Personalized approach in drug therapy is an essential line of modern psychiatry. Experimental and clinical studies of anxiolytics have shown differences in drug effects in dependence on genetically determined reactions to stress and personal features.

To evaluate of the therapeutic effects and effectiveness of bromodihydrochlorophenylbenzodiazepine and fabomotizole in dependence on individually-typological features of patients with anxiety disorders.

45 patients (mean age 33,3±9,7 years) with generalized anxiety disorder (n=22) and panic disorders with agoraphobia (n=23) participated in this open-label study. 13 patients treated with typical anxiolytics bromodihydrochlorophenylbenzodiazepine at dose 2 mg daily and 32 patients treated with atypical fabomotizole at dose 30 mg daily. The duration of treatment was 14 days. Minnesota Multiphasic Personality Inventory, Psychiatric Symptoms Severity Evaluation Questionnaire and CGI-E were administered.

Asthenic features (high pessimism, anxiety, individualism) were revealed in 26 patients and stenic features (high impulsivity, rigidity and optimism) were revealed in 19 patients. Patients with asthenic features had tranquilo-activating effect of bromodihydrochlorophenylbenzodiazepine, whereas patients with stenic features had tranquilo-sedative effect. The tranquilo-activating effect of fabomotizole was revealed in patients with stenic features. High efficacy of bromodihydrochlorophenylbenzodiazepine was observed in patients with asthenic personality traits (χ 2 = 7,8), whereas in fabomotizole-in patients with stenic individual typological features (χ 2 = 9,1).

Patients with stenic and asthenic features had differences in therapeutic effects and the effectiveness of anxiolytics. Personality features determine the sensitivity of patients with anxiety disorders to psychotropic drugs.

No significant relationships.

Generalized anxiety disorder (GAD) is associated with reduced attention, inhibition, decrease of processing speed. The impact of a new peptide antagonist of central cholecystokinin-1 receptors (GB-115) on cognitive processes in patients with GAD is reported.

To research the cognitive effects of GB-115 in patients with GAD.

25 patients with GAD in ICD-10 (mean age 35,76±8,55 years) treated with GB-115 in clinically relevant dose (6 mg/d) were enrolled to the study. The evaluation of cognitive functions was conducted at background, Day 3, Day 7, Day 14 and Day 21. The laboratory test toolkit included reaction time test, Shulte-Platonov tables, attention tests (using hardware and software complex “NeuroSoft-PsychoTest”). Statistical significance was ascertained by Wilcoxon signed-rank test.

Speed of reaction time increased on the Day 7 (418,17±61,49 msec, p≤0,01), the Day 14 (422,25±70,69 msec, p≤0,01) and the Day 21 of treatment (406,5±52,79 msec, p≤0,01) in comparison with background (449,19±64,91). Attention parameters improved on the Day 3 (305,95±45,31 msec, p≤0,05) and the Day 21 of treatment (300,14±47,74 msec, p≤0,05) in comparison with the background (316,41±42,35 msec). Decrease of time in performance of tables of Shulte-Platonov was also observed on the Day 7 (59,40±13,71 sec, p≤0,01), the Day 14 (57,88±12,82 sec, p≤0,01) and the Day 21 (53,40±13,19 sec, p≤0,01) in comparison with the background (68,84±16,78 sec).

GB-115 revealed cognitive effects such as an increase of processing speed and improvement of different aspects of attention (attentional resource allocation, attention span and switching) after the Day 7 of treatment.

No significant relationships.

The pilot clinical study of GB-115, a new peptide antagonist of central cholecystokinin-1 receptors, revealed that drug was clinically effective in patients with generalized anxiety disorder (GAD) at dose 6 mg daily. Here, we provide results of post-hoc analysis of changes of anxiety and fatigue symptoms to give characterization of its clinical effects in clinically relevant doses.

To research the changes of anxiety- and fatigue-related symptoms during GB-115 treatment in patients with generalized anxiety disorder (GAD).

