Pharmacopsychiatria最新文献

The discussion of some methodological problems of predictor studies led to the following conclusions: 1. Different outcome criteria result in a different classification of patients as responders or non-responders. 2. Predictor variables and outcome criteria should be better defined. 3. The clinical relevance of a result can be estimated by calculating the proportion of explained variance. 4. Cross validation of results is necessary. 5. Changes during a test therapy of 10 days result in a relatively reliable prediction of outcome in acute schizophrenia and depression.

The prognosis of a clinical neuroleptic treatment was prospectively examined in 26 schizophrenic patients using a predetermined set of predictors and outcome criteria. Prognosis before treatment did not discriminate significantly between patients with good and poor outcome. Significant differences of outcome were observed between the prognostic groups, if prognosis was established after 5 days of treatment. Retrospective analysis of individual predictors indicated the following rank order: initial improvement, age, duration of symptoms before treatment, sex, subjective tolerance of the treatment. The relative weight of the individual predictor in forming the prognosis is still an open question.

Three problems in the prediction of the long-term outcome of schizophrenia are illustrated by the results of three separate studies: The limitations of the possibility of generalizing results, the limits being due to the given historical and sociocultural settings. This determines the results of research. The relationships between different types of predictors and targets. The disease-related specificity of predictors. A prospective 1-year follow-up study comparing 100 schizophrenic patients in a rural region with 200 schizophrenic patients in an urban region shows regional differences in outcome criteria, such as rate of hospitalization. The prognostic significance of the various predictors is also different in the two regions. A follow-up study of 70 schizophrenic patients, who were continuously treated with neuroleptic drugs in our outpatient clinic after hospital discharge for an average of 14 years, shows a relatively good outcome. Several outcome dimensions (rehospitalization rate, symptoms, social and work adjustment, self-ratings) are partly mutually independent. The various outcome dimensions are predicted by different predictor patterns. A prospective follow-up study of 86 schizophrenic patients compared with 75 patients with other psychiatric diagnoses confirms the finding of the partly low intercorrelations of the different outcome criteria. The study additionally shows that the predictors of some outcome dimensions, such as work adjustment, are non-specific in respect of diagnosis.

Clinical and biological variables were investigated for their predictive value with respect to an antidepressant drug treatment. Thirty patients received clomipramine and thirty patients maprotiline. Characteristic features of the biography, the family anamnesis and the previous course of illness (apart from intermittent course) have no predictive value. The psychopathological symptoms before the start of treatment are also not suitable for prediction (except vegetative syndrome). The activity of the enzymes MAO, COMT and DBH before the start of treatment have no predictive value. The serum level of maprotiline on the seventh day of treatment does not correlate with the outcome of treatment. It is possible that patients, who have relatives with suicidal tendencies, are more likely to be clomipramine non-responders; patients with relatives who have a psychiatric history but without suicidal tendencies, are more likely to be maprotiline responders; i.a., relatives of the first degree manifesting psychiatric problems speak against a response to clomipramine and indicate a response to maprotiline. Patients with diurnal variations before the start of treatment are possibly more likely to respond to maprotiline than to clomipramine. There are statistically established findings for only the following variables: Diurnal variations during treatment speak in favour of an antidepressant response. A positive SD reaction indicates clomipramine response. A serum level of more than 75 ng clomipramine and more than 30 ng desmethyl-clomipramine/ml serum on the 7th day of treatment clearly predict a response to clomipramine.

