Olanzapine therapy in treatment-resistant psychotic mood disorders: a long-term follow-up study

BACKGROUND: Recent studies suggest a role for the atypical antipsychotic olanzapine in the acute treatment of psychotic mood disorders, but long-term data are unavailable. The purpose of this naturalistic study was to determine the long-term effectiveness and tolerability of olanzapine as add-on therapy in psychotic mood disorders. METHOD: Hospital records were reviewed for 125 inpatients at the state psychiatric hospital in Buffalo, N.Y., who received at least 6 weeks of add-on olanzapine treatment for psychotic mood disorders (schizoaffective disorders [bipolar and depressive type], bipolar disorders [I, II, and NOS], and major depressive disorder). A group of schizophrenic patients served as a control group (N = 50). Baseline measures, including age, gender, number of hospitalizations in the 2 years prior to olanzapine treatment, concomitant medications, the Clinical Global Impressions scale (CGI), and the Global Assessment of Functioning-Equivalent (GAF-EQ) and Kennedy Axis V psychological impairment, violence, social skills, and activities of daily living subscale scores, were obtained. Follow-up information was obtained from the patients at least 6 months after initiation of olanzapine or by chart review and discussion with the treating psychiatrist. Patients with a diagnosis of psychotic mood disorders were compared with patients with the non-affective psychotic disorder (schizophrenia) on a variety of outcome measures. RESULTS: Follow-up information was available on 102 patients (82%). Mean follow-up was 15 months; 50 (49%) of the 102 patients remained on olanzapine treatment at follow-up (32 psychotic mood disorder, 18 schizophrenic). The primary reason for discontinuation in both groups was lack of response. Both the psychotic mood disorder and schizophrenic groups had comparable outcomes on the CGI and GAF-EQ. Improvement on the Kennedy Axis V psychological impairment and social skills subscales was seen only in the psychotic mood disorders group (p < .01); both groups showed significant (p < .02) improvement in the violence subscale. Sustained mood-stabilizing effect was evident in only 7/27 (26%) of the psychotic mood disorders patients continuing on add-on olanzapine treatment at follow-up. CONCLUSION: Lack of response was the primary reason for discontinuation of add-on olanzapine in both groups. Mood symptoms predicted a better response to add-on olanzapine in patients with psychotic mood disorders on selective outcome measures. However, only 26% of the patients with psychotic mood disorders sustained a clinically meaningful mood-stabilizing effect with add-on olanzapine treatment at follow-up.     

Prospective study of adolescents with subsyndromal psychosis: characteristics and outcome

OBJECTIVE: The aim of this study was to examine the characteristics and outcome of adolescents with psychotic disorder not otherwise specified (PsyNOS) and brief psychotic disorder (BrPsy), two neglected subsyndromal diagnostic entities. METHODS: As part of an ongoing, naturalistic study investigating adolescents considered to be prodromal for schizophrenia, 29 youngsters (mean age, 16.2 +/- 2.7 years) with PsyNOS or BrPsy were identified as theoretically at highest risk for schizophrenia and followed for over 6 (mean, 22.8 +/- 19.4) months. RESULTS: Contrary to our expectations, only 7 of the 26 individuals (27.0%) with follow-up data developed schizophrenia or schizoaffective disorder, and only 2 subjects (7.7%) retained their diagnosis of BrPsy/PsyNOS. The most frequent other diagnoses at follow-up were mood disorders (34.6%), personality disorders (11.5%), and obsessive-compulsive disorder (7.7%). Regarding severity of outcome, 38.5% of the patients progressed to a syndromal psychotic disorder, 23.1% continued to have attenuated positive symptoms, and 38.4% improved to having attenuated negative symptoms only, or no positive or negative symptoms. BrPsy was associated with lower maximum levels of negative symptoms (p = 0.02) and higher likelihood of symptom remission (p = 0.02). CONCLUSIONS: This study indicates that psychotic symptoms not fulfilling criteria for schizophrenia or a psychotic mood disorder are unreliable predictors of a syndromal psychotic disorder outcome at 2 years. Long-term studies of PsyNOS and BrPsy are needed to clarify where these disorders fall in the developmental course of schizophrenia.     

