My first antidepressant was Prozac.
I do not know why I decided to appoint him to Cromwell Hospital. Once considered revolutionary, the drug is currently not the antidepressant of choice, there are significantly more effective analogues. In addition, in my case, I needed a drug of a completely different group. But first, let's talk a little bit about the history of antidepressants and their classification.
Nerve cells are connected to each other by means of special contacts, called synapses and consisting of the ends of the connected nerve processes, separated by synaptic or interneuronal gap. When a nerve impulse is transmitted from the end of one of the processes, neurotransmitters are released, which we have already mentioned above, and, migrating through the interneuronal gap, reach the receptor of the cell that perceives the impulse.
All antidepressants, regardless of the mechanism of action, have a therapeutic effect, increasing the concentration in the synaptic gap between the neurons of the brain of one or more neurotransmitters at once – serotonin, norepinephrine and dopamine.
The history of antidepressants, like many other drugs, began by accident, with the discovery in 1957 of antidepressant properties in a number of anti-TB drugs and the proposal to use these side effects in the treatment of patients with depression. The first such drug was iproniazid.
Iproniazid, as well as its analogues, refers to the so-called non-selective and irreversible inhibitors of monoamine oxidase (MAO), the enzyme responsible for the destruction of brain-secreted mediators. It is clear that when it is suppressed, the concentration of mediators increases, which leads to a positive therapeutic effect. Other drugs of this series include imipramine, isocarboxazid, nialamide, as well as derivatives of amphetamine – tranilcipromin, pargyline. A big disadvantage of MAO inhibitors is their toxicity and the need to follow a special diet during their use in order to avoid the development of “serotonin syndrome”, poisoning the body with an excess of serotonin.
In particular, while taking MAO inhibitors should avoid eating foods such as cheeses, smoked meats, marinades, bananas, sauerkraut, legumes, yeast extracts and brewer’s yeast, red wine, beer, chocolate, caffeine, dairy products. The fact that these products in the human body do some special amino acids: tyramine, its metabolic precursor Terezin and tryptophan. Tyramine, as well as serotonin, is cleaved by monoamine oxidase and has the ability to increase blood pressure; accordingly, its excessive accumulation can lead to the development of hypertensive crises. Tryptophan also serves as a source for the production of serotonin in the body.
Serotonin syndrome is a dangerous condition, manifested by agitation and confusion, trembling limbs, respiratory failure, fever. In severe cases, it can lead to the death of the patient. MAO inhibitors are also incompatible with a range of medications, such as psychostimulants, antidepressants of another chemical group, cough medicines containing sympathomimetics, and many others.
Work to eliminate these deficiencies of the first antidepressants led to the synthesis of selective Mao inhibitors, the next generation of agents that require less restrictions on their appointment. These include Moclobemide, Pirlindola (Pirazidol) Eprobemide and Metralindol. However, due to the current presence of antidepressants with fewer side effects, MAO inhibitors are now rarely used for special indications. In particular, they are well established in the treatment of atypical depression.
The next group of antidepressants on the market were tricyclic antidepressants. They had less side effects and did not require a special diet. Tricycles are also compatible with a large number of other drugs. These include amitriptyline, nortriptyline, imipramine, anafranil, trimipramine and others.
Part of the tricyclic antidepressants, along with the actual antidepressant, also has an anti-anxiety and sedative effect, this group includes, for example, amitriptyline and trimipramine. In the action of others, such as imipramine and nortriptyline, expressed, on the contrary, the stimulating effect.
In General, tricyclic antidepressants are quite effective drugs for the treatment of depression, they affect the exchange of several mediators and are characterized by a relatively fast time of therapeutic effect, compared with drugs of other groups. Their great disadvantage is the indiscriminate effects and the presence of serious side effects – lethargy, drowsiness, dry mouth, constipation, inhibition of libido and erection.
