What you should know about tricyclic antidepressants

Depression is one of the most common diseases. In terms of prevalence, it is second only to cardiovascular diseases. And of all those suffering from depression, no more than 20% seek qualified help.

In this article we will tell you about all the drugs used to treat depression.

All medications with antidepressant effects can be divided into several groups:

  1. Antidepressants.
  2. Normotimic drugs.
  3. Neuroleptics.
  4. Tranquilizers.
  5. Nootropics and metabolic agents.
  6. Herbal remedies.
  7. Amino acids.
  8. Psychostimulants.

Normotimic drugs

Medicines in this group have an antidepressant effect only in cases where the depressive state is caused by chronic affective diseases, such as bipolar affective disorder (BD, manic-depressive psychosis), cyclothymia, dysthymia, schizoaffective disorder. Most commonly used medications:

  • Carbamazepine (finlepsin)
  • Depakine chrono
  • Lamotrigine (Lamictal)
  • Lithium carbonate

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.

Neuroleptics

Despite the fact that most antipsychotic drugs depress the nervous system, among them there are drugs with antidepressant effects:

  • Flupenthixol (fluanxol).

    It has an antidepressant effect only when administered in small doses (less than 2 mg per day).

  • Aripiprazole.

    Effective for depression in bipolar affective disorder and schizitypal disorders.

  • Levomepromazine (tizercin).

    Prescribed for endogenous depression accompanied by insomnia.

Precautionary measures.

  • Tricyclic antidepressants may have a calming effect, so you may feel drowsy or less alert than usual. Therefore, you should know how you react to these medications before driving or operating any machinery.
  • These drugs may increase the effects of alcohol or other central nervous system depressants (medicines that depress the nervous system), which may cause serious side effects including severe drowsiness, memory problems, and loss of consciousness. While taking these medications, check with your doctor about your plans to drink alcohol or take any other medications.
  • If you are pregnant, planning to become pregnant, or breastfeeding, tell your doctor before taking these medications
  • Tell your doctor about allergies to any medications, as well as what medications prescribed or not prescribed by doctors you are taking
  • tell your doctor if you have glaucoma, urinary retention, or heart disease

Tranquilizers

  • Bromodihydrochlorophenylbenzodiazepine (phenazepam).

    The drug of choice for neurotic conditions with depression and post-stress conditions. That is, in cases where short-term treatment is required.

  • Clonazepam.

    Strong anti-anxiety and sedative effect. When taken for a long time it causes dependence.

  • Alprazolam.

    Prescribed for anxiety and depression. Recommended for short courses (no more than 10 days) due to the risk of developing addiction and dependence.

Tricyclic antidepressants

Antidepressants are among the most common medications in the world. Only antibiotics, painkillers and antipyretic drugs are in great demand. Some experts believe that taking such drugs does more harm than good. And the best doctor will not be able to know what will happen to the patient while taking such drugs.

It is imperative to study the instructions for the use of tricyclic antidepressants, their contraindications, and compare the benefits and harms of treatment. Do not take with alcohol under any circumstances; the consequences of such experiments can affect your entire life. Contraindicated for pregnant women, breastfeeding, those with problems with heart rhythm, prostate, cardiovascular diseases, thyrotoxicosis, glaucoma, impaired liver and kidney function. Tricyclic antidepressants have a withdrawal syndrome, which is characterized by headaches, vomiting, nausea, diarrhea, pain, burning in the abdomen, sweating, and even hallucinations.

The tricyclic antidepressant Coaxil was marketed as a miracle drug. Now it is difficult to say whether this medicine is good or evil. Uncontrolled use and over-the-counter use led to the drug exhibiting negative consequences. This antidepressant is used by drug addicts as a substitute for heroin.

Dependence on such a drug exceeds heroin and cocaine in severity, and withdrawal is especially scary, which lasts harder and longer. Even opiates cannot be used to quickly relieve withdrawal symptoms for drug addicts. The main symptom is the appearance of goose bumps with myalgia, they constantly migrate, the pain is so excruciating that a drug addict can cut his veins or injure other people. If such addicts are not treated, then this is a threat not only to their lives, but also to those around them. After all, withdrawal syndrome leads to very severe depression and the thoughts of a sick drug addict change with the speed of an electric current. Inexpensive help can only be provided by a special clinic where it is possible to quickly relieve withdrawal symptoms.

The power of the drug to destroy the body is such that thrombosis of the fundus vessels rapidly progresses, and vision cannot be returned. During intravenous administration of the drug, blockage of all blood vessels occurs, and this is gangrene. Young people's mouths are like old people's. Instead of teeth, young people have rotten remains, as cervical caries develops quickly. The psyche is suppressed much more than from heroin. When undergoing treatment at the Medic Group drug treatment center, where the principle of anonymity is applied, all services can be received in a calm atmosphere, the price is reasonable. The cost of treatment makes it possible for those who have a small income to be treated, when they need to quickly relieve withdrawal symptoms, go through the entire treatment process, rehabilitation, and restoration of the body.

We must not forget that tricyclic antidepressants are potent and very serious medications. Only a trusted doctor can prescribe such a drug. This happens strictly on an individual basis, in the appropriate dose.

Nootropics and Metabolic Aids

The remedies in this group help to get out of a depressive state that has developed against the background of stress, overwork, encephalopathy, the consequences of injuries and poisoning. By improving the blood supply to neurons and energy metabolism within cells, they contribute to the activation of cognitive functions and memory. The most effective drugs in this group:

  • Phenibut
  • Mexidol
  • Aminalon (GABA)
  • Piracetam (nootropil)
  • Picamilon
  • Pyriditol (encephabol)
  • B vitamins.