An overview of the genetics of psychotic mood disorders

This article presents a conceptual review of the genetic underpinnings of psychotic mood disorders. Both unipolar and bipolar forms of mood disorder sometimes feature psychotic symptoms. Some evidence from epidemiological research suggests that psychotic forms of mood disorder specifically might be heritable. Linkage studies of mood disorders in general have also provided some support for that notion, as have associated studies involving serotonin and dopamine genes and psychotic mood disorder. Some research suggests there might be a genetic connection between schizophrenia and bipolar disorder, undermining the Kraepelinian dichotomous classification of the psychoses. Future research should continue to examine psychotic forms of mood disorder using both epidemiological and molecular approaches.     

Multiple anxiety disorder comorbidity in patients with mood spectrum disorders with psychotic features

OBJECTIVE: The authors investigated frequencies and clinical correlates of multiple associations of panic disorder, obsessive-compulsive disorder (OCD), and social phobia in patients with severe mood disorders. METHOD: Subjects were 77 consecutively hospitalized adults with psychotic symptoms and with a diagnosis of bipolar I disorder, major depression, or schizoaffective disorder, bipolar type. Principal diagnosis and comorbidity were assessed by the Structured Clinical Interview for DSM-III-R-Patient Version. RESULTS: Of the entire cohort, 33.8% had a single anxiety disorder and 14.3% had two or three comorbid diagnoses. Patients with multiple comorbidity had significantly higher scores on the Brief Psychiatric Rating Scale and SCL-90 and abused stimulants more frequently than did those without anxiety disorders. CONCLUSIONS: Multiple associations of panic disorder, OCD, and social phobia are not rare among patients with affective psychoses and are likely to be associated with more severe psychopathology than is found in patients without anxiety disorders.     

Twelve-month follow-up of family communication and psychopathology in children and adolescents with a first psychotic episode (CAFEPS study)

We analyzed the potential influence of family relationships and history of psychiatric disorders on the presentation and course of early psychotic disorders. We recruited 110 subjects aged 9–17 years with a first psychotic episode and 98 matched healthy controls, and followed them for 1 year. Data were collected through clinical interviews and the Parent–Adolescent Communication Inventory. A family history of psychosis-related disorders was more common in patients' families, with a five-fold higher risk for psychoses related disorders than families of healthy controls. If we consider psychoses related disorder in first-degree relatives, the risk is even higher, rising to 15-fold. The families of patients with a first psychotic episode score themselves worse in communication than the families of healthy controls. More problems in communication at baseline correlated with a higher degree of psychopathology and a lower clinical improvement after 12 months of follow-up.     

Bridging the gap between schizophrenia and psychotic mood disorders: Relating neurocognitive deficits to psychopathology

BackgroundThe neurobiological relationship between schizophrenia and psychotic mood disorders is not well understood. Neurocognitive deficits have been described in both types of disorders and have been proposed to reflect underlying neurobiological dysfunction. Examining the relationship between neurocognitive function and psychopathology could help illuminate the neurobiological relationship between schizophrenia and psychotic mood disorders.MethodsParticipants included 72 individuals with DSM-IV schizophrenia, 25 individuals with schizoaffective disorder or bipolar disorder with psychotic features, and 72 community controls. Standardized scores and correlations between four domains of neurocognition and psychopathology were examined.ResultsIndividuals with schizophrenia and psychotic mood disorders scored similarly on several dimensions of neurocognitive function and psychopathology. The relationships between neurocognitive function and psychopathology were similar in the two groups.ConclusionsIndividuals with schizophrenia and psychotic mood disorders were similar in terms of both the level of impairment in neurocognitive function and psychopathology, as well as in the relationship between the two dimensions of illness. These results suggest that schizophrenia and psychotic mood disorders such as schizoaffective disorder and bipolar disorder with psychotic features are on a neurobiological continuum.     

Is the psychopathology of acute and transient psychotic disorder different from schizophrenic and schizoaffective disorders?