Patients with GAD without somatic diseases aged 18-55 years were eligible in the study. Patients were prescribed with GB-115 6 mg daily for 21 days. Anxiety and fatigue symptoms were assessed with Hamilton Anxiety Rating Scale (HARS) and Multidimensional Fatigue Inventory (MFI-20). Variables are described as medians and interquartile range (IQR). Pre-post comparisons were performed using the Friedman ANOVA at 2-side p-value <0.05.

25 patients diagnosed with GAD (8 males, 17 females; median [IQR] age: 34 [29.75, 43.0]) included in the analysis. Median [IQR] HARS total score decreased from 22 [20, 24.5] to 19 [16, 20], 13 [10.5, 15.5], 9 [5.5, 11] and 5 [3.5, 8] on the Day 3,7,14 and 21, respectively (χ2=95.07, df=4, p<0.001). Median [IQR] MFI-20 score decreased from 70 [46, 75.5] to 59 [41, 74.5], 52 [37.5, 64.5], 37 [26.5, 63] and 28 [24, 48.5] on the Day 3, 7, 14 and 21, respectively (χ2= 55.41, df=4, p<0.001). None of patients had stimulation-related side effects.

GB-115 action in the treatment of GAD patients is characterized with anxiolytic action with mild psychostimulant properties.

No significant relationships.

Despite frequent benzodiazepine use in anxiety disorders, the trajectory and magnitude of benzodiazepine response and the effects of benzodiazepine potency, lipophilicity, and dose on improvement are unknown.

We performed a meta-analysis using weekly symptom severity data from randomized, parallel group, placebo-controlled trials of benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in anxiety was evaluated as a function of medication, disorder, time, potency, lipophilicity, and standardized dose and compared among benzodiazepines.

Data from 65 trials (73 arms, 7 medications, 7110 patients) were included. In the logarithmic model of response, treatment effects emerged within 1 week of beginning treatment (standardized benzodiazepine-placebo difference = −0.235 ± 0.024, CrI: −0.283 to −0.186, P < .001) and placebo response plateaued at week 4. Doses <6 mg per day (lorazepam equivalents) produced faster and larger improvement than higher doses (P = .039 for low vs medium dose and P = .005 for high vs medium dose) and less lipophilic benzodiazepines (beta = 0.028 ± 0.013, P = .030) produced a greater response over time. Relative to the reference benzodiazepine (lorazepam), clonazepam (beta = −0.217 ± 0.95, P = .021) had a greater trajectory/magnitude of response (other specific benzodiazepines did not statistically differ from lorazepam).

In adults with anxiety disorders, benzodiazepine-related improvement emerges early, and the trajectory and magnitude of improvement is related to dose and lipophilicity. Lower doses and less lipophilic benzodiazepines produce greater improvement.

Gabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders.

We aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats.

Female Spraque–Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively.

It was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them.

These data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.

The need to manage psychological symptoms after disasters can result in an increase in the prescription of psychotropic drugs, including antidepressants and anxiolytics. Therefore, an increase in the prescription of antidepressants and anxiolytics could be an indicator of general psychological distress in the community.

The purpose of this study was to determine if there was a change in the rate of prescription of antidepressant and anxiolytic drugs following Cyclone Yasi.

A quantitative evaluation of new prescriptions of antidepressants and anxiolytics was conducted. The total number of new prescriptions for these drugs was calculated for the period six months after the cyclone and compared with the same six month period in the preceding year. Two control drugs were also included to rule out changes in the general rate of drug prescription in the affected communities.

After Cyclone Yasi, there was an increase in the prescription of antidepressant drugs across all age and gender groups in the affected communities except for males 14-54 years of age. The prescription of anxiolytic drugs decreased immediately after the cyclone, but increased by the end of the six-month post-cyclone period. Control drug prescription did not change.

There was a quantifiable increase in the prescription of antidepressant drugs following Cyclone Yasi that may indicate an increase in psychosocial distress in the community.

UsherK, BrownLH, BuettnerP, GlassB, BoonH, WestC, GrassoJ, Chamberlain-SalaunJ, WoodsC. Rate of Prescription of Antidepressant and Anxiolytic Drugs after Cyclone Yasi in North Queensland. Prehosp Disaster Med. 2012;27(6):1-5.