The use of alprazolam in clinical practice
Numerous published data indicate that alprazolam has a unique spectrum of psychotropic activity is substantially different from other tranquilizers. The drug is most effective in the treatment of disorders, clinical picture which is predominantly determined to varying degrees, expressed a disturbing component. These include panic disorder, generalized anxiety disorder, a variety of anxiety and depression, including reactive nature, anxiety disorders in somatic diseases, some embodiments of obsessive-compulsive disorder, withdrawal state, isolated phobia. It is indicated that in addition to actually effect anxiolytic drug apparently has antidepressant effect, which distinguishes it from other members of the benzodiazepine anxiolytics.
So, in held in 80-90 years in the European countries, the USA and Australia, large-scale study of alprazolam in the treatment of panic disorder, characterized by recurrent paroxysms of anxiety and related avoidant behavior, was found significantly greater efficacy of the drug compared to placebo after 4 weeks of application, and the average daily dose, according to different authors, ranged from 4 to 7 mg. In this case there were no linear relationship between the level of content of the drug in the blood plasma and clinical improvement, highlighting the need for individual selection of the dosage to achieve optimal effect.
In some comparative studies of the effectiveness of alprazolam and other benzodiazepine anxiolytics for the treatment of panic disorder was found that drug at least as effective as diazepam, clonazepam or lorazepam. Moreover, in some that alprazolam even in such cases has advantages over diazepam: a greater extent reduces the incidence of panic attack, reducing the severity of anxious and depressive symptoms. It is an opportunity to influence, in fact, the symptoms of a panic attack, not only on standby alert, according to some authors, "is radically different from other benzodiazepine tranquilizers".
Another aspect to which attention is drawn in the treatment of panic disorder, is the ability to influence the so-called secondary depressive symptoms. In general, in these cases use is proposed as a monotherapy alprazolam without additional antidepressant.
When comparing the efficacy and panic disorder alprazolam tricyclic antidepressant imipramine was observed more rapid (within the first week), the improvement of symptoms in the group treated with alprazolam and equal efficiency after 8 weeks of use. The average dosage of alprazolam was equal to 5.7 mg per day, and imipramine 155 mg. Furthermore, in the group of patients treated with imipramine had more disposed to the development of cholinergic side effects. Long-term treatment (8 months), panic disorder alprazolam showed that clinical improvement was achieved without significant changes dosage.
Generalized anxiety disorder (GAD), which manifests itself persistent diffuse anxiety is not limited by any circumstances, accompanied somatovegetativnymi manifestations and individual fears and forebodings, alprazolam therapy effectively exposed to an average daily dose of 0.5 mg to 3 mg compared with placebo. In the treatment of GAD is alprazolam is not as effective as benzodiazepine tranquilizers such as diazepam and lorazepam, but the number of side effects from alprazolam less. Moreover, some studies have found an advantage of alprazolam to diazepam for anxiolytic effect. When compared with imipramine, alprazolam was at least equal in overall efficiency, but superior to relief of somatic symptoms. Note sufficiently rapid onset of effect after receiving the drug, shown already in the first week of treatment.
The mechanism of drug action
In a study of the effectiveness of alprazolam with a combination of GAD, and irritable bowel syndrome after 4 weeks of active treatment showed a statistically significant decrease in anxiety in 98% of the participants and the reduction of gastrointestinal complaints in 89% of study participants. These findings persisted for 4 weeks of gradual decrease drug dosage and 4 weeks after cessation of therapy. In the treatment of anxiety, severe concomitant somatic diseases, such as Cancer nature, also achieved positive results in the first week of use. The effect was also observed in the treatment of moderate to severe anxiety that accompanies alcohol withdrawal states.
The above mechanism of drug action, as well as the data of a number of studies provide a glimpse of some antidepressant activity of alprazolam. It is shown that alprazolam at least as effective as the representatives of the group classic tricyclic antidepressants such as amitriptyline and imipramine. However, this conclusion is not confirmed in all studies. Nevertheless, represents a significant indication that the drug may prove effective not only in cases of neurotic depression, but also with endogenous depression. It is noted that, although in severe melancholic endogenous depression alprazolam therapy effectiveness has not been confirmed, its use may be useful in a variety of anxiety-depressive states. In particular, alprazolam in the appointment of 605 outpatients with anxiety and depressive symptoms (double-blind study) not inferior to such a reference antidepressant like amitriptyline, not only in their ability to normalize night's sleep and to stop the alarm, but also to influence the severity of the actual depression.
Physical effect of anxiety disorders
Additional indications for the use of alprazolam include premenstrual syndrome. A double-blind, placebo-controlled study showed that alprazolam is improved mainly in the luteal phase. It should be borne in mind that in the treatment of premenstrual syndrome placebo effect and facilitates the traditionally high of about 50% of symptoms in 20-60% of women, regardless of the time of contact with the doctor.
There is also evidence of successful use of alprazolam for treatment of acute stress disorder, and the effectiveness of benzodiazepine tranquillizers adjunctive therapy, particularly, alprazolam, obsessive-compulsive disorders. Appointment of the drug is possible in the beginning of the course for the treatment of severe anxiety, as well as with resistance or intolerance to selective serotonin reuptake inhibitors for. Although put forward suggestions, alprazolam is not proved to be effective in the treatment of post-traumatic stress disorder (PTSD). With the apparent reduction of anxiety symptoms, specific key symptoms of PTSD - persistent memories of the traumatic event and avoidance - remained unchanged. Given the current trend of the effective application of benzodiazepine tranquilizers for treating catatonic states, is an indication for alprazolam is likely impractical due to insufficient duration of action of the drug, as well as the absence of the Russian Federation registered form for parenteral administration.
Moving on to discuss the side effects of alprazolam, can not ignore the wide experience of the safe use of the drug in the US and European countries for nearly three decades. Although comparative studies was more prominent side effects in alprazolam when compared to placebo , patients generally report common to all drugs benzodiazepine gipersedatsii some phenomena, although in the case they are often alprozalama less pronounced relative to other tranquilizers. In particular, post-marketing study with the participation of more than 10 000 patients in the UK has not revealed any serious side effects, the most common side effects were sedation and somnolence. In general, during the course of treatment the above side effects, but greatly reduced. There is evidence that the side effects associated with the use of alprazolam are less pronounced than in the appointment of diazepam.
Termination of the daily administration of alprazolam must be carried out gradually in order to prevent the development of withdrawal syndrome. During this period, lasting from a few weeks to months, the daily dosage of the drug is gradually reduced to completely abolishing. In some panic disorder studies that reduced doses of benzodiazepine tranquillizers can be accompanied by symptoms cancel and return of clinical manifestations, with increasing alarm indicators, particularly at sharp cancellation therapy. It must be remembered that in some patients, withdrawal symptoms, and the impact may occur, in spite of the long period of low dosage, and therefore this aspect requires attention at all stages of therapy. In connection with the above features important to note that the period of effective reduction of dosage may last longer than the actual treatment phase alprazolam. In this age of over 40 years, the low level of anxiety before the treatment, as well as successful reduction of disturbances during the period of therapy correlated with less severe symptoms of cancellation and return