Integrated Human Practice
Depression has been a critical issue that penetrates our community, society, and the entire world. Since our team is ready to design possible solutions to help our community fight against depression, we consider it is essential to acquire perspectives that our community has shaped about depression. It is believed that absorption of these perspectives will help our team better shape our project on antidepressant.
The perspectives are classified into three categories:
1) General audience's Perspectives
2) Perspectives from Academia
3) Perspectives from Industry
Our team conducted various human practice activities to acquire the perspectives listed above, which in return helped us procced with our project on antidepressant.
Part 1 General Audience's Perspectives
In order to know how ordinary people regard depression as, our team designed a street interview questionnaire consists of six questions. Following is the complete questionnaire list.
How do you know about depression?
What do you think is the most significant cause of depression?
Which do you prefer in medication or psychotherapy to the treatment of depression?
How effective do you think the medical treatment is?
What do you think is the effectiveness of medication?
What do you think is the main reason for the recurrence of depression?
In addition, we randomly interviewed passers-by on the street to measure the public's understanding and perception of depression and antidepressants.
Our team finally collected over 50 fifty feedback (including interview and filled-in questionnaires). After analyzing this feedback, we have the following key findings.
Most people know about depression through the Internet and their friends, but it is usually at the level of awareness;
Most people think that the depression is caused by psychological factors and environmental factors, whereas, they know little about medical treatment, let alone the side effects of antidepressants;
Most people do not know about the effectiveness of medical treatment;
As for the cause of the recurrence of depression, most interviewees chose the environmental cause. It can be seen that the public has a certain cognition of the susceptibility to depression. They may not be exceptionally professional, but they have realized that the environment or atmosphere around the patient is not very favorable to their mental status after recovery;
We also designed the question of "medical therapy or psychological therapy for the treatment of depression". We received mainly two answers. One is that the two treatments are equally important, and should be combined to achieve better effects;the other one is pure psychotherapy should be adopted.
Conclusion of Part 1
In conclusion, we got to know that , except the doctors and related researchers, even though general public heard about depression and had some fundamental knowledge of it, their knowledge of the causes and medical treatment of depression was far from enough. Based on this, we consider that it is meaningful to enhance the general public’s understanding of depression (ranging from major causes, prevention methods, medication and etc.) and antidepressants by launching a series of promotion activities.
Attached is the original data collected from questionnaire survey.
Questions
Q: What source do you get information of depression from?
-Friend x12, book x2, once ill, common sense, network x34, do not know x4, doctor
Q: What do you think is the biggest cause of depression?
-Genetic x4, brain structure x1, psychological x19, environmental x19 every reason takes important place x3
Q: How effective is medication as a treatment of depression?
-Not sure x6, 60% x2, 70% x2, 0%, 50% x3, 40% x2, 80%, 20% x2, 30%
Q: What are the side effects of medications used to treat depression, and do they burden patients
-Don't know x9, some medicine can x3. yes, they do x24, no x6
Q: What do you think is the main reason for the recurrence of depression?
-Secondary shock x5, mental state x4, psychological stress x7, environment x11 drug withdrawal x2, I don't know
Q: Which do you prefer, medication or psychotherapy?
-Both x8 psychotherapy x10 not no x1 medication x6
Part 2 Perspectives from Academia
Part 2.1 Interview with Dr. Chongyang Liu，Chief Physician, Chief expert at the Anshan Mental Health Center
We interviewed Dr. Liu, whose clinical expertise includes psychiatric disorders, psychotherapy, and family therapy. He has provided us with much beneficial insights on depression and antidepressant, which has further enlightened our project future directions
Part 2.1.1 Diagnosis of Depression
Because there is a craze of pretending to be depressed on the Internet, it is difficult to judge whether people around them or even themselves are depressed. To answer this question, we inquired Dr. Liu about classical diagnosis criteria and major causes of depression.
Part 2.1.2General Judgement of Depression
Dr. Liu explained how to think if a person suffers from depression and what causes it. "There is an increasing concern about depression," he said. "We often refer to depression as mild depression, and the main manifestation of depressive symptoms is the expression of mood, which is when your mood swings are more than five to ten percent, and people around you can see significant changes in your mood easily. If Big mood fluctuations happen (e.g. some small stimulus causes a big emotional response), more than three times a week, a red flag for depression should be noted.
