Antidepressants in the treatment of alcohol withdrawal syndrome and alcohol dependence

Antidepressants in the treatment of alcohol withdrawal syndrome and alcohol dependence

Currently, efforts have intensified to find new methods and means of treating alcohol dependence. The main task is to achieve stable remission and prevent possible relapses. This problem can be solved with an adequate choice of therapeutic target. Today there is no doubt that the main target is the core disorder of the dependence syndrome - pathological craving for alcohol. In the complex clinical structure of pathological attraction syndrome, affective disorders, mainly of a depressive nature, are constantly present. Numerous studies of patients with chronic alcoholism have revealed a close connection between pathological craving for alcohol, its exacerbation and reduction with the intensification and weakening of depressive and dysphoric phenomena. These clinical data are supported by the results of biological studies indicating the commonality of the underlying neurochemical mechanisms of depression and pathological craving for alcohol.

In most cases, the doctor first encounters a patient when he is clearly diagnosed with a state of withdrawal syndrome. Adequate treatment of alcohol withdrawal and post-withdrawal syndromes largely determines the further course of the disease, since at this stage of therapy the foundation is laid for preventing early relapse of the disease. In recent years, various antidepressants have been increasingly used as pathogenetic therapy. However, there are still no studies devoted to the comparative analysis of antidepressants from different groups for the treatment of pathological craving for alcohol.

In this regard, the goal of our work was a comparative study of the therapeutic capabilities of such antidepressants as fluvoxamine, valdoxan, heptral, lerivon (mianserin), and their antikilytic, sedative, hypnotic, and vegetative-stabilizing effects. Particular attention was paid to the effect of these drugs on pathological craving for alcohol.

The study was conducted in abstinence and post-abstinence states. 40 patients received fluvoxamine for 10 days; some of them were in a state of withdrawal syndrome; in another part of the patients, an exacerbation of the pathological craving for alcohol outside the withdrawal syndrome was observed.

Coaxil was prescribed to 25 patients with alcoholism in withdrawal and post-withdrawal states for 40 days; heptral – 20 patients in withdrawal and post-withdrawal states for 30 days; lerivon – 30 patients in withdrawal and post-withdrawal states for 30 days. At the same time, for comparison, 15 patients received amitriptyline.

The study included only those patients who were diagnosed with alcohol dependence, alcohol withdrawal syndrome, or alcohol-related mood disorders according to the DSM-IV. The age of the patients ranged from 18 to 55 years. The duration of the disease varied from 4 to 25 years. The rate of development of the disease was different: from highly progressive (minority of patients) to low progressive. But in most patients the rate of development of the disease was classified as moderately progressive. The pseudo-binge form of alcohol abuse predominated. The clinical picture of alcohol withdrawal syndrome included somatovegetative and mental disorders. Mental disorders were characterized mainly by depressive disorders: depressed mood, feelings of internal tension, anxiety, irritability, mild ideational and motor retardation, hypochondriasis, ideas of self-blame and self-deprecation, recurrent suicidal thoughts, sleep disturbances, decreased interest in usual activities, loss of body weight, decreased libido, pronounced craving for alcohol. The patients had not been previously treated for depression.

The drugs were prescribed in the following doses: fluvoxamine – 50-100 mg/day, Valdoxan – 25 mg once a day (at night). Heptral was prescribed parenterally for the first 2 weeks at 800 mg per day; the next 2 weeks - in tablets - 1600 mg per day. Lerivon – 1 tablet 2 times a day (daily dose 50 mg).

To assess the effectiveness of these drugs, the following scales were used: a scale for assessing somatovegetative manifestations, a scale for assessing psychopathological manifestations, a scale for assessing affective and neurosis-like disorders in the post-withdrawal period, the Hamilton scale and a scale for general clinical impression.

