression.

Ten patients with histories of postpsychotic depression responsive to adjunctive imipramine added to fluphenazine decanoate and benztropine underwent a double-blind trial of imipramine discontinuation 6 months after responding to the adjunctive imipramine. Discontinuation of imipramine was associated with depressive relapse.

Exacerbation of schizophrenia associated with amantadine.

Administration of amantadine was associated with psychotic decompensations in two schizophrenic patients being maintained on concomitant neuroleptic medication. Despite a postulated dopaminergic mechanism, there seems to have been only one previous report of amantadine's precipitating psychosis in a schizophrenic patient.

Stages of onset of schizophrenic psychosis.

On the basis of a review of the literature describing the process of schizophrenic illness, the authors conclude that schizophrenic psychosis is one stage in a process of psychological and biological breakdown that has a specific structure and a characteristic unfolding consisting of the sequential appearance of hierarchically ordered, distinguishable, and recognizable psychological states. They present on illustrative case history of a patient who was able to describe her feelings during the process of decompensation to schizophrenic psychosis and two case histories of patients whose decompensations were rated according to the authors' State of Illness Rating Scale.

Changing patterns of neuroleptic dosage over a decade.

A study of patterns of neuroleptic dosage for 206 schizophrenic inpatients showed significant differences over time and among three centers--a general hospital psychiatric unit, a community mental health center, and a state hospital. In 1982 patients' mean dose at discharge was higher than the peak mean daily dose in 1973, and high-potency neuroleptics were being used almost exclusively. The mean length of stay decreased from 49 days in 1973 to 34 days in 1982. The possible relationship, if any, between increasing dosage, decreased length of stay, and the switch from low-potency to high-potency neuroleptics remains undetermined.

Psychotherapy and pharmacotherapy: conceptual lenses.

Of the many difficulties in maintaining an integration of psychotherapeutic and pharmacotherapeutic treatment, one of the most important is "the problem of bimodal relatedness", that is, the distinction between relating to the patient as a diseased organ or object of study and as a disturbed person. The authors identify the forces that act to inappropriately emphasize one mode or the other and discuss major difficulties that arise because of failure to maintain a bimodal relatedness. In a setting of combined therapy, maintaining and safeguarding the optimal relationship of collaborative subject-subject relatedness can prevent the emergence of problem destructive to effective psychiatric treatment and research.

Depression in first-episode schizophrenia.

OBJECTIVE: Because findings regarding the prognostic significance of depressive symptoms in schizophrenia and their effect on the course and treatment of schizophrenia have been limited by the effects of previous treatment, retrospective evaluations, and differing definitions and criteria, the authors sought to determine the prevalence and prognostic significance of depressive symptoms in first-episode schizophrenia. METHOD: Thirty-nine men and 31 women experiencing their first episode of schizophrenia were evaluated with behavioral and extra-pyramidal symptom scales before treatment (baseline), biweekly during acute treatment, and then monthly. Extracted scores on the Hamilton Rating Scale for Depression and a "syndromal" definition of depression based on Research Diagnostic Criteria were obtained. Patients were followed prospectively for up to 5 years and received open standardized treatment. RESULTS: The prevalence of depressive symptoms at baseline ranged from 75% (patients who met extracted Hamilton and/or syndromal criteria) to 22% (patients who met both criteria). Of 808 psychotic ratings given to the 70 patients over a 5-year follow-up period, 210 (26%) were concurrently rated as depressed; of the 1,754 nonpsychotic ratings, only 70 (4%) were concurrently rated as depressed. Of the 210 depressive symptoms that occurred concurrently with psychosis, 206 (98%) resolved as the psychosis remitted. Depressive symptoms were prodromal to a psychotic relapse in only two (7%) of 27 patients who relapsed. Depressive symptoms correlated more with positive and negative symptoms than with extrapyramidal symptoms. CONCLUSIONS: These findings suggest that depressive symptoms in patients experiencing their first episode of schizophrenia may represent a core part of the acute illness or may occur as a subjective reaction to the experience of psychotic decompensation. Since most of the depressive symptoms resolved as the psychosis remitted, antidepressant therapy should be limited to patients in whom the depression persists.

Postpsychotic depression and negative symptoms: an investigation of syndromal overlap.

The authors studied 46 patients with the operationally defined syndrome of postpsychotic depression following episodes of schizophrenia or schizoaffective disorder. Half of these patients were also found to satisfy criteria for negative symptoms. The patients with negative symptoms were rated as more severely ill on global measures, but there was only limited evidence that they were more depressed. Nevertheless, in a randomized double-blind trial of imipramine versus placebo as an adjunct to the fluphenazine decanoate and benztropine regimens of the patients with negative symptoms, the patients who received imipramine seemed to show more improvement.

Course-related depressive syndromes in schizophrenia.

The authors evaluated 20 patients, diagnosed by Research Diagnostic Criteria after 1 week of hospitalization as having schizophrenia, weekly throughout their hospitalization. Four patients developed syndromes of depression after resolution of their psychoses: three manifesting a "minor" and one a "major" postpsychotic depressive syndrome. Four other patients went on to develop syndromes equivalent to major depression at a time when they were still actively psychotic, and their cross-sectional diagnoses were therefore changed to schizoaffective disorder, depressed type. The authors discuss the implications of these findings for diagnosis.

Effects of dopamine blockade on gonadotropins and testosterone in men.

The authors found that plasma luteinizing hormone (LH), prolactin, and testosterone were initially normal in nine acutely psychotic males with schizophrenia or schizo-affective disorder; follicle-stimulating hormone (FSH) was normal in eight of the nine. When patients were treated with pimozide, a relatively specific dopamine receptor blocker, there were statistically significant declines in FSH and LH, although levels remained within normal limits. Prolactin rose significantly, but testosterone did not change. The observed reductions in FSH and LH concentrations are consistent with the hypotheses that dopamine and/or prolactin play a role in gonadotropin secretion. The maintenance of normal levels of gonadotropins and testosterone, however, suggests that these patients possessed relatively normal hypothalamic-pituitary-gonadal axis function before and during a course of neuroleptic treatment.

Three cases of akathisia and "acting out".

Three cases of akathisia are described in which the manifestations of motor restlessness were subtle enough to be easily missed, but in which the resultant propensities to behavioral "action" nonetheless contributed to significant difficulties for the patients. Appropriate medication adjustments, including adequate treatment with antiparkinsonian agents or suitable lowering of neuroleptic dosage, were beneficial. Subtle manifestations of akathisia of this sort may occur more frequently than is commonly recognized.

Akinesia and postpsychotic depression: a difficult differential diagnosis.

Detailed clinical case descriptions highlight the potential symptomatic overlap between the syndromes of akinesia and postpsychotic depression in neuroleptic-treated patients. The cases demonstrate that both syndromes may resemble major depression phenomenologically. However, the syndromes are not identical in medication response. Thus, differential medication response may potentially be a useful tool in teasing apart the various postpsychotic depressionlike states in the course of schizophrenia or schizoaffective disorder.