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Biomedical subjects

T Van Putten

Publications and source records attributed to T Van Putten.

At least 19 recordsLinked to original sources
PubMed1992

Haloperidol plasma levels and clinical response: a therapeutic window relationship.

OBJECTIVE: The purpose of the study was to assess the relationship between plasma haloperidol and clinical response. METHOD: Sixty-nine newly admitted drug-free schizophrenic men were randomly assigned to receive haloperidol, 5, 10, or 20 mg daily for 4 weeks, and clinical response was measured at the end of the fixed-dose period. Haloperidol was assayed by a sensitive and specific radioimmunoassay. RESULTS: The authors found a curvilinear relationship between clinical response and plasma haloperidol during fixed-dose treatment, with an apparent optimum between 5 and 12 ng/ml. When plasma levels above 12 ng/ml were lowered to the 5-12 ng/ml range, all patients improved to varying degrees and no patient deteriorated. When plasma levels of nonresponders within this therapeutic window were raised above 12 ng/ml (as in routine practice), they, on balance, deteriorated in that they became more dysphoric. With the 20-mg dose, half the patients had plasma levels above 12 ng/ml. CONCLUSIONS: In this sample of newly admitted schizophrenic men, optimal clinical response occurred with a plasma haloperidol range of 5-12 ng/ml.

Adult↗
PubMed1991

Neuroleptic plasma levels.

There is enormous variation in plasma levels of most neuroleptics in patients on the same dose. Much of the past research on the relation between plasma levels of antipsychotic drugs and clinical change, however, has been difficult to interpret. It does appear that decreased bioavailability, at least in public institutions, is rarely the cause of treatment failure. Aberrantly low plasma levels are more likely due to surreptitious noncompliance or drug interactions with enzyme inducers such as carbamazepine. Therapeutic plasma level ranges, in which good antipsychotic effect occurs without undue side effects, have been tentatively identified for perphenazine, haloperidol, fluphenazine, and chlorpromazine. The extent to which aberrantly high plasma levels are associated with inferior antipsychotic response is unclear. Antipsychotic plasma levels may be most useful when the distinction between side effects and worsening psychosis is unclear. The utility of high neuroleptic plasma levels in the treatment-resistant patient is unclear.

Antipsychotic Agents↗
PubMed1991

Plasma levels of fluphenazine in patients receiving fluphenazine decanoate. Relationship to clinical response.

The levels of fluphenazine and fluphenazine sulphoxide in schizophrenic patients who were randomly assigned to receive either 5 mg or 25 mg of fluphenazine decanoate every two weeks were monitored. Patients treated with 25 mg of fluphenazine decanoate required three months to reach a steady-state plasma level, indicating that those patients who are being converted from oral to depot fluphenazine should continue to receive oral supplementation during the first three months of treatment with fluphenazine decanoate. Plasma levels of fluphenazine sulphoxide were lower than levels of fluphenazine. At six and nine months following randomisation, there was a statistically significant relationship between lower fluphenazine plasma levels and an increased risk of psychotic exacerbations. A relatively weak relationship was found between fluphenazine plasma levels and akinesia, but non-significant relationships between fluphenazine levels and other neurological side-effects including akathisia, retardation, and tardive dyskinesia. Monitoring the plasma levels may be helpful to clinicians who are attempting to treat stabilised patients with the lowest effective dose of fluphenazine decanoate.

Adult↗
PubMed1991

Serum prolactin as a correlate of clinical response to haloperidol.

The rise in serum prolactin concentration in patients treated with neuroleptic drugs is well documented, but attempts to relate this rise to clinical response have yielded conflicting results. These conflicting results could be explained by design flaws in those studies attempting to relate prolactin to clinical response. Seventy-three newly (re)admitted drug-free schizophrenic men were randomly assigned to receive haloperidol either 5, 10, or 20 mg daily for 4 weeks. Prolactin levels post-treatment were significantly (p less than 0.02) related to global outcome by logistic regression. A serum prolactin level may be a useful guide to the lowest effective dose of haloperidol in newly treated schizophrenic men. Above a plasma prolactin level of approximately 30 ng/ml there was very little increase in response. Patients on the 5, 10, and 20 mg daily haloperidol doses had mean prolactin levels of 16, 32, and 34 ng/ml, respectively.

Adult↗
PubMed1991

Early prediction of relapse in schizophrenia: an application of receiver operating characteristic (ROC) methods.