When analyzing the results of using fluvoxamine, its ability to influence pathological craving for alcohol, manifested by low mood with irritability, anxiety, fear, and sleep disturbance in deprivation syndrome, was clearly revealed. The spectrum of activity of the drug is presented in table. 1. As can be seen from the table, in most observations from day 3 there was a clear effect of fluvoxamine on the pathological craving for alcohol. Its severity decreased by more than 2 times, and from day 4 the drug had a positive effect on mood and other mental disorders. To a lesser extent, fluvoxamine affected somatovegetative disorders; The hypnotic effect of fluvoxamine was insufficient. The spectrum of therapeutic activity of fluvoxamine in relieving pathological craving for alcohol outside of withdrawal syndrome is presented in Table. 2. In most observations, already on the 3rd day in an outpatient setting, a clear improvement in the patients’ condition was noted: the severity of pathological craving for alcohol decreased by 2 times, anxiety and irritability decreased. On day 4 my mood leveled off.

Thus, despite the pronounced effect of fluvoxamine on the pathological craving for alcohol and its sufficient anxiolytic, antidepressant, and sedative effects, in general it should be noted that the drug has a clearly weak hypnotic and vegetative-stabilizing effect. The effect of heptral on the somatovegetative manifestations of alcohol withdrawal syndrome was studied separately. Both Coaxil and Heptral have a slight effect on the pathological craving for alcohol, this is especially true for Heptral. In terms of sedative action, it should be noted that Coaxil has a significant advantage over Heptral. These drugs are ineffective as a means of normalizing sleep, which is extremely important for starting treatment for patients with alcoholism. The antidepressant, sedative and vegetostabilizing effects of heptral turned out to be quite low.

At the same time, a fairly high anxiolytic effect of Coaxil and Heptral has been established. In fact, on the 3rd day the feeling of anxiety disappears, although sleep disturbances still remain. This allows us to conclude that the hypnotic effect of these drugs is low. The effect of heptral on somatovegetative disorders in addiction syndrome was studied separately. The intensity of the vegetotropic effect of this drug is also very insignificant.

In addition, when comparing fluvoxamine, coaxil and heptral, another significant disadvantage of fluvoxamine should be noted - its high cost.

Assessing the results of a comparative study of the effectiveness of lerivone and amitriptyline, the following can be noted: lerivone had a pronounced suppressive effect on the desire for alcohol, reducing its intensity already on the 3rd day of treatment and by more than 4 times on the 7th day.

The therapeutic effectiveness of amitriptyline in this regard was lower.

The anxiolytic effect of lerivone was also significantly higher than that of amitriptyline. Clinical manifestations of anxiety were practically leveled out by the 3rd day of treatment with lerivone, while with amitriptyline these changes occurred much more slowly.

The same patterns emerged when assessing the sedative effect. Lerivon turned out to be clearly preferable: the intensity of such painful manifestations as irritability, while taking it, decreased by 2.5 times already on the 3rd day of treatment. The sedative effect of amitriptyline occurred later.

Normalization of sleep in patients taking lerivon occurred much faster compared to patients treated with amitriptyline.

In terms of antidepressant effect, lerivone was not inferior to amitriptyline - the results were almost identical.

An analysis of the therapeutic dynamics of somatovegetative disorders in a state of withdrawal syndrome showed a higher effectiveness of lerivone compared to amitriptyline. Symptoms such as ticcardia, tremor, hyperhidrosis, and lack of appetite were either completely stopped by the 3rd day of treatment with lerivone, or their intensity decreased by more than 2 times.

The higher therapeutic activity of lerivone compared to amitriptyline is visible in the total assessment of affective and neuropsychiatric disorders in the post-withdrawal period. This is evidenced by the dynamics of relief of such disorders as craving for alcohol, irritability, sleep disorders, which are of great importance for characterizing the period of remission. Normalization of mood, relief of anxiety, irritability, absence of sleep disturbances and a sharp decrease in the intensity of pathological craving for alcohol indicate a significant therapeutic effect of lerivone.

It should also be emphasized that lerivon was well tolerated by patients, there were no side effects or complications.

It should be especially noted that lerivone, unlike amitriptyline, does not produce such typical side effects as anticholinergic and cardiotoxic.

There were also no cases of addiction to the drug, which suggests the safety of its use.

