People generally always think that depression is a disease of the heart and ‘heart disease should be treated with heart medicine’. In fact, it is not, just like heart disease, hepatitis, cold and pneumonia, depression is a ‘disease’. In fact, this ‘disease’ shows not physical symptoms, but psychological symptoms such as depression; it is not a psychological problem or psychological blow, which causes this ‘disease’. Disease’ is the ’cause’ and ‘depression’ is the ‘effect’; not the other way around. Yan Wenwei, psychiatrist of Taicang Third People’s Hospital If a person suffers a psychological blow, such as losing a love or a loved one, of course he will be depressed; however, usually after 2 weeks of the incident, his mood will improve on his own. However, if the depression continues for more than 2 weeks and does not decrease, you should consider the possibility of ‘primary depression’ as a ‘disease’. The typical signs of depression are: depressed mood (state of mind) and lack of interest (in layman’s terms, ‘lack of energy’). Other functions (e.g., sleep, appetite, libido, etc.) may also be reduced. The most important of these is “loss of interest”. One patient wrote to me with a typical statement: “Often have a feeling of weakness; lack of desire, decreased appetite and sex drive. I can still sleep, but I often wake up early at three or four o’clock, and I am drowsy until the morning, without any feeling of morning freshness. All day long, I feel that life is dark and I have no hope for the future, as if I can see my head and the last day of my life, and I feel that there is no point in living. Especially in the morning, the mood is the worst, in the evening a little better, but into bed at night, and worry about insomnia, the mood is heavy again. People would laugh when they heard something funny, but I couldn’t laugh at all. I have thought about suicide, and I had a momentary thought of killing myself, but I never did it because I thought of my parents and family. I have no interest in work or play, and just want to stay in the house and do nothing. Work is often delayed until the last minute and the quality is seriously reduced. There is no more self-confidence, lack of sense of honor, and it is no big deal to do a bad job. Memory and expression skills are reduced, often stuck, as if they do not remember what to f, and even sometimes the mind is blank, as if it can not start. Lack of patience, temper, often for a small matter, in the heart blocked for half a day. …” For clinicians, this is an important point: depressed mood without lack of enthusiasm is not depression. For example, if someone is depressed because he or she has failed in stock trading, but is still interested in playing cards and going to karaoke, that is not depression. Depressed people are bound to lose interest, feel that life has no taste, no interest, and even feel that there is no point in living. Another important point is that a depressed person is bound to blame himself, he will blame himself for the problem, and he will not think that he is not well and that it is because of others. If a person is depressed but says that someone else is to blame for his or her bad mood, then it is not depression either, but most likely schizophrenia. Of course, people with schizophrenia may also have the symptoms of ‘depressed mood and self-blame and self-sin’. So, we can only say: depressed people are bound to blame themselves, but we cannot say that all those who blame themselves are depressed. Why do you get depression? It is mainly endogenous, because he has a gene for depression pathology (according to recent research it was found that such genes may be located on chromosome 10). About 5-10% of the world’s population has this gene and is prone to depression. The so-called psychological stress or shock is only the trigger; for the onset of depression, the trigger is optional. It is a waste of effort to bother to look for these triggers if you suffer from depression. If the trigger is the loss of love, and depression occurs there, even if she is told to get married quickly, the disease cannot be cured. With depression, no matter how much you channel and try to ‘untie the knot’, you can’t cure his disease. Because these are only the triggers. Just like lighting a firecracker with a lighter, even if the lighter is thrown away, the firecracker will still explode in the air. Therefore, we say that the internal causes must be addressed, and the internal causes of the onset of depression must be addressed with medication or other methods in order for the disease to get better. In a way, depression is a ‘self-limiting disease’, just like the flu, and it will get better without treatment. According to foreign studies, if depression is left untreated, 30% of the cases (the milder ones) will return to normal naturally, which takes about 6-12 months. The other 30% will recur and become chronic. Lin Daiyu was