Selective serotonin reuptake inhibitors (SSRIs) became the latest class of antidepressants, which gained huge popularity due to the selectivity of action and the presence of fewer side effects. As the name implies, the drugs of this series inhibit the reuptake of nerve endings already isolated in the intersynaptic gap of serotonin, which leads to an increase in its concentration and enhance its inherent effects. The first drug of this series was the famous Prozac. With his appearance, many predicted the beginning of a revolution in the treatment of depression, the final solution to the problem. This of course did not happen. SSRIs are really convenient to use and less poison the patient’s life with side effects, but the price for this is their lower efficiency, compared to tricyclics and MAO inhibitors.
In addition to Prozac (fluoxetine), this group includes sertraline (zoloft), paroxetine (paxil), fluvoxamine (Luvox), estsitalopram (Cipralex), citalopram (CELEX). Despite the lower frequency and severity of side effects, SSRIs are all the same from them is not free. The most common are insomnia or, conversely, drowsiness, headache, tremor, fatigue, sweating, nausea, libido and potency disorders, ejaculation delay.
Subsequently, selective drugs with the same mechanism of action as SSRIs acting on the exchange of other neurotransmitters were synthesized:
Selective norepinephrine reuptake inhibitors (SSRIS))
Reboxetine (Edronax), Atomoxetine (Straterra) are usually well tolerated and have a pronounced activity in melancholic depression.
Selective inhibitors of reverse takeover serotonin and noradrenalina (Sossin)
Venlafaxine (Effexor), DULOXETINE (Cymbalta), Milnacipran (Ixelles)
Modern antidepressants with small side effects, are more effective than SSRIs and SSRI, are approaching in this respect to tricyclic antidepressants. Proved to be effective in the treatment of severe depression.
Selective reuptake inhibitors of norepinephrine and dopamine (Cesnid)
Bupropion (Wellbutrin, Zyban)
A very interesting drug, has a pronounced energizing and stimulating effect, some researchers even treated previously to psychostimulants. It is effective in melancholic depression, has a disinhibiting effect on the libido, which distinguishes it from most other antidepressants that have the opposite effect. An interesting feature of Bupropion is to reduce the thrust to the use of nicotine, for use for this purpose it is produced under the commercial name “Zyban“.
Noradrenergic and specific serotonergic antidepressants (Nassa)
Mianserin (Lerivon, Bonseron) and Mirtazapine (Remeron)
Drugs in this group affect the metabolism of norepinephrine and serotonin, it is blocking the serotonin receptors responsible for the side effects at prima SSRIs, such as nausea, decreased libido, nervousness, insomnia. However, they have a pronounced sedative effect and contribute to weight gain, through the effect on insulin metabolism, increased appetite and water retention in the body.
Specific serotonergic antidepressants (SSA)
For drugs in this group include Trazodone (Desyrel, Trittico) and its newer derivative of Nefazodone (Serzon).
SSA, as well as Nyssa, block the “bad” receptors of serotonin and do not cause some side effects inherent in the classic SSRI. Trazodon, for example, has a stimulating effect on potency in men and can even lead to the development of priapism, painful long-term erection, requiring, approximately in every third case, surgery.
Nefazodon has a strong hepatotoxicity, which limits its use, it is currently banned for sale in the United States.
In General, there are several common stereotypes about antidepressants. Some patients believe that taking psychotropic drugs or even a consultation with a psychiatrist are equal to recognizing themselves as crazy and continue to endure their suffering, hoping that everything will resolve itself. This is self-deception, and self-deception is very dangerous. In any case, it is impossible to allow the chronification of the process, the earlier adequate treatment is prescribed, the more likely the positive outcome of the disease. It should be understood that depression is the same disease as hypertension or gastric ulcer, and requires appropriate therapy, the disease can not be anything shameful.
Another common opinion is the hypertrophied danger of taking antidepressants, an exaggeration of the degree of harm they cause to the body. Many people think that a serious dependence develops to antidepressants, almost as to drugs, and, having hooked on them once, it will be almost impossible to get off. This is certainly not the case. Antidepressants are designed for long-term use, and most of them do not cause any undesirable effects after completion of treatment and discontinuation of their use. There are some exceptions to this rule, which I will discuss later in this Chapter.
