Clinical issues related to depression in schizophrenia: an international survey of psychiatrists.

OBJECTIVE: Depressive symptoms in schizophrenia are associated with a substantial morbidity and mortality burden. The 'International Survey of Depression in Schizophrenia' was designed to evaluate current awareness and clinical approaches in this area. METHOD: A 48-item questionnaire was distributed to approximately 80 000 consultant psychiatrists world-wide. Responses were analysed using descriptive statistics. RESULTS: Respondents demonstrated considerable awareness of the prevalence and consequences of depression in schizophrenia. Although there was widespread adjunctive use of antidepressants, one-third of respondents indicated that they rarely or never prescribe these agents in combination with antipsychotic medication. There were considerable variations in opinions about the best approach to the treatment of depressive symptoms associated with schizophrenia. CONCLUSION: The considerable clinical burden of depressive symptomatology in schizophrenia was acknowledged by the majority of respondents to this survey. There was, however, little agreement on the best management strategy.

Suicide and schizophrenia.

Suicide and suicide attempts occur at a significantly greater rate in schizophrenia than in the general population. Common estimates are that 10% of people with schizophrenia will eventually have a completed suicide, and that attempts are made at two to five times that rate. Demographically associated with suicidality in schizophrenia are being young, being early in the course of the illness, being male, coming from a high socioeconomic family background, having high intelligence, having high expectations, not being married, lacking social supports, having awareness of symptoms, and being recently discharged from the hospital. Also associated are reduced self-esteem, stigma, recent loss or stress, hopelessness, isolation, treatment non-compliance and substance abuse. Clinically, the most common correlates of suicidality in schizophrenia are depressive symptoms and the depressive syndrome, although severe psychotic and panic-like symptoms may contribute as well. This review specifically explores the issue of depression in schizophrenia, in relation to suicide, by organizing the differential diagnosis of this state and highlighting their potentially treatable or correctable causes. This differential diagnosis includes both acute and chronic disappointment reactions, the prodrome of an acute psychotic episode, neuroleptic induced akinesia and akathisia, the possibility of direct neuroleptic-induced depression, negative symptoms of schizophrenia, and the possible co-occurrence of an independent depressive diathesis. The potential beneficial roles of 'atypical' antipsychotic agents, including both clozapine and more novel agents, and adjunctive treatment with other psychopharmacological medications are considered, and the important roles of psychosocial factors and interventions are recognized.

Depression in schizophrenia: recognition and management in the USA.

The recognition of depression as a distinct syndrome within schizophrenia is a relatively recent development. The International Survey of Depression in Schizophrenia was designed to evaluate current clinical practice and prescribing trends in the management of the depressive component of schizophrenia. A 48-item questionnaire, comprising fixed-response questions and questions stimulated by case scenarios, was distributed to 37513 psychiatrists in the USA. A total of 43484 psychiatrists in Canada, Australia and 21 European countries also received the questionnaire. A total of 1128 US psychiatrists responded. Analysis of the data revealed that US psychiatrists identify symptoms of depression in approximately one-third of patients with schizophrenia, and largely appreciate the magnitude of the resultant burden on patients and their families. Responses to questions regarding treatment approaches and case scenarios demonstrated that the level of adjunctive prescribing of antidepressants in the USA is often higher than in other regions. Levels of awareness of depression in patients with schizophrenia and recognition of the need for effective management appear to be high among US psychiatrists. However, more than a quarter of these specialists rarely or never prescribe adjunctive antidepressant medications. Disparities in treatment approaches varying from the existing scientific evidence base underscore the need for further investigation into ways of optimizing the management of this serious coexisting condition.

Hierarchical diagnosis in chronic schizophrenia: a clinical study of co-occurring syndromes.

Co-occurring or associated psychiatric syndromes (APS) such as depression, obsessive-compulsive disorder (OCD), and panic disorder have largely been hidden from view by exclusion rules that prohibit their being diagnosed in the presence of schizophrenia. This article presents data from a clinical study of APS in chronic schizophrenia and reviews the relevant literature. Thirty-seven chronic schizophrenia patients consecutively admitted to a day program were administered the Structured Clinical Interview for Diagnosis for DSM-IV and the Yale-Brown Obsessive Compulsive Scale symptom checklist. Exclusion rules prohibiting the diagnosis of APS were bypassed. Eighteen patients (48.6%) had one or more APS. Ten patients (27%) had major depression. Eleven (29.7%) met criteria for OCD. Four patients (10.8%) met criteria for panic disorder. These findings suggest that APS may be common in chronic schizophrenia and that there is a need to study these syndromes' clinical validity, including their treatability. A research plan to study the validity of these syndromes further is discussed.

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.

Clinical trials and tribulations: implementation processes in schizophrenia research outcome.

This article focuses on an area in clinical drug trials for new antipsychotic medications for the treatment of schizophrenia which has not received sufficient attention in the literature: the day-to-day implementation tasks performed by research staff which have potential effects on study results. Implementation tasks are viewed as dynamic processes involving interactions among research and nonresearch staff, patients, families, and pharmaceutical company staff. Research-related demands and possible sources of stress for all participants in the process, such as recruiting and maintaining patients in studies, are discussed. Suggestions are offered for increasing the ease of participation. Further investigation is called for in several areas including variability in the effectiveness of research teams and in the rarely discussed interactions between site staff and pharmaceutical company personnel, as they may affect research outcomes. It is posited that increased knowledge about implementation processes in schizophrenia drug development is needed to more fully understand study results and to enhance patients' and their families' willingness to participate.