OBJECTIVE: This study explores psychopathological aspects of acute and transient psychotic disorders (ATPD), a diagnostic category introduced with ICD-10, to elucidate its relationship with schizophrenia and schizoaffective psychoses. METHODS: We recruited all consecutive inpatients fulfilling the ICD-10 criteria of ATPD (F23) during a 5-year period as well as control groups with "positive" schizophrenia (PS) and bipolar schizoaffective disorder (BSAD) matched for gender and age at index episode. For the evaluation of psychopathological parameters during index episode a standardized symptom list was used. Prepsychotic (prodromal) symptoms were also assessed. RESULTS: During the prepsychotic period few differences between the groups were detected. The most important difference between ATPD and the other two other psychotic disorders regarding phenomenology of the full-blown episodes was a higher frequency of "rapidly changing delusional topics", "rapidly changing mood" and anxiety in ATPD. CONCLUSION: ATPD show a characteristic psychopathological picture consistent with earlier concepts such as cycloid psychoses and bouffée délirante. Nevertheless, psychopathology alone is not enough to establish ATPD as an independent nosological entity.     

Schizoaffective disorders are psychotic mood disorders; there are no schizoaffective disorders

Schizoaffective disorder (SA D/O), introduced in 1933 by Dr. Jacob Kasanin, represented a first, modest change in our concept about the diagnoses of psychotic patients away from the beliefs of E. Bleuler, i.e., that hallucinations and delusions define schizophrenia, and toward the recognition of a significant role for mood disorders. SA D/O established a connection between schizophrenia and mood disorders, traditionally considered mutually exclusive, a connection that has strengthened progressively toward the diagnostic unity of all three disorders. A basic tenet of medicine holds that if discrepant symptoms can be explained by one disease instead of two or more, it is likely there is only one disease. The scientific justification for SA D/O and schizophrenia as disorders distinct from a psychotic mood disorder has been questioned. The "schizo" prefix in SA D/O rests upon the presumption that the diagnostic symptoms for schizophrenia are disease specific. They are not, since patients with severe mood disorders can evince any or all of the "schizophrenic" symptoms. "Schizophrenic" symptoms mean "psychotic" and not any specific disease. These data and a very low interrater reliability for SA D/O suggest that the concepts of SA D/O and schizophrenia as valid diagnoses are flawed. Clinically SA D/O remains popular because it encompasses both schizophrenia and psychotic mood disorder when there is a diagnostic question. We present a review of the literature in table form based on an assignment of each article assigned to one of five categories that describe the possible relationships between SA D/O, schizophrenia and psychotic mood disorders. We conclude that the data overall are compatible with the hypothesis that a single disease, a mood disorder, with a broad spectrum of severity, rather than three different disorders, accounts for the functional psychoses.     

Course and outcome in paranoid disorders.

All consecutively admitted patients suffering from paranoid psychoses and admitted to the Department of Psychiatry, University of Oslo, during two defined periods (1946-1948 and 1958-1961) have been personally followed up by the author after 5-18 years and by Stein Opjordsmoen after 22-39 years. After the first follow-up period 65% were without psychotic symptoms, after the last period 44%. According to Scandinavian diagnostic tradition, there is a gradual shift from very good clinical and social outcome for patients with reactive psychoses to very poor outcome for schizophrenics, patients with schizophreniform psychoses being in between. According to the DSM-III system, patients with affective and schizoaffective psychoses score best, followed by those with paranoid and schizophreniform disorders. Those with schizophrenia score worst. Course and outcome are primarily dependent on the diagnostic category, not the type of delusion. Of the patients with Kraepelin's paranoia, about one-third were without psychotic symptoms at last follow-up.     

