Depressive Disorders: A Modern View of the Problem

Actualization of the problem

As shown by a recent study, the detection of cases of depression by general practitioners is difficult because in almost half of cases, patients try to keep silent about the symptoms of the disease ( suffering in silence ) [3]. Many are afraid of prescribing antidepressants and their side effects; some believe that it is their own business to control emotions , and not the concern of the doctor; there are also fears that the mention of the case of depression will end up in the medical record and become known to the employer; Finally, some are afraid of being referred to a psychiatrist for treatment . This shows that therapists should use more screening tools, including short questionnaires, in cases that do not rule out depression.            

It is no coincidence that depressive states are compared with an iceberg, the top of which is formed by pronounced forms – their recognition is not particularly difficult for both a psychiatrist and a doctor of another specialty . Most depressions, however, are located in deeper iceberg zones. These are erased forms, the clinical picture of which is dominated by neurotic, somatized, autonomic disorders. For such depressions, patients seek help from the institutions of the general medical network. Therefore, in modern conditions, the problem of depression is considered as one of the key not only in psychiatry, but also in general medicine.                 

WHO measures the global burden of disease in terms of disability-related life years (DALI). This time indicator combines the years of life lost due to premature mortality and the years of life lost due to health conditions that do not meet the criteria for normal functioning [4]. A 2010 WHO study of the global burden of disease found that depressive disorders are the second leading cause of disability worldwide, with depression accounting for 2.5% of global DALIs. According to the Canadian Association for the Treatment of Mood and Anxiety Disorders (CANMAT), the disease burden of depressive disorders is greater than the combined burden of breast, lung, prostate and bowel cancers . Depression leads to a significant deterioration in the quality of life and has a significant economic impact due to production costs, health care costs, and associated suicide. For example, in the United States, the economic costs associated with depression in 2010 were estimated at $ 210.5 billion.                      

Depressive disorders impair quality of life, workplace productivity, and social and family roles. In today’s knowledge and service economy , the mental capital of the population (the resources of cognitive, emotional, and social skills to function) becomes more valuable and vulnerable to the effects of depression.        

Depression is a mental disorder characterized by depressed mood (hypothymia) with a negative, pessimistic assessment of oneself, one’s position in the present, past and future. Along with depression, depression includes ideational and motor inhibition with a decrease in the impulses for activity or anxiety (up to agitation). Feelings of guilt, decreased self-esteem, and suicidal tendencies are also characteristic.         

At its worst, depression can lead to suicide. About 800 thousand people die of suicide every year . According to the WHO, suicide is the second leading cause of death between the ages of 15 and 29 . Suicidal thoughts, intentions, and attempts are common among people with depression. Each consultation with such a patient should include an assessment of the risk of suicide. Risk factors can be divided into modifiable and non-modifiable [5]. A history of suicidal attempts is the most potent risk factor. Non- modifiable include: male sex in old age; a history of a suicidal attempt and self-harm (self-harm) , a family history of a family history of suicidal attempts, and problems with the law. Modifiable risk factors are: active suicidal thoughts and intentions; the presence of anxiety, guilt, impulsivity and psychotic symptoms in symptoms; stressful life events; comorbid conditions – disorders caused by the use of psychoactive substances (especially alcohol), post-traumatic stress disorder, personality disorders and chronic somatic diseases (for example, arthritis, migraine), as well as oncopathology.                           

The development of depression is the result of a complex interaction of biological, social and psychological factors (biopsychosocial model). In everyday clinical practice, for screening for depression, it is important to identify risk factors that can lead to the onset of depressive disorders [5]. For clinical concern: the presence of depression in the history of the individual patient and the family, social problems, frequent requests for medical care, chronic illness (especially cardiovascular disease, diabetes, and neurological disorders), other psychiatric disorders and periods of hormonal changes (pregnancy and the postpartum period) as well as unexplained physical symptoms, chronic pain, fatigue, insomnia, anxiety, and substance abuse.             

Social factors have a complex relationship with depressive disorders, including a significant role in their development. Depressive mood, loss of interest, impaired concentration, and guilt are the symptoms most associated with social impairment. Parental depression can affect the health of children. Maternal depression is associated with multiple adverse effects in children, including emotional problems, behavioral disorders, hyperactivity, decreased social competence, adolescent depression, and negative consequences for cognitive development [6]. The consequences are the same in the case of paternal depression [7]. Effective treatment and remission of maternal depression is associated with improved parenting and decreased psychiatric symptoms in offspring.                

Depressive disorders are associated with many chronic conditions, including heart disease, arthritis, asthma, back pain, chronic lung disease, hypertension, and migraine. Depression is an independent risk factor for the development of coronary heart disease and cardiovascular mortality [8]. The presence of depression increases the level of disability and reduces the quality of life in people with chronic diseases [9]. Depression can affect overall health through several mechanisms. It also reduces compliance and interferes with participation in preventive health care. In addition, depression is associated with important risk factors for physical illness, including a sedentary lifestyle, obesity, and smoking.           