Thus, the comparative therapeutic activity of lerivone and amitriptyline allows us to draw the following conclusion: lerivone, as a means of suppressing the pathological craving for alcohol, is preferable to amitriptyline. It is also superior to amitriptyline in its anxiolytic, sedative, hypnotic, and vegetative-stabilizing effects, and is not inferior to amitriptyline in its antidepressant effect.

Summing up the overall results of the clinical data obtained in a comparative study of fluvoxamine, coaxil (tianeptine), heptral, lerivone and amitriptyline, we can say with confidence that none of the above antidepressants has such a wide range of therapeutic effects as lerivone, which is extremely important when treatment of patients with pathological craving for alcohol. Naturally, this indicates the advantage of this drug when recommending it for use in practical healthcare. An equally important factor is the cost of lerivon. It is much cheaper than fluvoxamine, coaxil, and heptral.

Thus, the results obtained are of great practical importance for the treatment of patients with alcohol dependence syndrome and allow us to recommend the inclusion of lerivone along with psychotherapy in complex therapeutic programs. The most optimal is the appointment of lerivone in the initial period of treatment of alcohol withdrawal syndrome.

Scale for the dynamics of psychopathological manifestations in the structure of withdrawal syndrome during treatment with fluvoxamine

Here and in Table 2, the severity of symptoms is assessed in points: 0 - absent, 1 - mildly expressed, 2 - moderately expressed, 3 - severely expressed.

Scale for assessing affective and neurosis-like disorders in remission

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Antidepressants may cause long-term weight gain

Author:

radiologist Kolesnik Dmitry

2 minutes

3292

Researchers from King's College London found that patients prescribed any of the 12 most commonly used antidepressants were 21% more likely to experience weight gain, compared with those not taking such medications. The scientific work was published in the British Medical Journal.

The study authors also found that the risk of weight gain peaked after two to three years of continuous use of these antidepressants. For those who were previously at a “normal” weight, the risk of becoming overweight or obese increased by 29% compared to those who did not take antidepressants.

Overweight patients also had a 29% higher risk of becoming obese than those not taking antidepressants.

The study found that some drugs were more strongly associated with weight gain. Patients taking mirtazapine (or Remeron), which is now rarely prescribed, had a 50% risk of gaining at least 5% of their body weight compared with people who were not taking antidepressants. Citalopram (a commonly prescribed drug sold under the brand name Celexa) was associated with an approximately 26% risk of weight gain.

Although previous studies have already found that short-term weight gain occurs after starting antidepressant treatment, the new study shows that the risk of weight gain increases over time and persists for several years.

The research team analyzed the electronic medical records of almost 300,000 British patients (136,762 men and 157,957 women) between 2004 and 2014.

The researchers took into account the timing of antidepressant prescription in patients of all categories - from patients with a “normal” body mass index of 18.5 to 14.9, to hyper-obese patients with a BMI of 45.0 or higher.

During the ten-year follow-up period, any increase in body weight of at least 5% was recorded. The researchers also found that the annual risk of weight gain was 8.1 per 100 for the group not taking antidepressants and 11.2 per 100 for those taking antidepressants.

During the second and third years of antidepressant use (the peak risk period), patients taking antidepressants were 46% more likely to gain weight by 5% than those not taking them. The risk of weight gain remained elevated for six subsequent years.

Speaking about the study, author Dr Rafael Gafoor said: “The results of our study show that treatment with antidepressants increases the risk of patients gaining weight over several years. From a clinical perspective, these observations reinforce the need for active and individualized weight management consistent with antidepressant use.”

However, the authors emphasize that patients should not stop taking their prescribed medications, and if they have any problems, they should consult their doctor or pharmacist.

At the same time, study co-author Martin Gulliford, professor of public health at King's College London, argues that increased use of antidepressants could contribute to long-term weight gain across the population, with associated health risks.

"These findings should be seen in the context of increasing weight in the general population, as new UK health data shows that the prevalence of obesity increased from 23% to 26% between 2004 and 2014," Professor Gulliford said.