Dependence on antidepressants: how it affects the human body

Since 1990 TCA antidepressants are replaced with SSRI antidepressants. With relatively the same level of effectiveness, SSRIs are safer than TCAs. However, SSRIs have side effects that may affect your treatment.

Tolerability and side effects are different, but very closely related concepts. One of the main reasons for stopping treatment with antidepressants is the severity of their side effects. 43% of people with depression stop taking antidepressants due to side effects. Patients taking TCAs are more likely to discontinue treatment and experience more side effects than patients taking SSRIs.

More information about the main side effects:

Bleeding

– SSRIs are thought to influence hemostasis by affecting the uptake of serotonin by platelets. The more strongly antidepressants act on serotonin uptake, the higher the risk of bleeding. This applies to SSRIs and venlafaxine, the antidepressant with the most potent serotonergic effect of the SSRI group.

– SSRIs increase the risk of gastrointestinal bleeding.

– The risk of bleeding is increased by SSRIs, but not by TCAs.

– The risk of bleeding increases the simultaneous use of SSRIs and aspirin, SSRIs and non-steroidal anti-inflammatory drugs.

SSRI

Venlafaxine and duloxetine block the reuptake of both serotonin and norepinephrine, and both are substrates of CYP2D6.

Venlafaxine (dosage 75-300 mg per day, half-life - 5 hours, active metabolite - desmethylvenflaxine) is characterized by low bioavailability (less than 20%) when taken orally. At low dosages, it is able to inhibit the reuptake of serotonin, and at high doses, norepinephrine, which, however, does not in any way affect its antidepressant potential. Venlafaxine is also capable of partially inhibiting dopamine reuptake.

Duloxetine (dosage 30–90 mg per day) blocks the reuptake of both neurotransmitters equally. As you can already guess, acting only on the reuptake of neurotransmitters, selective inhibitors of this group do not have atropinergic and sedating effects, unlike tricyclic antidepressants. Sometimes patients begin to complain of difficulty urinating, sweating and impaired potency, but this rarely leads to refusal to take medications. These drugs are contraindicated for liver disease, severe hypertension, epilepsy and glaucoma.

Side effects on the cardiovascular system

– SSRIs were originally introduced as a safe alternative to TCAs. Recently, there is emerging evidence that SSRIs produce cardiovascular side effects, such as prolonging the QT interval, thereby increasing the risk of ventricular arrhythmias. However, TCAs prolong the QT interval more significantly than SSRIs. Among the SSRIs, citalopram has the strongest effect on the QT interval.

– TCAs are more likely to cause cardiovascular adverse reactions than SSRIs; Mirtazapine has a very low risk of these types of side effects; SSRIs have the highest risk of increasing blood pressure; among SSRIs, venlafaxine (at a dosage of 150 mg/day) has the highest risk of increasing blood pressure; Increased blood pressure due to SSRI use is very rare.

– All antidepressants except SSRIs increase resting heart rate and reduce heart rate variability; This effect is most significant when taking TCAs.

Withdrawal syndrome

Many people do not trust such medications because they do not know whether antidepressants are addictive and are afraid that they will have to be on pills for the rest of their lives. This occurs due to misunderstanding of their actions and failure to comply with doctor's instructions when canceling them. You should know that you cannot stop taking it on your own after feeling a little relief, this will lead to the return of depression. The medicine must be taken as a full course, from 4 to 9 months, sometimes longer.

If you abruptly stop taking the drug, the following symptoms appear:

• 
  anxiety;

• headache and dizziness;
• fatigue,
• painful condition;
• muscle pain:
• sleep disorders;
• nausea;
• flu-like manifestations;
• tremor;
• paresthesia;
• nervousness;
• memory impairment;
• hallucinations.

Duration is from one to two weeks, after which all symptoms disappear . Therefore, the drug must be discontinued with a gradual dose reduction. Symptoms from each group of substances manifest differently, which leads to beliefs that there are antidepressants that cause addiction. Sometimes reducing the dosage does not relieve the withdrawal syndrome, which is accompanied by a long period of mild symptoms.

Hepatotoxicity

– The weakness of MAO and TCA antidepressants was considered to be their hepatotoxicity. Recent research confirms this idea and, in addition, shows the presence of a risk of hepatotoxicity with new antidepressants.

– The risk of hepatotoxicity is relatively higher when taking nefazadone, bupropion, duloxetine, agomelatine; the risk is relatively lower when taking citalopram, escitalopram, paroxetine, fluvoxamine.

– In the TCA group, clomipramine and amitriptyline have high hepatotoxicity.

– Agomelatine has the highest risk of hepatotoxicity.

– Milnacipran increases the risk of hepatotoxicity more significantly than duloxetine.