Diagnostic criteria for depression

Symptoms of depression can vary widely from person to person. Sometimes among the leading symptoms are various physical pains, feeling unwell or cognitive dysfunction – in such cases it can be difficult to identify the depression itself. A person with this disease often finds it difficult to describe their feelings to loved ones or a doctor, or instead of depression, they may talk, for example, about relationships with people, sleep problems , financial or health concerns.       

Diagnostic criteria for a depressive episode

The main symptoms are:

  • decreased mood, prevailing almost daily and most of the day and lasting at least 2 weeks, regardless of the situation;    
  • a distinct loss of interest or pleasure in activities usually associated with positive emotions;  
  • decreased energy and increased fatigue; 

Additional symptoms:

  • loss of ability to concentrate and concentrate;  
  • decreased self-esteem and feelings of self- doubt;  
  • ideas of self-deprecation and / or guilt (even with mild depression);
  • pessimistic vision of the future;
  • suicidal thoughts or actions;
  • disturbed sleep;
  • decreased appetite.

For the diagnosis of depressive disorders, the following screening scales are effective: hospital anxiety and depression scale (HADS) and PHQ – 9 (Tables 1, 2). HADS was developed by AS Zigmond and R.P. Snaith in 1983 to identify and assess the severity of depression and anxiety in general medical practice. The advantages of the method are the ease of use and processing (filling does not require a long time and does not cause difficulties for the patient). In 1999, RJ Spitzer et al. provided the patient’s health assessment questionnaire (PHQ – 9), which also are widely spread in the clinical and in laboratory practice for screening depressive disorders [10].                   

Depression therapy

The first antidepressants (AD) were created in the 50s. last century (tricyclic antidepressants [TCAs]) and were intended primarily for the effective treatment of patients in a hospital setting. They influenced several neurotransmitter systems, that is , they did not have a selectivity of action, which led to the appearance of many side effects (cardiotoxic, acute urinary retention, impaired consciousness, up to delirious , etc.), which made it difficult to treat patients on an outpatient basis. This prompted scientists to start looking for new effective and safe blood pressure. Research was carried out towards the synthesis of more selective drugs. In the future it was created SSRIs. They were obviously better tolerated than non-selective drugs. That is why SSRIs still represent the most numerous and “successful” AD group. At the same time, there is an opinion in publications that SSRIs are not effective enough for depression. They also have various side effects, which often persist for a long time. The most common are disorders of the gastrointestinal tract: nausea, vomiting, dyspepsia. Others – headache, dizziness, increased anxiety, anxiety, insomnia, less often increased sleepiness, sexual dysfunctions (anorgasmia, erectile dysfunction, delayed ejaculation, etc.).                        

New non-selective blood pressure appears quite naturally: SSRIs – venlafaxine, duloxetine, noradrenergic and specific serotonergic blood pressure (HACCP) – mirtazapine. In most of them, the main mechanism of action is aimed at activating both the serotonin and norepinephrine systems, which increases the effectiveness of their use in depression. Obviously, new nonselective blood pressure is synthesized taking into account the increased requirements for tolerance for wider use in outpatient practice. This evolution of blood pressure reflects, first of all, the clinical demand of doctors and patients for an effective and safe drug for the treatment of depressive disorders.               

At the same time, leading researchers emphasize the importance of preventive work, which can be the most effective and cost-effective way to combat depression. In particular, there are effective community- based depression prevention approaches that include targeted school programs to prevent child abuse, programs to improve cognitive, social and problem-solving skills in children and adolescents. Prevention covers specific areas of risk factors (smoking, alcohol, unhealthy diets, physical inactivity, etc.) as well as those for the development of mental disorders in general (sleep disturbances, social isolation, child abuse and neglect, medical disabilities and neurological diseases). The model of triple prevention is widely used: universal (for the entire population), selective (for risk groups) and necessary (for people with initial signs of depression) [11]. According to a meta-analysis of 32 major works on the prevention of depression, the risk of its development is reduced by 19 – 26%, depending on the approach [12]. The main target groups for large-scale selective prevention are adolescents, pregnant and newly born women, diabetics and the elderly. Internet technologies (mobile applications, electronic self-help resources, etc.) are becoming more and more popular for the rehabilitation and prevention of depressive disorders .                                 

Tasks of therapy for depressive disorders:

  • reducing the symptoms of depressive disorder and achieving complete remission;
  • reduction in mortality, in particular from suicide;  
  • restoration of professional and social productivity; 
  • decrease in the likelihood of relapse, both early and later. 

