A feasibility study evaluating lisdexamfetamine dimesylate for the treatment of adults with bulimia nervosa.

OBJECTIVE: This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN). METHOD: An open-label 8-week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined. RESULTS: Eighteen of 23 participants completed the study per protocol. There was no participant-initiated dropout due to adverse drug reactions and no severe and unexpected adverse drug reactions. An average increase in heart rate of 12.1 beats/min was observed. There was a mean weight reduction of 2.1 kg and one participant was withdrawn for clinically significant weight loss. In the intent-to-treat sample, there were reductions in objective binge episodes and compensatory behaviors from Baseline to Post/End-of-Treatment (mean difference = -29.83, 95% confidence interval: -43.38 to -16.27; and mean difference = -33.78, 95% confidence interval: -48.74 to -18.82, respectively). DISCUSSION: Results of this study indicate that a randomized controlled trial would be feasible with close monitoring of certain safety parameters (especially over a longer time period as long-term safety is unknown). However, the results should not be used as evidence for clinicians to prescribe LDX to individuals with BN before its efficacy and safety are properly tested. TRIAL REGISTRATION NUMBER: NCT03397446.

Evidence review and clinical guidance for the use of ziprasidone in Canada.

While indicated for schizophrenia and acute mania, ziprasidone's evidence base and use in clinical practice extends beyond these regulatory approvals. We, an invited panel of experts led by a working group of 3, critically examined the evidence and our collective experience regarding the effectiveness, tolerability and safety of ziprasidone across its clinical uses. There was no opportunity for manufacturer input into the content of the review. As anticipated, ziprasidone was found to be effective for its indicated uses, although its utility in mania and mixed states lacked comparative data. Beyond these uses, the available data were either unimpressive or were lacking. An attractive characteristic is its neutral effect on weight thereby providing patients with a non-obesogenic long-term treatment option. Key challenges in practice include the need for dosing on a full stomach and managing its early onset adverse effect of restlessness. Addressing these issues are critical to its long-term success.

Lack of extracellular superoxide dismutase (EC-SOD) in the microenvironment impacts radiation-induced changes in neurogenesis.

Ionizing irradiation results in significant alterations in hippocampal neurogenesis that are associated with cognitive impairments. Such effects are influenced, in part, by alterations in the microenvironment within which the neurogenic cells exist. One important factor that may affect neurogenesis is oxidative stress, and this study was done to determine if and how the extracellular isoform of superoxide dismutase (SOD3, EC-SOD) mediated radiation-induced alterations in neurogenic cells. Wild-type (WT) and EC-SOD knockout (KO) mice were irradiated with 5 Gy and acute (8-48 h) cellular changes and long-term changes in neurogenesis were quantified. Acute radiation responses were not different between genotypes, suggesting that the absence of EC-SOD did not influence mechanisms responsible for acute cell death after irradiation. On the other hand, the extent of neurogenesis was decreased by 39% in nonirradiated KO mice relative to WT controls. In contrast, while neurogenesis was decreased by nearly 85% in WT mice after irradiation, virtually no reduction in neurogenesis was observed in KO mice. These findings show that after irradiation, an environment lacking EC-SOD is much more permissive in the context of hippocampal neurogenesis. This finding may have a major impact in developing strategies to reduce cognitive impairment after cranial irradiation.

Sex differences in olfactory function in young patients with psychotic disorders.

Female superiority on many measures of olfactory function is well established, but debate remains as to whether this pattern extends to patients with psychotic disorders. The purpose of this large retrospective study was to re-examine whether male vs. female differences in olfactory identification exist in patients with psychotic disorders, and if so, whether any such differences were related to features of the psychotic disorder or could be explained by a generalized male-female difference. We examined 353 relatively young patients, recently diagnosed with a psychotic illness, (258 males and 95 females) and compared these with 89 healthy control subjects (45 males and 44 females). All individuals had been assessed birhinally using the University of Pennsylvania Smell Identification Test (UPSIT). Overall, females were superior to males, and patients underperformed healthy controls. No interaction was noted between these two variables, and there was no significant effect found as a result of age of the subjects. The data suggested that sex differences in olfactory identification ability exist in young patients with psychotic disorders. They do not appear to be related to exposure to antipsychotic medication or smoking habit. Therefore, it is likely that they represent basic male vs. female differences and not diagnosis-specific sex differences in olfactory performance-at least in those who are in the early stages of illness.

