A single-dose, randomized, double-blind, placebo-controlled trial of sublingual asenapine for acute agitation.

OBJECTIVE: To assess sublingual asenapine for acute agitation. METHOD: Agitated adults 18-65 years (any diagnosis) presenting for treatment in an emergency department and found to have a score of ≥14 on the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) were randomized to receive either a single dose of a sublingual 10 mg tablet of asenapine or placebo. Primary outcome measure was change in the PANSS-EC score from baseline to 2 h after medication or placebo administration. Secondary outcomes included the percentage of responders with a ≥ 40% reduction from baseline on the PANSS-EC score at 2 h. RESULTS: A total of 120 subjects were randomized, 60 each to sublingual asenapine or placebo. Mean (SE) baseline PANSS-EC scores for the asenapine-treated and placebo-treated subjects were 19.4 ± 0.66 and 20.1 ± 0.61, respectively. Mean PANSS-EC scores at endpoint (LOCF) was 7.4 ± 0.65 for the asenapine-treated subjects and 14.7 ± 0.98 for the placebo-treated subjects. Change in PANSS-EC score at 2 h was statistically significantly greater for the asenapine-treated subjects compared with the placebo-treated subjects. NNT for response vs. placebo was 3 (95% CI 2-4). CONCLUSION: Sublingual asenapine was efficacious in the treatment of agitation with an effect size comparable to that observed in prior studies of intramuscular antipsychotics.

Abnormal phospholipid metabolism in schizophrenia: evidence from epidemiological findings, clinical observations, and preliminary clinical trials.

Both epidemiological findings and clinical observations and have shaped our thinking as regards to the neuropathology of schizophrenia. Epidemiological findings implicating environmental risk factors, including maternal dietary deficiency and urban birth place, suggest schizophrenia is a developmental disorder, whereas clinical observations gave rise to the "dopamine hypothesis." Epidemiological findings lead to complex multifactorial models, while clinical observations lead to more readily to testable, but not necessarily generalizable, hypotheses. Points where findings from these different approaches converge may provide us with new insights and points of departure. In this paper, clinical observations and epidemiological findings are presented which suggests that a subgroup of schizophrenics have abnormalities in phospholipid metabolism. Preliminary clinical trials involving administration of omega-3 fatty acids thus far appear to support this hypothesis.

Gender differences in the relationship of homelessness to symptom severity, substance abuse, and neuroleptic noncompliance in schizophrenia.

This study examined gender differences in the relationship of homelessness in schizophrenia to symptom severity, risk behaviors, and prognostic features. Four hundred subjects with schizophrenia were studied: 100 homeless men, 100 homeless women, 100 never homeless men, and 100 never homeless women. Assessments included derivation of five symptom factors by using the Positive and Negative Syndrome Scale (PANSS). Homelessness for the entire sample was associated with greater severity of positive, activation, and autistic preoccupation symptoms, younger age at first hospitalization, and substance abuse (SA). For men only, homelessness was associated with neuroleptic noncompliance (NN). When NN and SA were statistically controlled, symptom severity was not different between the homeless and never homeless. Women, independent of residential status, had more severe negative, activation, and autistic preoccupation symptoms that were not associated with prognostic features or risk behaviors. For both men and women, SA was associated with homelessness, but independent of residence, SA was less severe in women. Additionally, SA was less severe in homeless women than never homeless men. Thus, symptom severity in homeless individuals with schizophrenia appears as an interaction of symptom profiles and risk behaviors that are gender specific. Although cross-sectional analyses cannot distinguish cause from effect, these findings suggest gender-specific routes to homelessness among indigent urban adults with schizophrenia.

Psychostimulants in the treatment of adults with psychosis and attention deficit disorder.

Whether conceptualized as comorbid ADD with psychosis or as a distinct diagnostic entity--ADD psychosis--patients with features of both ADD and psychosis benefit from treatment with psychostimulants. It is hypothesized that psychostimulants have their therapeutic effect via amelioration of frontal lobe dysfunction.

EEG biofeedback treatment of ADD. A viable alternative to traditional medical intervention?