We compared different methods of identifying prodromal periods with regard to their ability to predict relapse in schizophrenia. Fifty stabilized schizophrenic patients, who received a low dose of schizophrenic patients, who received a low dose of fluphenazine decanoate (5 to 10 mg every 2 weeks) were monitored with weekly evaluations to determine whether they met criteria for nonpsychotic prodromal episodes. We evaluated three different scales: (1) the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS); (2) a modification of the patient self-report Early Signs Questionnaire and (3) the Idiosyncratic Prodromal Scale (IPS). We used receiver operating characteristic (ROC) methods for comparing the different instruments as methods for predicting whether patients would or would not demonstrate a psychotic exacerbation in the 4 weeks following the assessment. Both the IPS and the BPRS cluster scores were better than chance at correctly identifying periods of vulnerability to psychotic exacerbation. The ROC analyses suggest that relatively small changes in the signs and symptoms of chronic schizophrenic patients in maintenance treatment may be clinically meaningful.

Humans↗
PubMed1991

Plasma fluphenazine levels and clinical response in newly admitted schizophrenic patients.

Seventy-two newly readmitted, drug-free men with the diagnosis of schizophrenia by DSM-III were assigned randomly to receive fluphenazine hydrochloride at 5 mg, 10 mg, or 20 mg daily for 4 weeks. Fluphenazine (FLU), fluphenazine sulfoxide, 7-hydroxyfluphenazine, and fluphenazine N-oxide were measured by highly specific and sensitive radioimmunoassays. Data were analyzed by logistic regression using the Clinical Global Impressions Disabling Side Effects and Global Improvement as the outcome measures. Disabling side effects were defined as "side effects that significantly interfered with patient's functioning" or "side effects that outweigh therapeutic effects" (National Institute of Mental Health 1985, p. 839). Higher plasma FLU levels (up to 4.23 ng/mL) were significantly (p = .015) associated with a higher rate of global improvement. However, close to 90 percent of these acute patients had disabling side effects at a plasma FLU level of 2.7 ng/mL. At least in the patient's view, these disabling side effects negated or compromised the improvement in psychosis. Fluphenazine N-oxide may be a toxic metabolite in that it was more powerfully associated with side effects than was the parent FLU.

Adult↗
PubMed1990

A controlled dose comparison of haloperidol in newly admitted schizophrenic patients.

Eighty newly admitted or readmitted men with DSM-III schizophrenia were assigned to receive 5, 10, or 20 mg/d of haloperidol for 4 weeks. Staff were not "blind" to dose. By Clinical Global Impression Scale ratings, the 20-mg dose appeared to be superior to both the 5- and 10-mg doses for the first 2 weeks of treatment but not thereafter. On the Brief Psychiatric Rating Scale Schizophrenia factor, the 20-mg dose was superior to the 5-mg dose throughout the trial and tended to be marginally superior to the 10-mg dose after the first 2 weeks of treatment. By the second week of treatment, however, the group receiving the 20-mg dose deteriorated significantly with regard to Brief Psychiatric Rating Scale ratings of Withdrawal-Retardation (blunted affect, motor retardation, and emotional withdrawal) as well as akinesia and akathisia ratings. Furthermore, 35% of patients given 20 mg/d of haloperidol insisted on leaving the hospital against medical advice vs only 4% of those given 5 or 10 mg/d of haloperidol. A 20-mg/d dose of haloperidol, therefore, may have substantial "psychotoxic" effects by the second week of treatment.

Adult↗
PubMed1990

Therapeutic monitoring of steady-state plasma levels of the N4'-oxide metabolite of fluphenazine in chronically treated schizophrenic patients determined by a specific and sensitive radioimmunoassay.

Highly specific and sensitive antisera for fluphenazine-N4'-oxide (FLUNO) were obtained from New Zealand white rabbits immunized with a bovine serum albumin conjugate of 7-(3-carboxypropionyl)propchlorperazine-N4'-oxide. One of the antisera was used to develop a radioimmunoassay (RIA) procedure that enabled for the first time the determination of steady-state plasma levels of FLUNO, an active metabolite, in patients treated with oral or intramuscular (i.m.) fluphenazine (FLU). This method has sufficient sensitivity to quantitate accurately 20 pg of FLUNO in 200 microliters of plasma extract with a coefficient of variation of less than 8%. The antiserum had negligible cross-reactivity (less than 2%) with FLU and its major metabolites such as FLU sulfoxide, 7-hydroxy-FLU, and N-deshydroxyethyl-FLU. To confirm that the developed RIA procedure specifically quantitated FLUNO, FLUNO was selectively reduced to FLU by sodium dithionite in plasma samples from patients. A good correlation (r2 = 0.9646) was observed between the total FLU level and the sum of FLU and FLU equivalent to FLUNO determined separately in the same plasma. The steady-state plasma concentrations of FLUNO in patients receiving a daily oral dose of 5 to 20 mg of FLU dihydrochloride ranged from 13 to 378% of that of FLU, whereas this value ranged from 10 to 214% in plasma samples from patients treated with a biweekly intramuscular (i.m.) dose of 5 mg of FLU decanoate.

