P Landau

Research Triangle Park Laboratories, Inc., Raleigh, North Carolina, United States

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Publications (9)46.71 Total impact

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    ABSTRACT: The noradrenaline (NA) hypothesis of depression is founded primarily on preclinical and clinically indirect evidence. In two three-compartment randomized parallel clinical trials conducted serially, we examined the significance of NA uptake for antidepressant activity. The racemic compound oxaprotiline (hydroxymaprotiline) is a highly specific inhibitor of NA uptake, whereas its R-(-) enantiomer levoprotiline is totally devoid of this property. Oxaprotiline significantly resembled amitriptyline in its antidepressant potential. Conversely, levoprotiline significantly resembled placebo in antidepressant potential. Therefore, NA uptake was necessary for the observed therapeutic effect of this experimental antidepressant.
    Biological Psychiatry 03/1993; 33(4):261-6. · 9.25 Impact Factor
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    ABSTRACT: Serotonin 1a and serotonin-2 receptors are implicated in anxiety. Serazepine (CGS-15040A, (R,S)-1,3,4,16b-Tetrahydro-2-methyl-2H,10H-indolo[2,1-c] Pyrazino-[1,2-a][1,4] benzodiazepine-16-carboxylic acid, methyl ester hydrochloride]) is a representative of a novel pentacyclic ring system containing a stabilized indole. In chemical assays it was a highly specific inhibitor of serotonin (5-HT2) binding, and it was active in preliminary preclinical assays of anxiolytic potential. This multicenter trial of CGS-15040A in patients with generalized anxiety disorder demonstrated clinical anxiolytic effects consistent with established preclinical effects. Doses greater than or equal to 10 mg reduced Hamilton Anxiety Scale scores. However, the dose-response relationship was nonlinear. Effects appeared primarily related to the psychic components of anxiety.
    Biological Psychiatry 01/1993; 34(1-2):41-4. · 9.25 Impact Factor
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    ABSTRACT: Children and adolescents with obsessive compulsive disorder were studied in an 8-week, multicenter, double-blind, parallel groups trial of clomipramine hydrochloride (CMI) versus placebo. Efficacy assessments included the child version of the Yale-Brown Obsessive Compulsive Scale and the National Institute of Mental Health Global rating scale. At the end of 8 weeks, CMI-treated patients showed a mean reduction in Yale-Brown Obsessive Compulsive Scale score of 37% compared to 8% in the placebo group. Side effects were typical of tricyclic antidepressants. In a 1-year open label treatment, CMI continued to be effective and well tolerated.
    Journal of the American Academy of Child & Adolescent Psychiatry 02/1992; 31(1):45-9. · 6.97 Impact Factor
  • Psychiatry Research 12/1990; 34(2):223-6. · 2.68 Impact Factor
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    ABSTRACT: The effects of clomipramine hydrochloride (CMI) versus placebo upon DSM-III-defined obsessive-compulsive disorder (OCD) were assessed in a 10-week double-blind multicenter trial and in a corresponding 1-year double-blind extension study. The NIMH global O-C scale, a 15-point ordinal severity scale, incorporating categorical features specific to OCD, was used to evaluate the severity of obsessive compulsive symptoms over the course of treatment, and a physician's rating of global therapeutic effect was used to assess overall change from baseline. In the core study, patients receiving placebo demonstrated minor and nonsystematic changes, whereas patients who received CMI had clinically and statistically significant reductions in the global severity of their disorder. Findings from the extension study were consistent with continuing efficacy for CMI, whereas corresponding data for patients receiving long-term placebo were difficult to interpret. Based upon shifts in categorical severity, symptoms for over half those patients who received CMI were rendered subclinical or within a range of normal functioning. In contast, less than 5% of patients receiving placebo had their symptoms reduced to a subclinical level. Generally, both treatments were well tolerated. Previous studies have indicated therapeutic potential for CMI in obsessive compulsive disorder. These findings confirm and extend previous observations.
    Biological Psychiatry 10/1990; 28(5):401-14. · 9.25 Impact Factor
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    ABSTRACT: Two multicenter, double-blind trials were conducted in adults with DSM-III (American Psychiatric Association 1980) defined Obsessive Compulsive Disorder (OCD), comparing clomipramine (Anafranil, CMI) up to 300 mg daily with placebo. Of 519 patients evaluated, 260 received CMI for up to 10 weeks. More than half of the CMI treated patients were significantly improved, approximately 30 percent were minimally improved, and 15 percent showed no improvement after CMI treatment. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess treatment effects and attempts were made to correlate change in Y-BOCS score from baseline with a number of baseline characteristics, including age, sex, duration of OCD, baseline Y-BOCS score, baseline Hamilton Rating Scale for Depression (HAM-D) score, presence or absence of secondary depression, and predominance of obsessions or compulsions. Pearson and/or Spearman correlations failed to reveal any statistically significant correlations between outcome and any of the baseline characteristics studied. While the differences were not statistically significant, it did appear that male patients and patients with a longer duration of illness may be less likely to respond to CMI treatment; however, the overall conclusion from this analysis is that none of the variables studied is a reliable predictor of responses to treatment with CMI.
    Psychopharmacology bulletin 02/1990; 26(1):54-9. · 1.35 Impact Factor
  • Progress in clinical and biological research 02/1990; 361:489-93.
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    ABSTRACT: Two multicenter, double-blind, placebo-controlled clinical trials were conducted to evaluate the effectiveness of 10 weeks of treatment with up to 300 mg daily of clomipramine in nondepressed patients with OCD. There were 575 patients enrolled in these clinical trials, and preliminary analyses of data from 384 of these patients demonstrate a virtual absence of placebo response, a very low rate of premature discontinuation, and for patients receiving clomipramine, a statistically and clinically significant improvement in OCD symptoms (40%-45% mean improvement with clomipramine vs. 4%-5% mean improvement with placebo). In general, clomipramine was well tolerated in doses of up to 300 mg daily.
    Psychopharmacology bulletin 02/1989; 25(1):36-40. · 1.35 Impact Factor
  • The British Journal of Psychiatry 01/1989; 153:845. · 6.61 Impact Factor