Part 2.1.3Typical Symptoms
Is there any typical symptom that indicate depression? We asked Dr. Liu this question to gain further knowledge about depression diagnosis. Dr. Liu’s explanations are listed as follows:
Three basic symptoms of depression are:
Fatigue or low energy;
Persistent sadness or low mood;
Loss of interests or pleasure
Seven additional symptoms are:
Disturbed sleep
Poor concentration or indecisiveness
Low self-confidence
Poor or increased appetite
Suicidal thoughts or acts
Agitation or slowing of movements
Guilt or self-blame
Reference: The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines World Health Organization
In the past two weeks, mild depression meets the two of the three basic symptoms and two additional symptoms, moderate depression meets two of the three basic symptoms plus three of the seven additional symptoms. It can be judged by filling in the depression test questions under the guidance of physicians. The authoritative ones are the Self-Rating Depression Scale (SDS), Self-Rating Symptom Scale (SCL-90), PHQ-9 Depression Test Scale and Hamilton Depression Scale (HAMD).
Part 2.1.4 Incidence Age
Dr. Liu showed that the most common age of depression is about 15-20 and 19 years old. The second part is 25-35 years old, which is also a high incidence age. Therefore, more depression is in the range of teenagers. As the majority of depression is young people, people are paying more and more attention to it. In 2019, the incidence rate of depression was about 7.6% in the national survey, but 75% of these 7.6% cases were mild depression. He also showed that mild depression in early treatment has a higher cure rate. Adolescents suffer from depression mostly because of going to school, family conflicts, and some social factors. At present, both family members, teachers, and the country are paying more and more attention to the occurrence of depression. In the national survey, PHQ-9 is explicitly stipulated to be used for depression screening. If five criteria are met, major depression is diagnosed. And some related institutions go to junior high school and senior high school to popularize common knowledge of depression and deliver feasible prevention methods.
Part 2.1.5 Recurrence of Depression
The recurrence rate of depression is a common issue and many respondents in our questionnaire survey proposed their opinions on this issue. We want to hear experts’ opinions about this challenging issue.
Dr. Liu gave a comprehensive answer to our question. Through the expert's response, we know that depression is a chronic central nervous disease. If we don't intervene, it will become gradually regular. He told us that the treatment of depression should intervene early to prevent it from becoming chronic. The expert says the high rate of recurrence of depression is similar to the common illnesses such as respiratory infections and diabetes. These medical diseases also have a high rate of self-healing and a high rate of recurrence. With early intervention and maintenance of treatment with a professional physician, self-healing can be improved, and recurrence rates can be reduced. But if you discontinue the medication immediately after a period of treatment, say three months or so, and you don't stick to the treatment. The disease may recur more than twice a year, and that makes depression a refractory disease. The answers from the experts have solved our doubts and helped us better understand the reasons and principles of the high recurrence rate of depression so that we can have a clearer direction and goal in future research to find a solution to the disadvantages of the high recurrence rate of antidepressants.
Part 2.1.6 Treatment of Depression
During the interview, we also asked Dr. Liu about the treatment of depression. We know that the treatment of depression is often a combination of psychological therapy, drug therapy, and family therapy. But antidepressant drugs still face some problems, such as strong side effects and high recurrence rates. Therefore, we asked the Dr. under what circumstances patients should take drug therapy and whether he needed psychological therapy in his clinical diagnosis process or whether drug therapy combined with psychological therapy was more common. He gave a very comprehensive explanation of it. To answer this question, he started from the causes of depression.
Because depression is caused by biological, social, and psychological problems, among these three problems, biology plays a dominant role, and the abnormality of neurotransmitter function is the key reason for the disease.
In the diagnosis of patients, we can judge from the biological perspective about whether patients need to be treated with drugs. For example, if a person has only mild depression, such as low mood, it can be cured with sustained psychological intervention. He also shared his own experience with the clinic. He said that 75 percent of people with depression are mild depression and that most of them can be cured with psychological therapy and family support. But if it is moderate or severe, it requires medication and psychotherapy. Dr. Liu also told us a short story about his clinical diagnosis process. And he had a very special treatment which was to give the families homework. At first, the families were reluctant to write, but as time went on, more and more families began to find that it worked. Even at the end, the book was filled with their child in therapy.
Dr. Liu's answer benefited us a lot. His response reminded us of the complexity of depression. For the treatment of mental illness, we should not limit ourselves to the study of drugs. Other treatments need to be combined. Therefore, we have been inspired that in the screening of lead compounds for antidepressants, we should consider whether the drug's therapeutic effect can be well-matched with other methods for treating depression. That is to say, is is possible to imagine some daily health supplements to protect us from being invaded by depression? Or is it possible to obtain some health supplement to be combined with drugs to enhance the overall effectiveness?
