Heather Milliken

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.

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.

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

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.

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.

Quetiapine treatment in early psychosis: 1 year outcomes

Objective  To determine clinical response, dosing and adverse events associated with quetiapine treatment in early psychosis.