– SSRIs, compared with other antidepressants, do not significantly increase the risk of hepatotoxicity.

Prevention of depression

The appearance and development of depression depends on the person himself, on his lifestyle, worldview, and relationships with the outside world. And if human activity is associated with stress and mental tension, then it is extremely important to prevent the occurrence of depression. Prevention is primarily a healthy lifestyle, proper sleep and rest.

Sleep should be from 21 o'clock to 5 o'clock in the morning - this is considered the best time for healthy sleep. Meals must be balanced, three times a day at the same time. It is important that 70% of food should be consumed before 15 hours.

To avoid depression, you also need to lead an active lifestyle, include in your regimen, if not morning jogging, then at least walking and visiting the pool.

Convulsions

– Bupropion is considered the riskiest drug for seizures. But a lot depends on the dosage form. Bupropion IR (immediate release) at a dose greater than 450 mg increases the risk of seizures by 10-fold. Bupropion SR (extended release) at doses up to 300 mg increases the risk of seizures by only 0.01-0.03%. The same slight increase is observed when taking SSRIs.

– TCAs have a higher epileptogenic potential than bupropion, so antidepressants of this group are contraindicated in patients with a predisposition to seizures.

– Current research complicates the understanding of the risk of seizures. New evidence suggests that all antidepressants appear to increase the risk of seizures.

– The riskiest antidepressants: trazodone, lofepramine, venlafaxine. In the SSRI group, the greatest risk is when taking paroxetine and citalopram, the lowest when taking escitalopram and sertraline.

– According to other data, SSRIs are more dangerous than TCAs and the highest risk of seizures occurs when taking sertraline.

– Large studies, however, show that grand mal seizures occur more often in patients taking TCAs rather than SSRIs.

What happens if during treatment the patient stops taking the prescribed drug?

It all depends on the situation. If the withdrawal is abrupt, there is a high risk that the body will not have time to adapt to the new regime, and the side effects will increase exponentially. This is called withdrawal syndrome and can be expressed in different ways. Most often, patients complain of dizziness, headaches, sleep disorders, spasms and tremors in the limbs. There is also a rebound syndrome, in which untimely withdrawal from the drug provokes the return of all the negative symptoms of depression. With gradual withdrawal, such consequences do not occur, so it is extremely important to adhere to the dosage regimen prescribed by the doctor.

Suicide

– The FDA in 2004 required manufacturers of antidepressants to place a warning on their packaging about the increased risk of suicide in children and adolescents. The controversy of this rule is that the disease, which is treated with antidepressants, itself increases the risk of suicidal behavior. Limited data on the association of antidepressant use with suicide attempts still does not allow us to draw a clear conclusion.

– A relative increase in suicide risks is observed with venlafaxine, escitalopram, imipramine, duloxetine, fluoxetine and paroxetine.

Treatment

If you feel that the quality of your psychological life has deteriorated or you see a problem in someone close to you, consult a doctor. Depression must be treated promptly to prevent its progression. It prevents a person from living a full life.

Antidepressants will help cope with depression, anxiety, and relieve weakness and apathy. Therefore, if the doctor, having assessed the condition, prescribes a treatment regimen, you must strictly follow it.

Any specialist will answer the question of whether there is dependence on antidepressants in the negative. And if after therapy and cessation of use the condition worsens, this is not addiction, but perhaps the wrong drug was selected and the disease was not treated. Even after taking pills for several years, a person can always refuse them by following the rules for exiting therapy.

Overdose safety

– Among those who commit suicide, the most common mental disorder is depression. One in four patients with depression attempts suicide. For this reason, the safety of higher doses of antidepressants is very important.

– The highest hazard index (number of deaths per thousand poisonings with antidepressants) is for amoxapine, maprotiline, and desipramine. All SSRIs and SSRIs have a lower hazard index than TCAs.

– The proportion of deaths in the total number of poisonings for SSRIs is less than for venlafaxine and mirtazapine.

Literature:

1. Pharmacology of antidepressants / I. A. Vinogradova, V. D. Yunash, S. V. Goranskaya, etc.; Ministry of Science and Higher Education of the Russian Federation, Federal State Budgetary Educational Institution of Higher Education "Petrozavodsk State University". — Petrozavodsk: PetrSU Publishing House, 2020. – 36 p.
2. Psychotropic drugs: reference book. practicing physician / F. Bochner et al.; scientific ed. rus. ed. Yu. A. Alexandrovsky; lane English A. N. Redkin. - Moscow: Litterra Publishing House, 2006. - 292 p.
3. A short reference book on psychopharmacology, pharmacotherapy and mental pathology / Kozlovsky, Vladimir Leonidovich. — St. Petersburg: SpetsLit, 2015

Sexual dysfunction

– Sexual dysfunction in patients with depression is caused by the disease and the medications prescribed to treat it. All antidepressants that affect serotonin or norepinephrine uptake cause sexual dysfunction. There is no evidence that SSRIs and SSRIs are less effective in this area than TCAs.

