Subjective response to antipsychotics in schizophrenic patients: clinical implications and related factors

Awad defined subjective response to medication as the subjective interpretation of the physiological changes that follow its intake. This response is involved in drug compliance and may relate to clinical outcome of the disease. This study examined the variables hypothesized to be related to subjective response to antipsychotics. Sixty schizophrenic in-patients were evaluated with a protocol that examined compliance, hospitalizations, psychopathology, familial and social relationships, degree of autonomy and motivation for life during the year prior to the study. Overall functioning in the previous year was assessed with the Global Assessment Scale (GAS), psychopathology with the Brief Psychopathology Rating Scale (BPRS), insight with the Birchwood scale and side-effects with the Uscandinavian Kociety of Usypharmacology (UKU) side-effects rating scale. Subjective response was evaluated with the Drug Attitude Inventory (DAI-30). The multiple regression analysis revealed that insight and the BPRS paranoid subscale predicted subjective response to antipsychotics (R2=0.31). No relationship was found between subjective response and sociodemographic variables or side-effects. A positive subjective response was related to drug compliance and variables that indicate a more benign clinical course over the previous year. Subjective response to antipsychotics in schizophrenia is related to insight and paranoid ideation.     

第二代抗精神病药对慢性精神分裂症患者的治疗作用

目的：探讨第1代抗精神病药（FGA）联合与未联合第2代抗精神病药（SGA）对慢性精神分裂症患者临床疗效、认知功能及社会功能的影响。方法：74例慢性精神分裂症患者被随机分为联合组和对照组,联合组为FGA联合SGA,对照组则为持续应用FGA,治疗至少12周。采用简明精神病量表（BPRS）分别于治疗前后评估患者临床疗效,以探究性眼动检测来评估患者的认知功能,采用个人和社会功能量表（PSP）评估社会功能。结果：探究性眼动检测治疗前凝视点数联合组显著低于对照组（P〈0.05）;尽管经过联合SGA治疗后两组间凝视点数虽不存在差异（P〉0.05）,但联合组治疗前后的凝视点数增加值却显著好于对照组（P〈0.001）;反应性探索（RSS）评分在疗前、疗后两组间均差异无显著性。所有联合SGA患者在治疗后PSP评分均显著优于未联合用药组（P〈0.05或P〈0.001）;LSD分析提示：尤以联合利培酮或阿立哌唑对患者PSP评分改善最为显著（P均〈0.001）。结论：联合SGA对慢性精神分裂症患者疗效显著,尤其对患者认知和社会功能改善明显。     

Ceruletide resembles antipsychotics in rats and schizophrenic patients. Preliminary report

Peptides related to the C-terminal part of cholecystokinin, including ceruletide, were found to be active in a number of behavioral test procedures in rats, predicting antipsychotic action. In a subsequent clinical trial ceruletide was administered intramuscularly in a dose of 40 micrograms twice for 2 consecutive weeks to 6 neuroleptic-treated schizophrenic patients following a single-blind design. In 3 patients, a pronounced long-lasting antipsychotic effect was observed, while in the other 3 the response was less marked. It is suggested that ceruletide may be a potential antipsychotic peptide.     

Performance of a neuro-fuzzy model in predicting weight changes of chronic schizophrenic patients exposed to antipsychotics

Artificial intelligence has become a possible solution to resolve the problem of loss of information when complexity of a disease increases. Obesity phenotypes are observable clinical features of drug-naive schizophrenic patients. In addition, atypical antipsychotic medications may cause these unwanted effects. Here we examined the performance of neuro-fuzzy modeling (NFM) in predicting weight changes in chronic schizophrenic patients exposed to antipsychotics. Two hundred and twenty inpatients meeting DSMIV diagnosis of schizophrenia, treated with antipsychotics, either typical or atypical, for more than 2 years, were recruited. All subjects were assessed in the same study period between mid-November 2003 and mid-April 2004. The baseline and first visit's physical data including weight, height and circumference were used in this study. Clinical information (Clinical Global Impression and Life Style Survey) and genotype data of five single nucleotide polymorphisms were also included as predictors. The subjects were randomly assigned into the first group (105 subjects) and second group (115 subjects), and NFM was performed by using the FuzzyTECH 5.54 software package, with a network-type structure constructed in the rule block. A complete learned model trained from merged data of the first and second groups demonstrates that, at a prediction error of 5, 93% subjects with weight gain were identified. Our study suggests that NFM is a feasible prediction tool for obesity in schizophrenic patients exposed to antipsychotics, with further improvements required.     

Effects of antipsychotics on prepulse inhibition of the startle response in drug-na?ve schizophrenic patients.

