A schematic representation of the psychopharmacological profile of antidepressants

1. 1. Using simple animal tests, “behavioural” and ”biochemical” aspects of depression, anxiolysis, disinhibition, psychostimulation and sedation were investigated in mice using a variety of antidepressant drugs.

2. 2. Dothiepin and mianserin (16 and 32 mg/kg), fluoxetine (32 and 64 mg/kg), maprotiline and imipramine (16, 32 and 64 mg/kg) and viloxazine (16 mg/kg) significantly potentiated mortality following acute administration with yohimbine.

3. 3. Dothiepin and imipramine (32 mg/kg), fluoxetine (16 and 32 mg/kg), viloxazine (8 and 16 mg/kg), maprotiline (32 mg/kg) and mianserin (32 mg/kg) reduced immobility time in the forced swimming test.

4. 4. In the black and white box, dothiepin (32 mg/kg) significantly increased the time spent in the bright compartment. Fluoxetine (8 and 16 mg/kg) significantly increased the number of crossings between compartments, an effect indicative of desinhibition.

5. 5. It can be concluded that dothiepin possesses both antidepressant and anxiolytic properties in these animal models. The present procedure is useful not only for the screening of compounds that may possess antidepressant properties, but is also of value in determining other properties that may contribute to the overall clinical efficacy of the drugs.

     

Drug treatment strategies for depression in Parkinson disease

Introduction: Depression is a common non-motor symptom in Parkinson disease (PD), occurring in approximately 20% of patients with PD. While depression can occur anytime in the disease process, it predates PD diagnosis in about 30% of patients. Between 20% and 60% of depressed patients with PD are either without recognition or treatment of their depression.

Areas covered: The pathophysiology of depression in PD is unclear. There are several structural changes seen in depressed patients with PD that are also seen in patients with depression. In addition, the neurotransmitters dopamine, serotonin, and norepinephrine are all depleted in PD. This article covers the pharmacological treatment of depression in PD; this involves standard antidepressant treatment such as selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. As with depression not associated with PD, most treatment is partially successful. Non-pharmacological approaches are also touched upon.

Expert opinion: Most antidepressant therapy shows partial efficacy in patients with PD. However, there is a need for better study design as well as more comparative studies for the treatment of depression in PD. Biomarkers will help identify patients with PD and depression earlier in the future.     

Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota–gut–brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic–pituitary–adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.     

Dibenz[b,f]azepines,Part 7[1]: Synthesis of New,Potentially CNS Active Dibenz[b,f]azepine Derivatives

Reactions of 5-carboxamido-5H-dibenz[b,f]azepines ( 1a–1d ) with glyoxylic acid methylester methyl hemiacetal (GMHA) led to 5-(carboxamido-N-α-hydroxy-acetic acid methyl ester)-5H-dibenz[b,f]azepines ( 2a–2d ). The reactions with glycols yielded the oligoethylene glycol derivatives ( 3,4 ). The new compounds were screened as anticonvulsants and/or antidepressants (AD).     

Amitriptyline vs. lorazepam in the treatment of opiate-withdrawal insomnia: a randomized double-blind study

Benzodiazepine use in the treatment of insomnia may cause benzodiazepine dependence, especially in opiate users. The aim of this study was to investigate the sedative-hypnotic effects of amitriptyline in treating opiate-withdrawal insomnia. A total of 27 patients with opiate withdrawal were given either amitriptyline or lorazepam in a randomized double-blind trial. Sleep was assessed by means of the Sleep Evaluation Questionnaire and three insomnia items of the Hamilton Depression Rating Scale. The scores of two sleep measures showed that all aspects of sleep, except for ease of awakening from sleep, in the two treatment groups were not significantly different. In conclusion, apart from the hangover effect, amitriptyline is as effective as lorazepam in the treatment of opiate-withdrawal insomnia.     

Treatment‐emergent mania/hypomania during antidepressant monotherapy in patients with rapid cycling bipolar disorder

Objective: To study treatment‐emergent mania/hypomania (TEM) associated with second‐generation antidepressant monotherapy in patients with rapid cycling bipolar disorder (RCBD). Methods: Data of patients with RCBD (n = 180) enrolled into two clinical trials were used to study the risk for TEM during second‐generation antidepressant monotherapy. History of TEM was retrospectively determined at the initial assessment by asking patients whether they were exposed to second‐generation antidepressants and if a hypomania/mania episode emerged during the first four weeks of treatment. Data were analyzed using t‐test, chi‐square, and logistic regression. Results: Of the 180 patients (bipolar I disorder, n = 128; bipolar II disorder, n = 52) with RCBD, 85% (n = 153) had at least one antidepressant treatment. Among these patients, 94.1% (144/153) had at least one antidepressant monotherapy treatment. Overall, 49.3% of patients had at least one TEM and 29.1% (116/399) of treatment trials were associated with TEM. In regression analysis, an inverse association between the number of mood episodes in the last 12 months and TEM was observed with an odds ratio of 0.9. However, gender, bipolar subtype, a lifetime history of comorbid anxiety disorder, substance use disorder, or psychosis, and age of mood disorder onset were not associated with TEM. For individual antidepressants, the rates of TEM varied from 42.1% for fluoxetine to 0% for fluvoxamine and mirtazapine. As a group, there was no difference between selective serotonin reuptake inhibitors and venlafaxine or bupropion in the incidence of TEM. Conclusions: Use of second‐generation antidepressants as monotherapy in RCBD is accompanied by clinically relevant rates of TEM. Even in patients with RCBD, differential vulnerabilities to antidepressant TEM may exist.