Современные лекарственные стратегии лечения алкоголизма

γ-Hydroxybutyrate (GHB), anticonvulsants, and α2-agonists have been studied as stand-alone or adjunctive agents in the treatment of alcohol withdrawal syndrome. Although these medications are promising for mild to moderate alcohol withdrawal syndrome, there is a dearth of information about their ability to prevent or treat complicated alcohol withdrawal.

Alcohol Disorders: Practical Tips From New Research

Исследования арбаклофена

The investigational γ-aminobutyric acid type B (GABA-B) agonist STX209 (arbaclofen, Seaside Therapeutics) may improve social function and behavior in patients with fragile X syndrome (FXS).

In a randomized, controlled phase 2 study of children and adults with FXS, investigators from Rush University Medical Center in Chicago found that treatment with arbaclofen was well tolerated and improved social avoidance and problem behaviors.

Drug Shows Promise in Fragile X and Possibly Autism 

Исследование ГАМКергической теории депрессии

This study of 85 people is the largest such research effort on GABA and major depressive disorder to date.
It compared four groups: 25 individuals with treatment-resistant depression, 16 with major depression who were unmedicated, 19 individuals with major depression who were successfully treated with medication and had normal mood, and a control group of 25 healthy individuals.
In all groups, a thumb twitch response to transcranial magnetic (brain) stimulation (TMS) was used to measure how GABA acts physiologically in the brain. GABA receptors were found to be dysfunctional in the three groups with major depressive disorder when compared to healthy subjects.
In people who were the least responsive (treatment-resistant) to medications, the physiological effect of GABA in the brain was at its lowest.

New Drug Strategy for Depression?

теория ГАМКергического дефицита при депрессии

tudies of depressed patients indicate that MDDs are accompanied by reduced brain concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and by alterations in the subunit composition of the principal receptors (GABAA receptors) mediating GABAergic inhibition. In addition, there is abundant evidence that suggests that GABA has a prominent role in the brain control of stress, the most important vulnerability factor in mood disorders. Furthermore, preclinical evidence suggests that currently used antidepressant drugs (ADs) designed to alter monoaminergic transmission and nonpharmacological therapies may ultimately act to counteract GABAergic deficits. In particular, GABAergic transmission has an important role in the control of hippocampal neurogenesis and neural maturation, which are now established as cellular substrates of most if not all antidepressant therapies. Finally, comparatively modest deficits in GABAergic transmission in GABAA receptor-deficient mice are sufficient to cause behavioral, cognitive, neuroanatomical and neuroendocrine phenotypes, as well as AD response characteristics expected of an animal model of MDD. The GABAergic hypothesis of MDD suggests that alterations in GABAergic transmission represent fundamentally important aspects of the etiological sequelae of MDDs that are reversed by monoaminergic AD action.

The GABAergic deficit hypothesis of major depressive disorder

Неотложные состояния при аффективных расстройствах

Pharmacological treatments for bipolar disorder can cause or compound patients' behavioral disturbances. Treatment with antipsychotics can increase the risk of agitation or aggression by causing akathisia, which can be associated with severe exacerbation of symptoms or even suicide attempts. The risk of akathisia is reduced but not eliminated by the use of atypical antipsychotics. Antidepressant agents can cause activation or mood destabilization, and some of these agents have been reported to cause akathisia.

Principles of treatment

A treatment strategy for impulsivity or aggression requires knowledge about possible interacting causes of the behavioral disturbance, its course, and its context. This information is helpful in formulating initial treatment and is even more helpful in developing a long-term strategy that will, if successful, reduce the patient's need for future emergency care.

Factors that influence treatment of pathological impulsivity and aggression include:

* Degree of premeditation versus degree of impulsiveness.
* Role of nonpsychiatric conditions (drug toxicity, drug withdrawal, delirium, dementia, infection, metabolic abnormality).
* Relationship to a DSM-IV Axis I psychiatric disorder.
* Relationship to a personality disorder.
* Course (acute/fluctuating versus chronic).
* Presence of prominent overstimulation.
* Environmental context (legal, relationship, and/or economic problems or changes).
* Personal context (personality characteristics, conflicts).

Candidate mechanisms of treatment for impulsive aggression or agitation include:

* Enhancing an inhibitory system, such as serotonin or GABA.
* Inhibiting an activating system, such as dopamine.
* Stabilizing fluctuations in inhibitory and/or excitatory systems.
* Protecting against overstimulation or normalizing arousal.

Psychiatric Emergencies in Bipolar and Related Disorders

Повышение уровня ГАМК может исправить когнитивный дефект при шизофрении

Raising GABA Levels Might Undo Cognitive Defect in Schizophrenia