Administration, Oral↗
PubMed1990

Fluphenazine plasma levels and clinical response.

We monitored fluphenazine plasma levels in 39 schizophrenic patients who participated in a 2-year double-blind comparison of 5 mg and 25 mg of fluphenazine decanoate (FD) administered every 14 days. We investigated the relationship between log-transformed plasma levels at 3, 6, and 9 months and subsequent psychotic exacerbations with logistic regression and survival analysis. Using logistic regression, the relationship was nonsignificant at 3 months (chi-square = .21, df = 1, p = .65), but significant at 6 months (chi-square = 4.38, df = 1, p = .04) and 9 months (chi-square = 8.98, df = 1, p = .003). Using survival analysis with fluphenazine levels as a covariate (Cox models), we also found significant relationships between the fluphenazine plasma level and the risk of exacerbations at 6 months (chi-square = 3.77, df = 1, p = .052) and 9 months (chi-square = 12.21, df = 1, p = .0005), but not at three months (chi-square = 0.87, df = 1, p = .65). These findings suggest that the measurement of fluphenazine plasma levels may be helpful in decision-making about the dosage of FD.

Adult↗
PubMed1989

Pharmacokinetics of long-acting injectable neuroleptic drugs: clinical implications.

The authors review the literature regarding the pharmacokinetics of long-acting injectable neuroleptic drugs (LINS). There are important differences between LINS and oral neuroleptics that affect their pharmacokinetics. By avoiding first pass metabolism in gut and liver, LINS result in lower circulating concentrations of metabolites than are found after oral administration. In addition, LINS take more time to reach a stable steady state than their oral counterparts. The clinical significance of these pharmacokinetic properties is discussed. The authors recommend that when patients are being changed from oral neuroleptics to LINS, that this conversion be done gradually over several months.

Antipsychotic Agents↗
PubMed1989

Plasma levels of parent drug and metabolites in patients receiving oral and depot fluphenazine.

We evaluated the metabolism of fluphenazine (FLU) in patients treated with either the oral form of FLU or with fluphenazine decanoate (FD). Samples for both patient populations were analyzed using four different radioimmunoassays developed in our laboratories for fluphenazine, fluphenazine sulfoxide (FS), 7-hydroxy fluphenazine (7OHFLU), and fluphenazine N-oxide (FLUNO). In patients receiving oral FLU the levels of FS and 7OHFLU were significantly higher than levels of FLU. In patients receiving FD, the levels of metabolites were significantly lower than FLU levels. This supports the view that drug metabolism is likely to be a more important factor for patients treated with an oral as opposed to a depot phenothiazine neuroleptic.

Delayed-Action Preparations↗
PubMed1989

Anticholinergic effects on memory: benztropine versus amantadine.

To evaluate anticholinergic effects on cognition and other functions, we studied 60 healthy volunteers in a double-blind crossover trial of two antiparkinsonian agents, benztropine and amantadine. Benztropine 4 mg/day, but not amantadine 200 mg/day, impaired free recall and perception of time, and subjects' perception of their own memory impairment was significantly greater with benztropine. Side effects in general were worse with benztropine, particularly such anticholinergic effects as dry mouth and blurred vision, and benztropine decreased measured salivary flow to a significantly greater degree than amantadine. Our findings support the hypothesis that drugs that decrease cholinergic transmission impair storage of new information into long-term memory, but have little effect on retrieval from memory or on tasks involving only immediate memory. Clinically, anticholinergic agents can levy a considerable burden on memory and time perception.

Adolescent↗
PubMed1988

Differential effect of low and conventional doses of fluphenazine on schizophrenic outpatients with good or poor information-processing abilities.

Thirty-six stabilized schizophrenic outpatients were randomly assigned to receive either 5 or 25 mg of fluphenazine decanoate biweekly and were followed up for two years. The best and worst outcomes were found in groups with good or poor information-processing abilities (as measured by a partial-report span-of-apprehension task) given the same 25-mg dose of fluphenazine decanoate. The 86% two-year survival rate of the patients with poor span performance was considerably better, while the 44% one-year and the 21% two-year survival rates of patients with good span performance were considerably lower than previously reported survival rates for schizophrenic patients receiving a conventional dose of fluphenazine. The significant correlations in a patient's span performance for periods up to one year were consistent with the hypothesis that this task taps processes associated with vulnerability to schizophrenic disorder.

Adult↗