Pharmacogenomics. 2005 Mar;6(2):139-49.
Pharmacogenetic studies of response to risperidone and other newer
atypical antipsychotics.
Lane HY, Lee CC, Liu YC, Chang WH.
China Medical University and Hospital, Department of Psychiatry, No.
2, Yuh-Der Road, Taichung, 404 Taiwan. hylane@pchome.com.tw.
Risperidone and other newer atypical antipsychotics are becoming the
mainstay for schizophrenia treatment. Recent studies suggest that the
5-hydroxytryptamine receptor 2A (5-HT2A) gene (HTR2A) T102C and G-1438A
polymorphisms may influence treatment response of risperidone or olanzapine
for schizophrenia's negative symptoms (e.g., blunted affect and social
withdrawal). In addition, the HTR6 T267C polymorphism has been linked
to risperidone response for positive symptoms (delusions and hallucinations).
The dopamine D2 receptor (DRD2) Ser311Cys polymorphism may also play a
role in determining risperidone efficacy for positive, negative and cognitive
symptoms, the DRD2 Ins-A2/Del-A1 diplotype may predict better risperidone
response, and the DRD3 Ser311Cys variant may affect general treatment
response of several atypical agents. Although investigators have started
to explore genetic effects on cognitions of schizophrenia patients receiving
antipsychotics, future larger sized pharmacogenetic studies on both psychotic
symptoms and cognitive functions are warranted.
Schizophr Res. 2005 May 12;
Patient characteristics and the likelihood of initiation on olanzapine
or risperidone among patients with schizophrenia.
Ren XS, Kazis LE, Lee AF, Huang YH, Hamed A, Cunningham F, Herz
L, Miller DR.
Health Services Department, Boston University School of Public Health,
Boston, MA, USA; Center for Health Quality, Outcomes, and Economic Research,
Veterans Affairs Medical Center, Bedford, MA, USA.
Although pharmacologic treatments are available for patients with schizophrenia, little is known about how prescription patterns of atypical antipsychotic agents are related to patient characteristics. In this study, we examined the association between patient characteristics and the likelihood of being initiated on olanzapine or risperidone, two of the most frequently prescribed atypical agents for schizophrenia. We selected patients who were diagnosed with schizophrenia or schizoaffective disorder based on >/=1 inpatient or >/=2 outpatient ICD-9-CM codes (>/=7 days apart) between 7/1/98 and 6/30/99 from the Veterans Health Administration (VA). We classified patients into one of three types of initiation: (a) not on olanzapine or risperidone, (b) not on any atypical agents, or (c) not on any antipsychotic agents for 6 months, and then subsequently being prescribed the target drugs. Using logistic regression, we examined whether the odds ratio of being initiated on olanzapine versus risperidone are related to patient sociodemographic and clinical characteristics. Compared to risperidone initiators, olanzapine initiators used more drugs for psychiatric conditions (including antiparkinsonian agents, typical antipsychotics, and mood stabilizers) than risperidone initiators. On the other hand, risperidone initiators had more medical comorbidities and more non-psychiatric hospitalizations. Olanzapine and risperidone appear to be prescribed to patients with different characteristics. Initiation of risperidone was more common among patients who presented with more medical comorbid conditions, whereas initiation of olanzapine was more common among patient who presented with more mental comorbid conditions. Future research needs to determine the reasons for those differences.
BMJ. 2005 Feb 18.
Quetiapine and rivastigmine and cognitive decline in Alzheimer's
disease: randomised double blind placebo controlled trial.
Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas
A, O'brien J, Everratt A, Sadler S, Maddison C, Lee L, Bannister C, Elvish
R, Jacoby R.
Institute of Psychiatry, King's College, London SE5 8AF.
OBJECTIVES: To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance. DESIGN: Randomised double blind (clinician, patient, outcomes assessor) placebo controlled trial. SETTING: Care facilities in the north east of England. PARTICIPANTS: 93 patients with Alzheimer's disease, dementia, and clinically significant agitation. INTERVENTION: Atypical antipsychotic (quetiapine), cholinesterase inhibitor (rivastigmine), or placebo (double dummy). MAIN OUTCOME MEASURES: Agitation (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery) at baseline and at six weeks and 26 weeks. The primary outcome was agitation inventory at six weeks. RESULTS: 31 patients were randomised to each group, and 80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom 71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26 placebo). Compared with placebo, neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six patients scored >10 on the severe impairment battery at baseline, 46 (82%) of whom were included in the analysis at six week follow up (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points (95% confidence interval -25.3 to -4.0) lower (that is, worse) than in the placebo group at six weeks (P=0.009) and -15.4 points (-27.0 to -3.8) lower at 26 weeks (P=0.01). The corresponding changes with rivastigmine were -3.5 points (-13.1 to 6.2) lower at six weeks (P=0.5) and -7.5 points (-21.0 to 6.0) lower at 26 weeks (P=0.3). CONCLUSIONS: Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline.
Int Clin Psychopharmacol. 2005 Mar;20(2):119-20.
Quetiapine-induced myoclonus.
Velayudhan L, Kirchner V.
Camden and Islington Mental Health and Social Care Trust, London, UK.