SSRI

Selective norepinephrine inhibitors (reboxetine, dosage 8–12 mg per day, half-life 13 hours, active metabolite desetylreboxetine) increase the concentration of norepinephrine in the synaptic cleft. Due to the numerous side effects associated with the influence of norepinephrine, SNRIs are used only for severe depressive episodes. Reboxetine is metabolized by CYP3A4, which limits its use in combination with drugs that affect the functioning of this cytochrome.

Are there non-drug treatments for depression?

In addition to medications, there are many non-drug treatments for depression. These are psychotherapy, biofeedback therapy, diet therapy, physical therapy, exercise therapy, reflexology, light and color therapy, sleep deprivation, etc. Most often, a combination of several methods is used to treat depression. For example: psychotherapy + drug treatment, biofeedback therapy + psychotherapy, medication + diet therapy, etc.

You cannot prescribe or use medications on your own. If you or your loved one is faced with the problem of depression, you need to see a psychiatrist or psychotherapist! Only according to his recommendations can you use drugs. Self-medication is life-threatening!

Directions for use

In many cases, these medications only need to be taken once a day, at bedtime. You may need to take them for several weeks before the condition begins to improve. Do not change the dose (take no less or more), or the regimen (take no more or less often), or stop taking your medication without talking to your doctor. Your doctor will help you choose the most appropriate medicine and dosage for you. To achieve the best treatment results, you need to carefully follow your doctor's instructions.

SSRIs

With selective blockade of only serotonin reuptake, the antidepressant effect of this group is better expressed. Drugs in this group include citalopram (dosage 10-60 mg per day, half-life - 33 hours, active metabolite - desmethylcitalopram), its more SERT-specific S-enantiomer escitalopram (dosage 5-20 mg per day), sertraline (dosage 50 -200 mg per day, half-life 24 hours, active metabolite - desmethyl sertraline), paroxetine (dosage 20-60 mg per day, half-life 8-30 hours), fluoxetine (dosage 10-60 mg per day, half-life 48- 96 hours, active metabolite - norfluoxetine) and fluvoxamine (dosage 50-300 mg per day). The last two drugs can also act on opioid receptors, producing an analgesic effect. Otherwise, the antidepressant effect of the above drugs is approximately the same. Also, their concentration does not change significantly in renal failure. According to many meta-analyses, escitalopram and sertraline have a better antidepressant effect, and citalopram has fewer side effects with good effectiveness. Escitalopram, depending on the dosage, can prolong the QT interval, which, unfortunately, does not allow the drug to achieve a better effect due to the need to reduce the dosage. Differences in the use of individual representatives of this group are presented in the table attached to the post. Fluoxetine and paroxetine are strong and citalopram and escitalopram are weak inhibitors of CYP2D6. Blocking this system increases the concentration of tricyclic antidepressants and antipsychotics in the blood, and the effect of tamoxifen (an estrogen antagonist, used in the treatment of breast cancer), on the contrary, decreases, since tamoxifen, being a prodrug, is activated in this system in the liver.

Blocking SERT itself causes a number of side effects, such as drowsiness and akathisia (internal restlessness due to serotonin 5HT2 receptors), especially at the beginning of therapy. Serotonin is also involved in platelet aggregation processes. The platelet membrane contains exactly the same serotonin transporter SERT as in neurons, therefore, due to a lack of serotonin, its vasoconstrictor effect on 5HT2A serotonin receptors is reduced. Therefore, drugs in this group should be used with caution if the patient has chronic inflammatory bowel diseases or is taking salicylic acid drugs (antiplatelet agents) or vitamin K antagonists (indirect anticoagulants). Due to increased stimulation of serotonin 5HT2A receptors in the very posterior field (area postrema) and 5HT3 receptors in the gastrointestinal tract, these drugs provoke vomiting, which can be stopped with 5HT3 serotonin receptor blockers (ondansetron). It is precisely because of the feeling of nausea that drugs in this group at the beginning of therapy lead to a decrease in the patient’s weight. Due to increased secretion of antidiuretic hormone, fluid retention occurs in the body, which leads to a decrease in sodium concentration in the blood in the first 4-6 weeks after starting medication in 10-20% of patients. Impaired potency is also observed when taking this group of antidepressants. Sertraline reversibly reduces sperm quality and causes ejaculation disorders. The reason for this is the indirect antagonism of dopamine receptors, which provokes hyperprolactinemia.

Dapoxetine is approved for use in the treatment of premature ejaculation. In this case, the drug received approval due to its side effects. However, in some cases, antidepressants of this group provoke reverse ejaculation (retrograde ejaculation of seminal fluid occurs proximally into the bladder, which can lead to inflammatory processes). Activation of serotonin receptors also affects the dopamine system: patients feel more tired (activation of 5HT2C receptors reduces the release of dopamine). Excess serotonin provokes tremors, headaches and osteoporosis, as well as pseudocholinergic dry mouth and particularly severe sweating of the scalp. An interesting fact is the following: at one time it was observed that an increase in determination and thirst for action with drugs of this group increased the number of suicides. It was assumed that increased readiness to act led to the fact that patients with depression were more likely to decide to commit suicide. But later, one large British study refuted this statement, proving that self-abstinence from drugs increases the number of suicides.

Separately, it is worth noting the drug bupropion (dosage 150-300 mg per day, half-life 20-37 hours, active metabolites - hydroxybuproprion, threohydrobuproprion, erythrohydrobuproprion), which is mainly an inhibitor of the reuptake of norepinephrine and dopamine, but also affects other transmitter systems . It is worth noting that its use does not lead to weight gain and only slightly affects sexual functions. This drug is also approved for use in the treatment of nicotine addiction.

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