BACKGROUND: Disturbances in sensorimotor gating measured by prepulse inhibition of the startle response (PPI) have frequently been reported in medicated and unmedicated schizophrenia spectrum patients and in their relatives, suggesting that the deficit represents a stable vulnerability marker for schizophrenia. Clinical data on the effects of antipsychotics on PPI disturbances are scarce, but from preclinical studies, antipsychotics have been shown to influence PPI. To differentiate pathogenetic mechanisms from drug related effects, longitudinal clinical studies on the effect of antipsychotic treatment on PPI in drug-naive first-episode schizophrenic patients are needed. METHODS: First-episode schizophrenic patients never previously medicated with antipsychotics were examined at inclusion and after 3 months of treatment with the atypical antipsychotic compound, risperidone, or the typical drug, zuclopenthixol. Healthy controls were used as a comparison group. RESULTS: The results confirm deficits in PPI in drug-naive first-episode patients. No effect of antipsychotic treatment on PPI dysfunction was observed in any of the treatment groups. CONCLUSIONS: The data are the first to show the possible effect of treatment with antipsychotic drugs on PPI disturbances in a longitudinal study of drug-naive schizophrenic patients. The data do not support any influence of treatment with antipsychotic drugs on sensorimotor gating deficits. Instead, the results point to the impairment in PPI as a stable vulnerability indicator.     

多巴胺D3受体基因多态性与精神分裂症初发期患者抗精神病药疗效关系的研究

目的　探讨多巴胺D3 受体 (DRD3)基因多态性与精神分裂症初发期患者精神症状严重度和抗精神病药疗效是否相关。方法　对 10 9例精神分裂症初发期患者分别进行利培酮治疗 [4 3例 ,3～ 5mg/d ,平均 ( 4 0± 0 5 )mg/d]和氯丙嗪治疗 [6 6例 ,15 0～ 6 0 0mg/d ,平均 ( 339± 87)mg/d],疗程 10周。采用聚合酶链反应 限制性片段长度多态性技术检测其中 10 8例患者 (男 5 2例 ,女 5 6例 )DRD3基因ser9gly多态性。采用阳性和阴性症状量表 (PANSS)评定患者治疗前和治疗第 10周末的精神症状 ,并分析基因型及其他临床指标与PANSS分值和减分率的关系。结果　DRD3ser9gly基因型在各患者组分布频率均符合Hardy Weinberg定律 (P >0 0 5 ) ;基因型在治疗显效和未显著进步组分布频率的差异有显著性 ( χ2 =6 4 4 ,ν=2 ,P <0 0 5 ) ;各基因型亚组临床指标的差异均无显著性 (均P >0 0 5 ) ;基因型与患者治疗前PANSS总分及治疗第 10周末PANSS总减分率、阳性症状减分率的差异均有显著性(均P <0 0 5 )。结论　DRD3基因ser9gly功能多态性可能是精神分裂症初发期患者精神症状严重程度和抗精神病药疗效 (尤其对阳性症状疗效 )的遗传影响因子。     

Sexual dysfunction and hyperprolactinemia in Japanese schizophrenic patients taking antipsychotics

This study aimed to estimate the prevalence of sexual dysfunction, evaluated by the Nagoya Sexual Function Questionnaire (NSFQ), and hyperprolactinemia in patients with schizophrenia and examine a relationship between sexual dysfunction and serum prolactin levels. This cross-sectional, comparative study was performed using a sample comprising 195 Japanese schizophrenic in- and outpatients treated with antipsychotics (117 males and 78 females). Data were collected from October 2009 to January 2010 using single, cross-sectional ratings of sexual function assessed by the NSFQ and concurrent measurement of serum prolactin levels. The prevalence of sexual dysfunction in patients with schizophrenia was high (males 66.7%; females 79.5%). Hyperprolactinemia (>25ng/ml) was highly prevalent among schizophrenia patients, affecting 53.8% of females and 51.3% of males. Among female patients, 16.7% had prolactin levels>100ng/ml. There was no relationship between sexual dysfunction and serum prolactin levels. The present study demonstrated a higher prevalence of sexual dysfunction and hyperprolactinemia in Japanese schizophrenia patients. Clinicians should keep these problems in mind and discuss potential solutions with patients to improve patients' quality of life and adherence to therapy.     

慢性精神分裂症血超氧化物歧化酶与精神病理关系研究

目的　探讨自由基及其防御酶超氧化物歧化酶 (SOD)在精神分裂症病理机制中的作用。　　方法　采用放射免疫法测定 66例慢性患者和 2 5例正常人SOD含量 ,同时评定BPRS、SAPS、SANS量表。　　结果　患者SOD含量明显升高 ,其中BPRS、SAPS高分组比低分组的SOD均显著升高 (P <0 0 5) ,SANS高、低分组之间无差异。相关分析结果表明 ,SOD与BPRS、SAPS、SANS量表总分均呈显著正相关 (P <0 0 5)。　　结论　自由基与精神分裂症精神病理之间可能有一些内在联系     

Suicide behaviour over 18 months in recent onset schizophrenic patients: the effects of CBT