Cognitive-behavioral treatment of panic attacks in chronic schizophrenia.

Although panic attacks have been described as relatively common in schizophrenia, few studies have examined treatments for this problem. Because cognitive-behavioral therapy (CBT) has demonstrated efficacy for panic disorder without schizophrenia, the authors conducted an open clinical trial of CBT for the treatment of panic attacks in schizophrenic patients. Eight patients meeting DSM-III-R criteria for schizophrenia and panic disorder were given a 16-week clinical trial of CBT. Ratings after treatment demonstrated both a statistically significant reduction in panic symptoms and a diminution in the number of panic attacks compared with baseline ratings. These results suggest use of CBT in the integrated treatment of patients with a diagnosis of schizophrenia and panic disorder is a promising approach that merits further investigation.

Adjunctive loxapine in a clozapine-resistant cohort of schizophrenic patients.

The purpose of this trial was to assess the potential utility of adjunctive treatment with a typical neuroleptic for patients with refractory psychosis insufficiently responsive to clozapine alone. Seven chronic schizophrenic or schizoaffective patients who remained stabilized for at least 9 months on clozapine received open clinical trials with adjunctive loxapine lasting from 18 to 50 weeks. Their symptoms were documented with periodic Brief Psychiatric Rating Scale assessments. All patients improved at least somewhat and two improved remarkably. In the four cases in which the assessment was made, the loxapine had no apparent effect on plasma clozapine levels. We conclude that adjunctive treatment with typical neuroleptics for patients with an incomplete response to clozapine merits further investigation.

Noncompliance with antiparkinsonian medications in neuroleptic-treated schizophrenic patients: three cases of an unreported phenomenon.

BACKGROUND: Depression is commonly associated with the longitudinal course of schizophrenia. Several etiologies for this problem have been proposed but, to our knowledge, noncompliance with antiparkinsonian medications has not been considered. METHOD: Case histories of two patients who were noncompliant and one who threatened noncompliance with antiparkinsonian medications are presented. All three patients were diagnosed with schizophrenia by DSM-III-R criteria and had been clinically stable for long periods. RESULTS: All three patients became depressed when their adjunctive benztropine was stopped, and their depressions remitted when their benztropine was reinstated. CONCLUSION: Noncompliance with antiparkinsonian medications may be associated with a reversible depression in patients receiving maintenance neuroleptics for schizophrenia. Since this is a newly described phenomenon, the scope of the problem is not known; however, it may contribute to the wide prevalence of depressive symptoms in schizophrenia. Clinical measures to facilitate detection of such noncompliance are discussed.

Suicidal ideation in postpsychotic depression.

Although approximately 10% of schizophrenics commit suicide, little is known about the clinical correlates of this behavior. This study investigated the relationships between suicidal ideation, anxiety, and psychosis in a group of schizophrenic and schizoaffective patients with operationally defined cases of postpsychotic depression. Psychosis contributed to the variance in suicidal ideation over and above the effects of depression and anxiety. Treatment and research implications of this finding are discussed.

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 medication in the maintenance treatment of schizophrenia and its conceptual implications.

Beyond the continuing use of neuroleptic medication, psychopharmacological treatment approaches during the maintenance phase of schizophrenia often involve adjunctive medication. Appropriate use of such 'polypharmacy' can be crucial to patients in achieving their optimal levels of symptom management and functional capacity, although the risks of side-effects and medication interactions must be weighed. This paper reviews the use of adjunctive anti-Parkinsonian medication, benzodiazepines, propranolol, antidepressants, lithium, and carbamazepine in this context. It also explores a strategy of identifying secondary syndromes in the longitudinal course of schizophrenia which can be approached psychopharmacologically.

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.

Histories of substance abuse, panic and suicidal ideation in schizophrenic patients with histories of post-psychotic depressions.

1. Forty patients who had had syndromally-defined episodes of post-psychotic depression at least 6 months previously were interviewed in detail for life-time histories of substance abuse, panic attacks, and suicidal ideation. 2. No relationship was found between life-time history of suicidal ideation and substance abuse. 3. Statistically significant associations were found between lifetime history of suicidal ideation and both a life-time history of panic attacks and the panic disorder syndrome.

Adjunctive imipramine in substance-abusing dysphoric schizophrenic patients.

Previous controlled studies have presented evidence that adjunctive tricyclic antidepressant medication may be useful in the treatment of schizophrenic and schizoaffective patients with phenotypic post-psychotic depressions and that tricyclic antidepressants may be useful in the treatment of certain substance-abusing nonschizophrenic patients. The potential value of adjunctive antidepressant medication among substance-abusing dysphoric schizophrenic and schizoaffective patients, however, has not previously been addressed. The present report details the results of carefully controlled adjunctive antidepressant trials among 11 such substance-abusing schizophrenic or schizoaffective patients. The results of this acute treatment trial appeared to be favorable for at least some individuals and can be interpreted in the context of models that heretofore have been advanced for the understanding of this clinical situation.