Caring for "Liu Xuezhou" - Inventory of the pathogenesis of depression and related drugs

Modern society is fast-paced and under great pressure, and more and more people have psychological problems and mental illnesses.
The high incidence of depression is not only a common psychiatric problem, but also an increasingly serious social problem
.
At the end of January 2022, Liu Xuezhou, a boy from Hebei who had been searching for relatives online, committed suicide by taking medicine in Sanya, Hainan.
His friend claimed that Liu Xuezhou suffered from depression, but he has been actively receiving treatment
.
The Hong Kong film "Ignorant One Mind" is China's first depression-themed film
.
The film is adapted from real news events in Hong Kong, China, and has a delicate and profound description of a typical form of depression—the clinical manifestations, causes, rehabilitation treatment, and social pressure of bipolar patients
.
The film focuses on the traumatic experience of depression patient Adong's reintegration into society, and uses his memories of family life as a sub-line.
It tells the life story of a young man troubled by depression, interacting with his original family and the surrounding society
.
Although the production cost of the film was only 2 million Hong Kong dollars and it took only 16 days to shoot, it has achieved remarkable artistic achievements and positive social effects
.
The following will briefly introduce the diagnosis, pathological mechanism and related drugs of depression
.
Depression is a disease characterized by significant and persistent depression, lack of interest, and delayed thinking and cognitive function.
It has the characteristics of high prevalence, high disability rate, high suicide rate, and high recurrence rate.
At the same time, it also brings a serious social and economic burden
.
According to statistics from the World Health Organization, it is estimated that by 2030, depression will surpass tumors and cardiovascular and cerebrovascular diseases to become the world's largest disease burden
.
Judging according to the diagnostic criteria for depressive disorders in the latest "Guidelines for the Diagnosis and Treatment of Mental Disorders (2020 Edition)" issued by the National Health Commission: If a person has the core symptoms of low mood, loss of interest, pleasure and/or easy fatigue, and accompanied by Depression can be diagnosed if 2 of the additional symptoms, such as decreased attention, decreased self-evaluation, guilt, pessimism about the future, suicidal tendencies, insomnia, and changes in appetite, persist for more than 2 weeks
.
Rational use of mental and psychological assessment scales Once depression is diagnosed, it is necessary to judge the severity of depression, so as to point out the direction for further treatment
.
The most important thing in evaluating the severity of depression is to use evaluation tools reasonably, mainly various mental and psychological evaluation scales, which can be further divided into self-rating scales and other rating scales: Common self-rating scales such as patient health Questionnaire depression scale, depression self-rating scale, symptom self-rating scale; common other scales such as Hamilton depression scale, Montgomery depression rating scale and TCM syndrome differentiation scale for depression
.
These evaluation scales can not only assist doctors to judge the severity of the disease, but also can be used to evaluate the efficacy of drugs
.
For example, the Patient Health Questionnaire Depression Scale in the Self-Rating Scale is used for rapid screening and assessment of depressive symptoms by patients: ● 5-9 points for mild depression; ● 10-14 points for moderate depression; ● 15-19 points Moderate to severe depression; ● 20 to 27 points for severe depression
.
The Hamilton Depression Scale is the most commonly used clinical depression scale.
The HAMD-17 score: ● 7-17 points may have depression; ● 18-24 points are definitely depression ; ● > 24 points with severe depression
.
HAMD-24 score: ● 9-20 points may have depression; ● 21-35 points must have depression; ● > 35 points have severe depression
.
However, there may be heterogeneity in different assessment results.
Therefore, in clinical practice, psychological assessment results should not be overly relied upon, but should be comprehensively assessed and judged based on the patient’s clinical symptoms.
Only after integrated analysis can the most accurate results be obtained. .
1 Genetic factors The genetic probability of major depression may be 31% to 42%, and the genetic level of recurrent major depression may be higher
.
2 Neurotransmitter system The monoamine hypothesis was put forward in the 20th century, and most clinical experiments show that the decrease in the concentration of monoamine neurotransmitters such as 5-HT and DA is one of the main reasons for the induction of depression
.
3 Brain-derived neurotrophic factor (BDNF) The NTF theory proposed by Duman et al.
believes that the physiological and pathological basis of the development of depression is the damage of neuroplasticity, and the possible mechanism by which some drugs can alleviate depressive behavior is to regulate the related signaling pathways.
neuroplasticity and cellular structure
.
Brain-derived neurotrophic factor (BDNF), one of the most common NTFs, plays an important physiological role in altering synaptic plasticity and increasing intersynaptic connections
.
4 Hypothalamus-pituitary-adrenal axis (HPA) HPA is an endocrine axis that can maintain homeostasis and stress response and has important regulatory functions.
It controls the secretion of various regulatory peptides and hormones, and plays an important role in depression.
It occupies a unique position in the occurrence and development of depression, and it is clinically found that patients with depression often have hyperactivity of HPA function
.
5 Inflammatory Factors Depression patients are often accompanied by an increase in inflammatory factors such as tumor necrosis factor-α (TNF-α) and a decrease in anti-inflammatory factors.
The levels of anti-inflammatory factors were significantly increased
.
6 Comprehensive effects of multiple factors Statistical analysis of the serum test results of most patients with depression showed that the content of monoamine neurotransmitters decreased, and the expression levels of cytokines and NTF also changed accordingly.
It was concluded that depression may be due to monoamines Neurotransmitters and their receptors, HPA dysfunction, NTF, and cellular responses, etc.
, interact and result from each other
.
In recent years, the research on the pathogenesis of depression and specific drug treatment targets has made rapid progress.