– The most common causes of sexual dysfunction are citalopram, fluoxetine, paroxetine, sertraline and venlafaxine. Imipramine is the same, but weaker than the five named antidepressants.

– Bupropion has the weakest sexual side effects compared to other modern antidepressants.

Use of antidepressants

Antidepressants are psychotropics for the treatment of depression, acting on neurotransmitters, reducing anxiety and apathy, and increasing mental activity. At first they were used only for depression, but then properties were discovered that influenced other somatic, mental and neurological diseases. Some have an analgesic effect and are used for chronic pain and migraines. They are also used for therapy:

• post-traumatic stress disorder;
• narcolepsy;
• phobias;
• bulimia nervosa;
• neuroses;
• enuresis;
• panic states;
• nicotine craving;
• obsessive-compulsive disorder.

Until the 20th century, it was believed that the cause of depression was a decrease in the level of the neurotransmitter serotonin, and if you stimulate its production, you can get rid of the painful condition. Many corrected this situation by taking opiates and cocaine, natural antidepressants, until they encountered the problem of addiction. Then it turned out that hormonal disorders, various somatic diseases, alcoholism and drug addiction, and seasonal depressive conditions can also lead to depression.

Weight gain

– Previously, it was believed that SSRIs and SSRIs contributed to excess weight gain. Among the SSRIs, the riskiest in this regard is paroxetine, and among the TCAs, amitriptyline. However, on average, weight gain occurs similarly with amitriptyline, sertraline, and fluoxetine.

– SSRIs and SSRIs may be associated with weight loss. After 4 months of treatment, this effect disappears, and paroxetine begins to contribute to the gain of extra pounds.

– Amitriptyline and mirtazapine promote weight gain in short-term and long-term treatment.

– Imipramine and bupropion promote weight loss or relatively slow weight gain in short-term and long-term treatment.

– In general, the latest evidence suggests that weight gain occurs to some extent when taking all antidepressants.

Does taking antidepressants guarantee a complete cure for depression?

Unfortunately no. Often, the causes of depressive disorders lie not in physiology, but in human psychology, so drug therapy has only a temporary effect, which gradually fades away after discontinuation of the drug. Knowing this, doctors usually use antidepressants as part of a comprehensive treatment that also includes psychotherapy sessions. However, some patients only need medication to recover. On the contrary, they don’t help some people. Depression is a very complex disorder, so doctors select their own treatment methods for each specific case.

Hyponatremia, sleep disturbances, sweating

– The first reports of hyponatremia due to antidepressants involved TCAs. But the risk of hyponatremia is higher with SSRIs than with TCAs.

– The highest risk in the SSRI group is citalopram and escitalopram.

– Venlafaxine has the same risk as SSRIs or higher.

– The risk of hyponatremia when taking antidepressants increases in elderly patients and in cases of concomitant use of diuretics.

– The effect of antidepressants on sleep can vary greatly. The duration of sleep may be reduced, or it may be increased.

– Venlafaxine reduces the REM sleep phase, which is why it is prescribed in the treatment of narcolepsy.

– Many TCAs have a very strong sedative effect.

– Bupropion may cause insomnia.

– Increased sweating occurs with TCAs, SSRIs, and SSRIs.

– Sweating is observed in 10% of patients taking SSRIs, venlafaxine, TCAs.

Are antidepressants compatible with alcohol?

During drug treatment of depression, alcohol consumption should be avoided. At the same time, different groups of antidepressants interact with alcohol in different ways. Mixing some (for example, tricyclic antidepressants) with alcohol can lead to serious consequences, including death. More modern drugs are not so dangerous in this regard. But MAO inhibitors, for example, can affect vasoconstriction (and therefore, indirectly, on erection), and can also enhance the effect of strong drinks and provoke, for example, damage to the liver or nervous system. Exactly how the drug interacts with alcohol is always written in the instructions. And in most cases this interaction is undesirable.