Schizophreniform disorder,delusional disorder and psychotic disorder not otherwise specified: clinical features,outcome and familial psychopathology

The relationship between DSM-III-R schizophreniform disorder, delusional disorder (DD) and psychotic disorder not otherwise specified (PD-NOS) and schizophrenia and affective illness (AI) remains uncertain. We explore this question in the Roscommon Family Study by examining symptoms, outcome and patterns of psychopathology in relatives. Probands were selected from a population-based case registry in the west of Ireland with an ICD-9 diagnosis of schizophrenia or AI. Personal interviews were conducted with 88% of traceable, living probands, a mean of 16 years after onset, and 86% of traceable, living first-degree relatives. Best-estimate diagnoses were made at follow-up. Schizophreniform disorder, DD and PD-NOS constituted 6.4%, 2.8% and 7.5%, respectively, of all probands with a registry diagnosis of schizophrenia. Probands with schizophreniform disorder had prominent positive psychotic symptoms, negligible negative symptoms and a good outcome, comparable to that seen in AI probands. Their relatives had an excess risk of schizophrenia spectrum illness but not AI. Probands with DD had prominent delusions but no other psychotic symptoms, few negative symptoms, fair to good outcome and an increased risk in relatives for alcoholism. Probands with PD-NOS had both moderate positive and negative psychotic symptoms, a poor to fair outcome and a substantially elevated risk in relatives of schizophrenia and schizophrenia spectrum disorders but not AI. These results suggest that i) DSM-III-R criteria for schizophreniform disorder define a good outcome disorder with prominent positive psychotic symptoms that probably has a familial relationship to schizophrenia, but not AI; ii) DD is a rare, monosymptomatic psychosis that may have a modest etiologic relationship with alcoholism, but probably not with schizophrenia or AI and iii) PD-NOS is probably heterogeneous but, of these 3 disorders, most closely resembles schizophrenia with respect to symptoms, outcome and familial psychopathology. These results should be seen as tentative given the small number of probands and relatives evaluated.     

A follow-up study of early onset psychosis: Comparison between outcome diagnoses of schizophrenia,mood disorders,and personality disorders

This study examined the outcome of youth previously diagnosed with psychotic disorders at a public-sector tertiary care hospital. Of 95 children and adolescents retrospectively identified, follow-up information (mean interval 3.9 years) was obtained on 24 subjects with an outcome diagnosis of schizophrenia, 9 with psychotic mood disorders, 5 with personality disorders (antisocial or borderline), and 1 with schizo-affective disorder. The schizophrenic group was more often odd premorbidly and functioned worse at outcome, while the mood-disordered group had a shorter follow-up period and was more often anxious or dysthymic premorbidly. The personality-disordered group resembled the schizophrenics in their degree of impairment and chronicity. All three groups had high rates of family disruption, low SES, substance abuse, and chronicity, and were similar in their degree of premorbid impairment, length of prodrome, age of onset, initial diagnosis, and family psychiatric history. Misdiagnosis at onset was quite common and highlights the need for systematic longitudinal assessment of early onset psychotic disorders.This study was funded in part by a grant from the Washington Institute for Research and Training.     

Conversion disorder in children and adolescents: a 4-year follow-up study

OBJECTIVE: To assess the outcome of conversion disorder in children and adolescents and to identify factors affecting the prognosis. METHOD: Forty adolescents with conversion disorder were reevaluated 4 years after their initial interview. Changes in demographic and clinical data and the presence of any mood and anxiety disorders were recorded using the Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I). In addition, Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) were applied. RESULTS: Thirty-four patients (85%) had completely recovered from their conversion symptoms and two patients had improved (5%), whereas only four (10%) were unchanged. Fourteen (35%) patients received the diagnosis of mood and/or anxiety disorder. Favourable outcome was associated with early diagnosis (P=.04) and good premorbid adjustment (P=.01). CONCLUSION: Conversion disorder has a favourable outcome in children and adolescents. However, mood and/or anxiety disorders are encountered at a considerable rate in these patients even after recovery from conversion symptoms. Long clinical follow-up seems appropriate in children and adolescents with conversion disorder.     