Literature searches dating back to 1968 were conducted through Psychlit and Medline services to review the scientific literature on EEG biofeedback treatment of ADD. While anecdotal and case reports cite promising evidence, methodological problems coupled with a paucity of research precludes any definitive conclusions as to the efficacy of enhanced alpha and hemisphere-specific EEG biofeedback training. One of the more promising EEG biofeedback treatment paradigms involves theta/beta training. Studies have reported that academic, intellectual, and behavioral gains have been attained with this approach. Significant behavioral and cognitive changes have also been reported following SMR training. However, research into these treatment approaches has also been marred by methodological inadequacies and lack of sufficient follow-up studies. A number of recommendations for future research into this treatment approach are made.

Risk factors for homelessness among indigent urban adults with no history of psychotic illness: a case-control study.

OBJECTIVES: This study identified risk factors for homelessness among indigent urban adults without dependent children and with no history of psychotic illness. METHODS: We conducted a matched case-control study, stratified by sex, of 200 newly homeless men and women and 200 indigent men and women with no history of homelessness. Newly homeless case subjects were recruited from shelter assessment centers in New York City. Never-homeless control subjects, selected from public assistance centers, were single adults applying for home relief. Control subjects were matched with case subjects according to ethnicity, age, and sex. Trained interviewers employed standardized research instruments to probe 3 domains of risk factors: symptom severity and substance use disorder, family support and functioning, and prior use of services. RESULTS: Significant interaction effects by sex were present for symptom severity, heroin use disorder, and prior service use. Greater numbers of the homeless of both sexes lacked a high school diploma and had less income from all sources, including from their families, than of the never homeless. CONCLUSIONS: Newly homeless men and women with no history of psychotic illness differed from their never-homeless counterparts in the 3 domains investigated, but socioeconomic factors were also important.

Dot Enumeration Perceptual Organization Task (DEPOT): evidence for a short-term visual memory deficit in schizophrenia.

The Dot Enumeration Perceptual Organization Task (DEPOT) evaluates the validity of 2 specific competing cognitive models of early input dysfunction in schizophrenic individuals: a primary Stage 1, sensory store, perceptual organization deficit vs. a Stage 2, short-term visual memory (STVM) deficit. DEPOT was also designed to assess the hypothesis that schizophrenic individuals tend to perform poorly on all cognitive tasks. In DEPOT both number and form judgments are made about the same dot patterns. A response delay manipulation assesses the persistence and operation of STVM. The study included 41 psychotic inpatients (8 with acute and 16 with chronic schizophrenia and 7 with bipolar and 10 with nonbipolar affective disorder) and 38 controls (22 college students and 16 hospital personnel). Although the pattern of results was consistent with neither the Stage 1 deficit nor the general deficit hypotheses, a Stage 2, STVM deficit hypothesis could account parsimoniously for the data.

Risk factors for homelessness among women with schizophrenia.

A study of risk factors for homelessness among the severely mentally ill was extended to include women, and a case-control study of 100 indigent women with schizophrenia meeting criteria for literal homelessness and 100 such women with no history of homelessness was conducted. Subjects were recruited from shelters, clinics, and inpatient psychiatric programs in New York City. Clinical interviewers used standardized research instruments to probe three domains of risk factors: severity of mental illness, family background, and prior mental health service use. Findings adjusted for ethnicity revealed that homeless women had higher rates of a concurrent diagnosis of alcohol abuse, drug abuse, and antisocial personality disorder. Homeless women also had less adequate family support.

Pharmacologic treatment of delusions.

Delusions usually respond to antipsychotic medications. When delusions are present within certain diagnostic categories, however, pharmacotherapy other than or in addition to antipsychotic agents is indicated. Many delusional disorders have been found to respond to pimozide even after failing to respond to other antipsychotic agents. Delusions accompanied by affective symptomatology should be treated with both antipsychotic medications and antidepressants or mood stabilizers. When delusions are the result of a medical condition, treatment of the medical condition may lead to resolution of the delusion.

Correlates of codisorders in homeless and never homeless indigent schizophrenic men.

