Progress in neuro-psychopharmacology最新文献

• 1.

  1. A specific anti-NAS antibody and fluorescein-labelled second antibody were employed to investigate the topographic distribution of immunoreactive NAS (INAS) in the hindbrain of the rat.

• 2.

  2. Positive identification of INAS was confirmed in the granular layer of the cerebellum, the spinal tract of the fifth cranial nerve and the pontine reticular formation.

• 3.

  3. INAS was also identified in neuronal cell bodies and processes of Purkinje cells, all cerebellar nuclei, the locus coeruleus and other brain stem regions.

• 4.

  4. The pattern of INAS distribution was found to be different from that of serotonin and melatonin.

• 5.

  5. Overlap of INAS- and NE- containing structures was identified in areas such as cerebellum and locus coeruleus, suggesting the possibility of a functional connection between these substances in some regions.

• 1.

  1. Adult male outbred albino mice were acutely injected with either of two dopamine (DA) agonists; Apomorphine, a receptor agonist, or Amantadine, a DA releasing agent.

• 2.

  2. Both drugs produced dose-related alterations in initial Y-maze behavior, consisting of significantly increased proportions of 2-arm entries.

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  3. This behavior has previously been shown to reflect an abnormal attentional process.

• 4.

  4. Thus DA activation may cause sensory perseveration.

• 5.

  5. The implications of this finding for DA theories of psychopathology is discussed.

• 1.

  1. Correlation between clinical response and plasma levels was investigated in seven patients with endogenous depression treated with 2×1 mg/kg/day of desipramine (DMI) for 21 days. Clinical response was measured by reduction in Hamilton Depression Rating Scale (HDRS) scores.

• 2.

  2. A beneficial effect of DMI was seen in five out of seven patients studied and was fully evident already one week after the beginning of treatment.

• 3.

  3. Great inter-individual differences were observed in DMI plasma levels both after a single dose and at ‘steady state’. The maximum plasma concentration after a single dose (C_max) ranged between 19 and 179 ng/ml and the mean ‘steady state’ concentration between 65 and 240 ng/ml.

• 4.

  4. No significant correlation was found between HDRS scores and plasma levels of DMI; however, a plot of plasma levels and amelioration scores at the end (22nd day) of treatment was suggestive of a curvilinear relationship.

• 5.

  5. Post ‘steady state’ plasma disappearance half-lives of DMI calculation in four patients ranged from 11.5 to 34.3 hr (mean ± S.E.M. = 26.2 ± 5.0).

General

Fifty out of 100 publications on multicenter trials and 21 on methods are listed and partly discussed. Our discussions concentrate only on double blind, therapeutic trials. Multicenter trials are the only way, to keep sources of heterogeneity or error under control. Making high demands, the advantages of well-done multicenter trials surpass by far the disadvantages.

• 1.

  1. How to conduct a multicenter trial.

  • 1.1.

    1.1 Introduction: In a trial the variabilities of interest are the efficacy and tolerance of drugs. Therefore all efforts have to be made to minimize all other non-treatment variances or to keep them constant. A multicenter trial has to be a logical, feasable, carefully planned and standardized sequence of events, carried out exactly as planned.

  • 1.2.

    1.2 Sample consideration: Heterogeneity of patients' diagnoses is an additional variance. Every variability beside the drug-effect will lower the success of the trial, the reliability and validity of the results. To prove or reject a hypothesis, the only target patients for an efficient proof are endogenous depressions (antidepressant), exacerbated paranoid schizophrenia (neuroleptic) and chronic anxiety states (minor tranquilizer) of medium to severe degree. Despite difficulties diagnostic labeling of patients (WHO-ICD 9) is an absolute necessity: symptoms are only meaningful in the context of the diagnosis concerned. Also the course of illness, past and present, is of importance (spontaneous remission during study). Statistical reasons require much higher sample sizes than are usually considered: with an $\text{α}$-risk of 5 %, a $\text{β}$-risk of 10 %, a 50 % expected improvement of a standard and a 60% improvement of a new drug, two times 422 patients are necessary to demonstrate a difference.

  • 1.3.

    1.3 Settings and investigators: Cross-study variabilities of numerous sources should be minimized as much as possible, concentrating on efficacy and tolerance of drugs: “prevention is better than cure”. The higher the qualification, experience and capability of investigators and nurses, the better will be the results and reliability.

  • 1.4.

    1.4. Experimental design: Clinical multicenter trials should be organized and conducted in a way which resembles ordinary clinical practice and being in the best interest of the (future) patients (Declaration of Helsinki/Tokyo). The design, the protocol, patient forms, execution and evaluation should be a master-piece of clarity. There is only one way to minimize undesired variability and deviations: standardization of every detail from the beginning to the end, considering logical thinking, reality, feasibility and practicability. One kind of standardization should never be attempted, a fixe