A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients.

We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4-20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions-Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.

[Premorbid characteristics and nature of the mental disorders in patients with neurocirculatory dystonia and heart rhythm disorders (clinico-psychological research)]. / Premorbidnye osobennosti i kharakter psikhicheskikh narushenii u bol'nykh neirotsirkuliatornoi distoniei s narusheniiami ritma serdtsa (kliniko-psikhologicheskoe issledovanie).

Forty-two patients with different types of functional cardiac arrhythmias were examined. Clinico-psychological examination revealed such general and relatively independent of the personality type features as conservatism, predisposition to anxiety reactions, hypochondriac readiness, symptomatic lability, poor self confidence in relation to interpersonal interrelations, poorly expressed ability to dominate with a tendency toward submission. Neurotic reactions and phases were a predominant feature in accentuated (n = 20) and psychopathic persons (n = 10). Slowly progressive schizophrenia and cyclothymia were diagnosed in 8 and 4 cases respectively. Treatment of functional cardiac arrhythmias with lexotan yielded good response in 50% of cases. In cases when lexotan alone failed to be effective, the use of this drug in combination with antiarrhythmic drugs effected good results in 61.8% of the patients.

[Use of psychotropic drugs in general somatic practice]. / Primenenie psikhotropnykh sredstv v obshchesomaticheskoi seti.

The present study is based on the results of a survey which has revealed psychic disorders in patients with general somatic diseases, who constituted 38.4% of the total number of the examined individuals. The proposed differentiation of the conditions for treating with psychotropic drugs of the given group of patients takes into account the clinical characteristics of psychic disturbances. Psychopharmacologic therapy is characterized by brief courses of treatment with low doses of psychotropic drugs in combination with psychotherapy and social influences. The authors proved advisability of further expansion of the network of psychiatric offices in community polyclinics.