Hsin-Nan Lin

Effects of Atypical Neuroleptics on Sustained Attention Deficits in Schizophrenia: A Trial of Risperidone Versus Haloperidol

To help determine whether sustained attention deficits as measured with the Continuous Performance Test (CPT) are stable vulnerability indicators of schizophrenia, we compared the CPT performance of schizophrenic patients before and after treatment with risperidone or haloperidol. In this double blind trial, 56 schizophrenic patients were randomly assigned to a 12-week regimen of either risperidone or haloperidol, after a 1-week washout period. The patients undertook two sessions of the CPT (undegraded and 25% degraded) twice, one at the end of the washout period and the other at the end of the study. Thirty-eight patients completed the study, 19 in each group. Both groups experienced significant improvements in clinical symptoms, and the risperidone group showed no change in the severity of extrapyramidal symptoms. Despite those improvements, the CPT performance indexes did not change significantly from the beginning to the end of the study. These findings indicate that sustained attention deficits might be stable vulnerability indicators of schizophrenia.

Symptom patterns and subgrouping of schizophrenic patients: significance of negative symptoms assessed on admission

This study subgroups schizophrenic patients based on symptoms assessed on admission and examines the validity of the subgrouping using follow-up data and other clinical outcome variables. Schizophrenic patients (n=163) from consecutive admission received ratings on the positive and negative syndrome scale (PANSS) on admission and during a 1-year follow-up course. An exploratory graphic analysis on the admission PANSS derived four symptom dimensions: negative symptoms, disorganized thought, hostility/excitement and delusions/hallucinations. This yielded two subgroups of patients on admission, a group with marked negative (GWNEG) and a group without marked negative (GONEG) symptoms. Compared with the GONEG, the GWNEG had a poorer recovery rate, more impairment in attention, a slower response of the delusion/hallucination symptoms to neuroleptic treatment and a longer duration of index hospitalization. At a one-year follow-up, the GWNEG assessed on admission had persistently higher scores on the negative symptom and disorganized thought syndromes, less relapse rate, a shorter duration on job, as well as worse social functioning than the GONEG. Thus, the GONEG might comprise patients having a pure paranoid syndrome with quick and better treatment response, while the GWNEG comprises patients with the blunt-disorganization syndrome having a poorer outcome.

Plasma homovanillic acid and treatment response in a large group of schizophrenic patients

Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r = 0.408, p < 0.0001). Good responders (BPRS improvement > or = 50%, n = 47) had higher pretreatment pHVA levels than poor responders (BPRS improvement < 50%, n = 48) (15.7 +/- 8.4 ng/ml versus 9.9 +/- 3.7 ng/ml, p < 0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA > or = 12 responded whereas 65% (31 of 48) who had < 12 did not respond (chi-square = 13.02, p < 0.0001). These results suggest that higher pretreatment pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.

Plasma Haloperidol and Reduced Haloperidol Concentrations in a Geriatric Population

Haloperidol (HL) and reduced haloperidol (RH) plasma concentrations were measured in geriatric patients (n = 45) and schizophrenic patients (n = 8). In the elderly patients, HL doses were 1-4 mg/day while only 2 mg/day was used in the schizophrenics. At HL 2 mg/day dose in both age groups, mean plasma HL levels were approximately twice as high in the elderly patients compared to the schizophrenics (1.39 +/- 0.82 vs. 0.56 +/- 0.23 ng/ml, p < 0.02). RH plasma concentrations were almost 5 times greater in the elderly patients (0.54 +/- 0.35 vs. 0.09 +/- 0.05 ng/ml, p < 0.0001). These results suggest that HL plasma concentrations in the elderly are greater than in adult schizophrenic patients treated with similar HL doses.

Dose-dependent reduced haloperidol/haloperidol ratios in schizophrenic patients☆

Plasma haloperidol (HAL) and reduced HAL (RHAL) concentrations were measured in 113 Chinese schizophrenic patients. Daily doses of HAL ranged from 8 to 65 mg. Samples were obtained under steady-state conditions and drawn 10-12 hours after the bedtime dose and before the morning dose. In all, 313 blood samples were collected. Multiple samples were obtained at the same doses in 63 patients and at two or three different doses in 31 patients. HAL and RHAL concentrations were assayed by high performance liquid chromatography. Interpatient variation in plasma HAL levels at a given dosage was up to sixfold. However, there was a high positive correlation between plasma levels and daily dosages with the equation of HAL plasma level (ng/ml) = 0.88 x dosage (mg/day) -0.56 or 46.0 x dosage (mg/day/kg) + 0.28. The expected values are about 15-55% higher than those obtained from non-Chinese patients as reported in the literature. The RHAL/HAL ratios were dose-dependent. The greater the dose used, the higher the ratio. An upper therapeutic limit of plasma HAL level is suggested to be 25 ng/ml, which can be achieved at dosages about 30 mg/day in most Chinese patients. Based upon the dose-dependent increase in RHAL/HAL ratios, the importance of RHAL in determining the therapeutic benefit of HAL treatment is discussed.

Serial dexamethasone suppression test in psychiatric inpatients

A sample of 100 consecutively admitted cases were recruited to test the hypothesis that an abnormal dexamethasone suppression test (AbDST) is associated with decreasing clinical severity during the course of hospitalization in various diagnostic categories. Serial DSTs and psychopathological ratings were done at the end of the first and the third week postadmission, and 1 week before discharge. DST was also done at 1-year follow-up after discharge. The results of this study strongly suggest that a dual mechanism is responsible for the prevalence of AbDST. One is related to the global psychopathology of a nonspecific quantitative mechanism in various diagnostic categories. The other is a specific qualitative mechanism relating to the depressive state, as reflected in the higher prevalence of AbDST and more consistent AbDST results across different study time points in melancholia, and also in higher AbDST rates in disorders with higher depressive scores.