As lithium has a wide range of biological effects, it is not surprising that the benefit from lithium treatment has been observed in several types of psychiatric disorders. Mood stabilization has been seen in episodic disorders; antiaggressive effect has been reported in mental retardation and other illnesses, and some endocrine and hematological effects have been utilized in internal medicine and neurology. To date, however, only the stabilizing effect on recurrent mood disorders appears to be reliably predictable. The prediction is based primarily on the diagnosis, quality of free interval and frequency of episodes; and several associated indicators can also be helpful. Results of the presented series of studies on the response to stabilizing lithium treatment suggest that such a response is predictable for most patients. The epitome of an excellent lithium responder is a patient with a good quality of remissions, a moderate frequency of recurrences, and a diagnosis of primary affective disorder. If the MMPI profile taken at the patient's optimum is abnormal, the chances of stabilization on lithium alone are greatly reduced. In addition, the responders more frequently have a family history of primary affective disorder and a positive M antigen. It appears that in the present practice the assessment of patients for stabilizing lithium treatment may frequently not be comprehensive enough. As a result, lithium is at present probably overprescribed in North America, and possibly elsewhere as well.

The present survey highlights the rationale for the use of state-dependent biological markers as predictors of clinical course in depression. Cortisol plasma levels after dexamethasone provide such a tool to monitor clinical progress. Since dexamethasone-resistant cortisol gradually returns to normalcy before a complete clinical remission is seen this measure has a possible predictive potential. Moreover, reversion to abnormal dexamethasone responses is prognostically infaust. Though the dexamethasone test has some merits, technical factors (e.g. exclusion criteria, dexamethasone-kinetics) which invalidate test results deserve careful consideration in future studies. Cortisol hypersecretion is considered as a physiological readout of a central disinhibition. This hypothesis is tested applying corticotropin-releasing factor and corticotropin in normal and abnormal DST responders. The data support the validity of the concept which assumes an intact but overactive pituitary-adrenal axis in a depressed subpopulation. A thesis is submitted which places the variety of biological disturbances in depression between two extreme viewpoints. One view considers all biological disturbances as sequelae to one particular dysfunction, e.g. disinhibition of corticosteroid secretion. The opposite view considers the myriad of biological disturbances as a sign of general loss of order, i.e. increased entropy, the precipitating mechanism of which is unknown.

Forty-nine patients with major depression and a reduced (less than 65.0 minute) REM latency were treated in a randomized, double-blind study with either amitriptyline or alprazolam. Predictors of response were sought for the whole group and for each drug cell individually. A longer current episode and a higher Beck Depression Inventory to Hamilton Rating Scale ratio were predictive of a poorer response for the whole group and for the alprazolam group. A longer current episode was also predictive of a poor response to amitriptyline. These data suggest that (1) a longer current episode and (2) a greater level of self-reported compared to clinician-observed symptoms correlate with a poorer response to antidepressant medications.

For psychopharmacological studies with caffeine two reliable non-invasive methods are available in order to determine pharmacokinetic parameters simultaneously with psychometric tests, without any appreciable impairment of the experimental subject. The investigation were performed in 13 healthy volunteers. Caffeine was determined in serum, saliva and urine. The caffeine level in saliva was about 70% of that in serum, corresponding to the percentage freely dissolved in serum. A good correlation was found to exist between elimination half-lives for serum and saliva levels (r = 0.9702) as well as serum and urine values (r = 0.8784). The amount of caffeine excreted in urine in its unmetabolized form was 1.1 +/- 0.2% of the dose administered. Furthermore, the saliva level was seen to represent the serum level on a broad scale. Sixty minutes after oral uptake, saliva levels were falsified due to adsorption of caffeine to the buccal mucosa. The special pattern of the saliva level during the phases of absorption and distribution is discussed.

The effect of L-deprenyl on neuroleptic-induced parkinsonism was evaluated in eleven patients. No significant improvement was observed during the treatment with L-deprenyl in the overall assessment. Four patients, however, were considered responders as their total scores on the modified version of Neurological Rating Scale decreased by at least 50%. No somatic or mental complications were observed during the study. The pretreatment platelet monoamine oxidase activity of the responders was slightly but not significantly higher than that of the non-responders. The plasma prolactin (PRL) levels of the patients with high pretreatment levels decreased significantly during the administration of L-deprenyl.