Factors that should be considered when choosing blood pressure in the treatment of affective disorders relate to both the severity of symptoms and its clinical features, comorbid conditions, side effects with previous use of blood pressure and patient preferences (patient factors), and the comparative efficacy and tolerability of blood pressure, potential interactions with other drugs, ease of use, cost and availability (drug factors). Maximum efficiency, safety, ease of use and affordability are important factors when choosing a blood pressure.       

Herbal therapy for depression

Recommendations for the treatment of depression with St. John’s wort are found in many modern international clinical protocols, authoritative guidelines for psychopharmacotherapy. For the treatment of a depressive episode of mild to moderate severity, it is recommended by CANMAT (2016), the German Society of Psychiatrists and Psychotherapists (2015), the British guide to psychopharmacotherapy S. Bazire [13].      

Recently in Ukraine, the British company Amaxa Pharma registered a new plant AD Remotiv , produced in Switzerland. The composition of the drug includes a standardized herbal extract of St. John’s wort, developed using a special technology, which guarantees the presence of the same amount of active substance in each tablet and, therefore, high efficiency and safety of therapy.      

The mechanism of action of the drug is similar to inhibitors of the reuptake of serotonin, dopamine and norepinephrine. As a result, the level of these neurotransmitters increases in the synapse of the neuron. As you know, it is their deficiency that leads to the development of depressive disorders. Due to its effect on β-adrenergic receptors, Remotiv has a modulating effect in the postsynaptic membrane.       

Several studies in recent years confirm the results of studies carried out in previous decades. In particular, a meta-analysis by K. Linde et al. (2015), which included 66 randomized controlled trials, showed that preparations with St. John’s wort extract had similar efficacy, but better tolerance than SSRIs and TCAs. Studies have compared the efficacy of drugs of different pharmacological classes or the efficacy of drugs versus placebo in the treatment of adult patients with unipolar depressive disorder. A total of 15,161 patients were included in the meta-analysis. As a result, preparations containing St. John’s wort extract showed comparable efficacy in the treatment of mild to moderate depression with SSRIs and TCAs, as well as in the comparison group with placebo. They were better tolerated and had fewer side effects.                    

A study by E. Seifritz et al. (2016) showed a better efficacy of St. John’s wort extract compared to paroxetine in reducing the intensity of depressive symptoms, namely the overall Hamilton scale for assessing depression (HAM-D). A favorable safety profile of St. John’s wort extract was also observed. The study included outpatients from 21 primary psychiatric care centers in Germany with mild to moderate depression (baseline HAM-D total score <25). The participants were divided into two comparison groups: the first (n = 31) received therapy with St. John’s wort extract at a dose of 300 mg three times a day, the second (n = 34) – 20 mg / day paroxetine.                  

As a result of therapy in both groups, significant improvement in depression scores was observed within 6 weeks and was characterized by a marked decrease in the total HAM-D scores . After 7 days of treatment, the average decrease in the total HAM-D score was statistically significantly more pronounced in patients treated with St. John’s wort extract compared with paroxetine. In 27 (87.1%) participants on the St. John’s wort extract preparation, there was a 50% decrease in the total HAM-D score compared to 20 (60.6%) in the paroxetine group; the difference is statistically significant (p = 0.017). During the treatment period, 19% of patients receiving St. John’s wort extract reported 15 potentially suspected side effects, while in the paroxetine group (61%) – about 61.                    

Thus, both studies showed significant efficacy Hypericum extract in comparison to placebo and other groups of drugs used for the treatment of depression as well as a high safety profile. This makes it possible to recommend it to patients prone to side effects or the elderly.     

The data obtained are consistent with previous studies and confirm the hypothesis that the safety profile of St. John’s wort extract is more favorable than that of synthetic AD (Kasper et al., 2010; Gastpar, 2013).    

The safety and good tolerance of the drug Remotiv is also explained by the technology for the production of a standardized extract, which ensures the presence of a low level of hyperforin (≤1%) in the composition. This leads to a low potential for interaction with other drugs and makes it possible to recommend Remotiv to elderly patients receiving therapy for the underlying disease.     

Based on data from current clinical studies, St. John’s wort extract can be recommended as a first-line treatment for patients with mild to moderate depressive episodes. It is also suitable as an alternative for long-term relapse prevention.   

Remotiv is recommended for depressive disorders of mild to moderate severity, accompanied by depressed mood, internal anxiety, a feeling of chronic fatigue, mood changes. It is also advisable to recommend the drug for depression in persons prone to or fearing side effects, as well as in elderly patients.     

Remotiv is easy to use: you need to take 1 tablet once a day, which helps to improve patient adherence to treatment. The effect of the drug is manifested after 2 weeks, and full effectiveness after 4 – 6 weeks.      

The main advantages of Remotiv are high efficacy, comparable to SSRIs, and a favorable safety profile with long-term use.  

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