We report a case of myoclonus induced by quetiapine. A 64-year-old man with schizophrenia developed myoclonic jerks when given higher doses of quetiapine. These movements were dose-related and completely abated on reducing the dose. To our knowledge, these movements have not been reported previously as an adverse effect of quetiapine.
Int J Neuropsychopharmacol. 2005 Mar 01;:1-8.
Effects of quetiapine and haloperidol on body mass index and
glycaemic control: a long-term, randomized, controlled trial.
Emsley R, Turner HJ, Schronen J, Botha K, Smit R, Oosthuizen
PP.
Department of Psychiatry, University of Stellenbosch, Cape Town, South
Africa.
The topic of antipsychotic-induced weight-gain and its relationship to
glucose metabolism is under-studied. We evaluated the long-term effects
of a new-generation antipsychotic, quetiapine and a conventional antipsychotic,
haloperidol on body mass index (BMI) and glycaemic control in patients
with schizophrenia previously treated with conventional antipsychotics.
Forty-five clinically stable patients with schizophrenia participated
in this randomized, investigator-blinded, parallel-group comparison of
flexible doses of quetiapine and haloperidol treatment over 52 wk. Primary
outcome measures were change from baseline in BMI and glycosylated haemoglobin
(HBA1c) levels. There were no between-group differences at any of the
time-points for BMI (F=1.90, p=0.1) and HBA1c (F=1.17, p=0.3) values,
and there were no significant changes in BMI from baseline for either
group. HBA1c levels decreased significantly at end-point for the haloperidol
group (-1.5%, p=0.04), but not for the quetiapine group (-0.3%, p=0.5).
Although the sample was not generally obese (mean baseline BMI 25.5+/-6.3
kg/m2), a large proportion exhibited evidence of abnormal glycaemic control
prior to randomization (mean HBA1c 6.7+/-1.9%), with 48% having values
that were at least mildly elevated (HBA1c >6.1%) and 19% markedly elevated
(HBA1c >7%). The number of subjects with elevated HBA1c values decreased
from baseline in both the haloperidol and quetiapine treatment groups.
These findings suggest that switching treatment from a conventional antipsychotic
to quetiapine is not associated with weight gain or worsening of glycaemic
control, even in the long term. The study also highlights the high incidence
of unrecognized glucose dysregulation in patients with schizophrenia receiving
conventional antipsychotic treatment.
Pharmacopsychiatry. 2005 Jan;38(1):17-9.
Switching female schizophrenic patients to quetiapine from conventional
antipsychotic drugs: effects on hyperprolactinemia.
Nakajima M, Terao T, Iwata N, Nakamura J.
Department of Psychiatry, University of Occupational and Environmental
Health School of Medicine, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
INTRODUCTION: Conventional antipsychotic medications are associated with
elevated prolactin levels, resulting in hyperprolactinemia and a number
of unwanted side effects. Several atypical antipsychotics, on the other
hand, are less likely to evoke hyperprolactinemia. The aim of this study
was to investigate the prevalence of hyperprolactinemia induced by conventional
antipsychotic drugs, examine changes in serum prolactin levels and psychiatric
symptoms after switching to quetiapine, and identify the relevant characteristics
of patients who may be suitable to switch to quetiapine. METHOD: Sixty-nine
of 74 consecutive female patients who had received conventional antipsychotic
drugs were initially included in the study. Of these, 49 (71 %) patients
suffered from hyperprolactinemia, of which a further 25 were subsequently
switched to quetiapine. Psychiatric symptoms were assessed by the Positive
and Negative Syndrome Scale (PANSS), and serum prolactin levels were measured
just before and at 4 and 8 weeks after switching. RESULTS: Eight of the
25 (32 %) "switch" patients dropped out due to psychotic exacerbation
during the 8 weeks. In the remaining 17 (68 %) patients, serum prolactin
levels were significantly decreased without any significant change in
PANSS scores after switching. The 17 patients who completed the switch
had previously demonstrated significantly lower positive symptom scores
compared to the 8 dropout patients. CONCLUSION: The present findings suggest
that 71 % of female patients receiving conventional antipsychotic drugs
may suffer from hyperprolactinemia and that approximately two-thirds of
patients can be switched to quetiapine, resulting in an improvement in
hyperprolactinemia. The main characteristic of the switched patients may
be fewer positive symptoms.
J Psychopharmacol. 2005 Jun;19(2):211-3.
Risperidone and breast-feeding.
Aichhorn W, Stuppaeck C, Whitworth AB.
Department of Psychiatry, University of Innsbruck, Innsbruck, Austria.
wolfgang.aichhorn@uibk.ac.at.
We present the case of a breast-feeding woman with acute psychotic symptoms
after delivery, which were treated with the antipsychotic agent risperidone.
Serum levels of risperidone and 9-hydroxyrisperidone could be detected
in both the mother and her infant. Drug-levels in breast milk were ten-fold
lower compared to maternal serum. The patient responded well to antipsychotic
treatment. Her infant did not display any adverse effects and psychomotor
development was normal. In this case, risperidone was a safe treatment
option for the breast-feeding mother and her infant. We also provide a
brief overview of the clinically relevant data concerning antipsychotics
and breast-feeding.