There are also concerns, mainly from creative professionals, about the possible negative impact of psychotropic drugs on creativity. What can we say about this? Yes, a number of drugs (not all!) has a sedative effect and enhances the braking processes in the brain. But if you suffer from depression, your creativity will be weakened in any case, and it is in your best interest to get out of this state as soon as possible. Antidepressants, with all their shortcomings, make it possible to bring your mind in order in the shortest possible time, compared to other treatments. In addition, the positive effect of their reception in most cases overlaps the negative and creative abilities can even improve on the background of taking drugs, compared with the same abilities in the absence of adequate treatment.
A big disadvantage of almost all antidepressants is the slowness of the effect, in most cases it takes at least 2-4 weeks to start the actual antidepressant action. Anti-anxiety or, on the contrary, a stimulating effect, may develop earlier. This feature causes certain difficulties in the selection of the drug for the treatment of a particular patient.
First of all, the doctor should evaluate the type of depressive disorder and prescribe an antidepressant to the patient, which has the necessary characteristics to combat this type of disease. For example, in case of anxiety depression should choose a drug with a sedative component of the impact, with inhibited, on the contrary, with stimulating.
Specific drugs are selected depending on the degree of disease. With mild depression, it is even possible to dispense with the appointment of herbal preparations based on St. John’s wort, which have moderate antidepressant activity.
St. John’s wort has practically no side effects, except for the phenomena of photosensitization, increasing the sensitivity of the skin to ultraviolet radiation: during its reception, it is contraindicated to sunbathe and visit the Solarium.
At an average, and in some cases of mild depression the drugs of choice are inhibitors of reuptake neurotransmitters, the SSRI, NARI, Sossin, Sioned. In severe depression, large doses of tricyclic antidepressants are prescribed, combined with drugs of another group. MAO inhibitors have proven themselves in the treatment of atypical depression, in which the symptoms of classical depressive disease are not expressed, vegetative disorders, anxiety prevail, the reverse cycle of daily mood fluctuations is characteristic, in the morning the emotional state is better than in the evening.
Two important factors should be taken into account when assessing the effectiveness of antidepressant action on a particular patient. It’s time and dosage. To develop the effect, it is necessary to give the drug a time of at least a month, after which, depending on the results, you can adjust the dosage upward or downward. If the result is unsatisfactory and after adjustments, which may be several, the doctor should either change the drug, or Supplement its effect with the appointment of another antidepressant.
It is clear that the selection of the drug occurs by trial and error, it may take many months before it is possible to determine the optimal scheme of drug treatment. The General rule of drug therapy for depression is to achieve the disappearance of all its symptoms, after which treatment continues for at least six months, after which a gradual decrease in dosage begins, until the complete abolition of the antidepressants used.
Unfortunately, this tactic is not always effective. Antidepressants do not treat the cause of depression, they only remove its symptoms, and if during treatment nothing has changed in the patient’s life, the traumatic factors have not gone or have not been worked out, the likelihood of relapse is very high.
It is important to keep in mind that antidepressants are incompatible with alcohol. First, there may be a cumulative sedative effect from the simultaneous intake of alcohol and a number of antidepressants used to treat anxiety depression. Can develop serious poisoning of the body, up to the suppression of the respiratory center and death. Secondly, alcohol further enhances the processes of inhibition in the brain of patients with melancholic depression. And thirdly, the interaction of alcohol and a number of psychotropic drugs has not yet been fully studied and the neurotoxic effect on the brain tissue of their metabolic products is not excluded.
As I said above, most antidepressants are not addictive and addictive. Antidepressants are designed for long-term, in some cases even life-long use. Very many of them do not cause any withdrawal syndrome. But for some drugs, there are certain difficulties associated with discontinuation of their use. Of those antidepressants that I have taken, these include Paxil and Effexor (Venlaflaxine).
The paxil by itself, the drug is very effective. It belongs to the SSRI, inhibits the reuptake of serotonin in the synaptic cleft and is in this respect stronger than Prozac and Zoloft. An additional advantage of Paxil is its positive effect on the treatment of social phobia, patients become more sociable, social activities frighten them to a lesser extent. At the same time, Paxil has a short half-life from the body, and therefore the risk of withdrawal syndrome at the termination of its reception is quite high.
