Clozapine-induced fevers and 1-year clozapine discontinuation rate.

BACKGROUND: Clozapine-induced fever is a known side effect that can occur during clozapine initiation. This study aims to characterize patients who experience clozapine-induced fever, the nature of the fevers, and rates of clozapine continuation at 1 year in patients who develop fever versus those who do not. METHOD: A retrospective chart review of 93 consecutive clozapine initiations (1991-1999) was conducted. Fever was defined as any 1 temperature at or above 38.0 degrees C (100.4 degrees F). Demographic information, presence or absence of clozapine-induced fevers, and continuation of clozapine treatment at 1 year were extracted from the charts. These variables were analyzed for significance, and subsample analysis was conducted for those with more severe fevers (at or above 38.5 degrees C [101.3 degrees F]). RESULTS: Of the 93 patients, 20.4% (N = 19) developed clozapine-induced fevers. At 1 year, there was no significant difference in clozapine discontinuation rate between those patients who experienced fever and those who did not. Patients who experienced higher fevers (> or = 38.5 degrees C [101.3 degrees F]) tended to be significantly older than those who did not (p < .027). The mean fever duration was 3.8 days (range, 1-9 days), with a mean temperature of 39.1 degrees C (102.4 degrees F) (range, 38.0-41.0 degrees C [100.4-105.8 degrees F]). At 1 year, the patients who experienced fever showed no increased risk of severe reactions such as agranulocytosis. All patients with fevers continued clozapine treatment with good 1-year continuation rate on treatment with this medication. CONCLUSION: Clozapine-induced fever is not an indication for discontinuing this effective medication. It is a benign, self-limited phenomenon not predictive of drug discontinuation at 1 year. Older age at time of treatment may be a risk factor for developing clozapine-induced fever.

Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone.

BACKGROUND: This study was conducted to prospectively examine the effect of switching from risperidone to olanzapine on female schizophrenia patients who experienced menstrual disturbances, galactorrhea, and/or sexual dysfunction. METHOD: Twenty female patients with DSM-IV schizophrenia who were taking risperidone and were suffering from menstrual disturbances, galactorrhea, and/or sexual dysfunction were enrolled. Patients were switched from risperidone to olanzapine over a 2-week period, then treated with olanzapine for 8 additional weeks. The serum prolactin concentrations were examined every 2 weeks. The Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), and questions from the Dickson-Glazer Sexual Functioning Scale were administered to evaluate efficacy, extrapyramidal side effects, and sexual and reproductive functioning at baseline and the endpoint of 10 weeks. RESULTS: Serum prolactin levels decreased significantly (p < .01) following the switch from risperidone to olanzapine. Scores of PANSS, AIMS, and SAS at the endpoint were also significantly decreased (p < .01) compared to those of baseline. Patients experienced improvements in menstrual functioning and perceptions of sexual side effects. CONCLUSION: Olanzapine reversed hyperprolactinemia in risperidone-treated female schizophrenic patients. This was associated with a decrease in amenorrhea, improved cycle regularity, and a decrease in sexual side effects that the women attributed to antipsychotic medication. This study suggests that switching to olanzapine is a safe and effective alternative method for patients with antipsychotic-induced hyperprolactinemia associated sexual and/or reproductive dysfunction. Long-term follow-up studies are warranted, with particular attention to the course of sexual and reproductive dysfunction.

The effects of antipsychotic drug treatment on prolactin concentrations in elderly patients.