actually chronically depressed, with a depressed mood that was gently heavy and could not be happy all the time (the psychiatric name is ‘bad mood’). The other 30% (heavier cases) will go to the end of the road, for example, Zhang Guorong, San Mao, a large pile of drugs at home, did not eat, and finally committed suicide. This ‘6-12 months’ mentioned above is the ‘natural course’ of depression. Take medication and other treatments, can change the symptom expression, probably less than 1 month, you can see the effect, the patient will no longer depressed. But these treatments cannot change the natural course of the disease, in other words, you have to wait for it to mend itself; if you stop the medication too early, it will rekindle and depression will appear again. That’s why we advocate that the medication should be taken for at least 6 months. It is generally said that 50% of depressed patients, after being cured, will not come back in this life, that is to say, 50% of patients, only once in their life; so we hope that patients will all take medication consciously for a longer period of time, and we hope they belong to this 50%, and we hope they will ‘break the root’ of this. As mentioned earlier, people with depression have genes that predispose them to the disease. In some cases, the gene is inherited from a previous generation of relatives who have had depression. Some people do not have such relatives, so where does the gene for depression come from? We need to know that just like physical characteristics such as eye size, whether or not we have double eyelids, or personality traits such as whether or not we are introverted, are burned into the chromosomes in the nucleus of the cell, called genes, which can be compared to the blueprints for building a house. When our parents give birth to us, they let the cells of the fertilized egg, divide in two, divide in two, divide in four, …, just like making copies with a photocopier. Sometimes, for some unknown reason, the handwriting appears blurred in certain places on the copied document. If the blur appears in an insignificant place, it does not matter; but if it appears in a place related to emotion regulation, then it mutates into a depression pathology gene, called ‘gene mutation’. In the human brain there are hundreds of millions of brain cells, called neurons, which are connected to other brain neurons by their outstretched nerve endings, forming a network. But they are not as close to each other as an electrical plug and socket; there is a gap between them (called a ‘synaptic gap’), and it is the nerve endings of the previous brain cell that must release neurotransmitters (like a postman) to carry information across the gap to the next brain cell. The place where the message is received is called a ‘receptor’ (like a mailbox). There are many different neurotransmitters, such as dopamine (DA), norepinephrine (NE), 5hydroxytryptamine (5HT), acetylcholine (ACh), etc. The depression pathogen mentioned above determines how much of the neurotransmitter 5HT (or norepinephrine) is produced, but even if it is less, there is not yet an immediate onset. However, under the ‘trigger’ effect of some trigger (like pulling the trigger of a pistol with your finger), the released 5HT neurotransmitter is recycled back in. For example, the nerve endings of the brain cells are like a post office, the original postman is relatively small, and now the back door of the post office has been opened, so that the postmen have slipped back, so that the real work of delivery is greatly reduced. When the transmission of information becomes a problem, the mood drops rapidly and the symptoms of depression are manifested. From here, we can see that psychological triggers such as loss of love only play a ‘trigger’-like ‘start’ role, even if we try to solve these psychological triggers, we can not solve the problem of depression. The problem of too little production of the neurotransmitter 5hydroxytryptamine must be addressed at the root, or the open ‘post office back door’ must be closed in order to cure depression. The former is to repair or modify the depression pathogen, a science that has not yet been reached; we can only treat from the latter doorway. The pharmacological action of antidepressants is: to inhibit 5hydroxytryptamine recycling. Previously used antidepressants, such as amitriptyline, mipramine (promethazine), clomipramine (chlorpromazine), in addition to inhibiting 5 hydroxytryptamine recycling this effect, there are other effects, so there are many side effects such as dry mouth, heartbeat, constipation, and even produce toxic effects on the heart; so has become less and less used. Nowadays, the most commonly used is ‘selective 5HT inhibitor’ (SSRI), which has only a relatively specific effect of inhibiting 5HT recycling and therefore has few side effects. Among the SSRIs, the first to be used was fluoxetine, an epoch-making drug that