Olfactory identification deficits in first-episode psychosis may predict patients at risk for persistent negative and disorganized or cognitive symptoms.

OBJECTIVE: One-third of patients with a schizophrenia spectrum disorder have a measurable olfactory identification deficit at first examination. The authors studied the relationship of this deficit to symptom remission after 1 year of treatment. METHOD: Fifty-eight patients naive to antipsychotic medication who entered the Nova Scotia Early Psychosis Program were symptomatically rated with the Positive and Negative Syndrome Scale (PANSS) (at baseline and 1 year). At baseline, the University of Pennsylvania Smell Identification Test (UPSIT) was also completed. Remission was determined for four symptom factors derived from the PANSS (positive, negative, cognitive/disorganized, and anxiety/depression). Patients with and without remission were compared on UPSIT scores. RESULTS: Patients with nonremission of negative and cognitive/disorganized symptoms had significantly lower baseline UPSIT scores compared with patients with remission. UPSIT scores were unrelated to remission of positive or anxiety/depression symptoms. CONCLUSIONS: UPSIT scores can be used to identify patients at risk for persistent negative and disorganized/cognitive symptoms.

Treatment of a first episode of psychotic illness with quetiapine: an analysis of 2 year outcomes.

BACKGROUND: The first episode of a psychotic disorder provides a unique opportunity to initiate optimal treatment but when a new medication becomes available, little data exist to guide the appropriate use in this population. OBJECTIVES: The objectives were to determine the optimal doses and titration of quetiapine for this group and to measure outcomes (including symptom response, social functioning, mood alterations, motor symptoms, metabolic parameters and cognitive functioning) over 2 years of treatment with quetiapine. DESIGN: Thirty nine subjects with a first episode of psychosis referred to the Nova Scotia Early Psychosis Program in Halifax, Canada, were invited to participate in this study. Standardized clinical, laboratory, and neuropsychological assessments were performed at baseline and following treatment with quetiapine at intervals out to 2 years. RESULTS: Quetiapine was effective in treating the psychotic and mood symptoms while not causing extra-pyramidal signs or symptoms (EPSS). Pre-existing motor dysfunction improved. No anticholinergic medications were required. Several domains of cognitive function also improved (sustained attention, the number of perseverative errors, visuomotor speed and sequencing, verbal fluency and verbal memory). Weight gain was observed along with increases in cholesterol levels but there was no glucose dysregulation. CONCLUSIONS: The results of this two year, naturalistic study of people with a first episode of psychosis indicated that quetiapine was well tolerated and effective for this population. Significant improvements in cognitive functioning also provided evidence for potential longer-term benefits of early and optimal treatment with this agent. However, monitoring metabolic parameters, as recommended for other atypicals, is likely prudent.

An Exploratory, Open-Label, Randomized Trial Comparing Risperidone Long-Acting Injectable with Oral Antipsychotic Medication in the Treatment of Early Psychosis.

Few studies have examined effectiveness and tolerability of risperidone long-acting injections (RLAI) in the early phase of a schizophrenia spectrum (SS) disorder using a randomized controlled trial (RCT) design. Eighty-five patients in early phase of an SS disorder were randomized to receive either oral second-generation antipsychotics (SGAs; n=41) or RLAI (n=44) over two years. Analyses were conducted on eligible participants (n=77) for the stabilization (maximum 18 weeks) and maintenance phases (up to Week 104) on primary outcome measures of time to stabilization and relapse, change in symptoms and safety, and comparisons made across the two groups. Both groups showed improvement on Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression-Severity (CGI-S) scores. There were no time X group interactions on any of the primary outcome measures. Post hoc examination revealed that the RLAI group showed greater change on CGI-S and PANSS negative symptom scores during the stabilization phase, while the oral group reached the same level of improvement during the maintenance phase. The current exploratory study suggests that-within an RCT design-RLAI and oral SGAs are equally effective and have similar safety profiles in patients in the early phase of SS disorders. Thus, RLAI offers no advantage to patients in early phase of SS disorders, but is likely to be effective and safe for those who may have problems with adherence and may either choose to take it or be prescribed under conditions of external control such as community treatment orders.

Unirhinal olfactory identification deficits in young male patients with schizophrenia and related disorders: association with impaired memory function.