OBJECTIVE: To describe the change in serum prolactin concentrations in elderly agitated nursing home patients with dementia who were newly initiated on olanzapine or switched to olanzapine treatment from either conventional antipsychotics or risperidone. METHODS: During an 8-week open-label olanzapine efficacy trial in elderly nursing home patients demonstrating clinically significant behavioral and psychological symptoms of dementia, serum prolactin concentrations were drawn on four occasions: at time of consent, following a washout period from previous therapy, midway through the study, and at endpoint. To assess post-hoc the effects of prolactin concentrations upon switching to olanzapine treatment, patients were divided into three different groups, based upon status at time of consent: those not taking antipsychotic medication, those taking any conventional antipsychotic, and those taking risperidone. Prolactin concentrations were assessed using a mixed-effect repeated-measures model. Symptom severity was measured using the Brief Psychiatric Rating Scale (BPRS), the Cohen-Mansfield Agitation Inventory (CMAI), the Clinical Global Impression (CGI)-Severity scale, and the Mini-Mental State Examination (MMSE), and the same repeated measures analysis was performed on these scales. RESULTS: Patients not on antipsychotic medication at study entry (29 females, 7 males) experienced a significant increase in prolactin concentration baseline to endpoint (P < 0.05) but remained below upper limit of normal for prolactin for both males and females. There was a nonsignificant increase in prolactin concentrations when patients were switched from conventional antipsychotic medications (mean dose 152.41 +/- 192.48 mg/day chlorpromazine equivalents) to olanzapine (2.5 to 10 mg/day) (22 females, 9 males). Patients who entered the study on risperidone (mean dose 1.31 +/- 0.91 mg/day) (13 females, 4 males) experienced a significant decrease in prolactin concentration (P < 0.001). While 62.5% of risperidone-treated patients had above-normal prolactin concentrations at baseline, only 21.4% had above-normal concentrations at endpoint (P = 0.033). Clear correlations between prolactin concentrations and clinical outcomes could not be determined. CONCLUSION: Consistent with previous findings in younger patients, olanzapine appeared to be a prolactin-sparing antipsychotic medication in the elderly with only modest prolactin increases observed. In addition, patients who were receiving risperidone and then switched to olanzapine experienced a significant reduction in prolactin concentrations that was sustained over the 8-week treatment course with olanzapine. One possible explanation for olanzapine's relatively modest increase in prolactin is that, unlike conventionals or risperidone, olanzapine binds less tightly with the dopamine D(2) receptor.

Time courses of improvement and symptom remission in children treated with atomoxetine for attention-deficit/hyperactivity disorder: analysis of Canadian open-label studies.

BACKGROUND: The relatively short durations of the initial pivotal randomized placebo-controlled trials involving atomoxetine HCl for the treatment of attention-deficit/hyperactivity disorder (ADHD) provided limited insight into the time courses of ADHD core symptom responses to this nonstimulant, selective norepinephrine reuptake inhibitor. The aim of this analysis was to evaluate time courses of treatment responses or remission, as assessed by attainment of prespecified scores on the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scales, during up to 1 year of atomoxetine treatment in children with ADHD. METHODS: Using pooled data from three Canadian open-label studies involving 338 children ages 6-11 years with ADHD who were treated with atomoxetine for 3, 6 and 12 months, and survival analysis methods for interval-censored data, we estimated the time to: 1) improvement and robust improvement defined by ≥25% and ≥40% reductions from baseline ADHDRS-IV-PI total scores, respectively; and 2) remission using two definitions: a final score of ADHDRS-IV-PI ≤18 or a final score of CGI-ADHD-S ≤2. RESULTS: The median time to improvement was 3.7 weeks (~1 month), but remission of symptoms did not occur until a median of 14.3 weeks (~3.5 months) using the most stringent CGI-ADHD-S threshold. Probabilities of robust improvement were 47% at or before 4 weeks of treatment; 76% at 12 weeks; 85% at 26 weeks; and 96% at 52 weeks. Probabilities of remission at these corresponding time points were 30%, 59%, 77%, and 85% (using the ADHDRS-IV scale) and 8%, 47%, 67%, and 75% (using the CGI-ADHD-S scale). The change from atomoxetine treatment month 5 to month 12 of -1.01 (1.03) was not statistically significant (p = .33). CONCLUSIONS: Reductions in core ADHD symptoms during atomoxetine treatment are gradual. Although approximately one-half of study participants showed improvement at 1 month of atomoxetine treatment, remission criteria were not met until about 3 months. Understanding the time course of children's responses to atomoxetine treatment may inform clinical decision making and also influence the durations of trials comparing the effects of this medication with other ADHD treatments. TRIAL REGISTRATIONS: clinicaltrials.gov: NCT00191633, NCT00216918, NCT00191880.

Tadalafil for treatment of erectile dysfunction in men on antidepressants.