Part 2.1.7 Current Medication Mechanism of Antidepressants
The three major problems that current antidepressants have are slow efficacy, strong side effects, and are proximity to relapse. So we asked the Dr. what he thought about these three questions. Due to the high recurrence rate, he has made a clear explanation in the second question, so he emphasized the slow efficacy and side effects. First, he says, many patients and their families have misconceptions about medications for depression. The first thing most families of depressed people say when their doctors prescribe a drug is, "Will the side effects be great?" As a doctor, though, Dr. Liu does not shy away from the lingering problem of side effects. But he says the treatment benefits of depression drugs far outweigh the side effects. At present, the effect of depression drugs has been in stable optimization, so people's inherent thinking about depression drugs should be broken.
Secondly, Dr. Liu also gave a professional explanation for the slow effect of depression drugs. He says drug treatment is a process, it has to be broken down, absorbed and then spread out of the brain. So psychotropic drugs usually take one to two weeks to work.
Dr. also explained to us how to choose antidepressant drugs for clinical more in-depth knowledge, each disease has target symptoms, depression also needs this kind of targeted research and development. In the process of clinical treatment, the choice of drugs for depression is also different according to the target symptoms. For example, at the beginning of treatment, for schizophrenic patients with strong physique and excitatory impulse, doctors will choose antipsychotic drugs with stronger sedative effect and injection preparations, such as haloperidol, chlorpromazine and perphenazine. For the patients with prominent negative symptoms, that is, the patients with schizophrenia mainly characterized by loneliness, laziness, poor thinking and apathy, they can choose the same dose of risperidone or sulpiride for treatment. For the patients whose diagnosis is not clear and the patients with negative symptoms or depression can not be distinguished, antidepressant drugs or sulpiride for treatment can be considered first. In fact, most of the antidepressant drugs are used to increase dopamine or pentahydroxytetramine, so that people with depression tendency can have good psychological and emotional regulation. Now more and more teenagers still have depression tendency, so for teenagers, the choice of medication needs more rigorous testing.
So what we learned from the interview is that in terms of the side effects of antidepressants, it's not as bad as I thought. But there are still some unbreakable problems that lead to anxiety about antidepressants. Second, antidepressants also need to make a breakthrough in terms of their slow efficacy. Therefore, this interview reinforces our conviction that screening of lead compounds for antidepressant drugs, which may have fast efficacy, is of great significance.
We also learned from Dr. Liu that in addition to the three limitations we found in the current research on antidepressants, such as large side effects, slow onset and high recurrence rate, there are still some limitations. Even in big cities, many antidepressants can be used from the age of six to sixteen, such as SSIR antidepressants, However, there are few people under the age of six with depression tendency, so in order to treat and protect teenagers, experiments should be done when developing antidepressant drugs for teenagers to determine whether the research results can be provided to teenagers.
Part 2.1.8 Dr. Liu’s suggestions on Screening Lead Compounds for Antidepressant based on Brain-gut Circulation
We also asked Dr. Liu about his personal opinions about our lead compounds for antidepressant screening based on brain-gut circulation. Dr. Liu said that according to his understanding, our project on antidepressant drugs is to make drugs use of the gut brain circulation, in which the nutrition absorbed by the gastrointestinal tract can change the level of adrenocortical hormone, thus affecting the neurotrophic factors in the brain. This cutting-edge method may be effective. In the future, this treatment method and research direction will be a major trend.
Meanwhile, Dr. Liu also encouraged that even though our project started from fundamental research, it would be promising. Only through the cooperation of scientific research and clinical practice can we develop a better drug. The research results can lay a good foundation for the development of new drugs in the future. As mentioned above, biological factors are dominant because there is no clear answer to the pathogenesis of depression.
Part 2.1.9 Key Learning Outcomes from Interview with Dr. Chongyang Liu
We gained crucial information about depression diagnosis criteria, causes, and medications. Based on these, we will launch a series of promotion activities to enrich the general audience’s knowledge on depression, hoping to enhance their mental health and help them stay away from depression;
We developed an understanding that to fight against depression, different treatment should be combined. Thus, apart from antidepressant drugs, health supplements may also be a beneficial choice. It also motivated us to imagine the possibility of designing a probiotic to fight against depression in our daily life;
We realized that the experiments we are doing about lead compounds screening based on brain-gut circulation are very important because of its novelty and it may partially solve the problem of low efficacy. Dr. Liu's encouragement did make us more confident in our research projects.We also realized the importance and cutting edge of our experiments.