Predictors of quality of life in major psychoses: a naturalistic follow-up study

BACKGROUND: Improved quality of life (QOL) of patients suffering from major psychoses has become an important treatment goal. We sought to determine predictors of perceived QOL and to explore the changes that occur regarding QOL among individuals with schizophrenia as compared to patients with schizoaffective/mood disorders. METHOD: In a naturalistic longitudinal design, 148 inpatients with schizophrenia and 51 inpatients with schizoaffective/mood disorders (DSM-IV) were tracked for 16 months (SD = 4.6 months). Subjects were assessed at 2 timepoints for psychopathology, stress process-related factors, and perceived QOL, as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire. Predictors of fluctuations in QOL index scores during the follow-up period were identified using multiple regression techniques. RESULTS: We found that poor QOL is not a more severe problem for schizophrenia patients than for schizoaffective/mood disorder patients. Improved QOL of schizophrenia patients is associated with reduced paranoid and distress (obsessiveness, somatization) symptoms and increased self-efficacy and self-esteem ratings. Individual changes in QOL index scores among patients with schizoaffective/mood disorders are associated with changes in depression, sensitivity, expressed emotion, and task-oriented coping scores. CONCLUSION: Predictors of changes in satisfaction with life quality over time among schizophrenia patients are distinct from those associated with schizoaffective/mood disorders. Changes in stress process-related factors, rather than psychopathology, predict change in perceived QOL and should be considered when evaluating QOL outcomes.     

The Kraepelinian dichotomy: preliminary results of a 15-year follow-up study on functional psychoses: focus on negative symptoms

In a 15-year follow-up study, we used a comparative approach to assess course and outcome for all functional psychoses. The presented results focus on negative symptoms and refer to a sample of 76 patients with schizophrenia, 38 patients with a schizoaffective disorder and 32 patients with an affective disorder according to ICD-9. These patients were assessed at their first psychiatric hospitalization and 15 years later. In summary, the findings indicate that the course and outcome of schizophrenia is less favorable than that of affective and schizoaffective disorders. Negative symptoms occurred in all functional psychoses, but were more frequent and prominent in the schizophrenic group than in the other two diagnostic groups at any time of assessment. Narrower concepts of negative symptoms, conceptualized as the deficit syndrome, seem to be specific for schizophrenia and appear quite rarely in patients with affective psychoses. Overall, our study supports Kraepelin's original hypothesis that bifurcated the psychoses into the affective psychoses and schizophrenia, whereby the latter have a more deleterious long-term course and outcome.     

Family history study of posttraumatic stress disorder with secondary psychotic symptoms

OBJECTIVE: A family history approach was used to determine if posttraumatic stress disorder (PTSD) with secondary psychotic symptoms was associated with a familial vulnerability to schizophrenia and other psychoses. METHOD: Family history methods were used to compare rates of familial psychopathology in the first-degree relatives of three proband groups: 1) patients with DSM-IV PTSD with secondary psychotic symptoms, 2) patients with DSM-IV PTSD without psychotic symptoms, and 3) healthy matched comparison subjects. RESULTS: PTSD with secondary psychotic symptoms was not associated with an excess of familial psychotic disorder but was associated with a higher morbid risk for depression. CONCLUSIONS: PTSD with secondary psychotic symptoms was not associated with familial psychosis, suggesting it does not reflect the presence of an underlying psychotic disorder.     

Lifetime psychopathology in child and adolescent offspring of parents diagnosed with schizophrenia or bipolar disorder: a 2-year follow-up study

Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood, and it also increases the risk of a wide range of mental disorders in the offspring. The aim of this study is to compare the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms, and global functioning in offspring of parents with schizophrenia or bipolar disorder and in offspring of controls at baseline and 2-year follow-up. This study included 41 offspring of parents with schizophrenia, 90 offspring of parents with bipolar disorder, and 107 offspring of controls (mean age 11.7 ± 3.2 at baseline and 13.9 ± 3.2 at follow-up). The prevalence of psychopathology and comorbidity was higher in offspring of parents with schizophrenia and offspring of parents with bipolar disorder than in offspring of controls at baseline and at 2-year follow-up. Interestingly, mood disorders were more prevalent in offspring of parents with bipolar disorder and disruptive disorders were more prevalent in offspring of parents with schizophrenia. Prodromal symptoms were more frequent in offspring of parents with schizophrenia than in offspring of controls, while the offspring of parents with bipolar disorder showed an intermediate pattern. Finally, global functioning was lower in the offspring of parents with schizophrenia than the offspring of parents with bipolar disorder and the offspring of controls. Screening patients’ children is clinically relevant, since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