We recently completed a case-control study of 100 literally homeless and 100 never homeless indigent schizophrenic men in New York City, in which concurrent substance abuse and antisocial personality disorder were widespread. In this paper we probe the correlates of 'pure' schizophrenia (single disorder, N = 60), schizophrenia and substance abuse (double disorder, N = 89), and schizophrenia, substance abuse, and antisocial personality disorder (triple disorder, N = 50), across the homeless/never homeless distinction. Subjects were recruited from a homeless shelter and mental health service programmes in Upper Manhattan. Psychologist and social worker interviewers administered the Structured Clinical Interview for DSM-III-R, I, and II and other structured instruments to explore social, family and illness history, the current illness, and aspects of treatment and family support. Codisorder subjects emerged from more disadvantaged family backgrounds, experienced greater school difficulties, began drug use in early adolescence, were more prone to hyperactivity in childhood, and were more likely to have spent time in jail. While codisorder groups did not differ on key aspects of schizophrenia, the triple disorder group was found to suffer from a more severe form of substance abuse than double disorder subjects, associated with an earlier age of onset and abuse of a wider array of substances. The widespread prevalence of codisorders among indigent schizophrenic men has major significance for clinical psychiatry. Study of the correlates of codisorders has revealed important differences in social, family, and illness history which may guide the development of more effective treatments and improved service delivery.

Relationship between neuroleptic dose and positive and negative symptoms.

The present study explored possible connections between neuroleptic dose and the positive and negative symptoms of schizophrenic patients. Zero-order correlations between medication dose as measured in CPZ equivalent units and standardized assessments of positive (hallucinations, delusions) and negative (blunted affect, poor rapport) symptoms were carried out on 28 hospitalized schizophrenics. While dose was positively related to over-all negative symptom scores as well as specific negative symptoms, no relation was found with positive scores. The discussion focused on the possibility that negative symptoms might represent medication-induced side effects and the need for further research.

Symptom profiles and homelessness in schizophrenia.

One hundred homeless schizophrenic men and 100 never homeless schizophrenic men were compared in terms of symptom ratings on the Positive and Negative Syndrome Scale (PANSS), which yields a positive, negative, and general psychopathology scale score, as well as evaluated on a number of other variables. The homeless group obtained significantly higher ratings on the PANSS positive and general psychopathology scales, but the two groups did not differ on the PANSS negative scale score. When symptom patterns for subsets of patients who did not abuse illicit substances or alcohol (N = 23 for homeless, N = 56 for nonhomeless) and who were compliant with medication (N = 63 for homeless, N = 82 for nonhomeless) were examined, the higher ratings on the positive and general psychopathology scales failed to achieve statistical significance, while the absence of between-group differences on the negative scale was maintained. Our results suggest that severity of positive and general psychopathology symptoms, but not of negative symptoms, predicts homelessness in schizophrenia and that illicit substance abuse and neuroleptic noncompliance contributed, at least in part, to our higher positive and general psychopathology symptom ratings in the homeless sample. Our findings underscore the need to undertake prospective longitudinal studies to unravel the multifactorial etiology of homelessness in schizophrenia.

Risk factors for homelessness among schizophrenic men: a case-control study.

OBJECTIVES: To identify risk factors for homelessness among the severely mentally ill, we conducted a case-control study of 100 indigent schizophrenic men meeting criteria for literal homelessness and 100 such men with no homeless history. METHODS: Subjects were recruited from shelter, clinic, and inpatient psychiatric programs in Upper Manhattan. Clinical interviewers employed standardized research instruments to probe three domains of risk factors: severity of mental illness, family background, and prior mental health service use. RESULTS: Homeless subjects showed significantly higher levels of positive symptoms, higher rates of a concurrent diagnosis of drug abuse, and higher rates of antisocial personality disorder. Homeless subjects experienced greater disorganization in family settings from birth to 18 years and less adequate current family support. Fewer homeless subjects than subjects in the never-homeless comparison group had a long-term therapist. These differences remained when demographic variables were adjusted statistically. CONCLUSIONS: Homeless schizophrenic men differed from their domiciled counterparts in all three domains we investigated; family background, nature of illness, and service use history. Findings are discussed in relation to policy and programs for the severely mentally ill.