Part 2.2 Interview with Dr. Liang Zhang, Professor, College of Basic Medical Science, Shanghai Jiao Tong University
Part 2.2.1. Project Pitch to Dr. Zhang
Since our project is mainly about foundational research, we considered it would be meaningful to consult a distinguished scholar in relevant areas to absorb useful information about foundational research. Thus, we invited Dr. Liang Zhang, a drug research and development expert from the School of Basic Medical Science of Shanghai Jiao Tong University, for an interview. Dr. Zhang was also eager to answer questions for us. First of all, we introduced the subject of our research and the sparkle of our experiment to Dr. Zhang.
Our experiment is to screen lead compounds based on brain-gut circulation, which may be further developed into antidepressant drugs. Meanwhile, we also proposed the idea to transformed the genes of E. coli to secrete enzymes which are converted into 5 - HT (lower brain 5 - HT levels could lead to depression), whose future application may be a probiotic used daily health supplement. but Dr. Zhang, after hearing that the two-part doesn't seem to connect. We explained to the Dr. that our two parts of the experiment started from different perspectives and were carried out simultaneously. What they have in common is that they all aim to increase the content of 5-HT and thus play an inhibitory effect on depression. But the difference is that the first part of the lead compounds screening is to develop new, more effective antidepressants, while the second part is designed to genetically modify E. coli bacteria to produce more 5-HT, which could later be used to produce probiotic, and then used in oral drinks or health supplements to prevent and relieve mild symptoms of depression.
Part 2.2.2 Dr. Zhang’s Comments
After hearing our explanations, Dr. Zhang spoke highly of our experiment, saying that it was a very novel idea. At the same time, he also stressed that we should pay attention to the experiment's focus, that is, to the positive and negative control. Because there are often hundreds of different drug screens, it takes a lot of time to try each one just the usual way. The negative and positive controls can help us to improve the efficiency of the compound screening. For the second part of genetic modification, we need to carry out the cell experiment of the first part simultaneously to ensure the progress of our two experiments.
In addition, the synchronization of the two experiments allowed the two experiments to be compared, and more information could be obtained about the 5-HT. Besides, we also consulted Dr. Zhang about the knowledge of the drug market and his own experience in pharmaceutical research. Dr. Zhang began by explaining to us the stages of drug development. Developing drugs is a long process, and biological research is inherently fraught with uncertainty.
The average time to market is about 10 years. That's why we're doing this two-part experiment. Having more alternatives ensures that we have a higher probability of success. We then asked about society's expectations of antidepressants with low side effects and the prospects for them. According to Dr. Zhang, antidepressants are currently better than nothing -- they are the only drugs that patients can take and are socially necessary, even with limitations such as side effects (drowsiness, inability to perform high-intensity mental exercises) and poor treatment. So the expectations for a better quality drug with fewer side effects are certainly very high.
In addition, with the increasing number of patients with depression and the younger age, their demands are increasing, and their quality requirements are higher, thus creating huge market demand. In recent years, depression has gradually become a hot topic of discussion. So there's a lot of commercial value to what we're doing with antidepressants. However, the size of the antidepressant market and the technical difficulties of the breakthrough are still in the development stage. At the end of the interview, we asked about drug standards that need to be strictly regulated. Dr. Zhang said drugs with side effects and antibiotics need to be strictly controlled to prevent addiction and cause additional harm to people's bodies. Drugs that treat mental disorders, for example, have considerable side effects, and most of them are regulated by standards. Therefore, it is the pursuit of our project and one of the sparkle and difficulties of our project to minimize the side effects of drugs and eliminate the need for the official control of drugs. Whether we can maximize the benefits depends on how well we can reduce the side effects of antidepressants.
Part 2.2.3 Key Learning from Dr. Liang Zhang’s Interview
Through this interview, we have a deeper understanding of the drug market and the production of drugs. We will also take action after the interview.
We also became determined in completing our project following a 2-stage flow, that is to say, exploring the feasibility of fighting against depression from both drug discovery pespective and probiotic construction perspective.