I took paxil for about two months and was dissatisfied with its effect, but trying to switch to another drug, experienced serious unpleasant effects, the mood has deteriorated, increased the frequency of panic attacks, I almost could not normally perform their social functions. I had to go back to him, given the fact that the second time to remove the drug is already under the supervision of a doctor and with great caution.
The effector did not come to me from the first days, I had difficulty sleeping, severe dizziness and stopped taking it less than a week after the start of the course. Personally, I didn’t have withdrawal syndrome, but I’ve met a few reviews online from people who have taken it significantly longer than I have, and for whom the rejection of the Effector has become a big problem.
Below I will briefly describe my experience of taking other antidepressants.
As I said, Prozac was my first psychotropic drug. I knew that the action of SSRIs, to which he belongs, develops slowly, but nevertheless laid great hopes on him, believing that bringing back to normal the disturbed balance of serotonin will eliminate all manifestations of my disease.
Prozac was released on the pharmacological market in the mid-80s of the last century and quickly gained immense popularity, becoming a cultural phenomenon, imprinted in several popular works of literature. With the advent of great hopes were linked, there were concerns about the decline of psychoanalysis, the uselessness of all the others that existed on the day of antidepressant drugs. Minimal, compared with MAO inhibitors and tricyclics, the number of side effects allowed to take it daily, without making significant changes in your lifestyle, a kind of lifestyle drug.
But it turned out that for better portability you have to pay less efficiency. I took Prozac for three months, initially 20 mg in the morning, then this dose was doubled. It was the most useless antidepressant I’ve ever been prescribed. It did not have any positive effect on me, these three months I add to the previous six, conducted without receiving adequate therapy.
As a result, I changed not only the antidepressant, but also the attending physician. The next in the list of my drugs was zoloft, the same SSRI, but more modern and considered more effective. I took it for a few months, and it had some antidepressant effects. Do zoloft stronger than Prozac, but the normalization of the exchange of serotonin for me was not enough, and I switched to Remeron.
The advantage of this drug is the effect on the metabolism of not only serotonin, but norepinephrine. Don’t know why, but it was in my case practically useless. In addition to some anti-anxiety action, I did not feel anything and two months later was transferred to the drug from the same group Lerivon (Mianserin).
Lerivon has a strong sedative effect, he removed the alarm, but with it eliminated any desire for any activity during the day. I had a feeling that I was wearing a helmet on my head, which protected my mind from any influence of the outside world, both negative and positive. On Lerivone I first felt a good antidepressant effect, in General, the drug for me was quite effective, and I took it for about six months. Its huge drawback is the water retention in the body and increased appetite, leading to rapid weight gain. For the first three months I added 10 kg, instead of 75 kg I began to weigh 85 kg. Before the therapy I did not think it was a big problem, but very quickly I realized that this weight strongly poisons my life. Dissatisfaction with my appearance and physical discomfort did not contribute to the improvement of my emotional state. In addition, the complete reduction of symptoms has not occurred, despite the constant increase in dosage.
As a result, I decided to turn to tricyclic antidepressants and started taking amitrip-Tylin. This is a very effective drug. With the right dosage, it can really eliminate all the symptoms of depression. In my case, this happened at 150 mg per day, which is not a very large, average dose. Amitriptyline affects the exchange of all three major mediators and has a pronounced sedative effect, in some sources indicate its stimulating, at a certain dosage, the effect, I did not notice.
Together with depression, amitriptyline cuts off all the emotions from a person, most of the day I was half asleep, slept for 10-12 hours a day. About any pleasure from life of the speech and could not be, I turned into the robot which did not test not only sufferings, but also in General more than anything. Besides, I have developed a normal weight for tricyclics, the side effects: constant thirst and dry mouth, severe urinary retention, confusion in thought and action, slow speech, almost totally killed libido and potency. The most unpleasant was the feeling of dullness, each thought had to be formulated with difficulty, suddenly the vocabulary became poor, writing a short e-mail became a big problem for me.