OBJECTIVE: The objective of this post hoc analysis was to evaluate tadalafil, a treatment indicated for erectile dysfunction (ED), in men on antidepressants. METHOD: A retrospective, pooled analysis of 19 double-blind, placebo-controlled trials (N = 3864) identified 205 men with ED, mean age of 55 years (range, 27-79 years) receiving antidepressants and tadalafil 10 mg (n = 38), tadalafil 20 mg (n = 113), or placebo (n = 54). Efficacy was measured by the International Index of Erectile Function erectile function domain score, the Sexual Encounter Profile diary, and a Global Assessment Question. Tolerability was assessed via collection and analysis of treatment-emergent adverse events. RESULTS: Patients on antidepressants who were treated with tadalafil showed significantly greater baseline-to-end point improvement on the International Index of Erectile Function score compared with placebo (end point: tadalafil 10 mg, 21.7; tadalafil 20 mg, 21.8; placebo, 14.5; both P < 0.01). The mean per-patient percent successful intercourse postbaseline was also greater with tadalafil 10 mg (54%) and tadalafil 20 mg (59%) than placebo (29%, both P < 0.05). Patients taking tadalafil 10 (72%) and 20 (76%) mg both reported significant improvement in erections on the Global Assessment Question compared with placebo (33%, both P < 0.01). The incidence of treatment-emergent adverse events was low in all treatment groups with the most common being headache, dyspepsia, and back pain. CONCLUSION: Tadalafil was well tolerated and improved erectile function in patients taking antidepressant medications.

A Canadian multicenter trial assessing memory and executive functions in patients with schizophrenia spectrum disorders treated with olanzapine.

Serial verbal learning task (explicit long-term memory) and verbal fluency (generation of a response) are tests that are usually severely impaired in schizophrenia. Despite the growing literature supporting the clinical efficacy of olanzapine, psychiatrists still question its cognitive consequences. This study assessed the efficacy of olanzapine on neurocognitive functioning. Patients (N = 134) meeting diagnostic criteria for schizophrenia, schizophreniform, or schizoaffective disorders began an 8-week, open-label olanzapine treatment at a dose of 5 mg/d, which was increased to 10 mg/d after 1 week. Daily dosage was subsequently adjusted between 5 and 20 mg/d based on individual clinical status. All previous antipsychotics were tapered and discontinued during the first 2 weeks of the study. Neuropsychologic assessments were carried out at baseline and at 4 and 8 weeks. Explicit long-term memory was assessed with the Rey Auditory-Verbal Learning Test: the average immediate recall score significantly improved (P < 0.001), as did the delayed recall score (P < 0.001). The average total score on category fluency improved from 34.6 words at baseline to 37.6 words at end point (P < 0.0001). Time on both Trail A and B making tasks significantly decreased (P < 0.0001). Lack of a control arm makes it impossible to exclude a practice effect as an explanation for the enhanced cognitive performance, although the Word List Recall test represents one of the better resources to avoid a practice effect. After switching to olanzapine, there was a statistically significant improvement of cognitive function in the 3 main domains tested and no significant worsening of any memory or executive function measure.

Attitudes about schizophrenia from the pilot site of the WPA worldwide campaign against the stigma of schizophrenia.

BACKGROUND: A series of surveys were conducted to assess the attitudes of the public, and other groups, toward those with schizophrenia. The aim of these surveys was to aid in the planning and evaluation of the WPA anti-stigma initiative in Alberta, Canada. METHOD: A questionnaire was devised and administered via telephone to over 1,200 individuals in three Alberta cities, and in paper and pencil format to 40 members of the Schizophrenia Society of Alberta and 67 medical students. RESULTS: In contrast to some earlier findings, "loss of mind" was rated to be more disabling than any other handicapping condition. In general, respondents showed a relatively sophisticated understanding of schizophrenia and a higher level of acceptance than might have been predicted. Nonetheless, this acceptance was not as high for situations where closer personal contact was likely, and fears of dangerousness continue to be associated with schizophrenia. The majority of respondents, however, felt that treatment aided those with schizophrenia, expressed support for progressive programmes for the mentally ill, and stated that they would be willing to pay higher taxes so that programming could be improved. CONCLUSIONS: The results do not support the utility of a broad approach for an anti-stigma campaign, but rather suggest a more specific focus, such as perceived dangerousness.