Around the above pathogenesis, according to different structural types, antidepressants can be roughly divided into the following categories: selective 5- First-line drugs such as HT reuptake inhibitors (SSRIs), 5-HT and NE reuptake inhibitors, NaSSA, NDRI, and melatonin receptor agonists; and second-line drugs such as SARI, NARI, SSRA, and TCAS
.
1 SSRIs SSRIs started in the 1980s, and their mechanism of action is mainly to specifically act on the 5-HT transporter, inhibit the reuptake of 5-HT, thereby increasing the content of 5-HT in the synaptic cleft, increasing the 5-HT function
.
SSRIs overcome the shortcomings of MAOIs and TCAs, and have the characteristics of broad antidepressant spectrum, strong applicability, and high bioavailability, especially in drug safety
.
Inadvertent overdose of patients will not cause serious consequences, especially for depressed patients with suicidal tendencies, and it has become a first-line antidepressant drug
.
The main representative drugs are fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram and escitalopram
.
SSRIs still have obvious adverse reactions, such as improper use by pregnant women, which may cause adverse effects on the fetus
.
2 SNRIs serotonin and noradrenaline reuptake inhibitor (selective serotonin and noradrenaline reuptake inhibitor): Representative drugs include venlafaxine, duloxetine and milnacipran
.
SNRI is also a first-line antidepressant, especially for patients with depressive disorder with obvious anxiety or somatic symptoms, SNRI has certain advantages
.
3 NaSSA noradrenergic and serotonergic antidepressants (noradrenergic and specific serotonergic antidepressant): the representative drug is mirtazapine
.
It is a first-line antidepressant and is effective for anhedonia, psychomotor depression, poor sleep (early awakening), and weight loss
.
4 NDRI noradrenaline and dopamine reuptake inhibitor: the representative drug is bupropion
.
It has a better effect on enhancing positive emotions and belongs to the first-line antidepressant
.
Compared with SSRIs, bupropion is more likely to cause weight loss and may improve sexual function in patients with depressive disorders
.
5 Melatonin receptor agonist The representative drug is agomelatine; it is a first-line antidepressant, which can regulate the sleep-wake cycle and improve sleep
.
There are few adverse reactions and no adverse effects on sexual function.
Liver function needs to be monitored before and during use
.
6 The representative drug of multimodal antidepressants is vortioxetine; it can improve the neurotransmission function of serotonin, norepinephrine, dopamine, acetylcholine, histamine, and glutamatergic neurons related to depression in the brain.
Thereby producing antidepressant effect and improving cognitive symptoms to some extent
.
7 SARI serotonin receptor antagonist/reuptake inhibitor: the representative drug is trazodone; it is a second-line antidepressant
.
Trazodone is less toxic to the cardiovascular system, suitable for elderly patients, has a sedative effect, and can improve sleep at low doses
.
8 NARI norepinephrine reuptake inhibitor, the representative drug is reboxetine
.
Research has shown that reboxetine can help improve motivation and energy in people with depressive disorders
.
Currently a second-line antidepressant
.
9 SSRA selective serotonin reuptake activator (selective serotonin reuptake activator): the representative drug is tianeptine
.
Tianeptine is between sedative antidepressants and stimulant antidepressants, and has obvious effects on physical discomfort, especially gastrointestinal symptoms related to anxiety and mood disorders; it belongs to second-line antidepressants medicine
.
10 Reversible type A monoamine oxidase inhibitor The representative drug is moclobemide; it is suitable for endogenous depression and elderly patients
.
Due to its dietary restrictions and safety concerns caused by drug interactions, it is currently only used as a third-line antidepressant
.
11 TCAs The representative drugs of tricyclic antidepressants are amitriptyline, clomipramine, doxepin, and imipramine; the representative drugs of tetracyclic antidepressants are maprotiline and mianserin
.
Both tricyclic and tetracyclic antidepressants belong to traditional antidepressants, which have strong curative effect.
However, due to their anticholinergic side effects, cardiotoxicity and high rate of turning into agitation, they are less acceptable and belong to second-line antidepressants.
medicine
.
In recent years, although people have revealed the potential occurrence and development mechanism of depression from various aspects, there is still no unified standard, and the marketed antidepressant drugs for various pathogenic mechanisms also have different advantages and disadvantages
.
However, people with depression have always been a marginalized and stigmatized social group
.
The public needs to understand their living conditions, and on the basis of understanding, they can actively care, help and support this group
.
As declared in the ending subtitle of the movie "Ignore One Mind": "Treatment of emotional disorders is a long-term struggle.
The treatment of traumatized minds not only requires appropriate treatment and community support, but also requires the public to remove negative labels, give understanding and support, and use empathy.
to feel and care
.
” Columnist Xingxinghu has a background in medicinal chemistry and has been engaged in target research, patent analysis and breakthroughs, improved new drugs, and molecular design of innovative drugs.
He loves the pharmaceutical industry and is willing to learn from and progress with all peers and witness the best of innovative drugs.
Times
.
References: 1.
Yuan Mengqian; Artistic Intervention of Film: The Life Story of Depressed Subjects-Trauma Construction and Image Empowerment; 2020 Issue 1·Academic Forum; 3.
Zhao Zhonghui et al.
; Integrated Traditional Chinese and Western Medicine for Depression; Chinese Journal of Clinicians, Vol.
49, No.
10, 2021; 4.
Xue-mei Qin et al; Research on the Pathological Mechanism and Drug Treatment Mechanism of Depression; Current Neuropharmacology, 2015, 13 , 514-523; 5, Gao Guiyuan, etc.
; The pathogenesis of depression and research progress of antidepressant drugs; China Medical Herald, Vol.
18, Issue 1, January 2021;