With all this, depression and anxiety was not, objectively, I no longer felt related to them of torment, the life of the vegetable was preferable to constant fear and depression. This went on for another 8 months, in full compliance with the existing medical doctrine, my doctor (the third in a row) and I achieved a complete reduction of symptoms in two months and waited another six months before the start of the dosage reduction.
With a decrease in the amount of amitriptyline taken, the symptoms began to return strictly in the same order in which they disappeared. I wasn’t just disappointed. I realized that drug treatment in my sense is simply meaningless without addressing the real causes of depression, which I still had a long time to understand. But this was still far away, and I had to think what to do next. I did not want to return to the previous dose of amitriptyline and drag out my former existence. All this time I was supported by the hope for a cure, the fact that in six months or a year everything will end and I have to endure this time, only temporarily live the life of a vegetable. The prospect of a permanent existence in this mode did not suit me.
I changed another psychiatrist. In fact, such throwing does not make much sense, in drug therapy of depression there is a certain pattern, which is followed by more or less versed in the subject of doctors. I see my behavior as another manifestation of illness, a break from reality, in the hope of finding a miraculous deliverance.
In this state, I began to combine drugs. Having reduced the dose of amitriptyline twice to feel something, I consistently added fluvoxamine, zoloft, paxil to it, without achieving a satisfactory result.
So here is a blind I picked up for myself an effective drug. They found Trazodone (Desyrel). These days, this antidepressant is not very popular, preference is usually given to serotonin drugs like Zoloft and Paxil, but I suddenly went very well. Expressed antidepressant effect I felt a few days after starting, which is unusual for most of these drugs. It was combined with a good anti-anxiety effect, due to the sedative nature of trazodone, but softer, not causing total dullness, as in the case of amitriptyline. Another advantage of trazodone was its positive effect on sexual function, as I wrote above, because of this effect, it is sometimes prescribed as an auxiliary drug for the treatment of erectile dysfunction, including that caused by taking other antidepressants.
In this combination, Amitriptyline + Trazodon, I lasted quite a long time. There was some compromise between depression and emotional stupidity, I was somewhere in the border area, not falling in any direction. Health is of course the name was not, moreover, such a therapeutic approach is wrong, because of incomplete reduction of the symptoms of depression leads to its stable of chronification. But what was I supposed to do?
The last time you start taking the drug in my case was Wellbutrin. Unfortunately, today it is not officially delivered to Russia and can be purchased only on Western websites. The drug is very interesting, and we can only regret that it is not available to most Russian patients. Its peculiarity is the effect on the exchange of dopamine and norepinephrine, as a result of Wellbutrin has a stimulating effect and is effective in the treatment of anhedonia, the inability to enjoy life. This is manifested in the disinhibiting effect on the libido, and in the General increase in human sensuality.
Wellbutrin suited me, I took the usual therapeutic dose, 150 mg every morning, combining it with trazodone and amitriptyline. The dosage of the latter varied depending on the effectiveness of other methods used by me at different times to combat the disease. For this cocktail I continued to hold on to the last two years. Manifestations of depression at the same time significantly reduced, but still not completely disappeared. I did not experience more panic attacks due to the sedative effect of trazodone and amitriptyline and could remain relatively active due to the stimulating effect of Wellbutrin. Actually tonight I took sadatoki to sleep, and stimulants to Wake up.
This regime is by no means universal, and the selection of antidepressants should be made individually in each case. But I hope that the information in this Chapter has given you some insight into the mechanism of action of various drugs and can help you in finding, together with your doctor, a suitable antidepressant or a combination of them.
Can antidepressants cure depression? In some cases. If the depressive episode occurred for the first time, was diagnosed in time and has not yet had time to be chronicled, if the correct treatment is prescribed from the beginning of the disease, and the traumatic situation was resolved during the course of therapy, then Yes, there is a chance that only drug therapy can defeat depression.
Unfortunately, this is not always the case. In most cases, antidepressants allow the patient to gain time, give a break, during which it is necessary, using psychotherapy and other methods, to cope with the cause of the disease, to deal with their own mental blocks and change the attitude to the traumatic situation.
To do this, it is important to undergo courses of psychotherapy.