     

Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia

BACKGROUND: Although growing research indicates that the atypical antipsychotic agent clozapine is effective in patients with schizophrenia, little is known about the efficacy of clozapine in patients with schizoaffective disorder or psychotic mood disorders. The purpose of this study was to assess whether or not clozapine is effective in some patients with schizoaffective disorder or psychotic mood disorders. METHOD: By surveying treating clinicians and chart data, we assessed treatment response in 85 consecutive patients, including 39 with schizophrenia, 25 with schizoaffective disorder, and 14 with bipolar disorder with psychotic features, who received clozapine for at least 6 weeks at our center. RESULTS: All patients were either inadequately responsive to or unable to tolerate standard somatic therapies. Compared to patients with schizophrenia, patients with schizoaffective disorder and bipolar disorder with psychotic features displayed significantly higher response rates to clozapine. CONCLUSION: Clozapine may be a useful drug in the treatment of patients with schizoaffective disorder or psychotic mood disorders who are treatment resistant or intolerant of side effects.     

Mobility limitations in persons with psychotic disorder: findings from a population-based survey

BACKGROUND: There are few reports on mobility limitations in persons with psychotic disorder although restrictions in mobility may aggravate the general functional limitations of these patients. Our aim was to investigate mobility limitations among subjects with psychotic disorder in a general population-based sample. METHODS: A nationally representative sample of 6,927 persons aged 30 and older self-reported mobility limitations in an interview and was examined in performance tests. Diagnostic assessment of DSM-IV psychotic disorders combined SCID interview and case note data. Lifetime-ever diagnoses of psychotic disorder were classified into schizophrenia, other nonaffective psychotic disorders and affective psychoses. RESULTS: Self-reported mobility limitations were highly prevalent in persons with schizophrenia and other nonaffective psychosis, but not in the affective psychosis group. After adjusting for age and sex, persons with schizophrenia and other nonaffective psychoses but not affective psychoses had significantly increased odds of having both self-reported and test-based mobility limitations as well as weak muscle strength. Schizophrenia remained an independent predictor of mobility limitations even after controlling for lifestyle-related factors and chronic medical conditions. Among persons with nonaffective psychoses, higher levels of negative symptoms predicted mobility limitations. CONCLUSION: Self-reported mobility limitations are prevalent already at a young age in persons with schizophrenia and other nonaffective psychotic disorders, and among older persons with these disorders both self-reported limitations and measured performance tests show lower capacity in mobility. Difficulties in mobility are associated with negative symptoms. Mental health care professionals should pay attention to mobility limitations in persons with psychotic disorder.     

Emerging roles for atypical antipsychotics in chronic post-traumatic stress disorder

Post-traumatic stress disorder is an anxiety disorder that may occur after the individual is exposed to severe psychologic trauma such as combat, sexual assault, or childhood physical or sexual abuse. Chronic post-traumatic stress disorder may result in considerable psychologic pain and suffering for the individual in addition to significant functional impairment. In addition to the heterogeneity of symptoms that occur in post-traumatic stress disorder, there may also be extensive comorbidity with other anxiety disorders, mood disorders, psychotic disorders, and other psychiatric disorders. This complicates the treatment picture. Currently, accepted treatments for post-traumatic stress disorder include psychotherapy, in particular cognitive behavioral-based approaches and antidepressant medication. However, many patients are refractory to these initial treatments or have only a partial response. In light of this, may clinicians combine additional classes of psychotropic agents and different psychotherapeutic approaches to enhance treatment response. This article reviews the literature on the use of atypical antipsychotics in the treatment of post-traumatic stress disorder. Most of the research to date has involved combat veterans partially responsive or refractory to treatment, namely with antidepressants. Studies have shown improvement across post-traumatic stress disorder symptom clusters, as well as improvement in comorbid psychotic symptoms or disorders. More research is needed to confirm these recent findings and further delineate the role of atypical antipsychotics in the treatment of post-traumatic stress disorder. Currently, possible indications for their use include treatment-resistant post-traumatic stress disorder and post-traumatic stress disorder with comorbid psychotic features.