The results of a trial of cognitive behaviour therapy, supportive counselling and treatment as usual in recent onset schizophrenia on suicide behaviour are reported. Treatment was delivered over a five week period during hospitalisation for an acute episode. Participants were assessed at baseline, 6 weeks, 3 and 18 months. Over the 18 months there were 3 definite suicides and 2 deaths by accidental causes. The rates of moderate to severe suicidal behaviour were 13% at admission, 4% at six weeks, 1.5% at three months and 6% at 18 months. There were no beneficial or adverse effects of psychological treatment on suicide behaviour that reduced significantly with clinical recovery. There is a general picture of those who suffer persistently higher levels of psychotic symptoms, poorer functioning, depression and low self-esteem have higher severity of suicide behaviour, although the numbers with clinically significant suicide behaviour are low. CBT may need to be modified to directly target suicide behaviour and its antecedents to significantly reduce risk; recommendations on this are made.     

Differences between chronic schizophrenic patients in the hospital and in the community.

Clinical differences between stable, chronic schizophrenic patients with long stays in the hospital and schizophrenic patients living in the community were investigated. Patients were matched for age, gender, and diagnosis. Hospitalized patients had more severe thought disorder and negative symptoms, and those in the community had a significantly higher incidence of depression and anxiety. The community-based patients were also receiving higher doses of neuroleptic drugs and had a higher incidence and severity of extra-pyramidal side effects. Results suggest that living in the community, despite its obvious benefits, may have its price in terms of the distressing effects of affective symptoms and neuroleptic side effects.     

Association between stereotypic behavior and polydipsia in chronic schizophrenic patients

We assessed temporal associations between polydipsia and motor stereotypies in chronic schizophrenia. Subjects included: (a) a polydipsic patient with marked stereotypies; (b) a polydipsic patient with no history of stereotypy; (c) a nonpolydipsic patient. Stereotyped grooming and pacing were significantly associated with drinking for polydipsic patients only (polydipsic patients evidenced a 87% and 66% concordance between excessive grooming and drinking versus 12% in the control). Our findings provide the first empirical demonstration that polydipsia is temporally associated with other repetitive behaviors. The use of behavioral assessment to examine etiological theories suggesting that polydipsia stems from interacting environmental, biological, and pharmacological variables is discussed.     

Predictors of response to high dose antipsychotics in chronic schizophrenics

Significant numbers of chronic schizophrenic patients do not experience sufficient symptom relief from usual doses of antipsychotic medication. Clinicians must decide if high doses of antipsychotics should be tried. In this study baseline symptoms, drug levels, and the symptomatic effects of an acute stimulant challenge were examined before 14 subjects received a 50% increase in their antipsychotic dosing. The group as a whole did not improve. Several individuals with lower drug levels, high baseline hallucinations, and stimulant-induced improvement in hallucinations improved mildly after 3 weeks on the higher antipsychotic dose.     

Predictive validity of proposed remission criteria in first-episode schizophrenic patients responding to antipsychotics

The objective of this study was to examine the predictive validity of the remission criteria proposed by Andreasen et al in first-episode patients responding to antipsychotics. Antipsychotic responsive patients with first-episode schizophrenia showing symptom remission (n = 60) were compared with patients who did not fulfill the proposed criteria (n = 65). Outcome in terms of symptom severity, social functioning, and quality of life was assessed after 18 months. Patients in the remission group showed a significantly better outcome during follow-up on all Positive and Negative Syndrome Scale subscale scores (positive, negative, and general symptom subscales) and a significantly higher level of social functioning. Quality of life did not differ between groups. The proposed multidimensional criteria for symptomatic remission convey significant information when applied to first-episode patients who responded to antipsychotics, predicting outcome on the domains of both psychopathology and social functioning. The criteria represent a practicable benchmark with clinical relevance. Their implementation should be promoted in research settings, clinical practice, and routine outcome assessment procedures.     

Comparison of the visually evoked response in drug-free chronic schizophrenic patients and normal controls.

Thirteen cooperative male drug-free chronic schizophrenic patients, and 11 mentally normal male controls were studied. The VER was recorded from scalp leads O1, O2, Oz, C3 and C4 to combined ear reference (A1--A2). The stimulus was an unpatterned flash of single intensity. Compared to normal controls, there were no consistent differences in wave peak latencies or amplitudes for chronic schizophrenics in any brain area tested. When the chronic schizophrenic patients were separated on the basis of high and low tryptophan uptake, using the Frohman--Gottlieb criteria, the high uptake group exhibited normal VERs while in the occipital regions the low tryptophan uptake group exhibited prolonged latencies and an increased amplitude for wave V when compared to normals. From BPRS scores the high tryptophan subgroup indicated a greater degree of psychopathology than the low tryptophan subgroup. The results obtained do not support an indole hallucinogen hypothesis for process schizophrenia.