has emerged in psychiatry in recent years and has been used by at least 70 to 80 million patients to date, making it a tried and tested drug. When it first came on the market, it was vilified by some who said it would prompt suicide. In fact, this is occasionally the case with all antidepressants: the earliest effect of the drug is that the patient’s mind is freed, the brain is opened, but the improvement in mood is often a little later, a week behind. Originally, depressed patients often had a blank mind and could not even think of ‘how to kill themselves’, but now it is easier to open the mind and they can easily think of ways to kill themselves. Therefore, during the first 2 weeks of taking any antidepressant (not only fluoxetine), family members must stay close to the patient to guard against this possibility. 2 weeks later, the depression will gradually improve and this will not be the case. Because of the excellent efficacy of fluoxetine, other pharmaceutical companies have developed one after another drugs with similar effects, forming a large class called SSRIs (I used to call them ‘five of a kind’ in my classes, but in fact there are now more than five); for example, paroxetine, sertraline, citalopram, fluvoxamine. They have almost identical pharmacological effects and should have the same efficacy as long as the dosage is in place. They also have exactly the same indications, all treating depression, anxiety, phobias (including social fears), and obsessive-compulsive disorder. Due to the need for market development of each pharmaceutical company, they will make up all kinds of claims to promote the so-called ‘specialties’ of their products, which can specifically treat blah blah blah, and I would like to advise doctors and patients not to be mistaken for the truth. Some pharmaceutical companies have declared to the FDA that they have been approved to treat a certain disease; in fact, other SSRIs actually have this effect, only that the pharmaceutical companies have not declared them. However, since their chemical structures are different, the side effects may not be identical, and doctors and patients should be aware of this point. In the case of fluoxetine, for example, the therapeutic dose is not the same for everyone. Just like the amount of meals, it varies from person to person. The average person has one bowl of rice per meal, but some people don’t have enough and don’t feel full even after a year of eating one bowl per meal, but once they have 2 bowls of rice, they feel full. This, can not be predicted, because there is no ‘one bowl’ ‘ 2 bowls’ written on the face. The same is true for the therapeutic dose of fluoxetine, where 80% of patients need only one capsule of 20mg daily, while 20% have to have 2 capsules daily or more. We generally advocate starting with a daily dose of one capsule and increasing it to two capsules daily early after a week of no movement. For example, the wife of an old director of a hospital in Shanghai was diagnosed with depression by the neurology department of the hospital and took fluoxetine 20mg a capsule daily for 2 months without improvement. The patient asked if she should change her medication; I told her that it was ‘brother’ and ‘brother’, there was no significant difference, the key was the dose, and she could increase fluoxetine to 2 capsules per day. In just over a week, the condition improved significantly. Another two cases of depression, which had been treated by a famous professor, used all kinds of antidepressants on the market and spent 20,000 yuan for two years without any improvement, and came to me for treatment. I asked the patient how many doses had been used; they said that they only used 1 capsule of each drug per day. I told them that this was the problem, or to go back to the oldest brand of fluoxetine and use 2 capsules per day, i.e. 40 mg. After 2 weeks of follow-up, all of them had broken into tears and regretted having spent 20,000 yuan for nothing. By the way: all those drugs mentioned above are now available domestically. Many patients often ask, “Is there any difference in efficacy between imported and domestic ones, and are the side effects the same?” In fact, all domestic generic drugs have been examined and approved by the pharmacognosy department, and the ingredients of imported and domestic drugs are identical; it should be said that the efficacy and side effects of the two are comparable and there is no significant difference. Generally speaking, there are almost no side effects when taking fluoxetine (correctly speaking, from the drug’s point of view, the drug has its therapeutic effect and also has its non-therapeutic side effects; from the patient’s point of view, the drug can produce therapeutic effects and also may produce non-therapeutic side effects). Very few patients may have some stomach discomfort during the first few days of taking the drug, but they get used to it after a