We have observed discreet subgroups of male patients with psychotic disorders who have unirhinal olfactory identification deficits (microsmia). The purpose of this study was to examine the relationship between left or right nostril microsmia and performance on literalised neuropsychological tests sensitive to lesions in brain areas implicated in the pathogenesis of schizophrenia. Sixty-six male patients diagnosed with schizophrenia or related disorders were assessed with a battery of neuropsychological tests, sensitive to literalised and regional (temporal and frontal lobe) dysfunction. The University of Pennsylvania Smell Identification Test (UPSIT) was administered unirhinally and resultant scores were used to classify patients into olfactory subgroups. Neuropsychological test scores were compared amongst subgroups. A mixed design MANOVA was performed on cognitive domains with olfactory status (right microsmic; RM, n=8, left microsmic; LM, n=20, and normosmic schizophrenic controls; NSzC, n=38) as the between subject factor while hemisphere (left versus right) and domain (executive/fluency versus memory) were within-subject factors. A three-way (olfactory subgroup by hemisphere by region) interaction was observed. Non-verbal memory impairment was observed in the right and left microsmic subgroups. Verbal memory deficits were demonstrated in patients with left nostril microsmia. These results indicate that unirhinal olfactory performance may provide a meaningful manner by which to subtype patients with schizophrenia. Moreover, the data suggest that olfactory deficits in patients with schizophrenia are associated with dysfunction of temporal lobe, rather than frontal lobe abnormalities. The data are consistent with reports linking the right temporal lobe integrity to adequate olfactory processing.

An investigation of a possible relationship between olfactory identification deficits at first episode and four-year outcomes in patients with psychosis.

OBJECTIVE: Olfactory identification deficits are found in a significant proportion of patients with schizophrenia spectrum psychotic disorders and appear to be predictive of incomplete remission of negative and cognitive symptoms. In the current study, we examined whether patients with first episode psychosis who have olfactory identification deficits (microsmic) have poorer functional outcome than those whose olfactory status is normal (normosmic). METHOD: Sixty-six (66) first episode psychosis patients (46 M and 20 F) were assessed with the University of Pennsylvania Smell Identification Test (UPSIT) at baseline. UPSIT scores served to classify patients into subgroups. The patients' psychiatrists completed the Social and Occupational Functioning Assessment Scale (SOFAS) and the Levels of Functioning Scale (LOFS) after at least 6 months of treatment. The Premorbid Assessment Scale (PAS) was rated by a parent at baseline. RESULTS: Thirty-eight percent (38%) of the sample was identified as 'microsmic'. LOFS and SOFAS scores were significantly lower in the microsmic group than in the normosmic group. Symptoms were significantly worse in the microsmic group in comparison to the normosmic group. PAS scores did not differ between groups. CONCLUSIONS: First episode patients identified as microsmic at baseline assessment went on to demonstrate poorer functional outcome compared to normosmic patients despite no differences in premorbid adjustment. Olfactory identification deficits at first episode may provide a marker for poorer outcome. Testing olfaction is simple and inexpensive, and could provide clinically valuable information at first episode to identify those patients who might benefit from more intensive interventions promoting functional recovery.

Expert Canadian consensus suggestions on the rational, clinical use of ziprasidone in the treatment of schizophrenia and related psychotic disorders.

Many atypical antipsychotic medications are becoming available for clinical use. Ziprasidone is a recent addition to this group and is expected to become available for clinical use in Canada in 2005. Ziprasidone has some significant differences compared with other atypicals currently available in Canada. Clinicians need to understand the benefits and risks associated with each of the antipsychotic medications available for the treatment of schizophrenia and related psychotic disorders to ensure their most appropriate utilization. At the suggestion of Professor Stan Kutcher (chair) and as part of an ongoing commitment to provide independent education pertaining to the utility of new psychotropic compounds to health professionals, a panel of Canadian experts in the treatment of schizophrenia spectrum disorders was convened to provide consensus suggestions for the appropriate clinical use of ziprasidone. The consultations regarding the development of these recommendations were organized by Brainworks International (BWI) with arms-length funding from Pfizer Canada. This paper describes the experts' consensus views on the efficacy and safety of ziprasidone, their suggestions on which patients may be suitable for ziprasidone treatment, and how to initiate treatment (including how to switch from other antipsychotic medications), manage side effects, and monitor patients in long-term therapy. These suggestions are those of the authors only and are not endorsed by or necessarily reflect the opinions of BWI or Pfizer Canada.