Part 3 Industry Perspectives
Zhejiang Huahai Pharmaceutical Co.,Ltd Visit
Since the final goal of our lead compounds screening is to develop an effective drug for depression, we visited the plant of Zhejiang Huahai Pharmaceutical Co., Ltd. and interviewed one of its R & D manager (Mr. Wei Zhao), to gain 1st hand information about drug production.
Part 3.1 Drug Safety of Consumers
We have learned that to protect the drug safety of consumers, Huahai Pharmaceutical has to meet high standards and high requirements for the production workshop and production technology, from the manufacturing of ampere bottles or bottles to cleaning and canning. To prevent any dust and bacteria from entering the drug (thereby threatening the safety of people's drug use), the whole plant has a high cleanliness level requirement, divided into 100,000 clean areas, 10,000 clean areas, and 100 clean areas. A clean grade in 100,000, for example, means that a volume of air containing less than 100,000 particles which larger than 5 microns is contained in a volume of 1ft3 [cubic foot]. (1ft=0.028m3) In particular, the sub-packing area should be 100 level cleans and sterile. In particular, the sub-packing area should be 100 levels clean and sterile. The production process includes scrubbing and disinfection of raw materials, rough and delicate washing of bottles, sterilization and drying, packaging, capping, lamp inspection, packaging, and other steps. The preparation of liquid medicine, bottle selection, drying and cooling, filling or packing, sealing and plugging, and other procedures should be controlled. And the air conditioning in the preparation workshop runs 24 hours a day and can filter 99.99 percent of particles greater than or equal to 0.5 microns. The cleaner the area, the higher the ventilation rate per hour. Operators should be fully protected when entering the dust-free workshop, including but not limited to goggles, protective clothing, masks, headgear, and so on. The goal is to reduce the number of particles released by the human body. And in place that requires asepsis will be regularly and comprehensively sterilized, such as alcohol disinfection, formaldehyde, hydrogen peroxide. In addition, the water used for cleaning glass bottles is distilled water many times to ensure that there are no magazines in the water.
Part 3.2 Drug Research & Development Process (Costs and Pricing)
In terms of quality and manufacturing, we also learned the development process and cost that goes into producing drugs. According to the description of the pharmaceutical expert, he mentioned that the whole manufacturing process is relatively simple and easy. However, the entire research and development process requires various experiments, which leads to very high costs. All the fees before the clinic process are 40 to 50 million, but the whole clinic process costs a few thousand to a few billion. As the number of patients increases from Phase I to Phase III so does the costs. But new drugs are more freely priced than generics. This means that our program (to study new compounds for marketing) has a significant advantage in the market. Generics, on the other hand, cost between a third and a half of the original price. In the pricing of drugs, the length of the cycle and the development costs is the two bases of pricing drugs, such as "orphan drugs" priced at a low price that cannot cover the cost. Some medicines are priced at more than a million dollars a shot. Because the number of patients suffering from these diseases is minimal, the research and development side has invested in many costs. With the low rate of inflation, the natural pricing will be high.
The drug factory we visited makes biomass similar to ours, which are also cultured by taking the original solution. The main concerns in the development and approval for the drug were safety and efficacy. In terms of production, it takes one month from the beginning of production to the end of production. Second, the experts answer our questions about side effects. In the screening of side effects, experts mentioned that "adverse reactions refer to adverse reactions in the clinical stage after the market by establishing their procedures to record adverse reactions. Adverse reactions are being tested not by volunteers but by patients in hospitals qualified to conduct clinical trials. Not every hospital is qualified to conduct clinical trials. Some hospitals have to be qualified, for example, for terminally ill patients, who are hoping that these new drugs will have some effect." In terms of the standard and range of side effects, the drug company will conduct some tests in the clinical department. The doctors will make certain judgments about the adverse reaction caused by the human body or the drug's negative reaction. Because any medication can have an adverse reaction, the doctor will judge what caused it and the severity after the clinical trial if the adverse reaction is not fatal.
Finally, we acknowledged a problem with the drug market. Because now there are so many people with depression, the pain is severe. People of all ages have it. So the prospects of the whole market are good. He commented that if we could screen out the compound, it could go directly to the drug market, which could help develop drugs for depression.
Part 3.3 Key Learning from Visit to Zhejiang Huahai Pharmaceutical Co.,Ltd
Consumer safety is a key issue, even the most important issue in drug production;
Drug research and development requires high costs, whereas, creates opportunities for freely pricing;
Lead compound screening for depression has a huge market potential.