few days. If the drug is taken at night, a few patients may have trouble sleeping, so we advocate taking it in the morning or in the morning. Taking fluoxetine will not increase your weight. Since fluoxetine inhibits the function of certain enzymes in the body, it can affect the metabolism of a few other drugs, and the dosage of these drugs may be reduced appropriately if taken at the same time. Some pharmaceutical companies advertise that paroxetine has a better sedative effect than fluoxetine, helps with sleep, and can treat anxiety. Their propaganda says that of 100 cases taking fluoxetine, 20 cases have poorer sleep, while only 10 cases of 100 cases of paroxetine. Actually, they are playing a mathematical statistical game, and we have to look at the other side, just with their published trials, there is no substantial difference between good sleep, 80% with fluoxetine, and 90% with paroxetine. All SSRIs, in fact, have the same therapeutic utility for anxiety; they also all lack the features that help address insomnia in depressed patients. We doctors should explain to our patients that “insomnia does not cause or worsen depression, but rather depression causes insomnia”, so that once the depression gets better, the insomnia will resolve itself. In order to fall asleep, sleeping pills can be taken temporarily. But sleeping pills are more addictive and should not be taken every day, especially clonazepam (clonazepam). Some doctors apply trazodone to help fall asleep, 50 mg, or less per night. Trazodone is an older antidepressant with side effects such as dry mouth and constipation, so it would be less appropriate and far less desirable than an SSRI to use larger doses to treat depression; however, it is still desirable to use its side effect of drowsiness to help patients fall asleep, and it is not addictive. Another drug that can be used is mirtazapine. It is an antidepressant with a different pharmacological effect than the SSRI. As mentioned earlier, the nerve endings of brain neurons release 5HT neurotransmitters, and these 5HT feed back to inform the brain neurons, telling them that ‘there is enough production’. If once this feedback pathway is blocked and the brain neurons do not get the feedback, then they will continue to produce and release 5HT neurotransmitters in large quantities. Mirtazapine relies on this pharmacological effect to treat depression and is, so to speak, synonymous with an SSRI. With mirtazapine, there may be a side effect, drowsiness, and that would just help with insomnia in depressed patients. However, in general, mirtazapine has a few more side effects (such as weight gain, or mild swelling) than an SSRI, and should be applied with care. Among neurotransmitters, besides 5HT, NE may also be associated with depression, so some pharmaceutical companies have developed drugs that inhibit both 5HT recycling and NE recycling, thus increasing the concentration of both in the synaptic gap, called SNRIs, such as venlafaxine and duloxetine. Since they affect both neurotransmitters, the side effects may also be more frequent. As a rule, these drugs mainly affect brain tissue, increasing 5HT and NE in the synaptic gap of brain neurons, but they can’t help but affect other parts of the body. An increase in 5HT may increase gastrointestinal motility, and an increase in NE may increase heart rate or blood pressure. Recently, the ‘little sister’ of citalopram, escitalopram, was listed. Older people may remember that at the beginning of the liberation, China introduced a process from the former Soviet Union to manufacture an antimicrobial agent for diarrhea called co-trimoxazole. It contains two ingredients, one is levorotatory, which has pharmacological effect, and the other is dextorotatory, which has no pharmacological effect; however, the process method is poor and cannot be separated, so it is called Hopomycin. Later, our country developed a new process to separate the left and right, and made a kind of left-rotated, called chloramphenicol. In fact, escitalopram is the left-sided citalopram, so 10mg per capsule; citalopram is a mixture of left and right, so 20mg per capsule. This table below lists the effective therapeutic dose of SSRI and how many side effects, it is only my personal clinical impression, for reference only. After understanding some of these, both doctors and patients will have the bottom of their hearts. SSRI (selective 5 serotonin receptor inhibitor) Treatment of depression Treatment of OCD Side effects 80% 20% 80% 20% * Fluoxetine (Benadryl) #1 #2 #2 #3-4 Generic paroxetine (Seroquel) #1 #2 #2 #3-4 More sertraline (Zoloft) #2 #4 #4 #6… Generic citalopram (Cipro) #1.5 #3 #3 #4… Least fluvoxamine (Lanxess) #6 #7… max. Note: [1]* refers to the number of cases requiring the number of pills. [2] Fluvoxamine has a short half-life and is taken multiple times a day; the rest of the drugs have a longer half-life and can be taken once a day.