Sources

1. Lacasse JR, Leo J. Serotonin and depression: a disconnect between the advertisements and the scientific literature // Florida State University College of Social Work, Tallahassee, Florida, United States of America PLoS Med. - 2005. - T. 2, No. 12.
2. Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry 1998 // https://www.uptodate.com/contents/discontinuing-antidepressant-medications-in-adults/abstract/17
3. Haddad PM Antidepressant discontinuation syndromes // Drug Safety journal. - 2001. - Vol. 24, no. 3. - P. 183-197. - PMID 11347722.
4. American Psychiatric Association. The Truth About Antidepressants // https://www.psychiatry.org/news-room/apa-blogs/apa-blog/2016/03/the-truth-about-antidepressants
5. Tarasenko O. A. Side effects of antidepressants // Pharmacist. - 2003. - No. 14. https://www.provisor.com.ua/archive/2003/N14/art_33.php
6. WHO Mental Health Program // https://www.who.int/mental_health/mhgap/evidence/depression/q2/ru/
7. F Hieronymus et al., Efficacy of selective serotonin reuptake inhibitors in the absence of side effects: a mega-analysis of citalopram and paroxetine in adult depression // Molecular Psychiatry, 2017; doi:10.1038/mp.2017.147
8. Rafael Gafoor. Antidepressant utilization and incidence of weight gain during 10 years' follow-up: population-based cohort study // BMJ 2018; 361 https://www.bmj.com/content/361/bmj.K1951
9. Megan Brooks. Antidepressants Worsen Sexual Dysfunction and Depression? https://www.medscape.com/viewarticle/870660
10. Kucher E. O., Shevchuk M. K., Sivak K. V. Experimental study of the influence of alcohol on the biological effects of antidepressants // Bulletin of St. Petersburg University. – 2010. – Series 11, issue 1. https://vestnik.spbu.ru/pdf10/s11/s11v1_10_S.pdf

Features of prescribing drugs to calm nerves and against depression

Medicines for depression and anxiety have a pronounced effect; these are potent drugs that have a number of contraindications and side effects if the doctor’s prescription and instructions for use are not followed.
This is why you cannot buy medications for depression without prescriptions in our country. It is impossible to either prescribe or stop taking anti-depression medications on your own; this can affect mental health and lead to the development of depressive conditions and even suicidal thoughts. Therefore, it is very important to follow all the doctor’s recommendations, take medications for depression and stress in the dosage in which the doctor prescribed them. Even if a person’s mood improves after a week and the main symptoms disappear, they cannot stop taking the medicine.

The drug method is quite effective for anxiety-depressive disorders and neurotic conditions. It is important that the diagnosis of depression be made by a specialist, since taking medications simply to lift your mood in the absence of mental abnormalities can only cause a number of side effects. Antidepressants, antipsychotics and tranquilizers are potent drugs that are prescribed only with a doctor-confirmed diagnosis. Self-medication is unacceptable. Next, we will consider the main medications for stress and depression that are prescribed to patients.

• You can't convince me to get treatment
  ?
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Nootropics for depression and asthenia

Nootropic drugs, also known as cerebroprotectors or neurometabolic stimulants, are an effective means for a specific effect on higher mental functions. It increases the resistance of the central nervous system to the effects of negative factors of traumatic episodes. Nootropics have a positive effect on a person’s intellectual and cognitive abilities, help them improve memory, concentrate on what’s important, increase learning ability and stress resistance.

These psychotropic medications are divided into the following groups:

• true;
• neuroprotectors;
• primary action;
• secondary action;
• neuroregulatory.

They have various effects: anticonvulsant, muscle relaxant, mnestic, antihypoxic, help with ischemia and intoxication, improve metabolism and metabolic processes in the central nervous system, and neurotransmitter metabolism.

Contraindications include pregnancy and lactation, stomach ulcers, kidney and liver diseases, and allergic reactions to the components of the drug. Before prescribing them, the doctor examines the patient and takes a urine test during the course of therapy to obtain accurate data on the results of treatment.

Antipsychotics for depression and anxiety

Today, drugs such as antipsychotics are actively used in the treatment of depression and neuroses. They eliminate panic fears, anxiety, and normalize sleep patterns.

Doctors classify them depending on their chemical structure.

1. Dibenzazepines are necessary to combat psychotic manifestations, they are perfectly combined with other medications, but they have a minimal sedative effect and have quite a few adverse reactions.
2. Aliphatic phenothiazines have a greater sedative and calming effect and eliminate sleep problems.
3. Phenothiazine derivatives are used in the presence of pain and problems with blood vessels.
4. Butyrophenones are drugs that are used in medicine to combat delusional disorders and hallucinations; they have practically no sedative effect.

There are 2 types of antipsychotics: typical and atypical (as well as those with prolonged and non-prolonged action). In the first case, these are drugs that are already a thing of the past; they did a really good job with their main task - relieving psychotic symptoms, but had a fairly large number of undesirable side effects.

In the second case, the use of atypical antipsychotics is more modern. These are the latest generation drugs, antipsychotics, which have virtually no side effects. If drugs have a prolonged effect, this means that they have a long-term effect on the body, for example, for a month.